For many reasons related to the administration duties from the majority of the Portal staff (myself included), the activities in the Portal have been slowed down. In addition to the fact that OAEs and neonatal screening are NOT the new kids in the block anymore, and as a consequence new software and hardware developments are hard to come by.

In 2025, the members of my lab with a cooperation from  the Institute of Physiology and Pathology of Hearing in Warsaw, will present a series of Reviews on the hearing screening practices across the globe. We have identified 4 major geographic areas, such as Europe, Africa, West Asia and South America. We have purposely omitted data from North America and Australia, where the majority of advances are usually reported in the Literature.

The Reviews will appear in the peer-reviewed journal Children in various thematic Issues.

The First published review on the European NHS practices, will appear in March 2025.

The Otoacoustic Emissions Portal is on-line for almost 24 years (we started in June 2000). While we did not expect the COVID crisis to affect us  ,in terms of time and functionality, unfortunately the implications were more severe than expected. The overall team was dismantled for more than 18 months and  I have seen signs of recovery, in the end of 2023. Our scientific and personal lives have changed for good.

Meanwhile, users can browse over the materials we have deposited for all these years and hopefully this year we will go over the areas which has changed a lot the last 5 years, such as the Hardware and Software sections.

Also we have programmed a number of technical insertions regarding the performance of various OAE and AABR screeners, versus the second and forth trimester of 2024.

A lot of things have occurred in 2020, one of which is the lock-down policy of the Italian government in order to prevent the spread of the SARS-CoV-2 pandemic.

Despite the fact that the Portal is an on-line entity, the various global lock-downs have impacted significantly our internal update procedures. At this very moment we do not have any estimate of when things will go back to normal and when the Portal contributors will be back on-line !!

I have been following the race to find a cure against the virus, my personal opinion is that this will be rather difficult till we understand exactly what is the SARS-CoV-2 and which  are exactly the targeting tissues. The respiratory complications are ONLY a part of the global infection activity.

In terms of drugs Chloroquine and Hydroxychloroquine have been widely promoted in various clinical setups, but data in the literature have suggested that in many treated cases side effects such as sensorineural hearing loss, tinnitus, and/or persistent imbalance, are  common. Azithromycin,  has been administered often in combination to Hydroxychloroquine, reinforcing its action, in SARS-CoV-2 patients. It has also been reported to cause both reversible and irreversible sensorineural hearing loss and tinnitus. Remdesivir and Favipiravir, are antiviral, adenosine nucleotide analogues, reported as a possible useful treatment against SARS-CoV-2. However, ototoxicity has been included amongst the possible side effects of adenosine nucleotide analogues; specifically, data in the literature report that patients may develop irreversible unilateral or bilateral hearing loss and tinnitus due to the use of these antivirals, usually after few weeks of administration.

The reason I presented the above excursus on the SARS-CoV-2 drug treatment strategies,  is that the fastest and most accurate methods to detect objectively ototoxicity are protocols based on otoacoustic emissions.

Me and my team have authored two papers on the topic of SARS-Cov-2 and ototoxicity. The links to my Researchagate pages are:

1. Ototoxicity prevention during the SARS-CoV-2 (Covid-19) emergency : Researchgate link 

2. Don’t forget ototoxicity during the SARS-CoV-2 (Covid-19) pandemic ! : Researchgate link

A lot of things have occurred in 2020, one of which is the lock-down policy of the Italian government in order to prevent the spread of the SARS-CoV-2 pandemic.

Despite the fact that the Portal is an on-line entity, the various global lock-downs have impacted significantly our internal update procedures. At this very moment we do not have any estimate of when things will go back to normal and when the Portal contributors will be back on-line !!

I have been following the race to find a cure against the virus, my personal opinion is that this will be rather difficult till we understand exactly what is the SARS-CoV-2 and which  are exactly the targeting tissues. The respiratory complications are ONLY a part of the global infection activity.

In terms of drugs Chloroquine and Hydroxychloroquine have been widely promoted in various clinical setups, but data in the literature have suggested that in many treated cases side effects such as sensorineural hearing loss, tinnitus, and/or persistent imbalance, are  common. Azithromycin,  has been administered often in combination to Hydroxychloroquine, reinforcing its action, in SARS-CoV-2 patients. It has also been reported to cause both reversible and irreversible sensorineural hearing loss and tinnitus. Remdesivir and Favipiravir, are antiviral, adenosine nucleotide analogues, reported as a possible useful treatment against SARS-CoV-2. However, ototoxicity has been included amongst the possible side effects of adenosine nucleotide analogues; specifically, data in the literature report that patients may develop irreversible unilateral or bilateral hearing loss and tinnitus due to the use of these antivirals, usually after few weeks of administration.

The reason I presented the above excursus on the SARS-CoV-2 drug treatment strategies,  is that the fastest and most accurate methods to detect objectively ototoxicity are protocols based on otoacoustic emissions.

I am assuming that around the end of the year we will see the first publications coming out in the literature.

Telehealth, or telemedicine, is the provision of health care services using a telecommunications medium (American Speech-Language-Hearing Association, 2005; Ricketts, 2000; Wootton, 2001). Specifically, telehealth indicates that practitioner services are provided to patients using an electronic medium such as a computer network, the telephone, satellite or two way radio (Mun & Turner, 1999; Stanberry, 2000).Telehealth services are used to serve people with limited healthcare access who typically live in rural or inner city communities. 

Applications have advanced substantially since the first telehealth services were explored. Also, it is likely that the most important telehealth advancements have occurred in the past decade spurred by lower interactive video costs and the advent of powerful but affordable personal computers. In addition, the greater accessibility to cost effective Internet services, and rapid computerization of medical devices are important contributing factors leading to telehealth service development.

A pdf version of the editorial is also available

Terminology.

Although telehealth is a common term, similar terms are often used today. These terms include telemedicine, e-care, e-health, telepractice, and telecare. Telemedicine is frequently used to describe physician and other medical services. In contrast, telehealth is more broadly defined to include those services provided by allied health-care professionals and by physicians alike. This view led to the Comprehensive Telehealth Act of 1997 in the United States in which all health care services provided over a telecommunications system were defined as telehealth.  It is with this perspective that the term, telehealth , will be used for the remainder of the paper.

A brief history of telehealth.

Telehealth is over a century old (Stamm, 1998; Stanberry, 2000). While the first telehealth service was not documented, it was probably conducted using a telephone (or the telegraph) and was likely a consultation. In the early 1900’s, maritime telehealth services were provided to sailors on ships from land based physicians using two-way radio. It is interesting that similar maritime telehealth services continue today even though the transmissions are likely satellite based in most cases. In the 1960’s, the National Aeronautics and Space Administration (NASA) used telehealth technology with astronauts to measure vital signs and radiation exposure while in space. Because of the continued need to provide care to individuals in remote locations, telehealth services are commonly used in many professions, including cardiology, radiography, otology, pediatrics, pharmacology, psychology, psychiatry, and speech-language pathology (Blackham, Eikelboom, & Atlas, 2004; Krumm & Sims, 2011; Nickelson, 1998; Perednia & Allen, 1996; Spooner, Gotlieb, & the Steering Committee on Clinical Information Technology and Committee on Medical Liability, 2004; Stamm, 1998).

Telehealth models.

Telehealth services can be delivered by synchronous (real-time) or asynchronous (store and forward) methods. Synchronous data communication is typically conducted via interactive video and can be augmented by information sent in an asynchronous mode. In contrast, asynchronous telehealth services require that patient data has been recorded first at the patient site and then, after some period of time, sent electronically to the clinician for interpretation. Asynchronous procedures are commonly employed when there is inadequate bandwidth for synchronous procedures. In addition, asynchronous applications may be utilized when time is less of a concern regarding the diagnosis or when the clinician is unavailable to conduct services. Finally, analog equipment which cannot be used for remote computing purposes, often can be gainfully configured for asynchronous applications. For example, an old tympanometer, which can only print out immittance results, can still be used for asynchronous applications by scanning patient immittance results into a computer and sending the data (via email attachment) to an audiologist for interpretation.

Asynchronous telehealth technology. 

Asynchronous data transfer is probably used by audiologists today and may in fact be a common practice. Specifically, this form of telehealth technology is utilized when information such as tympanograms, audiograms, auditory brainstem response recordings, or video-otoscopy images are transmitted via E-mail or by fax (see Figure 1).

                                       Figure 1. Modes of asynchronous services.

Asynchronous studies have been published evaluating the efficacy of telehealth with  tympanometry, video-nystagmography (VNG), and video-otoscopy (Birkmire-Peters et al, 1999; Yates and Campbell, 2005).  In addition, E-mail communication was used to deliver cognitive-behavioral therapy for tinnitus treatment (Kaldo-Sandström et al, 2004) and for counseling new hearing aid users (Laplante-Lévesque et al, 2006).

One appealing asynchronous application is self-assessment of hearing sensitivity. Presently, self-assessment procedures involving hearing testing online appear to suffer from questionable calibration, poor validation, and the lack of control over environmental noise levels. Nevertheless, as this is an emerging area of audiology telehealth, it is likely problems associated with self-assessment will be solved in the future.

Synchronous services.

Synchronous services are characterized by the clinician delivering services to clients in real time or “live” (See Figure 2). Such services may include the use of online chat, the telephone, interactive video, or remote computing technology. Interactive video is typically utilized with synchronous services to observe client responses to stimuli and to assure clinicians that audiometric equipment (transducer, probes, and electrodes) are properly placed. Interactive video may be provided by a laptop Webcam or by a dedicated camera system that is interfaced directly to the computer network. While interactive video can require substantial bandwidth, the benefits are obvious, providing the clinician and patient with services that are essentially “face-to-face”. High costs have limited routine use of interactive video but it is increasingly available and affordable in rural communities.

Audiologists may use two models of synchronous telehealth models. The first model is the traditional model used in other professions. This model requires the extensive use of high-quality interactive video in which the clinician supervises testing by a technician at the remote site. Once the technician obtains patient data, the clinician will typically provide a diagnosis and recommend management. This model has already been used successfully by Marincovich (M. Marincovich, personal communication, April 5, 2009) to provide hearing evaluations and hearing aid fittings in a rural region of California in the USA. For this model to be effective, the technician must be trained well enough to administer, but not necessarily interpret, audiology test results. Rather, interpretation and counseling is done by the audiologist. This is an effective solution when the technician turnover is low and ongoing technician training is possible. Also, the traditional model has the benefit of comparatively modest technology requirements.

                                     Figure 2. Synchronous services using interactive video

Another form of synchronous audiology services incorporates remote-control in so that clinicians can test patients at distant sites. This is a reasonable telehealth strategy to consider as many audiology systems are computerized, utilizing a Windows platform; and as a result can be incorporated for remote computing applications.  Consequently, a clinician at one site can control computerized audiology equipment at a distant site using application sharing software through a network, modem or the Internet. The greatest advantage to this method is that a technician is not required to do testing at the patient site. However, a technician is still required to do tasks such patient basic instructions, transducer placement, otoscopy, and have some skills in running the computer at the patient site.  Figures 3 and Figure 4 show the equipment that is typically used with a synchronous program.

Figure 3. The clinician equipment configuration for an audiologist administering telehealth services. Note only a computer (with remote computing software) and a webcam is required at the clinician site.

1. 1.     Using this paradigm, investigators have employed synchronous protocols to administer a variety of common hearing tests to subjects including pure tone, speech, otoacoustic emissions and the auditory brainstem evoked response (Choi, Lee, Park, Oh, & Park, 2007; Givens & Elangovan, 2003; Krumm, Ribera & Klich, 2007; Ribera, 2005; Swanepoel,  Koekemoer & and  Clark, 2010,Towers, Pisa, Froelich, & Krumm, 2005).

            Figure 4. Equipment required at the patient site. For remote computing purposes, a computer, web cam or dedicated camera, computerized audiometric equipment (an audiometer is pictured), video-otoscopy, immittance (not shown) and a LAN connection would permit basic audiology telehealth services.

In addition, synchronous technology has been utilized to program cochlear implants (Franck, Pengelly & Zerfoss. 2006;Ramos et al., 2008), program and verify hearing aids functioning (Fabry, 2004; Ferrari & Bernardez-Braga, 2009;Wesendahl, 2003) and to provide neural response/telemetry assessment (Shapiro, Huang, Shaw, Roland & Lalwani, 2008).  This telehealth technique presently requires further validation but been used successfully to administer hearing tests over considerable distances (Krumm, Ribera & Klich, 2007; Ribera, 2005; Towers, Pisa, Froelich, & Krumm, 2005).

The hybrid model.

While the sole use of asynchronous or synchronous technology appears to be reasonable in some circumstances, audiologists should consider the most efficient system to deliver telehealth services. In many cases, a combination of synchronous and asynchronous technology will yield the best solution for hearing health-care services. This combination of technology is considered a hybrid model and is regularly used in many telehealth programs.

Telehealth services and otoacoustic emissions in adults. Evoked otoacoustic emissions (EOAEs) have obvious applications for hearing assessment and, therefore, it is not surprising that investigators incorporated EOAEs in early audiology telehealth research. The first of these studies was a master thesis written by Schmiedge (1997) assessing the validity of DPOAEs recordings using synchronous methods. In this investigation, an Apple (Power PC) computer system was interfaced to a computer peripheral capable of generating and recording DPOAEs (Virtual Systems model 330, version 1.9). Timbuktu desktop remote computing software was installed on the computer controlling the DPOAEs for remote computing (synchronous) purposes. 

Subjects assessed in this study were college aged students who exhibited normal hearing sensitivity and no significant history of hearing loss. These subjects were tested in a sound treated booth equipped with the Virtual DPOAEs system connected to a high speed computer network and to a modem. An audiologist (in the same building as the subjects) operated another Power PC computer equipped similarly as the subject computer and, therefore could control the subject DPOAE system using the computer network or modem. Subjects’ DPOAE amplitudes were obtained and compared in the following conditions: face-to-face in a “typical” clinical condition with an audiologist; through a modem connection capable of achieving a 33,600 baud/second connection; and through a high speed local area network (LAN) connection. DPOAE recordings were obtained in 1/3 octave intervals in the frequency range of 1000-4000 Hz using an f1/f2 ratio of 1.21and a stimulus presentation of 65/55 dB SPL. 

Results of this study revealed high agreement of DPOAE means and standard deviations between face-to-face, modem and LAN conditions. The outcome of these data suggested that DPOAE recordings could be accurately measured using telehealth technology with “off the shelf” otoacoustic emissions system hardware and desktop remote computing software. However, in this study there were problems with recording DPOAE data. Computer recordings of DPOAE data would were somewhat unstable during both telehealth conditions and would periodically result in corrupt DPOAE recordings. A caveat is that corrupt data is always possible and should remain a concern.

            Following this work by Schmiedge,a paper was published by Elangovan (2005), describing a customized otoacoustic emissions system developed for synchronous telehealth applications. Elangovan found that this system produced comparable distortion product otoacoustic emission DPOAEs results for five adult subjects when telehealth and face-to-face comparisons were made. Although the outcomes for the otoacoustic emissions systems were impressive, the investigators made their measurements in the same location of the subjects. Consequently, further validation was needed at a distance to determine the value of the system described by Elangovan.

            The first research which demonstrated that EOAEs could be measured at a substantial distance was published by Krumm at. al (2007). In their study Krumm et al. (2007) utilized an off-the-shelf computerized Biologic Scout EOAEs system and a low cost video-conferencing system to record DPOAEs in 30 adult subjects. The EOAEs system was interfaced to a PC connected to a LAN at the subject test site. A second PC was used to provide telehealth services at approximately 1000 Kilometers (Km) away from the subjects. PCs at both sites, running the Windows 2000 operating system, were configured with an interactive video system (VIGO, Emblaze-Vcon, Hackensack, New Jersey) bundled with Meeting Point 4.6 video conferencing software. Remote computing was made possible by application sharing software bundled within the Meeting Point program.  A schematic of this system is found in Figure 5. Results of this suggested that the synchronous measurement of DPOAEs over long distances was feasible as telehealth and face-to-face DPOAE measurements were equal. Further, no technical problems occurred that were described earlier by Schmiedge (1997).

Figure 5. A schematic of the DPOAE system used by the author for synchronous DPOAE research over a distance. 

Telehealth and DPOAEs measurements in Infants.  In all likelihood, EOAEs in telehealth will be used with infant and young children involved in an early hearing detection and intervention (EDHI) program.  But EDHI program goals can be difficult to achieve due to inadequate professional expertise, lack of program planning and insufficient funding ((Mencher, Davis, Devoe, Bereford & Bamford, 2001). Also an EDHI program should exhibit continuity of services up-to-date information, operate as a community-based health program, and provide accurate tracking information for newborns requiring further screeing or assessment (Mencher et al., 2001).  O’Neil, Finitzo, and Littman (2000) addressing similar EDHI issues suggested new paradigms should be developed to insure that each infant is provided needed services regardless of circumstances.

            Such a paradigm may incorporate telehealth services.  Telehealth has been an effective medium of providing medical expertise to isolated communities and is a common practice in many health care professions.

            One intriguing nature of EOAE systems is that many of these systems are commonly operated through desktop personal computers (PCs). Consequently, many EOAE systems can be employed for synchronous telehealth applications including remote computing. Further, remote computing applications for infant hearing assessment seem to have at least three advantages over asynchronous applications. For example, when hearing screenings cannot be accomplished face-to-face, a hearing heath care professional could conduct hearing screening from another location. Also, once personnel are trained to conduct infant hearing assessment in underserved area, these individuals can be mentored and supervised by a hearing health care professional in real time while testing clients. Remote computing also allows observation at distant centers for quality control purposes to achieve appropriate referral rates deterring referrals with excessive false positives.

Finally, diagnostic hearing assessment can be accomplished by hearing health care professionals using remote computing technology. This consideration is important as research indicates that infants with hearing loss require appropriate amplification and aural habilitation before reaching six months of age. Even under ordinary circumstances it can be difficult to conduct follow-up screening, comprehensive hearing assessment and a hearing aid fitting in this time frame unless the infant is precisely managed. In comparison, an infant in an isolated community requiring services at distant medical centers may ultimately suffer from the lack of continuity of care resulting in untimely intervention. Hearing assessment completed remotely by a competent hearing health care professional could serve to reduce the lack of continuity of care and hasten the diagnostic and hearing aid fitting process if needed.

A few papers have been published concerning telehealth and EOAEs in pediatric populations. The first which paper discussed pediatric applications of telehealth and otoacoutic emissions, was by Krumm, Ribera and Schmiedge (2005). This paper provided rationale, models and pilot data supporting the use of telehealth technology with infant hearing screening programs.  Additionally, described some of the issues associated with creating a telehealth service including establishing connectivity at the clinic site, use of a VPN to provide patient privacy, and the need to work collaboratively with computer network personnel who do not necessarily share an enthusiasm for telehealth procedures. 

In 2008, Krumm, Huffman, Dick and Klichdescribed a study in which they used remote computing technology to record DPOAEs and automated auditory brainstem audiometry response (AABR) data with infants. Specifically, 30 infants ranging in age from 11–45 days (with an average age of 16 days) were seen for this study. Subjects recruited for this study did not pass prior DPOAEs screening at birth and were being seen for re-screening at their regional medical hospital.

The Biologic ABAER  system ( Natus, San Carlos, California, USA) was used to conduct all automated ABR (AABR) and DPOAE measurements. The ABAER system was interfaced to a computer and interactive video system in the same manner described previously Krumm et al. (2007). This system was interfaced to a personal computer (PC) running the Windows 2000 operating system and connected to a LAN at the subjects’ site. A second PC was utilized by the audiologist conducting telehealth measurements 200 Km away from the subjects. PCs at both sites were configured with a VCON Vigo desktop videoconferencing system and vPoint software which was used for remote computing applications. Consequently, the audiologist conducting synchronous testing could control both DPOAE and ABR applications at the subject site using the Internet and a broadband connection.  A screen capture of a remote session utilizing remote computing technology to measure DPOAEs in a young subject is found in Figure 5. A virtual private network (VPN) connection was provided by the hospital at which the infant hearing re-screening was conducted to protect subject data transmission over the Internet. In addition, immittance and video-otoscopy images were sent from the subject site after being scanned into a computer system to simulate a complete infant telehealth hearing screening service.

Data analysis of this study indicated that DPOAE and AABR screening results were essentially equal when telehealth and face-to-face trials were compared. Figure 6 displays DPOAE representative results obtained in this study by telehealth and face-to-face methods.

As might be expected, most of the subjects passed the follow-up rescreening in this study.  However, some subjects were judged to need further referral. Specifically, one infant was referred on the basis of both DPOAE and AABR screening. Two other infants were referred by the AABR screening, probably as a result of excessive movement, but passed DPOAE screening. Hence, 29/30 infants passed DPOAE screening and 27/30 infants passed AABR screening in this study. Therefore, this study displayed some promise of providing ABR and DPOAE hearing screenings by remote computing to infants over the Internet.

Figure 6. Screen capture of a remote computing session in which DPOAEs are being measuring in a young child.

A rating scale was administered to the parents immediately following all infant hearing screenings to assess their satisfaction with telehealth services. One parent of each infant was provided a rating scale to complete. Twenty-six of thirty parents completed the rating scale. Four surveys were not answered as one parent was erroneously not offered a rating scale, and three declined to answer the rating scale.  The parents ages ranged from 20-34 years of age and respondents were mostly female (female n=19; male n=7). Parents rated telehealth screening results as excellent (n=22), very good (n=3), or acceptable (n=1). Concerning privacy of infant testing over the Internet, five parents were unsure about privacy, while others were a little concerned (n=8) or not concerned (n=13) about privacy. Although there seemed to be some parental ambivalence about privacy of screening results, all but one parent (n=25) indicated they would permit further telehealth infant hearing screenings.

Figure 7. A comparison of infant DPOAEs recording obtained by telehealthtechnology (top) and face-to-face by a clinician (bottom).

Although the outcome of this study was generally positive, it should be recognized there were a number of limiting factors to this study. First of all, the small n size of this study means that comparatively few infants with hearing loss were identified. Consequently, further studies are needed to determine the validity of the telehealth system described in this study on the basis of sensitivity and specificity measurements.  No such data has been published in a juried source at this time.

In addition, this study was conducted with one audiologist on-site to provide face-to-face assessments and a second audiologist provided telehealth services at a distance. The fact that testing face-to-face and via telehealth was done by audiologists probably resulted in the high agreement between the telehealth and face-to-face conditions describe in this study. Obviously, assistants at distant sites must apply EOAE probes, ear phones and electrodes to newborns or infants when actual hearing screenings are conducted by telehealth. Also, assistants must be trained to adjust malfunctioning or improperly fitting screening probes, electrodes or earphones during hearing screenings. So, further investigation examining the use of a trained assistant is necessary in future audiology telehealth studies.  Again, no such data has been reported in a juried source. Fortunately, the equipment used in this study provides the capacity to monitor AABR electrode application and DPOAE ear probe placements online when conducting remote computing sessions. Therefore, clinicians can identify and inform screening assistants to correct mechanical problems when infant hearing screenings are provided

There was one notable problem in this study concerning connectivity.  Although Internet connections between subject site and investigator site normally exceeded 384 Kilobits per second (Kbs), on two occasions the bandwidth was compromised by Internet congestion resulting in the loss of interactive video between sites. Even so, remote computing measurement could be continued and hearing screening results were successfully recorded using bandwidth below 100 Kbs. It is interesting that the parents did not respond negatively to the lack of interactive video other than indicating that the testing seemed slow.

Results and conclusions.

Although preliminary telehealth results are encouraging for infant hearing screening, additional investigation with telehealth procedures is needed to validate synchronous procedures with greater numbers of infants exhibiting hearing loss. The federal government in the United States has funded several telehealth projects for infant hearing screening and assessment. However, the results of these studies have not appeared in scientific journals.    

In addition to synchronous research, asynchronous and hybrid telehealth models should also be studied for EDHI screening, diagnostic and intervention services in rural communities. For example,in Northern Ohio (USA) one audiologist used asynchronous technology to measure DPOAEs with preschool children during hearing screenings (B. Whitford,personal communication, September 4, 2008). Further, clinicians providing direct EDHI services may consider the need to implement different newborn hearing screening protocols proposed in the literature to reduce false positives and follow-up visits (Gravel, White & Johnson et al.,2005; Lieu, Karzon, &Mange, 2005). These protocols include auditory brainstem response (ABR) testing at the time when newborns fail initial screenings; simultaneous use of both AABR and EOAE screenings at newborn screenings; and detecting middle ear disorders through high frequency tympanometry measurements. An audiologist could employ telehealth technology to provide some of these services.

Remote computing might also prove valuable as a means to provide ongoing instruction to hearing screening assistants established in rural areas. Specifically, clinicians can mentor and monitor assistants using remote computing applications while viewing newborn hearing screenings in real time. These services would be dispensed with the goal to enhance personnel expertise for newborn hearing screenings.

For clinicians contemplating telehealth applications, a few issues need to be reviewed. First of all, additional licensure or other clinician certification, may be needed to provide services in different regions and certainly countries. Also, informing the proper licensing authorities that telehealth services are being considered is sensible even if the clinician license permits such services.  Reimbursement for telehealth services may be unclear so funding sources must be clearly identified before telehealth services are initiated. Also, while it has been the experience of the author that most computerized audiology systems work well for remote computing applications, clinicians must prototype prospective computerized audiology systems for the remote computing and asynchronous applications to be assured that the telehealth technology will work as desired. 

Remote computing software is abundant. However, web-based conferencing software may be faster and just as cost effective as PC based video-conferencing software. Programs such as Teamviewer, Skype and DimDim may be used to provide low cost means to remote computing services but privacy must be assured through encryption or through a virtual private network (VPN). Teamviewer offers good encryption capabilities. Skype has offered encryption under paid plans. So, video/data encryption  or the use of a VPN must be carefully considered. Finally, the author would also advise clinicians to conduct telehealth services at distant sites first in which there is enthusiastic support. Even though telehealth is powerful, it is of no value if key personnel at the distant clinical site do not support new service methods.

In conclusion, while telehealth technology seems reasonable to use for screening and diagnostic services, the author recommends cautious validation and program review. Questionnaires should be provided to consumers who are served through telehealth services. Also, planning committees consisting of consumers, administrators and clinicians should be formed to assure proper procedures are developed for EDHI telehealth services.  Following the establishment of these mechanisms, clinicians could implement substantial telehealth strategies to bolster rural community services for parents and their hearing impaired infants.

On-line Examples

Tele-Audiology from the Tester side: https://ksutube.kent.edu/playback.php?playthis=4oup7d12r


Tele-Audiology from the patient/assistant site:  https://ksutube.kent.edu/playback.php?playthis=ys5yj2z6i

References

American Speech-Language-Hearing Association, (2005). Audiologists providing clinical services via telepractice: Technical report. Available from www.asha.org/policy.

Birkmire-Peters, D.P., Peters, L.J. & Whitaker, L.A. (1999). A usability evaluation for telemedicine medical equipment: a case study. Telemed J, 5(2):209–212.

Blackham, R., Eikelboom, R. H. & Atlas, M.D. (2004). Assessment of utilisation of ear, nose and throat services by patients in rural and remote areas. Australian Journal of Rural Health, 12, 150–151.

Choi, J., Lee, H., Park, C., Oh, S. & Park, K. (2007). PC-Based Tele-Audiometry. Telemed J E Health, 13(5):501–508.

Elangovan, S. (2005). Telehearing and the Internet. Semin Hear, 26:19–25.

Ferrari, D.V. & Bernardez-Braga G.R. 2009. Remote probe microphone measurement to verify hearing aid performance. J Telemed Telecare, 15, 122-124.

Franck, K., Pengelly, M. & Zerfoss S. (2006). Telemedicine offers remote cochlear implant programming. Volta Voices, 13(1):16–19.

Givens, G. & Elangovan, S. (2003). Internet application to tele-audiology-"nothin' but net." Am J Audiol, 12:50–65.

Gravel, J., White, K., Johnson, J., et al. (2005). A Multisite study to examine the efficacy of the otoacoustic emission/automated auditory brainstem response newborn hearing screening protocol: recommendations for policy, practice, and research. Am J Audiol2005; 14: S217–S228

Kaldo-Sandström,V., Larsen, H.C. & Andersson, G. (2004). Internet-based cognitive-behavioral self-help treatment of tinnitus: clinical effectiveness and predictors of outcome. Am J Audiol, 13(2):185–192.

Krumm, M., Huffman, T., Dick, K. & Klich, R. (2008). Providing infant hearing screening using OAEs and ABR using telehealth technology. J Telemed Telecare, 14(2):102–104.

Krumm, M., Ribera, J. & Klich R. (2007). Providing basic hearing tests using remote computing technology. J Telemed Telecare, 13(8):406–410.

Krumm, M., & Sims, M. (2011). Teleaudiology. Otolaryngol Clin North Am, 44 (8). 1297- 1304.

Laplante-Lévesque, A., Pichora-Fuller, M.K. & Gagné, J.P. (2003). Providing an internet-based audiological counselling programme to new hearing aid users: a qualitative study. Int J Audiol, 45:697–706.

Lieu, J., Karzon, R. &Mange C. (2006). Hearing screening in the neonatal intensive care unit: follow-up of referrals. Am J Audiol 2006; 15: 66–74

Mackert, M. & Whitten, P. (2007). Successful adoption of a school-based telemedicine program. J Sch Health, 77(6):327–330.

Mencher, G., Davis, A., Devoe, S., Bereford, D. & Bamford, J. (2001). Universal neonatal screening: past, present, and future. Am J Audiol, 10:3–12

Mun, S. & Turner, J. (1999). Telemedicine: emerging e-medicine. Ann Rev Biomed Eng 1:589–610.

O’Neal, J., Finitzo, T. & Littman, T. Neonatal hearing screening: followup and diagnosis. In: Roeser RJ, Valente M, Hosford-Dunn H, eds. Audiology Diagnosis. New York, NY: Thieme Medical Publishers, 2000; 527–44

Nickelson, D. (1998). Telehealth and the evolving health care system: Strategic opportunities for professional psychology. Professional Psychology: Research & Practice, 29, 527–535.

Perednia, D. & Allen A. (1996). Telemedicine technology and clinical applications. J Am Med Assoc, 273:483–488.

Ramos, A., Rodriguez, C., Martinez-Beneyto P., Perez D., Gault A., Falcon J.C. & Boyle P. (2009). Use of telemedicine in the remote programming of cochlear implants. Acta Otolaryngol, 129, 533-540.

Ricketts, T. (2000). The changing nature of healthcare. Annual Review of Public Health, 21, 639–657.

Ribera, J. (2005). Interjudge reliability and validation of telehealth applications of the Hearing in Noise Test. Semin Hear, 26:13–18.

Spooner, A.S., Gotlieb, E., & Steering Committee on Clinical Information Technology and Committee on Medical Liability, (2004). Telemedicine: pediatric applications. Pediatrics, 113:e639–e643.

Shapiro, W., Huang,T., Shaw, T., Roland, J. & Lalwani, A. (2008). Remote intraoperative monitoring during cochlear implant surgery is feasible and efficient. Otology & Neurotology,29:495-498.

Swanepoel, D.,  Koekemoer, K., &  Clark , J.,(2010). Intercontinental hearing assessment

        – a study in tele-audiology. J Telemed Telecare, 16 (5) 248-252

Stamm, B.H. (1998). Clinical applications of telehealth in mental health care. Prof Psychol Res Pr, 29:536–542

Standberry, B. (2000). Telemedicine: barriers and opportunities in the 21st century. J Intern Med, 247:615–627.

Towers, A.D., Pisa, J., Froelich, T.M. & Krumm M.  2005. The reliability of click-evoked and frequency-specific auditory brainstem response testing using telehealth technology. Semin Hear, 26, 19-25.

Wesendahl, T. (2003). Hearing aid fitting: application of telemedicine in audiology. International Tinnitus Journal, 9(1), 56-8.

Wootton, R. (2001).  Recent advances: telemedicine. Br J Med, 60:557–560.

Yates J.T. & Campbell, K.H. (2005). Audiovestibular education and services via telemedicine technologies. Semin Hear, 26:35–42.

About the Author

[email protected] is an associate professor in the School of Speech Pathology and Audiology at Kent State University in Kent, Ohio (USA).  He has been involved with telehealth applications for over a decade and has published a number of papers describing audiology telehealth use with pure tone audiometry, otoacoustic emissions, immittance, video-otoscopy and the auditory brainstem response (ABR). Dr. Krumm has also chaired the American Speech Language and Hearing Association (ASHA) committee on Telepractice and is presently the co-chair of the American Academy of Audiology (AAA) task force on telehealth.

As we have already announced  the book "Advances in Audiology, Speech Pathology and Hearing Science", to be published by Apple Academic Press (Around June 2020), will use a dedicated section of the Portal for all the relative multimedia references of the book.

The advantages of the use of Multimedia material in education are well-known. Now the book "Advances in Audiology, Speech Pathology and Hearing Science" was written as an aid to graduate classes in Audiology, ENT, Speech Pathology and Hearing Science and the possibility to constantly update its multimedia contents is a unique event in our fields.

We truly hope that the contributors to the book .. will continue to update the multimedia part of their chapter contributions, so that  the book can be always be in-vogue with the latest advances in our fields.

This is a very important period  for the OAE Portal. It is the first time when a book in the field of Audiology uses the Portal as a reservoir of Multimedia Material.

As we have already announced  the book "Advances in Audiology, Speech Pathology and Hearing Science", to be published by Apple Academic Press (in late 2019), will use a dedicated section of the Portal for all the relative multimedia references of the book. I would like to thank again our sponsor Horentek for believing in the project and for providing the necessary context for the re-modeling of the Portal's database structure.

The advantages of the use of Multimedia material in education are well-known. Now the book "Advances in Audiology, Speech Pathology and Hearing Science" was written as an aid to graduate classes in Audiology, ENT, Speech Pathology and Hearing Science and the possibility to constantly update its multimedia contents is a unique event in our fields.

We truly hope that the contributors to the book .. will continue to update the multimedia part of their chapter contributions, so that  the book can be always be in-vogue with the latest advances in our fields.

As it has been the tradition the last years, we occasionally focus on technology-related issues. The OAE technology has reached, as it was expected, a plateau the last 5-10 years, but information technologies continue to grow and new aspects of Tele-Health are emerging. We have also observed developments in the area of implantable devices (hearing aids and cochlear implants), but the main contributions are mainly in the area of software development than in new hardware implementations. Some interesting ideas have been reported about Implant systems releasing anti-inflammatory agents like dexamethasone in the inner ear, to suppress post-surgical side effects, but clinical trials have not started yet.There are some interesting trends in the area of wearable medical devices (mostly sensors ) which can connect to our mobile phones for data visualization and control, but we do not have reports for any Audiology / Hearing Science applications so far. This idea is intriguing and we are seeking authors for an editorial or a white paper on this topic. 

It would be nice to hear your opinion on this issue, since the OAE Portal is an Open  Access depository of Knowledge. It would be a great privilege for me and my collaborators to listen what you have to say.

As it has been the tradition the last  years, we occasionally focus  on technology related issues. The OAE technology has reached, as it was expected, a plateau the last 5-10 years, but information technologies continue to grow and new aspects of Tele-Health are emerging. We have also observed developments in the area of implantable devices (hearing aids and cochlear implants), but the main contributions are mainly in the area of software development than in new hardware implementations. Some interesting ideas have been reported about Implant systems releasing anti-inflammatory agents like dexamethasone in the inner ear , to suppress post-surgical side effects, but clinical trials have not started yet.There are some interesting trends in the area of wearable medical devices (mostly sensors ) which can connect to our mobile phones for data visualization and control, but we do not have reports for any Audiology / Hearing Science applications so far. This idea is intriguing and we are seeking authors for an editorial or a white paper on this topic. 

It would be nice to hear your opinion in these issue, since the OAE Portal is a Open  Access depository of Knowledge. It would be a great privilege for me and my collaborators to listen what you have to say.

About the guest Editor:  

Dr. Jay Hall III  <script type='text/javascript'> <!-- var prefix = 'ma' + 'il' + 'to'; var path = 'hr' + 'ef' + '='; var addy29970 = 'mkrumm' + '@'; addy29970 = addy29970 + 'kent' + '.' + 'edu'; document.write('<a ' + path + '\\'' + prefix + ':' + addy29970 + '\\'>'); document.write(addy29970); document.write('<\\/a>'); //-->\ </script><script type='text/javascript'> <!-- document.write('<span style=\\'display: none;\\'>'); //--> </script>This email address is being protected from spambots. You need JavaScript enabled to view it. <script type='text/javascript'> <!-- document.write('</'); document.write('span>'); //--> </script>is an internationally recognized audiologist with 40-years of clinical, teaching, research, and administrative experience. He received his Ph.D. in audiology from Baylor College of Medicine under the direction of James Jerger.  During his career, Dr. Hall has held clinical and academic audiology positions at major medical centers. Dr. Hall now holds appointments as Professor at Salus University and the University of Hawaii, and as Extraordinary Professor at the University of Pretoria South Africa. Dr. Hall is the author of over 160 peer-reviewed journal articles, monographs, or book chapters, and nine textbooks including the 2014 Introduction to Audiology Today and the 2015 eHandbook of Auditory Evoked Responses.

OBJECTIVE ASSESSMENT OF INFANT HEARING: ESSENTIAL FOR EARLY INTERVENTION

James W. Hall III, PhD

Osborne College of Audiology, Salus University, Elkins Park, Pennsylvania, USA 

Department of Audiology & Speech Pathology, University of Pretoria, South Africa 

Department of Communication Sciences and Disorders, University of Hawaii, Honolulu, Hawaii, USA

INTRODUCTION

Rationale for Objective Infant Hearing Assessment

The coordination of prompt identification, diagnosis, and management of hearing loss in children is now often referred to as Early Hearing Detection and Intervention, abbreviated EHDI. The “1-3-6 Plan or Principle” guides EHDI efforts. That is, hearing loss is detected before 1 month, diagnosis of hearing loss is complete within the first 3 months after birth, and intervention begins within 6 months. Substantial research evidence supports the benefits of early intervention for the acquisition of effective and efficient communication skills along with psychosocial development (JCIH, 2007). Rich, consistent, and reasonably normal auditory stimulation beginning with the first 6 months after birth drives nervous system development and takes full advantage of brain plasticity.

The evolution of this rather accelerated schedule for EHDI essentially eliminates the role of behavioral hearing assessment in the initial diagnosis of hearing loss and the first habilitation efforts with hearing aids and other devices. Fortunately, objective auditory tests are available for early and accurate diagnosis of infant hearing loss. These include aural immittance measurements, otoacoustic emissions (OAEs), and auditory evoked responses such as auditory brainstem response (ABR), auditory steady state response (ASSR), electrocochleography (ECochG), and cortical auditory evoked responses like the auditory middle latency response (AMLR), the auditory late response (ALR), and the P300 response. The ALR is also referred to as the cortical auditory evoked potential (CAEP).

Cortical auditory evoked responses, and really all auditory evoked responses, appear sequentially following presentation of effective stimulation. In this discussion of objective auditory measures in infants and young children, it’s relevant to point out that there is no clear and invariable distinction in the latency characteristics of the cortical auditory evoked responses. For example, the ALR and P300 responses occur within the same general post-stimulus analysis time. And, components of the AMLR when recorded from infants actually appear in the analysis time associated with the ALR for older children and adults.

Objective hearing procedures all share one major clinical advantage. They are not dependent on behavioral infant responses. The many general clinical strengths of objective hearing procedures are summarized in Table 1. This article reviews current application of four objective auditory assessment applied most often in the diagnosis of hearing loss in infants and young children, specially: 1) aural immittance measures, 2) OAEs, 3), ABR, and 4) ASSR. The important diagnostic roles of two other categories of objective auditory measures … ECochG and cortical auditory evoked responses … are only mentioned in passing due to space constraints.

________________________________________________________________

• Do not require a behavioral response from the patient
• Results are not influenced by motivation
• Results are not influenced by cognitive status
• Results generally are not influenced by state of arousal
• Measurements can be made with patient sedated or anesthetized
• Results are not influenced by native language
• Patient is not required to follow detailed verbal instructions
• Motor status does not influence test results
• Measures provide information on regions of the auditory system from the middle ear to the cerebral cortex
• Generally high degree of sensitivity to auditory dysfunction
• In combination provide site specific information on auditory dysfunction
• Valid measures are possible from infants and young children
• Reasonable test time

________________________________________________________________

Table 1. This is a listing of the general clinical strengths and weaknesses of objective auditory measures available to clinical audiologists. Specific advantages associated with each measure are detailed within the text.

Other Clinical Applications

There are multiple clinical applications of objective auditory measures. We’ve already touched upon newborn hearing screening and diagnosis of hearing loss in infants and young children. Although these applications are indeed crucial, others also play an important role in children and also in adults. Diagnosis of auditory neuropathy spectrum disorder (ANSD) is only possible with a combination of objective techniques, including ECochG. Objective measures, such as OAEs and tympanometry, offer the most efficient and accurate means of screening for hearing loss in pre-school and school age children. Objective auditory procedures permit prompt and unequivocal identification and diagnosis of false or exaggerated hearing loss and, therefore, timely and appropriate management of pediatric and adult patient populations. Finally, objective measures supplement behavioral diagnostic audiometry procedures in the assessment of auditory processing disorders, including those resulting from traumatic brain injury (TBI). Objective test data is particularly useful when analysis of behavioral findings is confounded due to listener variables such as cognition, motivation, and native language or specific language impairment. In short, objective test procedures are essential in audiology today.

Historical Perspective

Initial efforts to objectively assess hearing in children date back more than 60 years. In the 1950s, several teams of otolaryngologists and audiologists applied ECochG was applied in estimation of auditory thresholds in difficult-to-test children who were delayed in speech and language, with hearing loss strongly suspected (see Hall, 2015 for review). The technique, however, was far from standard of care because ECochG recording in children then required a surgeon for placement of an electrode close to the cochlea with the patient under general anesthesia. 

In the 1960s, other groups of research-oriented audiologists and neurologists reported the application of the auditory late cortical evoked response in estimation of auditory thresholds in children who were unable to be assessed with behavioral audiometry. The good news was anesthesia and surgical support wasn’t needed for clinical measurement of cortical evoked responses, but the strategy was heavily dependent on patient cooperation and was very age dependent. Children undergoing auditory late response measurement needed to be almost motionless, yet awake.  Unfortunately, cortical auditory evoked response measurement required almost as much cooperation as behavioral audiometry. Until at least the mid-1970s, however, objective assessment of hearing in children using ECochG and cortical auditory evoked responses was available only in relatively few major medical centers throughout the world.

Cross Check Principle: A 40-Year Perspective

The modern objective hearing test battery was introduced in the 1970s.  Leading researchers, notably James Jerger, reported in dozens of peer-reviewed publications compelling evidence from large-scale studies in varied patient populations that objective auditory assessment was clinically valuable and necessary. Robert Galambos in the mid-1970s clearly demonstrated the unique contributions of ABR in newborn hearing screening and diagnosis of hearing loss in infants and young children (Hecox & Galambos, 1974).

In 1976, Dr. Jerger and then clinic supervisor and PhD student Deborah Hayes first articulated the enduring “cross-check principle.”  In their classic “The Cross-Check Principle in Pediatric Audiometry, Jerger & Hayes (1976) illustrate vividly with presentation of 5 case studies the limitations and pitfalls associated with exclusive reliance on behavioral test results. The authors then make a strong case for the use of independent test procedures, principally aural immittance (impedance) measures and ABR to verify or “cross-check” the behavioral test results. Jerger and Hayes confidently state: “In summary, we believe that the unique limitations of conventional behavioral audiometry dictate the need for a “test battery” approach. The key concept governing our assessment strategy is the cross-check principle. The basic operation of this principle is that no result be accepted until it is confirmed by an independent measure.” (Jerger & Hayes, 1976, p. 620).

The objective test battery did not expand further until approximately 20 years later when OAE technology became available as a routine clinical procedure. Within the next decade, the Joint Committee on Infant Hearing in 2000 recommended strongly the routine application of ABRs elicited with frequency-specific tone burst stimulation and also bone conduction ABR measurement for auditory assessment of infants and young or difficult-to-test children. During the same time period, the ASSR emerged as a clinically feasible technique for objective estimation of auditory thresholds, especially in children with severe to profound hearing impairment.  More recently ECochG has resurfaced once again as a valuable clinical tool, this time in the diagnosis of children with suspected ANSD. We now have readily available for use in patients of all ages, an assortment of objective techniques for early and accurate identification and diagnosis of every type and site auditory dysfunction, from middle ear disorders to ANSD to central auditory processing disorders.

Thousands of journal articles, hundreds of book chapters, and even entire textbooks, describe in detail the functional anatomy of objective auditory tests and how the procedures are performed and findings are analyzed. This paper reviews briefly advantages of four major objective auditory tests in the detection and diagnosis of infant hearing loss. It also highlights the unique contribution of each of these objective auditory procedures to the pediatric test battery.

AURAL IMMITTANCE MEASURES

Making the Most of Middle Ear Measurements

Aural immittance measures are valuable clinically for a variety of reasons. They are quick, technically simple, easily recorded in persons of all ages without regard to developmental or cognitive status, and they have relatively high sensitivity and specificity to middle ear disorders. The many compelling clinical advantages specific to aural immittance measurements, particularly in pediatric patient populations, are summarized in Table 2. 

________________________________________________________________

Strengths                                        

• Equipment is widely-accessible
• Clinical proven with over 40 years of clinical experience and research
• Normative data are available
• Anatomy and physiology relatively well defined
• Relatively independent of developmental age or status
• Brief test time
• Relatively simple techniques
• Useful as a screening technique
• Measurement does not require sedation or anesthesia
• High degree of sensitivity to middle ear dysfunction
• Tympanometry provides information on middle ear mechanics
• Detects and confirms perforation of the tympanic membrane
• Detects and confirms patent ventilation tubes
• Acoustic reflex provides information on afferent auditory pathways
• Acoustic reflex is sensitive to retro-cochlear auditory dysfunction
• Acoustic reflex provides information on lower brainstem auditory pathways
• Acoustic reflex provides information on 7^th cranial (facial) nerve
• Acoustic reflex objectively detect or rule out sensory hearing loss

Weaknesses

• Not a measure of “hearing”
• Measurement requires an air-tight seal within external ear canal
• Tympanometry only provides information on middle ear status
• No information on higher brainstem auditory function
• No information on cortical auditory function
• No information on speech perception or understanding
• Does not provide precise index of the degree of hearing loss
• Acoustic reflex findings limited in patients with normal middle ear status

 Table 2. Selected clinical strengths versus weaknesses of aural immittance measures. All objectives measures share a number of clinical advantages, as summarized in Table 1 and described in detail in the text. Strengths of aural immittance measures that are discussed in the text are highlighted in bold font.

Research confirms that multi-frequency and multi-component techniques for tympanometry are more sensitive to low-impedance pathologies, such as tympanic membrane and ossicular chain abnormalities, than measurement of admittance recorded with a single low-frequency probe tone, usually 226 Hz. Nonetheless, audiologists typically rely on single component and single frequency tympanometry for detection and diagnosis of auditory dysfunction. Tympanometry and analysis of tympanogram findings is simpler when one component is recorded for one probe tone frequency. Most middle ear pathology in pediatric populations is detected and described with single-component and single-frequency tympanometry.

There are clear clinical indications for the use of high frequency tympanometry in addition to low-frequency tympanometry in infants up to the age of at least 4 months (Hall, 2010; Hall, 2014). Aural immittance characteristics differ substantially for infants versus older children and adults. Specifically, in comparison to older persons the middle ears of infants have a higher resistance component for a low frequency probe tone of 226 Hz. Ear canal volume measurements in infants, however, should be conducted with a low frequency probe tone in children under the age of 6 months.

Wide Band Reflectance/Absorbance

Another approach for middle ear assessment, measurement of wide band reflectance or absorbance, offers potential advantages over conventional tympanometry, particularly for detection of pathology in neonates and young children (Feeney et al, 2013). The WMEP involves essentially simultaneous measurement of power reflectance, impedance, and admittance using either a broadband (chirp) stimulus or multiple sinusoidal stimuli over a relatively wide frequency range of about 250 Hz to 6000 Hz.

Test time for wideband reflectance or absorbance is less than one minute and measurements are made at ambient pressure or with induced ear canal pressure. An airtight seal between the probe and the ear canal wall is not required. Wide band reflectance or absorbance has considerable potential value for detection of auditory dysfunction in infants and older children. And, measured in combination with OAEs using the same instrumentation including a single probe, wide band reflectance or absorbance may result in an unusual and desirable combination of high sensitivity and high specificity for detection of middle ear disorders.

The Diagnostically Powerful Acoustic Stapedial Reflex

Background Information. The acoustic stapedial reflex is one of several muscle responses to sound. It falls in the same general category as the post-auricular muscle response, the eye blink reflex, and the startle response. Another middle ear muscle, the tensor tympani muscle, is involved in the startle response. Careful measurement of stapedial acoustic reflexes yields considerable information on the anatomical status of the auditory system, especially when recorded in four conditions, that is, measurement of ipsilateral and contralateral acoustic reflex activity with right and left ear stimulation.

The major pathways in the acoustic reflex arc can be divided anatomically into five general portions: 1) the middle ear, the cochlea and the afferent pathway consisting of the 8^th (auditory) cranial nerve on the side of the stimulus, 2) brainstem neurons within the cochlear nuclei , 3) for contralateral acoustic reflex measurement the trapezoid body and medial superior olivary complex plus polysynaptic pathways including neurons within the reticular activating system, 4) an efferent pathway involving motor fibers within the 7^th cranial nerve on the side of the probe, and 5) the stapedius muscle and middle ear on the side of the probe. The presence of acoustic reflexes is highly dependent on normal middle ear function. Most middle ear abnormalities obscure confident detection of acoustic reflexes, even relatively subtle disorders that are not associated with markedly abnormal tympanograms or a significant (> 10 dB) gap between air- and bone conduction pure tone thresholds.

Identification of Sensory Hearing Loss. Tympanometry has unquestionable value as a screening tool for the detection of middle ear abnormalities. However, hearing requires integrity of much more than the middle ear. The application of hearing loss estimation with acoustic reflex thresholds was first reported in the early 1970s (Jerger et al, 1974). Presuming normal middle ear function, acoustic reflexes permit quick, ear specific objective differentiation of normal versus abnormal cochlear function. As clinical experience with acoustic reflex measurement accumulated, a direct relation was observed for hearing loss and the acoustic reflex for noise signals. In particular, the acoustic reflex threshold for broadband noise (BBN) increases rather systematically with worsening pure tone thresholds for sensory hearing loss. In contrast, acoustic reflexes elicited with pure tone signals showed little change in threshold from normal hearing sensitivity through 50 or even 60 dB HL, a reflection of the loudness recruitment phenomenon.

In a study of 326 adult subjects with varying degrees of sensory hearing loss, Hall, Berry & Olsen (1982) evaluated the acoustic reflex threshold for a BBN signal presented in the contralateral condition in differentiating patients with a pure tone average < 35 dB HL from those with a pure tone average > 35 dB HL. Figure 1 illustrates the differential effect of sensory hearing loss on acoustic reflex thresholds elicited with tonal versus BBN signals.  No subject with hearing loss (pure tone average > 35 dB HL) had an acoustic reflex threshold for BBN of less than 85 dB SPL.  The lower the acoustic reflex threshold for the BBN stimulus, the more likely hearing sensitivity is normal within the speech frequency region. Conversely, BBN acoustic reflex thresholds greater than 90 dB are invariably associated with sensory hearing loss.

Figure 1: Acoustic reflex thresholds for pure tone versus broadband noise (BBN) stimuli are depicted as a function of hearing threshold levels

The results from a study of acoustic reflex thresholds in neonates provides further support for the use of a BBN stimulus in objectively differentiating between normal hearing sensitivity versus sensory hearing loss. Kei (2012) reported acoustic reflex threshold data collected with pure tone and BBN stimuli and a 1000 Hz probe tone in a group of 66 health newborn infants who had passed hearing screening. Acoustic reflexes were recorded in all stimulus conditions from all of the infants. The median acoustic reflex threshold in the normal hearing infant group was 55 dB HL for the BBN stimulus with a range of 50 to 75 dB HL. These findings confirm that an acoustic reflex threshold of 75 dB HL or better is consistent with normal hearing sensitivity.

Diagnostic Value of Acoustic Reflex Patterns

Possible Pathways and Test Conditions. A brief explanation of acoustic reflex conditions and patterns might be helpful (see Hall, 2014 for review).  In discussing acoustic reflex patterns, it’s important to make the distinction between “probe ear” and “stimulus ear.” Tympanometry is performed with the probe ear. For ipsilateral reflexes, the probe ear and stimulus ear are one in the same. Acoustic immittance change indicating the presence of an acoustic reflex occurs in the same ear as the acoustic stimulation. The term uncrossed is also used for the ipsilateral test condition, as the acoustic reflex pathways do not cross the midline of the brainstem.

The stimulus is presented to the ear opposite the probe ear in the contralateral acoustic reflex condition. Acoustic immittance change indicating the presence of an acoustic reflex occurs in the ear opposite the stimulation. The term crossed is interchangeable with contralateral, as the acoustic reflex pathways cross the midline of the brainstem via the trapezoid body and perhaps other decussating structures before coursing to the region of the motor nucleus of the 7^th cranial (facial) nerve and then to the stapedius muscle via motor fibers within the 7^th cranial nerve.

There are, then, four possible distinct and different measurement conditions in acoustic reflex measurement: 1) right ear ipsilateral, 2) left ear ipsilateral, 3) contralateral reflexes with the probe in the right ear and sound in the left ear, and 4) contralateral reflexes with the probe in the left ear and sound in the right ear. These four measurement conditions and normal findings for each are often shown graphically in a diagram like the one shown in Figure 2. An open box in the figure indicates the presence of normal acoustic reflexes with thresholds of < 90 dB HL. A shaded box indicates abnormally elevated acoustic reflex thresholds, whereas a filled in black box indicates that no acoustic reflex activity was detected in the test condition.

Figure 2: A diagram for plotting findings for tympanometry, acoustic reflexes in the ipsilateral and contralateral conditions, and pure tone audiometry. Findings are shown for a person with normal hearing sensitivity.

Combinations or patterns of findings for pure tone audiometry, tympanometry, and acoustic reflex recordings are generally related to likely clinical etiologies or diagnoses. The figures cited in the explanation below depict distinct patterns of acoustic reflex findings. In viewing these figures, and real world clinical findings, it’s useful to first examine the findings for tympanometry to confirm or rule out middle ear disorder followed by analysis of the acoustic reflex pattern for the four measurement conditions. The audiogram offers additional evidence of conductive hearing loss.

Vertical Acoustic Reflex Pattern: Mild Conductive Hearing Loss. The vertical pattern is often encountered clinically, particularly in pediatric populations where middle ear disorders are commonplace. Figure 3 shows an example of the vertical acoustic reflex pattern. The tympanogram on the right ear is clearly abnormal, immediately alerting the clinician to the likelihood of a conductive hearing loss. Referring to the lower portion of the figure, acoustic reflexes are absent whenever the probe is in the right ear with middle ear dysfunction. Detection of a normal contralateral acoustic reflex with sound in the right ear and probe in the normal left ear confirms, even before reference to pure tone findings, that the conductive hearing loss is mild at most.

Figure 3: Findings for tympanometry, acoustic reflexes in the ipsilateral and contralateral conditions, and pure tone audiometry in a patient with middle ear dysfunction and mild conductive hearing loss for the right ear. The combination of findings is sometimes referred to as the vertical acoustic reflex pattern.

Greater conductive hearing loss for the right ear would result in elevation of the contralateral acoustic reflex measured with stimulation of the right ear and the probe in the left ear. A conductive hearing loss essentially reduces the effectiveness of the acoustic reflex stimulation by the magnitude of air bone gap. Since the acoustic reflex is normally activated with an intensity level of 85 dB HL, a conductive loss of 25 to 30 dB raises the contralateral acoustic reflex threshold for stimulation of the ear with conductive hearing loss to about 110 to 115 dB HL. 

Keep in mind that no acoustic reflex is typically measured with the probe in an ear with middle ear disorder, even in conductive hearing loss associated with a very modest 5 to 10 dB air-bone gap. The audiogram showing a slight air-bone gap in the top portion of Figure 3 confirms the acoustic reflex pattern. Prediction of degree of conductive hearing loss from the acoustic reflex pattern is especially useful in infants and young children for whom pure tone audiometry is not yet possible.

Vertical Acoustic Reflex Pattern: Facial Nerve Disorder. Facial nerve disorder is a second explanation for the vertical pattern of acoustic reflex abnormality. The pattern arises because the facial nerve is the final efferent pathway to the stapedius muscle. Acoustic reflexes are abnormal and usually absent whenever the probe is in the affected ear, as illustrated in Figure 4.  Two factors clearly distinguish this vertical pattern from the acoustic reflex pattern typical of mild conductive hearing loss illustrated earlier in Figure 3. The most obvious factor is normal tympanometry in facial nerve disorder, consistent with normal middle ear function. A normal audiogram or at least no difference between air and bone conduction pure tone thresholds also argues against middle ear disorder. Careful measurement of acoustic reflexes in the four test conditions permits identification of facial nerve disorder in patients of all ages, even infants and young children with syndromes or diseases the include as a sign facial nerve pathology and paralysis.

Figure 4: Findings for tympanometry, acoustic reflexes in the ipsilateral and contralateral conditions, and pure tone audiometry in a patient with facial nerve dysfunction for the right ear in combination with normal middle ear function and normal hearing sensitivity bilaterally.

“Inverted L” Acoustic Reflex Pattern: Moderate Conductive Hearing Loss. The “inverted L” pattern (Jerger & Jerger, 1977) for acoustic reflexes is really a vertical pattern with the addition of an abnormality in the contralateral acoustic reflex with stimulation of the ear with conductive hearing loss and the probe in a normal ear. This pattern is reflected in Figure 5. Almost any degree of conductive loss will produce some elevation of the contralateral acoustic reflex with sound stimulation in the conductive loss. Greater degrees of conductive loss and larger air-bone gaps are associated with progressive elevations of the acoustic reflex.

Figure 5:  Findings for tympanometry, acoustic reflexes in the ipsilateral and contralateral conditions, and pure tone audiometry in a patient with middle ear dysfunction and moderate conductive hearing loss for the right ear. The combination of findings is sometimes referred to as the “inverted L” acoustic reflex pattern.

Diagonal Acoustic Reflex Pattern: Sensory Disorder. When acoustic reflexes are abnormally elevated in threshold or absent with stimulation of one ear, the most likely explanation is a sensory hearing loss. The diagonal pattern is illustrated in Figure 6. The chances of detecting acoustic reflex activity decline as the degree of sensory hearing loss increases. Normal acoustic reflex findings are anticipated in mild and even moderate sensory hearing loss, reflecting the loudness recruitment phenomenon. Generally, acoustic reflexes for pure tone signals are recorded until the degree of loss exceeds about 60 dB HL. The presence of normal acoustic reflexes with the probe in each ear under at least one condition confirms normal middle ear function in both ears.

Figure 6: Findings for tympanometry, acoustic reflexes in the ipsilateral and contralateral conditions, and pure tone audiometry are shown for a patient with severe sensory hearing loss on the right side. The combination of findings is sometimes referred to as the diagonal acoustic reflex pattern.

Diagonal Acoustic Reflex Pattern: Neural Disorder. At first glance the diagnostic pattern seen in Figure 7 may appear similar to, perhaps indistinguishable from, the diagnostic pattern just illustrated in Figure 6. Close inspection of all available findings clearly differentiate the two patterns. The big difference is the degree of hearing loss. With neural auditory dysfunction secondary to an acoustic tumor such as a vestibular schwannoma, the diagonal acoustic reflex abnormality is often associated with only mild hearing loss. The neural pattern may also be suspected due to acoustic reflex decay.

Figure 7:  Findings for tympanometry, acoustic reflexes in the ipsilateral and contralateral conditions, and pure tone audiometry are shown for a patient with neural hearing loss on the right side.

“Inverted L” Acoustic Reflex Pattern: Neural Disorder. A marked neural abnormality can produce the “inverted L” pattern, described earlier for a severe conductive loss. Abnormality of the 8^th cranial (acoustic) nerve affecting sound stimulation of the involved ear produces the diagonal component of the pattern. A large neoplasm compressing the brainstem as well as the 8^th cranial nerve may also affect the crossed or contralateral acoustic pathways within the brainstem with a resulting abnormality of both contralateral acoustic reflexes. The “inverted L” neural pattern is consistent with a larger tumor involving the 8^th cranial nerve and brainstem, whereas the diagonal neural pattern is found usually in smaller tumors affecting only the 8^th cranial nerve. Two findings distinguish the inverted L acoustic reflex pattern for conductive hearing loss versus neural disorder. For the neural pattern, tympanometry is normal for the neural pattern and there is no evidence of air-bone gap with pure tone audiometry.

Horizontal Acoustic Reflex Pattern: Brainstem Disorder. A horizontal acoustic reflex pattern, as depicted in Figure 8, is encountered in patients with brainstem auditory dysfunction, yet entirely normal peripheral auditory function. The presence of normal ipsilateral acoustic reflexes and normal tympanometry unequivocally rule out conductive hearing loss, sensory hearing loss, neural auditory dysfunction, and facial nerve disorder. The only appropriate anatomic explanation is brainstem auditory disorder.

Figure 8:  Findings for tympanometry, acoustic reflexes in the ipsilateral and contralateral conditions, and pure tone audiometry are shown for a patient with brainstem auditory dysfunction. The combination of findings is sometimes referred to as the horizontal acoustic reflex pattern.

Whenever the horizontal acoustic pattern is found clinically, it is very important to rule out technical problems and to verify that the appropriate stimulus intensity is being presented to each ear in through the contralateral stimulus transducer. If supra-aural earphones are used for contralateral stimulation, collapsing ear canals must also be ruled out. The horizontal acoustic reflex pattern is a strong sign of brainstem auditory dysfunction in patients at risk for central auditory nervous system dysfunction, including those with head injury and suspected auditory processing disorder (APD).

As noted at the beginning of this chapter, acoustic reflexes offer a completely objective auditory measure not influenced by the many listener variables like motivation, cognition, age, language, attention that might compromise behavioral measures of auditory function. The horizontal acoustic reflex abnormality strongly suggests the need for a comprehensive assessment of central auditory function and, depending on the outcome of the assessment, otolaryngology and/or neurology referral.

“Uni-Box” Acoustic Reflex Pattern: Brainstem Disorder. Jerger, Jerger & Hall (1979) first described rare pattern of acoustic reflex findings. The pattern is characterized by an abnormality is only one contralateral acoustic reflex condition as shown in Figure 9. All pathologic explanations other than an isolated unilateral brainstem auditory abnormality are convincingly ruled out due to the presence of normal acoustic reflexes in the other three acoustic reflex conditions, plus normal tympanograms and typically normal hearing sensitivity bilaterally. Observation of the uni-box acoustic reflex abnormality prompts a comprehensive assessment of central auditory function and, in many cases, otolaryngology and/or neurology referral.

Figure 9:  Findings for tympanometry, acoustic reflexes in the ipsilateral and contralateral conditions, and pure tone audiometry are shown for a patient with localized brainstem auditory dysfunction. The combination of findings is sometimes referred to as the “unibox” acoustic reflex pattern.

Clinical Efficiency of Acoustic Aural Immittance Measurements. The diagnostic efficiency of aural immittance measurements, including acoustic reflexes in the four test conditions, is unequalled in clinical audiology. With an investment of only a few minutes of test time and with equipment available in most audiology clinics it’s possible to objectively and sensitively identify facial nerve dysfunction and auditory dysfunction affecting a rather expansive region of the auditory system, from the middle ear to the lower brainstem. Patterns of findings for aural immittance measurements made at the start of a hearing assessment and before behavioral hearing assessment contribute to prompt and logical decisions on additional diagnostic testing and also appropriate patient management. 

OTOACOUSTIC EMISSIONS (OAEs)

Multiple Evidence-Based Applications of OAEs

OAEs contribute importantly and in a truly unique way to the diagnosis of auditory dysfunction, even though they have essentially no value in defining the degree of hearing loss. Some of the many clinical applications of OAEs are listed in Table 3. Each of the applications listed in Table 3 is evidence-based. That is, research findings in support of the clinical application are published in peer-reviewed journal articles. In terms of anatomic site sensitivity and specificity, in particular the detection and verification of outer hair cell dysfunction, OAEs have no rival in the hearing test battery. A full description of generation and mechanisms of OAEs, OAE measurement and analysis and the many evidence-based clinical applications of OAEs in children and adults is far beyond the scope of this brief review. A current review of the topic is available in a book devoted entirely to OAEs (Dhar & Hall, 2011).

________________________________________________________________

Pediatric Applications

• Newborn hearing screening
• Diagnosis of auditory dysfunction in infants and young children
• Differentiation of site of auditory dysfunction
• Identification of auditory neuropathy
• False hearing loss
• Monitoring ototoxicity
• Pre-school and school screenings

Adult Applications

• Diagnosis of cochlear versus neural auditory dysfunction
• Identification of false and exaggerated hearing loss
• Industrial and military hearing screening and conservation
• Identification and monitoring of auditory dysfunction in noise/music exposure
• Diagnosis and management of tinnitus and hyperacusis

Table 3. Selected evidence-based applications of otoacoustic emissions (OAEs) are listed for pediatric and adult patient populations.  Applications are not listed in order of importance.

Simple Guide to Measurement and Analysis

Pre-School Hearing Screening. Two selected clinical applications of OAEs are highlighted here. The first to be noted is the use of OAEs as a tool for hearing screening of pre-school children. There are many hundreds of publications describing newborn hearing screening with OAEs, but relatively little mention of their test performance or value in screening pre-school children (Kreisman, Bevilacqua, Day, Kreisman  & Hall, 2013). Detection of hearing loss in children in the age range of 3 months to 5 years is just as critical as it is for newborn infants. 

There are four compelling reasons why screening for hearing loss after the neonatal period is important: 1) Hearing loss in young children can have a major negative impact on speech/language acquisition, social development, emotional and psychosocial status, and pre-academic skills, such as reading readiness, 2) Pre-school hearing screening permits detection of young children with hearing loss who did not undergo hearing screening in the nursery before hospital discharge, 3) Screening during pre-school years detects progressive or delayed-onset cochlear hearing loss, a major contributor to the increased prevalence of hearing loss at school age, 4) Children who do not pass newborn screening and who are “lost-to-follow-up” in EHDI programs are found with pre-school OAE screening, and 5) Ongoing screening efforts detect conductive hearing loss secondary to middle ear disease.

The limitations of pure tone hearing screening in the pre-school years are well appreciated, especially by audiologists and others who have attempted this challenging task. Drawbacks to pre-school hearing screening include poor reliability, the adverse effect of a variety of test actors (e.g., cognitive status of the child, noise in the test setting, and skill and experience of the tester), sizable proportion of children who cannot be validly tested, and considerable test time.

In contrast, OAEs are quick, technically rather simple and, perhaps most importantly, not influenced by the troublesome listener variables. Research indicates that OAEs stand up well to the traditional pure tone hearing-screening standard (Hall & Swanepoel, 2010; Kreisman, Bevilacqua, Day, Kreisman  & Hall, 2013), when certain assumptions are met. Reliance on a simple signal to noise ratio (SNR) criterion for a pass or refer outcome is not sufficient. A DPOAE hearing screening test is enhanced with more rigorous criteria for a pass outcome, such as a SNR of > 6 dB plus an absolute distortion product amplitude of > 0 dB SPL.

This point is shown in Figure 10 with distributions for normal hearing versus hearing impaired persons as a function of DPOAE amplitude. DPOAE amplitude is plotted on the X-axis. Distributions of Pass and Refer outcomes are shown in relation to the criterion for a Pass outcome. Two criteria must be met for a Pass outcome: 1) A SNR of > 6 dB confirming the presence of a DP and 2) minimal DP amplitude of 0 dB representing the lower limit of normal DP amplitude. The use of these combined criteria for concluding a ‘refer’ result, detects almost 100% of ears with pure tone hearing thresholds of > 20 dB HL.

Figure 10 : A decision criterion is illustrated for the use of OAE amplitude findings in screening pre-school children for hearing loss.

OAEs in Tele-Audiology. Another exciting advance in clinical application is remote measurement of OAEs via tele-health techniques (Swanepoel & Hall, 2010; Swanepoel et al, 2010). Investigation of newborn hearing screening with DPOAEs showed no difference in findings for on-site face-to-face hearing screening versus hearing screening remotely with tele-medicine technology. In other words, hearing screening with DPOAEs conducted remotely was validated against the conventional approach for hearing screening with these technologies (Krumm, Hoffman, Dick, and Klich, 2008). A trained technician or facilitator can perform hearing screening with an OAE device with immediately electronic storage in an Internet accessible file. An audiologist then reviews OAE hearing screening outcomes remotely with an official reporting of the results. Asynchronous tele-audiology application of OAEs in hearing screening is inexpensive and highly efficiently.

AUDITORY BRAINSTEM RESPONSE (ABR)

Introduction to Auditory Evoked Responses

Published literature on the multiple and varied applications of auditory evoked responses in clinical audiology is vast (see Hall, 2015 for review). There is also remarkable accumulated clinical experience with electrophysiological responses elicited from the cochlea, auditory brainstem and auditory cerebral cortex. ECochG was the first auditory evoked response to be discovered and applied clinically.  Reports of the use of ECochG in the objective hearing assessment of difficult-to-test children date back to the 1960s. With the discovery of ABR, however, ECochG fell out of favor as an objective technique for auditory assessment. However, ECochG soon re-emerged as an electrophysiological procedure contributing to the diagnosis of Meniere’s disease. In the 1980s, ECochG techniques were first applied in intra-operative neurophysiological monitoring during surgeries putting the auditory system at risk. Most recently we have witnessed a resurgence of interest in ECochG as a critical test in the accurate diagnosis of ANSD, in particular the differentiation of pre-synaptic inner hair cell versus post-synaptic neural sites of auditory dysfunction (e.g. McMahon, Patuzzi, Gibson, & Sanli, 2008).

Auditory evoked responses are also useful in objectively evaluating function at the other end of the auditory system. Cortical auditory evoked responses were first recorded in 1939, less than 10 years after the discovery of ECochG. The literature on cortical auditory evoked responses, including the auditory middle latency response, the auditory late response, the auditory P300 response, and the mismatch negativity (MMN) response is even more extensive than for ECochG or ABR.

Many thousands of papers confirm the value of tonal and speech evoked cortical evoked responses in objective assessment of central auditory nervous system function in diverse patient populations ranging from a variety neuropsychiatric diseases to children and adults with suspected auditory processing disorders. One of the most recent and exciting applications of the auditory late responses is objective evaluation of cortical functioning in infants with sensory hearing impairment and ANSD undergoing habilitation with hearing aids and/or cochlear implants. Readers are referred to original research publications and current textbooks (Hall, 2015; Picton, 2011) for detailed information on cortical auditory evoked responses. The following review focuses exclusively on the ABR.

45 Years of ABR Research and Clinical Application

In the 45 years since Jewett and Williston (1971) discovered the ABR, effects of virtually every possible measurement parameter on the response have been investigated and described in the literature. Early studies of pediatric ABR application (e.g., Hecox & Galambos, 1974) laid the foundation for the later emphasis on newborn hearing screening and for today’s protocols for frequency-specific electrophysiological estimation of the audiogram using ABRs evoked with tone burst stimuli and the ASSR. Bone conduction ABR is now within the standard-of-care for hearing assessment of infants and young children (e.g., JCIH, 2007; NHSP, 2013). The ABR is unrivaled as a powerful diagnostic tool for in objective assessment of infant hearing and the identification and diagnosis of auditory neuropathy. A short list of clinical applications of ABR would also include:

• Automated newborn hearing screening
• Diagnosis of cochlear versus neural disorders in children and adults
• Neurophysiological monitoring in the operating room
• Neurophysiological monitoring of head injured patients in the neuro-intensive care unit
• Remote diagnosis of infant hearing loss via tele-audiology
• Measurement of the neural representation of speech processing within the auditory brainstem

A PubMed search (www.nlm.nih.gov) with the key words “auditory brainstem response” now produces over 12,200 articles. More than 300 articles were published annually from 1990 through 2010, but the number of papers on ABR has exceeded 400 per year since then. Admittedly, this vast literature consists of at least 4000 papers describing ABR in non-human animal species. Still, it would be reasonable to ask whether after 45 years and approximately 8000 reports of clinical ABR studies there is any new information that is worthy of publication. Multiple and varied lines of research contribute to the unabated volume of publications on ABR. Some of the articles describe application of the ABR in assessment of new clinical entities, often patients with rarely encountered diseases or genetic disorders.

Other investigators report technological advances in instrumentation that may lead to enhancement in ABR measurement or analysis. Remote ABR measurement via tele-audiology is now an option for provision of clinical services in regions where audiology expertise is lacking (Ramkumar et al, 2013). A sizeable proportion of recent publications are devoted to innovative stimuli for eliciting ABRs, including chirps and complex stimuli like speech. A substantial number of studies reported in the literature during the last decade are “cover studies” conducted in developing countries or countries with emerging audiology and hearing research professions, such as India, China, Brazil, and Iran to name a few. These papers describe replications of early investigations, but with current ABR instrumentation and with data from much larger samples of subjects.

The review that follows highlights the recent use of chirp stimuli in clinical measurement of the ABR in infants and young children. It is excerpted from the eHandbook of Auditory Evoked Responses (Hall, 2015).

Chirp Click Stimulus

What is a Chirp? As just noted, there is consensus that the ABR evoked with conventional click stimulation is dominated by activation of the basal region of the cochlea. Attempts to enhance the contribution of other regions of the cochlea to ABR generation include the creation of rather unique types of stimuli called “chirps”. Chirps are sounds that sweep rapidly from low-to-high frequencies or vice versa. Upward chirps are applied in recording auditory evoked responses. The term chirp is derived from the sound that birds and some other animals produce. The chirp stimulus is designed mathematically “to produce simultaneous displacement maxima along the cochlear partition by compensating for frequency-dependent traveling-time differences” (Fobel & Dau, 2004).

Since the 1980s various authors have reported detailed technical descriptions and mathematical models for chirp stimuli for use in measurement of auditory evoked responses (see Hall, 2015 for review). In theory, the chirp version of the click stimulus optimizes synchronization across a broad frequency region at high and low intensity levels, yielding a more robust ABR than the conventional click stimulus. A detailed explanation of the model of cochlear biomechanics and the mathematical functions important in the rationale for and generation of chirps is far beyond the scope of this discussion. The article authored by Fobel & Dau (2004) provides a useful source of background information on the topic.

Rationale for Chirp Stimuli. The overall physiological goal with chirp stimuli is to simultaneously activate a wide range of the cochlea from base to apex.  This is achieved with temporal compensation for the traveling wave delay as it moves from the high to the low frequency portions of the cochlea. Estimations of the traveling wave delay are available from extensive analysis of the differences in the latency of wave V for ABRs evoked with high frequency versus low frequency tone burst stimulation and also from systematic study with the derived-band technique for isolating contributions to the ABR of different frequency regions.

Dr. Manny Don of the House Research Institute, and others, studied the effects of ipsilateral high pass masking on “cochlear response times” associated with traveling wave distance and velocity along the basilar membrane (Don et al, 1994). Traveling wave time from higher frequency regions of the cochlea to lower frequency regions is approximately 5-ms. Factors influencing traveling wave times in cochlea include stimulus intensity level, hearing loss, and subject age. Most early research on chirp stimuli was conducted with ABRs recorded at moderate-to-low intensity levels from normal hearing adult subjects.

The following is a clinically oriented and admittedly oversimplified description of broadband chirp stimuli, or chirp versions of click stimuli that have been used to elicit ABRs since the pioneering studies of Jewett & Williston in early 1970s. Tone burst versions of chirps are described later in the same chapter within a discussion of frequency-specific stimuli. Briefly, spectrum of the chirp click stimulus like the conventional click stimulus includes energy across a wide frequency region. With chirp stimulation, however, lower frequency energy is presented earlier than higher frequency energy.

A click chirp stimulus is illustrated in Figure 11. Low frequency portions of the stimulus appear first with a progressive increase in time as frequency is increased. Rising or upward frequency chirp stimuli are mathematically designed to compensate temporally for travel wave times. Higher frequency energy in chirp stimuli is delayed relative to lower frequency energy. Low frequency energy essentially is given a “head start” as it begins its journey to the distant apical region of the cochlea. Mid-frequency energy in the region of 1000 Hz is presented milliseconds later and high frequency energy is delivered relatively last.  Travel waves for each of the frequency regions reach their cochlear destinations at the time harnessing synchronous activity from most of the cochlear, not just the high frequency portion.

Figure 11: Illustration of chirp stimulus used to evoke ABR. Earliest portion of the temporal waveform activates more apical regions of the cochlea and later portions of the waveform activate more basal regions.

Another way of considering the concept of click chirp stimulation is to describe the effect on ABR waveforms. Without the temporal compensation produced with chirp stimuli, ABR wave V latency for stimulation in the region around 500 Hz is about 5-ms longer than latency for 4000 Hz stimulation. Delivering lower frequency stimulus energy to the cochlea about 5-ms earlier than higher frequency stimulus energy essentially produces a corresponding shift in wave V latency.

ABR Wave V latency evoked with lower frequency stimulation occurs earlier than it typically does and at the same time as the ABR wave V for higher frequency stimulation. The overall effect is to evoke an ABR wave at the same latency for stimuli in each frequency region.  Amplitude of the chirp-evoked ABR is enhanced with the addition of super-imposed wave V components for stimuli within each of the frequency regions. This complex temporal compensation process is illustrated in Figure 12.

Figure 12:  Illustration of the concept of temporal compensation for enhancement of amplitude for chirp-evoked ABR

Larger amplitude for ABR wave V is not a trivial goal. The significant clinical advantages of a larger wave V, often a doubling in amplitude, and an increase in the ABR versus noise difference include: 1) more confident identification of wave V near the minimum response level or threshold, 2) detection of an ABR at lower intensity levels for presumably more accurate estimations of thresholds, and/or 3) decreased test time required for recording ABRs.

Factors Influencing Chirp-Evoked ABR. As noted already, early research on chirps focused almost exclusively on data collected at low-to-moderate intensity levels in carefully controlled laboratory settings from normal hearing adults. Early and more recent clinical investigations in normal hearing infants and young children have consistently confirmed larger amplitude for ABR wave V at low-to-moderate intensity levels (see Hall, 2015 for review).

There are well-appreciated effects of intensity level on the duration of chirp stimulus and also on cochlear mechanics and physiology underlying level-dependent changes cochlear traveling waves and delays. Mathematical formula and models developed for low intensity chirp stimuli are not appropriate for higher intensity levels. Level-dependent variations in ABRs evoked with chirp stimuli pose a clinical problem. Amplitude of ABRs recorded at high intensity levels with chirp clicks developed for low-level stimulation is actually smaller than ABR amplitude for conventional click stimuli. The clinical value of chirp stimuli in recording ABRs would certainly be diminished if it were limited to infants and young children with normal hearing or at most a mild hearing loss. Amplitude of ABR wave V tends to decrease as hearing loss increases. Therefore, one might argue that enhanced ABR amplitude with chirp stimulation would be of greatest value in patients with hearing loss.

Level-specific (LS) chirps offer an option for obtaining the benefits of chirp stimulation at a variety of different intensity levels. LS chirps are based on a unique level-specific delay model (Kristensen & Elberling, 2012). In contrast to fixed chirps developed for use only at lower intensity levels, duration of LS-chirps changes with stimulus level. The LS-chirps at each intensity level are based on a different delay model with the goal of eliciting the largest possible ABR amplitude. Intensity levels are calibrated using International Standards Organization reference values (dB p.-p.e. RETSPL). The is standard “specifies reference hearing threshold levels for tests signals of short duration applicable to the calibration of audiometric equipment where such signals are used.”

Several additional comments about chirps are worth noting at this juncture. Chirp stimuli and their effectiveness in enhancing the amplitude of ABRs are dependent on specific mathematical formulae and models. Not all chirps are created the same way. The forgoing discussion focused mostly on CE-chirps developed by and described in the publications of Claus Elberling (CE) and colleagues who designed stimuli designated as “CE-chirps”. It’s reasonable and advisable to inquire about the development of and clinical research evidence in support of chirps before applying them in ABR measurement from patients.

The second point has to do with clinical applications of chirp stimuli. The focus of this discussion has been the use of air conduction chirp stimuli in recording ABR in infants and young children. Chirp stimuli also appear to contribute to the additional applications of ABR, such early detection of retrocochlear auditory dysfunction and as bone conduction ABR. And, chirp stimuli play a role in the measurement of ASSR and cortical evoked responses.

Role of ASSR in the Pediatric Test Battery

An appreciation of the strengths and weakness of the ASSR, listed in Table 4, guides decisions on when it should be applied clinically and its role in the diagnostic process. Consistent with the cross check principle and in common with behavioral hearing tests and other electrophysiological auditory procedures, ASSR should not be recorded in isolation but, rather, as a component in an appropriate test battery. The literature reveals papers describing diagnostic applications of ASSR in various pediatric populations in addition to estimation of auditory thresholds, including:

• Objective assessment of hearing aid gain in the sound field environment
• Benefit from cochlear implantation
• Diagnosis of ANSD
• Detection and diagnosis of neurological auditory disorders
• Assessment of auditory processing in dyslexia

This is a good place to dispel two common misconceptions. ASSR and ABR are not competitive electrophysiological procedures. In other words, the decision clinically is not to record either tone burst ABR or ASSR. The two procedures are complementary. Diagnosis of hearing loss and plans for intervention are often based on results of some combination of ABR recordings and ASSR recordings in the same child, along with findings for other objective auditory tests. Also, clinical experience suggests that test time is equivalent for tone burst ABR and ASSR measurement. Claims that tone burst ABR assessment is excessively time-consuming and ASSR requires relatively little test time are not supported with clinical research or experiences. A skilled clinician can complete a frequency-specific ABR assessment for both ears in 30 minutes or less with a sleeping patient, a clear plan of action, a carefully constructed tone burst protocol including options like chirp stimuli, and consistently good use of test time.

________________________________________________________________

Advantages

• Frequency-specific signals are employed for estimation of thresholds at audiometric frequencies from 250 Hz to 8000 Hz.
• Frequency-specific auditory thresholds can be estimated with air conduction and bone conduction signals.
• Stimulus intensity levels as high as 120 dB HL can be used in eliciting frequency specific thresholds. The ASSR is, therefore, useful for electrophysiological assessment of severe to profound degree of hearing loss in infants and young children.
• ASSR detection and analysis is automated and statistically based. Clinician experience in waveform analysis is not necessary.
• Clinical devices are available from multiple manufacturers.

Potential Disadvantages

• ASSR recording requires a very quiet state of arousal. Movement artifact and interference may preclude testing or may invalidate results with overestimation of actual auditory threshold levels in young children who are not sleeping. ASSR usually requires that the patient sleep naturally or with sedation. Anesthesia is sometimes necessary for valid ASSR assessment of hearing sensitivity.
• The influence of deep sedation and anesthesia on the ASSR evoked by high modulation frequencies (e.g., > 60 Hz) requires further investigation. Sedation and anesthesia invalidates threshold estimations for ASSR evoked with slow modulation frequencies (e.g., < 60 Hz).
• Modest discrepancies between ASSR thresholds and either behavioral and/or ABR thresholds are reported in the literature.
• Discrepancies between ASSR thresholds and behavioral thresholds are possible for patients with conductive hearing loss.
• Estimation of ear-specific thresholds with bone conduction signals requires the use of masking to the non-test ear. Unlike ABR, there is no biological marker for test ear with ASSR.
• There is little site-specific information for patients with hearing loss since the ASSR waveform cannot be analyzed. ASSR cannot be used to differentiate sensory versus neural auditory dysfunction.
• Absence of ASSR does not differentiate between profound sensory hearing loss versus ANSD.
• In the USA there is no current procedural terminology billing code specifically for ASSR.

 Table 4. Strengths and weakness of ASSR as a clinical tool are listed here.

The ASSR like the ABR offers an opportunity for estimation of auditory thresholds in infants and young children who cannot be properly assessed with behavioral audiometry techniques. The ASSR provides a distinct edge over behavioral audiometry and in several respects even the ABR in this clinically challenging patient population (see Figure 13) . One strong feature of the ASSR, in comparison to the ABR, is the capacity for defining severe to profound hearing loss, that is, estimating hearing thresholds within range of 80 to 120 dB HL. The limitation of ABR in defining the degree of severe-to-profound hearing loss > 90 dB HL is well appreciated by clinicians and well documented in the literature.

Figure 13:  A graph illustrating the value of ASSR in estimating auditory thresholds in patients with severe-to-profound hearing loss that exceeds the intensity limits of ABR.

ABR and ASSR each can contribute importantly and rather uniquely to diagnostic auditory assessment of children. However, it is important, however, to keep in mind that neither the ABR nor the ASSR are actually tests of hearing. Each technique must be applied within an appropriate evidence based test battery consistent with the crosscheck principle (Jerger & Hayes, 1976) and with clinical guidelines for pediatric hearing assessment (JCIH, 2007).

Chirp-Evoked ASSR in Infants

Papers are beginning to emerge describing comparison of chirp-evoked ASSR with hearing thresholds and with ABR thresholds (Venail et al, 2015). Preliminary evidence suggests that chirp-evoked ASSRs are equivalent to and perhaps superior to conventional ASSR techniques for quick and accurate estimation of behavioral thresholds in adults and, most importantly, in infants and young children with normal hearing or hearing impairment (Venail et a, 2015; Mühler, Mentzel & Verhey, 2012). Efficiency and accuracy of technique chirp-evoked ASSR appears to be related to increased amplitude. One of the major clinical benefits of chirp stimuli is reduction in test time. For example, Mühler and colleagues (2012) in a study with normal hearing and “mildly to moderately hearing impaired” adult subjects reported a mean time of 18.6 minutes for completion of ASSR for four test frequencies in both ears, using a “semiautomatic adaptive algorithm.” Such brief test times open up the possibility of performing ASSR assessments in reasonably cooperative infants and young children who are sleeping naturally without the assistance of sedation or anesthesia.

CONCLUDING COMMENTS

Each of the objective measures reviewed here offers compelling advantages for the auditory assessment of infants and young children. However, the diagnostic power of objective auditory tests is fully realized only when they are applied in combination. Careful analysis of findings for an objective auditory test battery almost always yields prompt and precise description of auditory status, and it often leads to accurate diagnosis of auditory dysfunction. The key to meaningful analysis of findings for a test battery is the recognition of patterns associated with major auditory disorders. This is not a novel concept. It’s simply the modern day implementation of the 40-year old crosscheck principle.

Our review concludes with examination of selected patterns of auditory findings displayed in Table 5.  Normal test findings are indicated with two “minus” or negative symbols. The “+” or positive symbol is used to indicate abnormal findings, those that are positive for a disorder. In addition to the objective measures discussed in this review, the table includes representative findings also for ECochG and cortical auditory evoked responses. Even a cursory glance of information in the columns representing various auditory disorders in Table 5 confirms that none of the patterns is duplicated. Each pattern of findings is uniquely associated with a specific disorder.

______________________________________________________________________

                                                                              Auditory Disorder

                                                _______________________________________________

                                                Normal   Middle Ear      Cochlear         ANSD     CNS   APD

Test                                                                             OHC     IHC

______________________________________________________________________

Aural immittance                       

            Tympanometry              --                   +            --         --            --         --         --   

            Acoustic reflexes*          --                   +            +/-        +/-           +          +         +/-

OAEs                                         --                   +            +          --            --         --         --

ABR: click stimuli                                                        

            Air conduction               --                   +            +/-        +/-           +          --         --

            Bone conduction           --                   --           +/-        +/-           +          --         --

ABR: tone burst stimuli              --                  +/-           +/-        +/-           +/-        --         --

ASSR                                        --                  +/-           +/-        +/-           +/-       --          +/-

ECochG

            CM                                 --                  +             +          --            --        --          --   

            SP                                  --                  +             --         +             +/-       --          --

            AP                                 --                  +             +/-        +/-           +         --          --

Cortical auditory responses           --                  +/-           --         --            +/-       +           +

______________________________________________________________________

Table 5 : Patterns of objective test findings in selected types of auditory disorders.

Key to symbols: -- = Normal; + = Abnormal; +/- = Variable

* Acoustic reflexes elicited with broadband noise (BBN)

 Exclusive reliance on only one or two objective auditory measures often results in equivocal outcome. That is, the patient’s diagnosis is not clear. The patient’s hearing loss could be associated with one of multiple disorders. With an appropriately complete test battery, however, auditory disorders are confidently differentiated. An example might be useful to clarify this statement. Let’s assume a 3-month old infant undergoes follow-up diagnostic auditory assessment after failing neonatal hearing screening. The patient is a graduate of the intensive care nursery whose history includes management with several potentially ototoxic drugs plus neurological risk factors, such as pre-mature birth and asphyxia. Concerns include the possibility of cochlear hearing loss, neural disorder (e.g., a form of ANSD), or possibly central auditory nervous system dysfunction. Findings for common objective tests, such as acoustic reflexes, OAEs, ABR, and perhaps ECochG clearly point to the most likely auditory disorder.

In summary, the application of a complete objective test battery is the most effective and efficient strategy for prompt and accurate diagnosis of auditory dysfunction and hearing loss in infants and young children. Objective auditory assessment is essential for a successful EHDI program. Hearing assessment with a collection of objective auditory tests defines standard of care in pediatric audiology.

REFERENCES

1. Dhar S & Hall JW III (2011). Otoacoustic Emissions: Principles, Procedures & Protocols. San Diego: Plural Publishing
2. Don M, Ponton C, Eggermont J, and Masuda A. (1994). Auditory brainstem response (ABR) peak amplitude variability reflects individual differences in cochlear response times. Journal of the Acoustic Society of America, 96, 476-3491
3.  Feeney MP, Hunter LL, Kei J, Lilly DJ, Margolis RH, Nakajima HH, Neely ST, Prieve BA, Rosowski JJ, Sanford CA, Schairer KS, Shahnaz N, Stenfelt S & Voss SE (2013). Consensus Statement: Eriksholm workshop on wideband absorbance measurements of the middle ear. Ear and Hearing, Supplement 1
4.  Fobel O and Dau T (2004). Searching for the optimal stimulus eliciting auditor brainstem responses in humans. Journal of the Acoustic Society of America, 116, 2213-2222
5.  Galambos R & Hecox, K (1978). Clinical applications of the auditory brainstem response. Otolaryngology Clinics of North America, 11, 709-722
6.  Hall JW III, Berry GA and Olson K (1982).  Identification of serious hearing loss with acoustic reflex data:  Clinical experience with some new guidelines. Scandinavian Audiology, 11, 251-255
7.  Hall JW III & Swanepoel, D (2010). Objective Assessment of Hearing. San Diego: Plural Publishing
8.  Hall, JW III (2010). Aural immittance measures in audiology: More useful now than ever before. The Hearing Journal 63, 15-15
9.  Hall JW III (2015). Introduction to Audiology Today.  Boston: Pearson Educational
10.  Hall JW III (2015). eHandbook of Auditory Evoked Responses. Amazon.com, Kindle Direct Publishing (http://www.amazon.com/dp/B0145G2FFM)
11.  JCIH (2007). Joint Committee on Infant Hearing Year 2007 position statement: Principles and guidelines for early hearing detection and intervention programs. Pediatrics, 120, 898-921
12.  Jerger J, Burney P, Mauldin L & Crump B (1974). Predicting hearing loss from the acoustic reflex. The Journal of Speech and Hearing Disorders, 39, 11-22
13.  Jerger JF & Hayes D (1976).  The cross-check principle in pediatric audiometry. Archives of Otolaryngology, 102, 614-420
14.  Jerger JF, Jerger S and Hall JW III (1979).  A new acoustic reflex pattern. Archives of Otolaryngology, 105, 24-28
15.  Jewett, D. L., & Williston, J. S. (1971).  Auditory evoked far fields averaged from the scalp of humans.  Brain, 4, 681-696
16.  Kei J (2012). Acoustic stapedial reflexes in healthy neonaets: normative data and test-retest reliability. Journal of the American Academy of Audiology, 23, pp?
17.  Kreisman BM, Bevilacqua E, Day K, Kreisman NV & Hall JW III (2013).Preschool hearing screenings:  A comparison of distortion product otoacoustic emission and pure tone protocols. Journal of Educational Audiology, 19, 49-57
18.  Kristensen SGB & Elberling C (2012). Auditory brainstem responses to level- specific chirps in normal-hearing adults. Journal of the American Academy of Audiology, 23, 712-721
19.  McMahon, CM, Patuzzi, RB, Gibson, WP & Sanli, H (2008). Frequency-specific electrocochleography indicates that presynaptic and postsynaptic mechanisms of auditory neuropathy exist. Ear and Hearing, 29, 314-325
20.  Mühler, R, Mentzel, K & Verhey, J (2012). Fast hearing-threshold estimation using multiple auditory steady-state responses with narrow-band chirps and adaptive stimulus patterns. Scientific World Journal, 2012:192178. doi: 10.1100/2012/192178. Epub 2012 Apr 24
21.  NHSP (2013). Newborn Hearing Screening Program. “Guidance for Auditory Brainstem Response testing in babies.”
22. http://www.thebsa.org.uk/wpcontent/uploads/2014/08/NHSP_ABRneonate_2014.pdf
23.  Picton, TW (2011). Human Auditory Evoked Potentials. San Diego: Plural Publishing
24.  Ramkumar V, Hall JW III, Nagarajan R, Shankarnarayan VC & Kumaravelu S (2013). Tele-ABR using a satellite connection in a mobile van for newborn hearing testing. Journal of Telemedicine and Telecare, 19, 233-237
25.  Swanepoel, D & Hall JW III. (2010). A systematic review of telehealth applications in audiology. Telemedicine and e-Health, 16, 181-200
26.  Swanepoel D, Clark JL, Koekmoer D, Hall JW III, Krumm M, Ferrari DV, McPherson B, Olusanya BO, Mars M, Russo I & Barajas JJ. (2010). Telehealth in audiology: The need and potential to reach underserved communities. International Journal of Audiology, 49, 195-202
27.  Venail F, Artaud JP, Blanchet C, Uziel A & Mondain M (2015). Refining the audiological assessment in children using narrow band CE-chirp-evoked auditory steady state responses International Journal of Audiology, 54, 106-113

As it has been the tradition the last  years, we occasionally focus  on technology related issues. The OAE technology has reached, as it was expected, a plateau the last 5-10 years, but information technologies continue to grow and new aspects of Tele-Health are emerging. We have also observed developments in the area of implantable devices (hearing aids and cochlear implants), but the main contributions are mainly in the area of software development than in new hardware implementations. Some interesting ideas have been reported about Implant systems releasing anti-inflammatory agents like dexamethasone in the inner ear , to suppress post-surgical side effects, but clinical trials have not started yet.There are some interesting trends in the area of wearable medical devices (mostly sensors ) which can connect to our mobile phones for data visualization and control, but we do not have reports for any Audiology / Hearing Science applications so far. This idea is intriguing and we are seeking authors for an editorial or a white paper on this topic. 

It would be nice to hear your opinion in these issue, since the OAE Portal is a Open  Access depository of Knowledge. It would be a great privilege for me and my collaborators to listen what you have to say.

About the guest Editors:  

Dr. Mark Krumm is an associate professor in the School of Speech Pathology and Audiology at Kent State University in Kent, Ohio (USA).  He has been involved with telehealth applications for over a decade and has published a number of papers describing audiology telehealth use with pure tone audiometry, otoacoustic emissions, immittance, video-otoscopy and the auditory brainstem response (ABR). Dr. Krumm has also chaired the American Speech Language and Hearing Association (ASHA) committee on Telepractice as well as the first American Academy of Audiology (AAA) task force on Telehealth.

Vidya Ramkumar is a faculty member at the Department of Speech, Language and Hearing Sciences at Sri Ramachandra University, Chennai, India. She is also a PhD candidate in Audiology at, Sri Ramachandra University,  in the area of tele-audiological application in newborn hearing screening in rural villages. She worked in the area of tele-audiological applications in testing hearing among school children as a part of her Fulbright-Nehru Doctoral Professional Research fellowship, which she completed in 2014. She was co-investigator of project titled “Newborn hearing screening using tele-audiology” and received funding from the Indian Council of Medical Research, Government of India. She has also been involved in development of mobile phone based applications in hearing screening and tinnitus. She has published articles in the area of tele-audiology, tinnitus and community based hearing screening programs. 

An Update: Use of OAEs in Telehealth (Teleaudiology) Applications

By Mark Krumm, Ph.D and  Vidya Ramkumar, M.S.

Introduction

Telehealth is the provision of services by practitioners from their location (the distant site) to clients located at site in another location (the local site). Audiologists have been using telehealth (tele-audiology) services in one form or another since the 1990s. There were obvious benefits to using otoacoustic emissions and telehealth including supporting newborn hearing screening and diagnostics programs (see Figure 1).

Figure 1. DPOAEs and TEOAEs could be used with telehealth technology to create better hearing healthcare for all individuals including infants

           The first known attempt to use otoacoustic emissions for telehealth purposes can be traced to proof of concept trials by Virtual Corporation in the mid-1990s. This work formed the basis of a master’s thesis produced by Schmiedge (1997). In his thesis, Schmiedge described a comprehensive study employing the Virtual Corporation system and PC Anywhere software to obtain DPOAEs remotely. While most of the thesis was dedicated to assessing the reliability of remote computing of DPOAEs over a local area network (LAN), Schmiedge also conducted remote computing trials with subjects located in another country (Canada) using a telephone modem.

           Schmiedge’s thesis was interesting for a number of different reasons. First, his thesis demonstrated that remote computing technology using DPOAEs was practical in the mid-1990s. He also found that DPOAEs could be reliably obtained using different mediums of telecommunications technology including a telephone modem. This study also implied that telehealth could be utilized with relative ease using off the shelf software and computerized audiology test systems as suggested in Figure 2.

Figure 2. Remote computing components indicated by Schmiedge (1997). This model would work either over a network or by modem connection.

                    Schmiedge’s interest in the use of DPOAEs for this thesis stemmed from the objective nature of otoacoustic emissions. Specifically, one could evaluate remote computing technology using DPOAEs without the bias of the subjects. In addition, DPOAEs are conducted rapidly and provide significant diagnostic information to determine hearing status. A further advantage to the use of DPOAEs (or TEOAEs) is these recordings provide a measurement of the noise floor in the ear canal. Consequently, clinicians could use this information to determine if the level of background noise at the client test  site was appropriate for testing.

                   Yet another compelling reason for Schmiedge was the ever-growing evidence that TEOAEs and DPOAEs would take a central role in universal newborn hearing screening and diagnostic programs. To be successful, these programs would have to be provided to newborns living in underserved areas. Hence audiologists would be required to work in distant communities or infants (and their parents) would have to travel significant distances to metropolitan centers for hearing health care services. A probable outcome was that travel would create barriers and infants would be lost to follow-up services. O’Neal et al. (2000), addressing the subject of service discontinuity, suggested that new paradigms must be developed to ensure that each infant is connected to needed services regardless of circumstances .One such paradigm was audiology services provided via telehealth. As webcam quality and speeds increasing by leaps and bounds, it became possible to see clear images of the client and OAE results on a computer screen early in the last decade (see Figure 3)

                         Figure 3. Telehealth screen capture of infant testing via telehealth in 2003

                 There were other obvious advantages to using telehealth to supplement universal newborn hearing programs. Health care personnel involved with newborn hearing services in rural locations would need consistent training, oversight and feedback by audiologists in order to provide quality services. Telehealth technology could be used to provide that oversight via video conferencing. Further, if necessary, the practitioner could actually control testing of otoacoustic emissions directly using remote computing technology if a computerized OAE system was available at the client (local) site.

                 Citing the benefits of telehealth, Krumm and Schmiedge (2005) wrote a paper discussing the implications of telehealth to support EDHI services. Synchronous applications were described by these authors as a method in which the clinician could test a client over a network or modem in real time. Krumm and Schmiedge also suggested that synchronous applications could include interactive video, remote computing software and computerized auditory brainstem response (ABR) or OAE systems for remote computing applications (see Figure 4). Asynchronous (or "store and forward") telehealth procedures were also described. Asynchronous telehealth methods are employed when client data is printed out, scanned in a computer (or faxed) and sent to a clinician for interpretation. Such data may include immittance results, hearing aid analyzer or real ear results, case history information, video otoscopy images, and video clips of the client being tested. An asynchronous system is diagramed in Figure 5.

Figure 4. A schematic of remote computing hardware, software and personnel  needed for remote computing testing. Remote computing software and interactive video are used at both sites. Audiology hardware is only located at the community test site.

                                Figure 5. An asynchronous method of sending DPOAEs to clinicians  involved with EDHI services.

               Additionally, a hybrid model was described in which a combination of synchronous and asynchronous technology is utilized for the provision of audiology telehealth services (Krumm 2007; Swanepoel and Hall, 2010).  For example, audiologists using a hybrid model might wish to use interactive video and remote DPOAEs testing procedures (which is synchronous technology). These results could be supplemented through asynchronous technology with local site assistants sending clinicians scanned files of information such as immittance, prior ABR/OAE results or video otoscopy records. Used in this way, hybrid telehealth systems appear to offer the most flexibility for practitioners wishing to provide a full array of hearing health care services. In other words, the hybrid model invites an “anything that works” mindset that results in the use of both synchronous and asynchronous audiology systems for hearing assessment. Figure 6 offers how both synchronous and asynchronous results might be transmitted to a clinician from the infant test site.

                      Figure 6. A hybrid system utilizing diagnostic tests for EDHI services.

              The first published study in which telehealth technology was used to assess infant hearing was described by Krumm, Huffman, Dick and Klich (2008). In this study, the investigators used distortion DPOAEs and automated ABR (AABR) to provide follow-up screenings to infants who had failed their initial hospital hearing screening at birth. Approximately 30 newborns, ranging 11-45 days of age, were rescreened using face-to-face measurements and by telehealth technology. The results of this study indicated that no significant differences existed between the use of telehealth and face-to-face measurements when infants were rescreened for DPOAEs and screening ABR. As this was a proof of concept study, further investigations or needed to examine "real world" applications.

                 The next telehealth study incorporating the use of hearing measures with young children was conducted by Ciccia et al. in 2010. This study was unique in that it was conducted with preschool children attending an inner-city medical center in Cleveland, Ohio (USA) for hearing healthcare services. While most telehealth projects are conducted in rural areas, it should be recognized that individuals who live in inner-city communities also have significant barriers to hearing healthcare. These barriers include professional shortages, accessibility of clinical locations to families and socio-economic issues (Ciccia et al., 2010).

                  In the study by Ciccia et al, the investigators provided preschool aged children with hearing screening services including otoscopy, pure tone testing, DPOAEs, tympanometry and otoscopy. As most of the children were under 6 years of age, children were generally screened using play audiometry and/or with DPOAEs. This project length was two years and over 411 children were screened during this time.

                   During the first year, the hearing screening was conducted by an audiologist supervising a trained assistant via interactive video. The audiologist trained the assistant in conducting otoscopy, immittance testing, screening DPOAEs and in play audiometry for preschool children. The assistant was a student in a local undergraduate speech-language and hearing program.  The “video only” model in year one was adopted to address the immediate need to provide hearing screenings at the screening site. During the second year, all of the hearing screening was done synchronously by remote computing technology using webcams, a video otoscope, a computerized audiometer and remote computing software, a computerized tympanometer and distortion product otoacoustic emissions systems. The results of the first year of telehealth screening results were compared to the second year results. Interestingly, virtually no difference existed between the two vastly different telehealth protocols of year one and year two.

                   The results of this study are notable for a couple of reasons. The first is that a relatively simple telehealth model was employed for hearing screening in the first year of the study. This telehealth model required a supervising audiologist (using interactive video from the distant location) to oversee screening procedures of an assistant at the screening site. In contrast, during the second year, the audiologist actually conducted the hearing testing using synchronous (and remote) computing technology. This study suggests that while remote computing is a reasonable and desirable method for audiologist employ in telehealth, the use of interactive video may be used to effectively supervise well trained assistants\\s to do preschool hearing screenings (including possibly play audiometry). In addition, the parents of the children screened in the study indicated they favored telehealth technology and thought this technology was equally as good as those services provided face-to-face. This outcome may be due to the fact that telehealth services were provided as a community based service in which clients and their parents felt comfortable. Consequently, this project offers valuable information about using more than one telehealth model to provide hearing screening services for preschool children.

                    An EDHI telehealth study described in two papers by Ramkumar et al. were published in 2013 and in 2014. In this study, many infants in rural India were tested with remote computing technology through satellite and DSL connections. A mobile van equipped with satellite technology for telemedicine applications was utilized at the infant test site in rural Indian villages (see Figure 7).  Additionally, local DSL services were located by project personnel finding hotspots in the local community where DSL services were available. As bandwidth for connectivity was restricted, the remote computing technology at the infant site required a dedicated interactive video line to one laptop and a separate line to a laptop dedicated for remote computing services.

Figure 7. The telemedicine van stationed in the rural community (top centre), health  worker cleaning a neonates skin for ABR (bottom left), Tele-ABR conducted inside the mobile tele-van (bottom right) 

               Further, the researchers trained community health workers employed in rural villages to act as facilitators for EDHI diagnostic services. These village health care workers were trained in depth in providing necessary services at the local site including equipment troubleshooting, OAE probe placement and ABR electrode placement. The village health care workers were local and trusted individuals that parents often knew in their communities (Rajendran et al. 2014). Consequently, there was little doubt these facilitators were important for establishing rapport with local community members who agree to have their newborns tested via telehealth (see Figure 8).

                                 Figure 8. Village health worker screening a neonate in the rural community in India.

                 One of the obstacles in this study was obtaining the desired bandwidth to provide telehealth services in rural India. In spite of technology issues associated with slower satellite mediated Internet and land based DSL speeds, these researchers were eventually able to provide EDHI diagnostic services to over 100 infants using remote computing technology (Ramkumar et al., 2014). Comparison of outcomes between tele and face to face ABR on neonates demonstrated no significant difference even in spite of tremendous connectivity barriers (Ramkumar et al., 2013).

          In a study that paralleled the work of Ramkumar et al. (2013), Hayes et al.  (2015) described comprehensive infant hearing services which were provided from clinicians located in the USA  to infants located in Guam utilizing mostly remote computing technology. Specifically, Hayes et al. were able to conduct complete EDHI evaluations using DPOAEs, ASSR, ABR, video otoscopy and tympanometry. These evaluations were made possible through trained EDHI assistants located in Guam who were responsible to prepare newborns for hearing testing. Various videos of teleaudiology sessions with children can be seen at the National Center for Hearing Assessment and Management, Utah State University at the following link:. http://www.infanthearing.org/teleaudiology/videos.html

                 Hayes et al. detailed significant programmatic needs such as training of assistants, considerations for parent satisfaction, clinician satisfaction and troubleshooting hardware issues. Of particular interest, this paper documented the need to test telehealth equipment (including both diagnostic and interactive video equipment) to ensure quality services to the local site in Guam. Noted in this study were issues relating to poor audio associated with the interactive video equipment and occasional loss of connectivity with the Internet. To overcome the poor audio issues associated with interactive video, a telephone was used to provide communication between the USA and Guam sites (Hayes et al., 2012). They also found the disconnection of the Internet was not disruptive even when occurring during a test session.

                     Finally, it is apparent that Hayes et al. (2015) spent a great deal of effort to provide in-depth training of facilitators at the client site in Guam. In addition to this systematic training, audiologists from Colorado were sent to Guam for a week of in-service training with Guam EDHI personnel and to inspect the local telehealth site facilities for suitability of service provision.

                     An important comment in the article by Hayes et al., (2015) concerns the cost and sustainability of audiology and telehealth services. Specifically these researchers indicated the startup cost for the telehealth services were substantial with equipment costs exceeding $60,000. Also, as this project was supported by a federal grant, the infants evaluated in this project were not charged a fee for service. Hayes et al. (2015) indicated sustainability of the project would require continued forms of income. This comment is of interest as virtually all audiology telehealth projects which have been described in the literature are either proof of concept or grant funded projects. These projects often end because no further source of funding is available. A notable exception appears to be projects which are supported by the federal government funding. Clearly, innovative entrepreneurship funding strategies may be needed to sustain teleaudiology programs.

Conclusions

OAE assessment has a long history with telehealth applications. Virtually all work in telehealth is with EDHI applications.  Clearly, OAEs can be used effectively and reliably with telehealth technology in both synchronous and asynchronous methods with essentially the same outcomes. But researchers indicate that telehealth assistants must have substantive training when supporting audiologists at client test sites. In addition, internet connectivity and audio communication may be problematic in telehealth services. However, prototyping telehealth equipment should lead to identification of these issues.

Data is lacking concerning the provision of EDHI services for children and behavioral testing. Visual reinforcement audiometry (VRA) appears difficult to do under a telehealth paradigm due to complex equipment needs. However, play audiometry appears reasonable with proper assistant training.

Finally, telehealth has limitations and clinicians must determine boundaries when clients should be seen in person. Such circumstances might include (but are not limited to) clients who are hard to test, second opinions, pediatric ear mold impressions, pediatric hearing aid fittings or parental concern over telehealth technology.  On the other hand, it is clear that telehealth offers the capability for providing services to individuals in underserved locations even when the clinician is literally a continent away.

References

Ciccia, A,Whitford, B, Krumm, M, McNeal, K. (2011).  Improving the access of young urban children to speech, language and hearing screening via telehealth.  J Telemed Telecare, 17,(5), 240-244.

Hayes, D., Eclavea, E., Dreith, S., & Habte, B. (2012). From Colorado to Guam: infant diagnostic audiological evaluations by telepractice. The Volta Review, 112(3), 243–253.

Hayes, D., Boada, K. and Coe, S. (2015). Early hearing detection and intervention by telepractice. SIG 18 Perspectives on Telepractice, 5, 38-47. 

Krumm, M. (2007). Audiology telemedicine. Journal of Telemedicine and Telecare,13(5) 224-229.

Krumm M, Huffman T, Dick K, Klich R. Telemedicine for audiology screening of infants. J Telemed Telecare 2008;14:102–4.

Krumm, M., Ribera, J., and Schmiedge, J., (2005).Using a telehealth medium for objective hearing testing: Implications for supporting rural universal newborn hearing screening programs (UNHS).  Seminars In Hearing.  26 (1), 3-12.

O’Neal J, Finitzo T, Littman T. Neonatal hearing screening: follow-up and diagnosis. In: Roeser, Valente, Hosford-Dunn, eds. Audiology Diagnosis. New York: Thieme; 2000:530.

Rajendran, A., Ramkumar, V. & Nagarajan, R., 2014. Perception of “mothers of beneficiaries” regarding a rural community based hearing screening service. International Journal of Pediatric Otorhinolaryngology, 78(12), pp.2083–2088

Ramkumar, V., Hall, J. W., Nagarajan, R., Shankarnarayan, C. V., & Kumaravelu, S. (2013). Tele-ABR using a satellite connection in a mobile van for newborn hearing testing. Journal of Telemedicine and Telecare, 19, 233–237.

Ramkumar, V., Nagarajan, R., Kumaravelu, & Hall, J.W.  (2014). Providing tele ABR in rural India. SIG 18 Perspectives on Telepractice, March 2014, 4,:30-36.

Swanepoel, D., & Hall, J. (2010). A Systematic review of telehealth applications in audiology. Telemedicine & E-Health, 16(2), 181–200.

The last few months  we had the opportunity to exchange some opinions on the possible directions the OAE Portal might take and whether we should introduce material geared for specific areas , showing a great expansion, such as India and Africa. 

The material in the Portal was designed with the Hearing Scientist / Audiologist in mind . The last few years the FORUM space was opened to a greater non-professional public, but only this year we have realized that we need more information for the ordinary non professional people, mainly for families who seek information on hearing deficits and intervention strategies (hearing aids, rehab, cochlear implants, speech therapy approaches etc).

We STILL don't have a definite answer on how to assist this important category of users. Some colleagues of mine have suggested the separation of the material for professional and non-professional users , but this division is very artificial and personally I am against it. The Portal material  has to be expanded .. and the task of the Portal user is to find it . Of course we need to make the exposure of non-technical material an easy process not buried in endless menus ... and although this seems very straight-forward  .. it is difficult to implement easily. 

It would be nice to hear your opinion in this issue, since the OAE Portal is a Open  Access depository of Knowledge. It would be a great privilege for me and my collaborators to listen what you have to say.

And now, another important point: 

We are seeking collaborators from areas where information is kind of difficult to get (India, Nothern, Central, & Southern Africa),  so please if you reside in these areas  drop us a line and tell us what you think about the information we provide in the Portal and how we can establish a connection / collaboration with you.

About the Guest-Editor

[email protected] is a senior scientist at Mimosa Acoustics, Illinois, USA, where she works remotely from Wellington, New Zealand. She obtained her PhD in Psychology in 1999 from Victoria University of Wellington on the psychophysics of human hearing. Her background is in psychophysics, otoacoustic emissions, and hearing conservation.

Dr Lapsley-Miller specializes in translational hearing research; bridging the gap between new technologies forged in research laboratories and clinicians wanting state-of-the-art easy-to-use tests for their patients.

Why WAI ????

Wideband acoustic immittance (WAI) provides a new window on the middle ear, by showing us how the middle ear is working over a wide frequency range (0.2 to 8 kHz). Information about middle-ear status helps us make more nuanced interpretations of inner-ear status seen through otoacoustic emission (OAE) testing. This is especially true in universal newborn hearing screening programs. For no extra effort, WAI also provides improvements in stimulus calibration that can increase OAE validity and reliability.

• WAI terminology is confusing – here’s a handy look-up guide

To make an OAE measurement, an acoustic stimulus is played into the ear canal. This stimulus propagates through the middle ear to the inner ear. Within the inner ear, OAEs are evoked by the stimulus and propagate back out through the middle ear into the ear canal where they are measured by a sensitive microphone. We cannot get a clear view of inner-ear status with OAEs without considering middle-ear status too.

For instance, if there is middle-ear dysfunction such as negative middle-ear pressure or fluid in the middle-ear space, sound propagation can decrease. This is readily apparent when viewing middle-ear reflectance, which is a quantity derived from a WAI measurement. To understand what middle-ear reflectance represents, consider the sound power measured in the ear canal. It is a superposition of two pressure waves: the incident pressure due to the sound emitted by the probe, which travels towards the tympanic membrane; and the reflected pressure wave, which is primarily the sound reflected by the tympanic membrane, ossicles, and cochlea. Reflectance is the percentage of acoustic power reflected, relative to the incident acoustic power, and is plotted as a function of frequency. In a normal ear, reflectance is high below 1 kHz, low from 1-4 kHz, and high around 4-6 kHz. For an example, see the green line in the top panel of Figure 1. When reflectance is high, more acoustic power is reflected from the tympanic membrane and other structures back into the ear canal. When reflectance is low, more acoustic power propagates through the middle ear. The reflectance pattern over frequency can assist with differential diagnoses.

Figure 1. Reflectance and TEOAEs before (green) and after (pink) a Toynbee manoeuver that changed TPP from 0 daPa to ‑135 daPa. The black spectrum is the TEOAE noise level.

OAE measurements get hit with a double-whammy when middle-ear reflectance is higher than normal. First, the middle-ear attenuates the OAE stimulus as it propagates through the middle ear into the inner ear. This can decrease the effective OAE stimulus level. (Typically OAEs increase with increasing stimulus level, so a lower effective stimulus level decreases the OAE magnitude.) Second, the already-diminished OAE is attenuated further as it propagates back out through the stiffened middle ear. The measured OAE is smaller than it would have been had the middle ear been healthy. The resulting OAE can be lowered so much that you get a false-positive for sensorineural hearing loss. Or if you are tracking changes in OAEs over time, say in a hearing-conservation program or when monitoring for ototoxicity, you may see a false-positive decrease in OAE level.

In Figure 1, you can see the difference in a transient-evoked OAE (TEOAE) when there is negative middle-ear pressure (case example from the study reported in Marshall et al. (2015)). In this plot there are two measurements: one done with the participant’s middle-ear at ambient pressure (green line, tympanometric peak pressure 0 daPa) and one after a Toynbee manoeuver (pink line, tympanometric peak pressure -135 daPa), where the participant held their nose and swallowed. The top plot shows reflectance and the bottom plot shows the TEOAE spectrum. When the ear is pressurized, more acoustic power is reflected, especially at lower frequencies. The impact is seen in the TEOAE spectrum with a noticeable decrease in TEOAE amplitude, especially around 1 kHz where the biggest change in reflectance occurred.

As well as middle-ear conditions, reflectance can also be high if the probe is partially blocked or is pressed up against the side of the ear canal. Poorly fitting probes are also apparent, with acoustic leaks showing up as low reflectance at very low frequencies. Making a WAI measurement after fitting the probe is a great way to see if there is a good probe fit prior to making an OAE measurement.

The goal of universal newborn hearing screening (UNHS) programs is to detect babies who have sensorineural hearing loss so they can benefit from early intervention. UNHS programs provide a Pass or Refer result from either OAE or ABR tests. These screening tests are not diagnostic, but are used to determine referrals for more extensive diagnostic follow-ups.

It has long been best-practice in UNHS programs to rescreen babies who get a Refer result to reduce false-positives for diagnostic referrals. This rescreening is usually done after a delay, because testing within 24 hours of birth is much more likely to produce a refer result than testing after 24 hours (and preferably 36 hours). The majority of these false-positive referrals are from transient middle-ear dysfunction from the birth process (e.g., amniotic fluid, mesenchyme, and meconium in the middle-ear space), which clears within the first few days of life. Hunter et al. (2010) showed why rescreening OAEs after a delay was often successful – middle-ear reflectance tends to decrease over time, presumably as the middle ear clears, allowing more sound to propagate into the inner ear and back.

This transient middle-ear dysfunction is not reliably picked up with tympanometry in newborns. Hunter et al. (2010) and Sanford et al. (2009) both showed that WAI reflectance was vastly superior to tympanometry in predicting which ears would show low OAE levels due to middle-ear dysfunction. Adding WAI to OAE screening can potentially identify those babies most in need of diagnostic follow-up, help determine the best time for repeat screening, and reduce false-alarm referrals.

When using WAI with OAEs in testing newborns, a pass/refer result can be assigned to each test, giving four possible outcomes. Each outcome is illustrated in Figure 2 with real examples from the Hunter et al. (2010) study. This study showed that the reflectance around 2 kHz was the best predictor for whether the DPOAE test passed (DPOAE levels at 3 or 4 out of 4 frequencies are normal) or not (DPOAEs at 2 or more out of 4 frequencies are abnormally low). So although the spectrum is plotted from 1 to 6 kHz, pay particular attention to the 2 kHz region in the reflectance plot. Reflectance below 1 kHz is not plotted because in babies this region is often noisy and therefore is less diagnostic (Hunter et al., 2010).

Also plotted are two normative regions in gray. For the WAI plot, the gray norm represents an ambiguous region. Reflectance below this region (especially at 2 kHz), was associated with DPOAE pass results. Reflectance above this region (especially at 2 kHz) was associated with DPOAE refer results. Similarly, for the DPOAE plot, the gray norm also represents an ambiguous region (from the Boystown norms (Gorga et al., 1997)). DPOAEs above this region are associated with normal hearing. DPOAEs below this region are associated with abnormal hearing.

A complication with interpreting WAI and DPOAEs is there is not a one-to-one relationship between reflectance frequency and DPOAEs frequency, in part because the DPOAE is first generated by two tones at different frequencies (F1 and F2) and is measured at a third (2F1-F2), which is then plotted against F2. So for a DPOAE plotted at 2 kHz, the frequencies involved are 1.3, 1.7, and 2.0 kHz. Reflectance at all three frequencies may affect the resulting DPOAE measurement.

Figure 2. Four outcomes are possible when using WAI with DPOAEs in a newborn hearing screening program. The WAI plots show power reflectance (green line, %) and the normative ambiguous region (gray region, %). The DPOAE plots show DPOAE amplitude (green bar, dB SPL), the noise floor (black bar, dB SPL), and the Boystown 90% ambiguous region (gray region, dB SPL), where DPOAEs below the region are considered refer results. For the screening protocol used in this study, if 3 or 4 out of 4 DPOAE frequencies get a pass result, the overall result is a pass (left plots). If 2 or more out of 4 DPOAE frequencies get a refer result or are noisy, the overall result is a DPOAE refer (right plots). We can reduce these referrals by considering the WAI result. If the WAI result is elevated, the DPOAE refer is probably due to middle-ear dysfunction (top right). However, the possibility of underlying sensorineural hearing loss cannot be excluded, so repeat screening is needed. If the WAI result is normal, the DPOAE refer needs diagnostic follow-up for possible sensorineural hearing loss (bottom right). Sometimes the WAI result will be elevated but the DPOAEs are so strong, they are able to overcome the reduction in middle-ear transmission (bottom left).

How could WAI be used in UNHS programs? Specific guidance is still in development, but potentially WAI can be used to enable smarter timing for rescreenings and follow-ups.  For instance, in the examples in Figure 2, the following courses of action may be appropriate:

1. Normal reflectance – normal DPOAEs across all frequencies (top left). Screening passed and no rescreening or follow-up is needed.
2. Elevated reflectance – low DPOAEs: possible middle-ear fluid (top right). Wait a few hours and rescreen to see if reflectance is lower and DPOAEs pass. Refer for diagnostic follow-up if DPOAEs do not pass on rescreening. Chances are reflectance will decrease as the middle-ear clears and the true DPOAE status will be more clearly revealed.  Elevated reflectance and low DPOAEs is commonly seen in newborn hearing screening programs, and causes undue worry for parents and an increased workload due to unnecessary diagnostic follow-ups. With WAI + DPOAEs, testers can immediately see if there is middle-ear dysfunction and can reassure parents that this is common and not of concern.
3. Normal reflectance – low DPOAEs (bottom right). This ear is a priority for diagnostic follow-up because it may be permanent sensorineural hearing loss.  Rescreening is optional because we have eliminated the usual reason for DPOAE false-alarms – high middle-ear reflectance from transient middle-ear dysfunction. Any rescreening can occur immediately because the WAI results show the middle ear is not impeding sound propagation into the inner ear.
4. Elevated reflectance – normal DPOAEs (bottom left). The DPOAEs are strong enough to overcome what is possibly a probe blockage or transient middle-ear dysfunction. Check for probe or ear canal blockage, or a collapsed ear canal, and then retest reflectance.  Since DPOAEs passed, rescreening is optional because an outer or middle-ear condition is not typically a reason for referral.

Although tympanometry is more reliable in older infants, children, and adults, the same principles for newborns apply for interpreting WAI + OAE tests in these age groups. In these older age-groups; however, high reflectance is also cause for follow-up for middle-ear dysfunction like otitis media.

It is especially convenient to have a clinical device that can measure WAI and OAEs with the same probe fit and without the need for pressurization. This provides many opportunities for differential diagnoses. With Mimosa Acoustics OtoStat system, both WAI and DPOAE results are achieved within a minute and are displayed on the same screen. A further benefit to using WAI is that the WAI measurement itself can be used to calibrate the DPOAE stimuli. This clever trick means the combined WAI + DPOAE test takes no more time than the DPOAE test on its own. Saving time is crucial when testing uncooperative patients like infants and small children. Once the WAI test is started, it automatically goes on to the DPOAE test without further button pressing.

Enhanced calibration using WAI

WAI allows for a new type of calibration: forward pressure level (FPL) calibration. FPL calibration is perhaps the most significant advancement in calibration techniques in recent years.

You may have noticed that above 4 kHz (and in some ears even above 2 kHz) that calibration and the resulting OAE levels are unreliable (Siegel, 1994). This can be due to standing wave nulls. The larger the distance between the probe tip and the tympanic membrane (referred to as the residual ear canal), the lower the standing-wave null frequency. In a null, it is not possible to accurately set the OAE stimulus level using normal in-the-ear calibration. The calibrated level could be higher or lower than intended depending on how the system adjusts its levels. This difference can be up to 20 dB! (Siegel, 1994). This is a particular problem when monitoring an ear over time, because if the probe depth is different at each measurement, the null frequency changes. This can change the actual OAE stimulus level, and therefore evoke a higher- or lower-level OAE. Changes in OAEs could be merely due to probe placement and not inner-ear dysfunction.

So what does FPL calibration do? Remember earlier how the sound pressure in the ear canal is a superposition of two waves? When doing a regular in-the-ear (ITE) calibration the pressure is measured at the microphone, which can be some distance away from the tympanic membrane, and is the combination of both the forward and backward - traveling pressure wave.

Because the WAI measurement separates out the forward and backward components of the pressure, it allows us to set the level for just the forward-going (incident) part of the pressure in the ear canal – the part propagating into the middle and inner ear – and ignore the backward-going (reflected) component. This circumvents the problematic standing-wave nulls allowing for accurate levels throughout the entire frequency range. This is only possible with a WAI system where the probe is calibrated with known impedance (Allen, 1986). The resulting FPL stimulus level is still measured in dB SPL.

Figure 3 shows an example of DPOAEs measured in an adult ear using a standard screening protocol. The top plot shows the in-the-ear calibrations and the bottom plot shows the resulting DPOAE levels. The measurement in pink used regular in-the-ear calibration to set the DPOAE stimulus levels, where the pressure is measured at the microphone-end of the ear canal.  The dip at 4 kHz is characteristic of a standing wave null. This dip disappears when FPL calibration is used instead (green line). When setting the levels for the DPOAE measurement, the regular in-the-ear calibration overestimated the level needed around 4 kHz and underestimated below 2 and above 4 kHz.  

The resulting DPOAE levels were quite different. In this example, the effect is particularly noticeable at 4 kHz and above. At 8 kHz, the DPOAE measured with FPL calibration was more than 7 dB SPL higher.

FPL calibration not only increases the validity and reliability of OAE measurements, but also pure-tone audiometry (Withnell et al., 2009; Withnell et al., 2014). It is currently only available to researchers, but is soon to be released for clinical use.

Figure 3. Two DPOAE measurements with the same probe position in the ear canal. The first measurement uses regular in-the-ear calibration (pink) where the pressure is measured at the probe-microphone end of the sealed ear canal. The second measurement uses the forward going component (green), which estimates the pressure at the tympanic membrane end of the ear canal. The resulting DPOAE levels differ, especially at 6 kHz. Black bars represent the noise level; the gray region represents the Boystown 90% ambiguous norm.

Why use WAI with OAE testing? By providing a view of the middle-ear while doing inner-ear testing with OAEs, using the same equipment, inner-ear status can be more accurately determined in a quick and convenient way. By providing a more accurate calibration, result validity and reliability is increased. WAI + OAE systems are set to revolutionize OAE testing.

Mimosa Acoustics would like to thank the OAE Portal for this opportunity to describe how WAI can benefit OAE testing. We would also like to thank :

Lisa Hunter (PhD, FAAA, Scientific Director, Audiology, Cincinnati Children's Hospital, and Associate Professor at University of Cincinnati) for her helpful feedback on UNHS programs ;

Linton Miller for editing.

Allen, J. B. (1986). "Measurement of eardrum acoustic impedance," in Peripheral auditory mechanisms, edited by J. B. Allen, J. L. Hall, A. E. Hubbard, S. T. Neely, and A. Tubis (Springer-Verlag, New York), pp. 44-51.

Gorga, M. P., Neely, S. T., Ohlrich, B., Hoover, B., Redner, J., and Peters, J. (1997). "From laboratory to clinic: a large scale study of distortion product otoacoustic emissions in ears with normal hearing and ears with hearing loss," Ear Hear. 18, 440-455.

Hunter, L. L., Feeney, M. P., Lapsley Miller, J. A., Jeng, P. S., and Bohning, S. (2010). "Wideband Reflectance in Newborns: Normative Regions and Relationship to Hearing-Screening Results," Ear Hear. 31, 599-610.

Marshall, L., Lapsley Miller, J. A., and Reed, C. M. (2015). Evaluating otoacoustic emission shifts due to middle-ear pressure with tympanometry and wideband acoustic immittance. (Poster presented at the 42nd Annual Scientific and Technology Conference of the American Auditory Society, Scottsdale, AZ), Mar 5-7. https://www.researchgate.net/publication/273001208

Sanford, C. A., Keefe, D. H., Liu, Y. W., Fitzpatrick, D., McCreery, R. W., Lewis, D. E., and Gorga, M. P. (2009). "Sound-conduction effects on distortion-product otoacoustic emission screening outcomes in newborn infants: test performance of wideband acoustic transfer functions and 1-kHz tympanometry," Ear Hear. 30, 635-652.

Siegel, J. H. (1994). "Ear-canal standing waves and high-frequency sound calibration using otoacoustic emission probes," J. Acoust. Soc. Am. 95, 2589-2597.

Withnell, R. H., Jeng, P. S., Parent, P., and Levitt, H. (2014). "The clinical utility of expressing hearing thresholds in terms of the forward-going sound pressure wave," Int. J. Audiol. 53, 522-530.

Withnell, R. H., Jeng, P. S., Waldvogel, K., Morgenstein, K., and Allen, J. B. (2009). "An in situ calibration for hearing thresholds," J. Acoust. Soc. Am. 125, 1605-1611.

      For the period of May - July  2015 we will focus on OAE software updates.  We have planned a series of updates in the area of OAE signal processing, neonatal tracking solutions and overall applications as in Telemedicine.

      Historically the first category (OAE Signa Processing) was developed in the late nineties when researchers required additional tools to analyze the TEOAE & DPOAE responses. The  developments in this area have been delayed significantly due to the  format of the available data. The latter  was caused by a lack of consensus regarding OAEs.  Every vendor used a proprietary solution (i.e. format) to save the data acquired with a specific family of devices and export options to other universal formats were not available. Most of the processing solutions which exist today are based on the data - format of the early Otodynamics TEOAE devices. Of course various solution shave been tested in the MATLAB programming environment , but none has been trully evolve.

     Neonatal hearing screening tracking has been developed well in the US, the other countries and continents show very little in terms of programs and overall flexibility in user-interface. Several updates are programmed in this area .. presenting the solutions present in today's market.

      A second editorial on Telemedicine  by Dr. Krumm will appear in late June 2015.

About the Guest-Editors

[email protected] is an assistant professor at the Institute of Physiology and Pathology of Hearing in Warsaw, Poland. Dr. Sliwa specializes in biomedical engineering and his professional interests focus on objective testing of hearing. He is also involved in developing and conducting educational programs on audiology in Poland.

[email protected] got his MD degree from the  Medical University of Warsaw in 2008 and a MSc from the  Department of Management (University of Warsaw) in 2010. He received his PhD degree from the  Medical University of Warsaw in 2012. Currently he  works in the Institute of Physiology and Pathology of Hearing as a resident, in Medical University of Warsaw as an Assistant and Academic Teacher and in the Institute of Sensory Organs as Director of Science and Development. He is an active member of many scientific societies. He chairs the vice Chairman position in the Junior European Rhinology Society from 2010. His academic and research work can be summarized by  652 congress presentations and posters, 29 round tables and more than 183 publications. His main interests this period of time are international projects including Asian and African countries.

About the Editor

Stavros Hatzopoulos PhD, is the web editor of the OAE Portal since 2001. His interests involve biomedical signal processing and applications of neonatal hearing screening technologies in national and international programs.

Introduction

Otoacoustic emissions (OAEs) or cochlear echoes is a term coined by David Kemp in 1978, describing the transient responses from the inner ear, upon its stimulation by an acoustic click stimulus. The last 20 years OAE protocols have been used in many areas of Audiology and Hearing Science (Robinette and Glattke, 1997). The most significant contribution of OAEs is in the area of Universal Neonatal Hearing Screening (UNHS).

While the main objective of neonatal hearing screening (NHS) is the identification of infants with a hearing deficit (≥ 30 dB HL), the objectives of a UNHS program have a broader vision. Two important phases are considered: (i) the identification of infants with mild and moderate hearing deficits; and (ii) an intervention in terms of hearing improvement (hearing aids, cochlear implants) and neural rehabilitation, aiming at the restoration of hearing and the normalization of the quality of life of the young patient.

Within the last decade, numerous new challenges have appeared in the UNHS arena, such as : (i) the need to validate the automated OAE/ ABR screeners; (ii) the need to qualify the responses from the automated devices; (iii) the need to obtain additional information (i.e. hearing threshold) for the subject under assessment, in a short period of time; (iv) and the need to integrate numerous measurements in a single portable automated device. To respond to these clinical demands, several new methodologies have been introduced to the UNHS clinical practice. In this context, the aim of this editorial  is to provide information on these new technological trends.

1. Automated Auditory Brainstem Responses.

In the early 2002, the first 4rth generation OAE devices appeared in the market and offered the possibility to integrate information from different testing protocols such as automated OAE (AOAE) and automated ABR (AABR) responses. The combined screening protocols (AOAE + AABR) targeted the identification of auditory neuropathy, most prevalent in the neonatal intensive care (NICU) environment.

         With the introduction of the AABR protocols in the NHS programs, several issues became evident and among those questions related to screening-times and screening costs. The latter is outside the objectives of this paper and will not be addressed.  A previous study of our group, in the context of the regional NHS project CHEAP in Emilia-Romagna, Italy (Ciorba et al, 2007), provided evidence suggesting that in terms of time-requirements, portable ABR (Audioscreener, Viasys; Accuscreen, GN-Otometrics;  Algo 3i, Natus)  and OAE devices were converging to the same time values. Data from the above study suggested that : (i) the average time for AOAE responses is less than 10s in a cooperative subject and less that 120s (2 min) in non-cooperative subjects ; (ii) the test times of AABR, in cooperative subjects, were less than 120 s, while uncooperative subjects were tested within 10 min (per ear). While it takes some minimum expertise to properly handle and position the OAE probe, the ABR electrode placement presents more complications especially in cases where the subject shows high electrode impedance. In the latter case the AABR testing is difficult to complete and the test times are unavoidably longer.

          Theoretically the combined 2-stage approach (i.e. AOAE + AABR) eliminates the risk of not identifying infants with Auditory Neuropathy and assures that the screening sensitivity is high. Contrary to this hypothesis, data from an American study (White et al, 2005) suggest that this is not the case. The study assessed information from 86634 infants and for the infants who were screened for hearing loss, using a typical 2-stage OAE/A-ABR protocol, approximately 23% of those with permanent hearing loss at 8–12 months of age, would have passed the AABR. These data suggest that stringent criteria should be incorporated in the final evaluation of the current OAE and ABR automated devices.

            Another interesting development in the ABR / AABR area is in the area of the evoking stimulus. Traditionally ABR and AABR protocols use click stimuli to synchronize as many neural fibers as possible and to obtain an ABR response of large amplitude with less sweeps. Recently chirp stimuli have been used to optimize the ABR / AABR responses. According to Kristensen and Elberling (2012) upward chirps are often designed to compensate for the cochlear traveling wave delay which is regarded as independent of stimulation level. A chirp based on a traveling wave model is therefore referred to as a level-independent chirp. Another compensation strategy, for instance based on frequency-specific auditory brainstem response (ABR) latencies, results in a chirp that changes with stimulation level and is therefore referred to as a level-dependent chirp. One such strategy, the direct approach, results in a chirp family that is called the level-specific chirp. The data from studies using level-dependent chirps (Ferm et al , 2013; Rodriguez et al , 2013; Zirn et al , 2013;  Cebulla et al, 2014; Rodriguez and Lewis , 2014; Stuart and Kobb, 2015) are very encouraging, reporting ABRs recorded in less time and with higher amplitude values. The latter is very important for the statistical algorithms of the AABR devices, meaning that higher statistical accuracy can be obtained in the chirp-evoked AABRs.

2. Middle Ear Reflectance and Middle Ear Power Analysis -MEPA

Editors Note : some material in this section is copied from the Mimosa Acoustics website

Data from studies which have evaluated the performance of NHS programs in the well baby clinic or in the NICU  (White et al, 2005; Aithal et al, 2012; Vos et al, 2015) have reported that the majority of “screening refers” are due to transmissive factors such as the amneotic fluid or any substance blocking the propagation of the acoustic stimulus. Usually these conditions are transient (i.e. they last 24-30 h) and infants can pass the OAE test when the fluid is absorbed or when the auditory meatus is clean.

Using a middle ear power analysis (MEPA) testing procedure, it is possible to determine whether the middle ear conducts properly acoustic stimuli, and in this context the OAE screening results can be interpreted more clearly. Data from the literature (Sanford et al,  2009; Hunter et al, 2010) have showed that one of MEPA metrics, the middle ear reflectance,  is more sensitive to Distortion Product OAE (DPOAE) status than the 1 kHz tympanometry values. Power reflectance is a measure of middle-ear inefficiency. It is the ratio or percentage of power reflected from the eardrum to the incident power, as a function of frequency. Acoustic power measurements objectively quantify middle-ear function or malfunction.

Currently there is only one manufacturer (Mimosa Acoustics) offering reflectance measurements. The company offers two devices capable of MEPA, DPOAE and general OAE measurements : the Otostat (handheld) and the HearID research oriented) model. These devices can measure wideband power reflectance up to 6 kHz and most importantly without the need for a pressurized ear canal.

To interpret the clinical usefulness of the MEPA approach Hunter et al (2010) constructed normative regions for newborns, relating Middle Ear Reflectance values, evoked by chirp stimuli and DPOAE amplitudes at 1.0, 1.5, 2.0, 3.0, 4.0 and 6.0 kHz. Three regions were described as :

• (1) a Retest area (where the values of reflectance are high);
• (2) an Ambiguous area (where the values of reflectance are moderate); and
• (3) a Pass area (where the values of reflectance are low).

These areas are depicted in Figure 1. In terms of interpretation, If the MEPA reflectance values fall above the "Pass" area, especially around 2 kHz, outer or middle ear problems may be the cause, and a re-screening session after a few hours or a day is recommended prior to diagnostic referral.  If the outcome is still a refer, then clinical assessment is necessary. If the MEPA reflectance values fall within the "Pass" area, especially around 2 kHz, the middle ear is more likely to be normal and associated with a DPOAE pass result. If the DPOAE result is ambiguous or a refer, then middle ear issues are not suspected as a hearing deficit cause and further clinical assessment is necessary.  Table 1 summarizes all these outcomes.

Figure 1: Pass, ambiguous, and retest regions for wideband reflectance using chirp (solid regions) and sine (symbols) stimuli. Results above this region, especially at 2 kHz, are associated with false-positive DPOAE refer results. Data from Hunter et al., 2010 taken from the Mimosa Acoustics website

Table 1 : How to interpet Distortion Product OAEs and Reflectance Results in Newborns. Data taken from the Mimosa Acoustics website

3. Auditory Steady State Responses  (ASSR) in Neonatal Screening

Both OAE and ABR technologies utilize as stimuli electrical clicks and the acquired information is clearly more related to the audiometric frequencies of 1.0 and 2.0 kHz. Within this context, there has been a speculation of whether other technologies could be used in a fast hearing assessment of neonates, children and adults. A group of electrophysiological measurements similar to OAEs and AABR  includes electro-cochleography (EcoG), Middle latency  (ML)  and Steady State Responses (SSR). From this group the latter category has shown interesting characteristics due to fact, that by changing the modulation frequency of the stimuli one can get responses from the Auditory cortex (low modulation frequencies around 40 Hz) or from the Brainstem (Cone-Wesson et al; 2002; Dimitrijevic et al , 2002: John and Picton, 2002). The SSR protocol has already passed to an automated one (ASSR) and for the last 10 years numerous publications have been devoted to the threshold estimation via the ASSR technique. The ASSR protocols have been greatly optimized, (Gorga et al, 2004) and the SSR responses are detected in the frequency domain by robust probabilistic algorithms.

In 2002 Conne-Wesson et al,proposed the use of ASSR as a hearing screening tool, with the objective that ASSR could substitute the AABR. A few reports have been available since (Stueve and O’Rourke, 2003; Luts et al, 2004; Swanepoel et al; 2004) indicating a good agreement between ASSR and AABR at 2.0 kHz and various differences at 0.5, 1.0 and 4.0 kHz. Most studies recommended the use of the SSR technique in the clinic but the point of substituting the AABR with ASSR is not fully supported by the available data.

The factors which affect the AABR (ambient noise and electrode impedance) interfere with the ASSR recordings as well. In order to resolve these issues Vivosonic presented in 2010 a new line of devices using preamplifiers at the level of the scalp-electrodes (called amplitrodes) which suppress the level of ambient noise and provide very clean AABR and ASSR traces. It is to be seen how these electrodes will be intergraded in the normal clinical reality since the pre-amplifiers require electrical energy which translates into changing batteries every x tests.

In the context of neonatal screening, an ASSR screening protocol can target a few frequency points (i.e. 1.0 & 2.0 kHz or 2.0  & 4.0 kHz) which show immunity to ambient noise (see the neonatal data in Figures 2 A, B). One of the problems of the early ASSR devices  (Audera by Viasys; Master by Natus) was that the hearing threshold estimates were characterized by large variance.  Recent data from the literature and specifically from the Audix equipment developers (Neuronic)  report significant advances both in terms of software and hardware and a superior performance of a multiple SSR protocol to the conventional ABR (Mijares et al, 2013; Perez-Abalo et al; 2013).

Recently a study (Ciorba et al, 2013) presented data on the relationship between ABR, ASSR estimates and data from Conditioned Orientation Responses (COR), a technique widely diffused in the intervention phase of many UNHS programs. The data suggested a very good relationship between the outcomes of the ASSR and COR techniques, with the ASSR data being closer to the ABR estimates. Data from large-scale studies along this direction (i.e. comparing ASSR with other protocols) could support this hypothesis and eliminate the use of ABR and COR in the intervention phase of a UNHS program.

Figure 2: Panel A : ASSR response from a well baby who was crying using the AUDERA device from VIASYS. The lowest tested frequency of  500 Hz was not available due to noise. The length of the testing procedure was 22 min (14 min longer than the successfully completed  AABR test). Despite the theoretical noise immunity at 2.0 and 4.0 kHz the size of the error bars indicate that the measurements are too variable to be considered. The “x” symbols indicate the mean threshold level of the measurements. Panel B : ASSR response from a well baby using the AUDERA device. The length of this test was also longer that the AABR (16 vs 7 min). The AABR suggested a REFER probably due to conductive complications. In this case the 2.0 and 4.0 kHz frequencies show good noise immunity  (suggested by the small size of the error bars). The “x” symbols indicate the mean threshold level of the measurements.

4. Threshold estimation via DPOAE measurements

An interesting challenge for otoacoustic emissions has been the relationship between the amplitude of the OAE response and the hearing threshold (Whitehead et al 1995a; 1995b; Shera et al, 1999). For cases where no conductive losses are present there is a good agreement between OAEs and the hearing threshold. In such cases Input-Output distortion product OAE (DPOAE) protocols may offer more information (Whitehead et al, 1995a, Janssen et al, 1998; Dorn et al, 2001; Gorga et al, 2003b). Besides the relationship to pure-tone thresholds, DPOAE I/O-functions provide an estimate of the compression related to the  outer hair cell amplifier. Data supporting this hypothesis are available from animal studies where the hearing of the animals was  impaired with acute furosemide intoxication (Mills and Rubel, 1996) and human studies with subjects suffering from cochlear hearing loss (Janssen et al., 1998; Kummer et al., 1998; Boege and Janssen, 2002; Neely et al., 2003). In these studies the slope of the DPOAE I/O-function increased with increasing hearing loss revealing a loss of compression of the outer hair cell amplifiers. In this context by using numerous combinations of I/O  DPOAE recordings one can obtain very precise information related to the status of the cochlear amplifier (Gorga et al, 2003a, 2003b). Extrapolated DPOAE I/O-functions were constructed from neonates to estimate pure-tone threshold levels and the corresponding cochlear compression values (Janssen et al., 2003). The estimated hearing threshold was found to be increasing within the early postnatal period (average age: 3 days), predominantly at the higher frequencies, and to be normalized in a follow-up measurement (after four weeks). However, the slope of the DPOAE I/O-functions obtained in the first and second measurement was unchanged revealing normal cochlear compression. Consequently, these findings were interpreted as temporary conductive hearing losses due to the presence of amniotic fluid and/or Eustachian tube dysfunction. In this clinical scenario, especially during the first days of life, a hearing screening test may lead to false positive results due to a temporary conductive hearing loss. The use of the slope of DPOAE I/O-functions could be used as an index of conductive losses which might result in less false positives an in less time spent for audiological clinical diagnostics. According to the data of Janssen et al (2003) the values  of the DPOAE slope can discriminate and differentiate  conductive from  sensorineural hearing losses. In addition DPOAE I/O-functions have been reported to be correlated with loudness (Neely et al. 2003), so DPOAE I/O information would also offer the potentiality of assessing information to basic hearing aid fitting.

The research findings from Janssen et al (2003) and Gorga et al (2003a) have been commercialized in a device called Cochlea-Scan (Osvald et al, 2003) by Natus. Hearing threshold can be extrapolated up to values relative to 50 dB HL in the frequency range from 1.5 to 6 kHz. Figure 3 shows a typical hearing threshold profile and the corresponding Cochlea-Scan mediated estimation of hearing threshold. At present, the Cochlea-Scan device offers a platform for a third generation OAE testing (TEOAEs, DPOAEs), I/O DPOAE estimation with hearing threshold extrapolation.

Figure 3: Cochlea-Scan data in comparison to behavioral threshold levels, from an adult subject : Top panel, Cochlea-Scan responses and threshold estimation from the right ear; Middle Panel, behavioral data ; Bottom panel: Cochlea-Scan responses and threshold estimation from the left ear. The Cochlea-Scan panels report the estimated threshold values per frequency.  The acronym “NA” means that no threshold estimation was possible at the tested frequency. 

Further analyses  (Hatzopoulos et al, 2009) on the efficacy of the Cochlea-Scan DPOAE algorithm, relating hearing threshold data and Cochlea-Scan estimated thresholds from a group of adult sensorineural cases, suggested a different scenario than the one proposed initially by Janssen (2003). In the Hatzopoulos et al (2009) study behavioral and Cochlea-Scan data were analyzed with logistic regression models in order to find the probability (≤ 0.9) of a robust DPOAE response at 2.0, 3.0, and 4.0 kHz .The data suggested that the max behavioral levels where valid DPOAEs could be detected were equal to of 32.8, 21, and 34 dB respectively. For normal hearing adults the detection levels were lower. Figures 4 and 5 depict the relationship between behavioral data (at 2.0, 3.0 and 4.0 kHz) and Cochlea-Scan estimates from the cases presenting hearing loss. For example in Figure 4 and for 2.0 kHz, a probability of  90% Cochlea-Scan response detection corresponds to a threshold approximately of 15 dB HL.  In this context, it is still possible to have a detection threshold as high as 50 dB HL the corresponding probability falls below 30% and as such, limits the usefulness of the Cochlea-Scan protocol.

Figure 4: Logistic regression model for normal hearing threshold Cochlea-Scan data at 2.0 and 3 kHz. The equation relating the two variables (c= Cochlea-Scan data; p= behavioral data)  is shown at the top of each graph. The x axis shows behavioral threshold in dB HL and the y axis the probability of a Cochlea-Scan response. For a fixed response probability of 90% the detectable threshold level is approximately 15  and 20 dB HL, for the data at 2.0 and 3.0 kHz. This implies that in order to obtain a Cochlea-Scan response for a 50 dB HL hearing threshold the probability of finding a true response drops to  40% and 10% respectively ( for 2.0 and 3.0 kHz).

 Figure 5: Logistic regression model for normal hearing threshold Cochlea-Scan data at 4 kHz. The equation relating the two variables (c= Cochlea-Scan data; p= behavioral data) is shown at the top of each graph. The x axis shows behavioral threshold in dB HL and the y axis the probability of a Cochlea-Scan response. For a fixed response probability of 90% the detectable threshold level is approximately 35 dB HL. For a 50 dB HL threshold the probability of a true response drops to 15%. The relationship between the behavioral and Cochlea-Scan data at 4.0 kHz is optimized, but the sensitivity of the method drops very quickly as we move to higher thresholds 35 dB HL.

The authors at this point in time, could not verify if Natus has intentions of developing further this product. Cochlea-Scan threshold estimation could be greatly improved by introducing changes in the device’s algorithms related to : (i) the sample size which was used to calibrate the prototype device. Sampling a larger population can minimize the variance of the average DPOAE amplitude per tested frequency; (ii) by inserting correction factors in the algorithm which extrapolates DPOAE amplitudes to hearing levels. Janssen  (2003) has used a linear regression model to achieve this, but higher order models (quadratic, cubic) can offer higher precision in the threshold estimation.

5. Integration of multiple hearing assessment protocols into an automated device.

The success of the NHS screening practices challenged another area of pediatric audiology , the area of school-children screening. Data from large-scale screening programs, as in Poland, suggested that in this area different protocols could be applied than in UNHS programs, with emphasis on pure tone behavioral responses, tympanometry and ABR (Sliwa et al, 2009; 2011). The OAEs were found the less effective tool in the battery of screening tests, suffering mainly from the ambient noise present in schools.

       Recently fifth generation OAE equipment appeared in the market. A number of OAE manufacturers  (Natus, Path Medical solutions) proposed hand-held devices capable of testing subjects with OAEs / AOAEs, AABR and ASSR. A tympanometry assessment has not appeared so far due to complications in the probe of the device (canal pressurization issues). Mimosa Acoustics offers wide-reflectance measurements (which can substitute acoustic immitance) and OAEs but not evoked potentials.  

         The proposal from Path Medical Solutions (model: Sentiero - advanced) is a device capable not only of AOAE / AABR/ ASSR protocols, but also of protocols for speech Audiometry. Such a device can be easily implemented in both phases (identification , intervention)  of a UNHS program and it is hoped that other manufacturers will follow this protocol-integration trend.

Conclusions

The last 10 -15  years significant advances have been made towards  the integration of various protocols and technologies in UNHS strategies. The most important contribution is in the area of Auditory Steady State Responses which have been shown to be well correlated with other metrics in Audiology such as the AABR, ABR, OAEs and COR. The current technological trends call for an integration of even more protocols and algorithms in a hand-held device. The clinical robustness and response-quality of these new entries is yet to be evaluated.

References

Aithal S, Aithal V, Kei J, Driscoll C. Conductive hearing loss and middle ear pathology in young infants referred through a newborn universal hearing screening program in Australia. J Am Acad Audiol 2012 23: 673-685

Boege P, Janssen T. Pure-tone threshold estimation from extrapolated distortion product otoacoustic emission I/O-functions in normal and cochlear hearing loss ears.  J Acoust Soc Am 2002 111: 1810-1818.

Cebulla M, Lurz H, Shehata-Dieler W. Evaluation of waveform, latency and amplitude values of chirp ABR in newborns. Int J Pediatr Otorhinolaryngol 2014; 78: 762-768.

Cone-Wesson B, Dowell R, Tomlin D, Rance G, Ming Wu. The Auditory Staedy State Response. Comparisons with the Auditory Brainstem Response.  J Am Acad Audiol 2002; 13: 173-187.

Dimitrijevic A, John S, Roon P, et al. Estimating the Audiogram Using Multiple Auditory Steady State Responses. J Am Acad Audiol 2002; 13: 205-224.

Dorn PA, Konrad-Martin D, Neely ST, Keefe DH, Cyr E, Gorga MP. Distortion product otoacoustic emission input/output functions in normal-hearing and hearing-impaired human ears. J Acoust Soc Am. 2001;110:3119-31.

Ciorba A,  Hatzopoulos S,  Camurri L,  Negossi L,  Rossi  M,  Cosso*  D , and Martini A.

Neonatal Newborn Hearing Screening:  Four Years Of Experience At The Ferrara University Hospital (Cheap Project) Acta Otorhinolaryngol Ital, 2007;27:10-16.

Ciorba A, Hatzopoulos S , Petruccelli J,  Mazzoli M , Pastore A , Kochanek  K, Skarzynski P , Wlodarczyk A  and Skarzynski H.Identifying congenital hearing impairment: preliminary results from a comparative study using objective and subjective audiometric protocols Acta Otorhinolaryngol Ital 2013;33:29-35.

Ferm I, Lighfoot G, Stevens J . Comparison of ABR response amplitude, test time and estimation of hearing threshold using specific chirp and tone pip stimuli in newborns. Int J Audiolo 2013;52:419-423.

Gorga MP, Neely ST, Hoover BM, Dierking DM, Beauchaine KL, Manning C. Determining the upper limits of stimulation for auditory steady-state response measurements. Ear Hear. 2004;25:302-7.

Gorga MP, Neely ST, Dorn PA, Hoover BM . Further efforts to predict pure-tone thresholds from distortion product otoacoustic emission input/output functions. J Acoust Soc Am 2003a;113:3275-3284.

Gorga MP, Neely ST, Dierking DM, Dorn PA, Hoover BM, Fitzpatrick DF.        Distortion product otoacoustic emission suppression tuning curves in normal-hearing and hearing-impaired human ears. J Acoust Soc Am. 2003b;114(1):263-78.

Hatzopoulos S, Petruccelli J, Ciorba A  and Martini A. Optimizing otoacoustic emission protocols for a UNHS program Audiol  Neurotol, 2009;14(1):7-16. 

Hatzopoulos S, Ciorba A, Petruccelli J, Grasso D, Sliwa L, Skarzynski H and Martini A. Estimation of the Hearing Threshold Using behavioral Audiometry, CochleaScan and ASSR protocols Int J Audiol  2009;48:625-631. 

Hunter L, Feeney P, Miller JL, Jeng P, and Bohning S. Wideband reflectance in Newborns. Normative regions and relationship to Hearing-Screening Results  Ear Hear 2010;31:599-610.

Janssen T, Kummer P, Arnold W .Growth behavior of the 2f1-f2 distortion product otoacoustic emission in tinnitus. J Acoust Soc Am 1998;103 (6):3418-3430.

Janssen T, Klein A, Gehr D.  Automatische Hörschwellenbestimung bei Neugeborenen mit extrapolierten DPOAE-Wachstumsfunktionen. Eine neue Hörscreening-Methode.  HNO  2003 16 : 125-128

John MS, Picton TW. Human auditory steady-state responses to amplitude-modulated tones: phase and latency measurements. Hearing Research 2000; 141: 57-79.

Kemp DT. Stimulated acoustic emissions from within the human auditory system. J Acoust Soc Am. 1978:1386-91.

Kristensen SG, Elberling C. Auditory brainstem responses to level-specific chirps in normal-hearing adults. J Am Acad Audiol 2012; 23:712-721.

Kummer P, Janssen T, Arnold W .The level and growth behavior of the 2f1-f2 distortion product otoacoustic emission and its relationship to auditory sensitivity in normal hearing and cochlear hearing loss. J Acoust Soc Am 1998 ;103 (6):3431-3444

Kummer P, Janssen T, Hulin P, Arnold W .Optimal L1-L2 primary tone level separation remains independent of test frequency in humans. Hearing Research 2000; 146: 47-56

Luts H, Desloovere C, Kumar A, Vandermeersch E, Wouters J. Objective assessment of frequency-specific hearing thresholds in babies. Int J Pediatr Otorhinolaryngol. 2004 68(7):915-26.

 MIjares E, Perez Abalo MC, Herrera D, Lage A, Vega M. Comparing sttistics for objective detection of transient and steady-state evoked responsed in newborns. Int J Audiol 2013;52:44-49.

Mills DM, Rubel ED . Developement of the cochlear amplifier. J Acoust Soc Am 1996; 100:  428-441.

Oswald JA, Janssen T Weighted DPOAE I/O-functions: A tool for automatically assessing hearing loss in clinical application. Z Med Physik 2003; 13: 93-98.

Perez Abalo MC, Rogriguez E, Sanchez M, Santos E, Torres Fortuny A. New system for neonatal hearing screening based on auditory steady state responses. J Med Eng Technol 2013;37:368-374.

Robinette M and Glattke T editors . Otoacoustic Emissions:Clinical Applications. Thieme, 1997, New York.

Rodriguez GR, Ramos N, Lewis DR. Comparing auditory brainstem responses to toneburst and narrow band CE-chirp in young infants. Int J Pediatr. Otorhinolaryngol 2013;77:1555-1560.

Rodriguez GR , Lewis DR. Establishing auditory steady-state response thresholds to narrow band CE-chirps in full term neonates. Int. J. Pediatr. Ororhinolaryngol 2014;78:238-243.

Sanford C, Keefe D, Liu YW, Fitzpatrick D, McCreery R, Lewis D, and Gorga M. Sound-Conduction Effects on Distortion-Product Otoacoustic Rmission Screening Outcomes in Newborn Infants: Test Performance of WideBand Acoustic Transfer Functions and  1 kHz Tympanometry. Ear Hear 2009;30: 635-652.

Shera CA, Guinan JJ Jr. Evoked otoacoustic emissions arise by two fundamentally different mechanisms: a taxonomy for mammalian OAEs. J Acoust Soc Am. 1999;105:782-98.

Sliwa L, Kochanek K, Pilka A, Senderski A, Sulkowski W, Skarzynski H. Assessment of usefulness of objective and audiometric methods in hearing screening of school children, in: 9th EFAS Congress, Puerto de la Cruz, Tenerife, 21–24 June, 2009.

Sliwa L, Hatzopoulos S,  Kochanek K, Piłka A, Senderski A  and Henryk Skarzynski. A comparison of audiometric and objective methods in hearing  screening of   school children. A preliminary  study. Int J Pediatr Otorhinolaryngol  2011 ;75: 483-488.

Stuart A, Cobb KM. Effect of stimulus and number of sweeps on the neonate auditory brainstem response. Ear Hear 2014;35:585-588

Stueve MP, O'Rourke C. Estimation of hearing loss in children: comparison of auditory steady-state response, auditory brainstem response, and behavioral test methods. Am J Audiol. 2003;12:125-36.

Swanepoel D, Hugo R, Roode R. Auditory steady-state responses for children with severe to profound hearing loss. Arch Otolaryngol Head Neck Surg. 2004;130:531-5.

White KR, Vohr BR, Meyer S, Widen JE, Johnson JL, Gravel JS, James M, Kennalley T, Maxon AB, Spivak L, Sullivan-Mahoney M, Weirather Y. A multisite study to examine the efficacy of the otoacoustic emission/automated auditory brainstem response newborn hearing screening protocol: research design and results of the study.Am J Audiol. 2005 ;14:S186-199.

Whitehead ML, McCoy MJ, Lonsbury-Martin BL, Martin GK . Dependence of distortion-product otoacoustic emissions in primary tone level in normal and impaired ears. I. Effects of decreasing   L2 below L1. J Acoust Soc Am 1995a 97: 2346-2358

Whitehead ML, Stagner BB, Lonsbury-Martin BL, Martin GK . Effects of ear-canal standing waves on measurements of distortion-product otoacoustic emissions. J Acoust Soc Am 1995b 98: 3202-3214

Vos B, Lagasse R, Leveque A. Main outcomes of a newborn hearing screening program in Belgium over six years. Int J Pediatr Otorhinolaryngol 2014 78:1496-1502.

Zirn S, Louza J, Reiman V, Wittlinger N, Hempel JM, Schuster M. Comparison between ABR with click and narrow band chirp stimuli in children. Int. J. Pediatr Otorhinolaryngol 2014; 78:1352-1355.

  For the period of March & April  2015 we will continue focusing on the OAE hardware updates. Unfortunately so far many manufacturers have not responded to our requests for inside-information ( apart those taken directly from their websites) so we will keep open the hardware update window. Now continuing from last month : 

There are several patterns emerging from the available OAE hardware as of today.

(i) Screening applications have totally overshadowed OAE research and the majority of devices offer OAE tests in moderate frequency ranges rarely exceeding 6.0 kHz. Only a handful of devices offer DPOAE testing up-to 12 kHz. This is not a surprise since the area of "clinical OAE applications" has reached a plateau for at least 10 years. Innovations arrive only in the area of OAE signal processing (new theoretical approaches to OAE spectral estimation) which contribute lightly to emerging clinical applications.

(ii) The majority of platforms / devices offer a combination of AOAE & AABR testing to address issues of Auditory Neuropathy. A number of portable devices goes even further incorporating standard and high frequency immitance testing. Thus a portable device can address the screening requirements of both neonatal and children populations.

In the past we have wondered what the future holds for OAEs technologies.  As time passes the answer seems to be that of a total integration. OAE technologies will be closely integrated with other audiological protocols to address "hearing impairment" by more efficient and less time-consuming means.  I am referring to a unification of modular technologies (AOAEs, AABR, AASSR, hearing aid testing, Cochlear Implant testing and calibration etc)  under a single container (operating system).

This speculation is based on the fact that the major players in the OAE/ ABR industry are few and that most technical innovations usually part from the European manufacturers (Madsen, Interacoustics. Otodynamics) . To note that the major players represent also the major hearing aid companies  and it will take little to pass to the next step that is a consortium between them and the 4 major Cochlear Implant firms.

Of course this position is open to discussion .. so let us know what you think .. or my contacting us or even better by posting something in the OAE Forum .

NOTE : After the period dedicated to hardware  we will pass to the area of OAE software .. which unfortunately till today .. is kind of inadequate.

       For the first semester of 2015 we have planned two guest-editorials in the areas of OAE hardware and Telemedicine applications. The March-June editorial was authored by myself and two well-known colleagues from the Institute of Physiology and Pathology of Warsaw, Drs Lech Sliwa and Piotr H Skarzynski. It is an in depth review of the technologies we have at our disposal in the area of Universal Hearing Screening and Intervention. Some of the material has appeared in other sections of the Portal but the editorial collapses all the recent advances in a single document.

  First of all our best wishes for a fulfilling and "clinically creative" 2015 !!  There is a reason why I have highlighted the term "clinically" since the next few months our focus will be dedicated to updates in the area of OAE Hardware.

There are several patterns emerging from the available OAE hardware as of today.

(i) Screening applications have totally overshadowed OAE research and the majority of devices offer OAE tests in moderate frequency ranges rarely exceeding 6.0 kHz. Only a handful of devices offer DPOAE testing up-to 12 kHz. This is not a surprise since the area of "clinical OAE applications" has reached a plateau for at least 10 years. Innovations arrive only in the area of OAE signal processing (new theoretical approaches to OAE spectral estimation) which contribute lightly to emerging clinical applications.

(ii) The majority of platforms / devices offer a combination of AOAE & AABR testing to address issues of Auditory Neuropathy. A number of portable devices goes even further incorporating standard and high frequency immitance testing. Thus a portable device can address the screening requirements of both neonatal and children populations.

In the past we have wondered what the future holds for OAEs technologies.  As time passes the answer seems to be that of a total integration. OAE technologies will be closely integrated with other audiological protocols to address "hearing impairment" by more efficient and less time-consuming means.  I am referring to a unification of modular technologies (AOAEs, AABR, AASSR, hearing aid testing, Cochlear Implant testing and calibration etc)  under a single container (operating system).

This speculation is based on the fact that the major players in the OAE/ ABR industry are few and that most technical innovations usually part from the European manufacturers (Madsen, Interacoustics. Otodynamics) . To note that the major players represent also the major hearing aid companies  and it will take little to pass to the next step that is a consortium between them and the 4 major Cochlear Implant firms.

Of course this position is open to discussion .. so let us know what you think .. or my contacting us or even better by posting something in the OAE Forum .

NOTE : After the period dedicated to hardware  we will pass to the area of OAE software .. which unfortunately till today .. is kind of inadequate.

  Continuing our discussion from last editorial I was pinpointing that the organization of the information in the Portal was designed with strict scientific criteria in mind, i.e. as a service to the  the Hearing Scientist / Audiologist. To provide a partial service to the non-professional audience thematic channels in the FORUM space were dedicated to a greater non-professional public, but only this year we have realized that we need more information for the ordinary non-professional people, mainly for families who seek information on hearing deficits and intervention strategies (hearing aids, rehab, cochlear implants, speech therapy approaches etc).

We have considered various strategies .. with the most obvious being the division of the material into two containers one for the scientific use and one for the non-professional. This solution was way -off our possibilities due to the financial restrictions we face the last few years (and maintaining a FREE Portal .. is an economic adventure). We STILL don't have a definite answer on how to assist this important category of users.  The Portal material  has to be expanded .. and the task of the Portal user is to find it easily . Of course we need to make the exposure of non-technical material an easy process not buried in endless menus ... and although this seems very straight-forward  .. it is difficult to implement easily. Nevertheless this is going to be our objective for the remaining 2014 and for the whole 2015.

It would be nice to hear your opinion in this issue, since the OAE Portal is a Open  Access depository of Knowledge. It would be a great privilege for me and my collaborators to listen what you have to say. So please drop us a line and tell us what you think about the non-professional entries in the Portal pages.

A partial solution to the exposure of material for non-professionals is the possibility to add dedicated channels in the FORUM space. From this November you can find in the FORUM space a thematic channel dedicated to Cochlear Implants and the information which arrives to us from the families of the implanted patients. In this channel the attention will be focused on young patients and their families .. so that the information can be easily shared among other interested parties. I this point we should thank the Institute of Physiology and Pathology in Warsaw , because not only they sponsor the general OAE activities of the OAE Portal  but they have provided valuable information from the implanted patients of Prof. Skarzinsky and his team.

I should also clarify that the Cochlear Implant Channel of the main FORUM will be dedicated mainly to issues related with post screening conditions (the Intervention phase of a EDHI program)

After the standard period of the summer interruption,  me and my collaborators are back on line. During last June and July we had the opportunity to exchange some opinions on the possible directions the OAE Portal might take. The Portal this year celebrates 13 years (from June 2001) and as such new insights and future directions are sought out.

The material in the Portal was designed with the Hearing Scientist / Audiologist in mind . The last few years the FORUM space was opened to a greater non-professional public, but only this year we have realized that we need more information for the ordinary non professional people, mainly for families who seek information on hearing deficits and intervention strategies (hearing aids, rehab, cochlear implants, speech therapy approaches etc).

We STILL don't have a definite answer on how to assist this important category of users. Some colleagues of mine have suggested the separation of the material for professional and non-professional users , but this division is very artificial and personally I am against it. The Portal material  has to be expanded .. and the task of the Portal user is to find it . Of course we need to make the exposure of non-technical material an easy process not buried in endless menus ... and although this seems very straight-forward  .. it is difficult to implement easily. Nevertheless this is going to be our objective for the remaining 2014 and for the whole 2015.

It would be nice to hear your opinion in this issue, since the OAE Portal is a Open  Access depository of Knowledge. It would be a great privilege for me and my collaborators to listen what you have to say.

So please drop us a line and tell us what you think about the non-professional entries in the Portal pages.

I am very glad to announce that all the  Educational material (PowerPoint presentations and White Papers) have been transferred to the new platform. Next,  we have scheduled to transfer the rest of the material from the Guest Editorials from 2001 to 2004.

The topics of emphasis for the next few months will be: (i)  TEOAE signal processing and Time Frequency analyses ; (ii) Post Screening Intervention policies (mainly in the Cochlear Implant area). For the latter we have observed an increased interest from the Portal visitors and as such we are evaluating the creation of a dedicated FORUM space with various arguments.

Most probably what is of interest to everybody is the experience of families who have children implanted , after the initial experience of hearing screening.  These issues will be tackled later on this year, as we need to liaison with Sponsors and affiliated Institutions.

Monica Jubran Chapchap* and Flavia Martins Ribeiro**

Brazilian Task Force on Universal Newborn Hearing Screening*

Coordinators of NHS program of Hospital Sao Luiz, Sao Paulo, Brazil* ** 

Introduction

 Newborn Hearing Screening (NHS) has been addressed in Brazil in the last 15 years and the number of NHS programs has increased significantly the last 3 years. The past decade was of great importance for the development of NHS (see introduction Newborn Hearing Screening Programs in Brazil, part 1, editorial 2002).

Current outcomes

          In September 2003 we acknowledged 174 NHS programs in 20 different states, and 68 of them are located in the state of Sao Paulo. Most of the NHS programs in this state use TEOAEs as a first choice (72%) or DPOAEs (15%) and a few programs use OAE and ABR combined specially for the NICU babies (13%). Brazil has 5794 hospitals and from those only a 174 (0.03%) have implemented NHS programs. The distribution of theses programs among the Brazilian states, taken from the Brazilian Task force on Universal Newborn Hearing Screening web site (www.gatanu.org) is shown in Figure 1. The implementation of new programs has increased significantly in the last years as shown in Figure 2.

Figure 1 

Figure 2

Actual problems

              Besides the progress in the number of NHS programs, we are facing some issues related to our social, cultural and economical situation. Our public health system cannot fully support the UNHS demand and we are developing some approaches to move towards UNHS models, which fit better the present economical resources in Brazil. On September 5-7^th, 2003 the first National Meeting of Newborn Hearing Screening, was coordinated by GATANU and several points were identified about the course of NHS in Brazil :

•  Most of the NHS programs are involved only with the detection step, using mainly OAEs with automated or conventional equipment based on standardized protocols of pass/fail criteria as mentioned in part 1 of this editorial. The diagnosis is still a difficult step mainly because it is made in different centers usually distant from the screening site. The other concern is the lack of knowledge in the hearing development and the handling of the audiological evaluation of the infant, especially in the area of electrophysiological procedures (ABR) . It is still argued in Brazil by a number of professionals that the diagnosis at this early age ( 40 weeks or less) is not totally reliable due of the immaturity of the auditory system. 
        The Joint Committee on Infant Hearing (2000) has recommended a complete electrophysiological test battery such as bone conducted and frequency-specific ABR, but only a few centers in Brazil use these procedures. This lack of know-how could delay the identification of the hearing loss and the consequent intervention policies.
• The use of data management systems which can track and manage the NHS information and control the quality of data inserted in the NHS databases, needs to be extended to all participating NHS programs because only a minority is using such kind of data management. The Brazilian NHS programs are mostly based on private initiatives coordinated and run by audiologists that have a tertiary part in the program.

  There is a goal of concluding a multi center study by 2005 and for this purpose it is mandatory to use a standardized data management system . NCHAM (makers of the HITRACK software system) has been supporting us with no cost for the first 150 NHS programs using the software and GATANU is in charge of the technical and practical support at no charge as well.
  
  

• To face the financial difficulties related to UNHS implementation, we have designed a new approach called Optional Newborn Hearing Screening (ONHS), testing babies with no risk indicators for hearing loss. In these programs the parents are informed about the importance of NHS and they have to assume the cost of the test. This is a step toward the implementation of a true UNHS program.
• The screening equipment are very expensive considering the economical status across the country and the public health system that supports the majority of our population pays only US$ 1,00 per test making the UNHS a difficult challenge.
• The legislation varies through the country by city and state policies. There are 1 state (Parana) and 12 counties laws. The implementation of NHS at this point is not related to the law support. In Brazil , the majority of the programs are implemented in cities and states without any hearing screening specific legislation. Brazil has 5561 counties which 74 have NHS and from those only 12 have relative legislation policies.  
• Professionals related to the infant health care should get involved and cooperate for the early diagnosis of hearing loss.
• The Task Force of Brazilian Society of Pediatrics (founded in 2000) has started the first national wide action campaign informing and involving all the pediatricians with the NHS programs.

Models and Screening protocols of a program in Sao Paulo

           The NHS program of the private Hospital Sao Luiz in Sao Paulo, was initiated in 1991 and until today has progressed through numerous steps (ie testing populations) as shown in Figure 3.

Figure 3

          The model, protocols for screening and diagnosis stages and the NHS program results from 1999 to 2002 are presented in Figures 4-11. It should be noted that the positive outcomes of this successful program are related to numerous resources, which are not readily available outside the Sao Paulo State.

Figure 4

Figure 5

Figure 6

Figure 7

Figure 8

Figure 9

Figure 10

Figure 11

This Editorial is a Synopsis from the chapter on Ipsilateral Suppression by George A. Tavartkiladze, Gregory I. Frolenkov, Alexandr V. Kruglov, Serge V. Artamasov  in the book Otoacoustic Emissions and Clinical Applications . M. Robinette & T. Glattke editors, 

1. Introduction

Many studies have been devoted to the suppression of transient evoked otoacoustic emissions (TEOAEs) by contralateral acoustic stimulation starting with the 1993 paper by the Collet group in France. It is believed that this effect is mediated by the medial olivocochlear system (Durrant, 1998; Veuillet, Collet & Morgon, 1992), and it is relatively small. Typically the TEOAE suppression associated with contralateral stimuli of 70-75 dB SPL is about 1 to 2 dB (Veuillet et al., 1991). In contrast to contralateral stimulation, ipsilateral masking can result in more pronounced suppression of TEOAE (Kemp & Chum, 1980; Tavartkiladze et al., 1993; Wilson, 1980). The mechanisms underlying this effect seem to be twofold. From one view, the suppression results from intracochlear masking processes; from another view, it appears to be mediated through the olivocochlear system. This chapter describes various aspects of TEOAE masking properties under simultaneous and forward masking conditions that have been investigated for several years (Frolenkov et al., 1995; Tavartkiladze, et al., 1991, 1996).

2. Ipsilateral Simultaneous Masking of TEOAEs

Since the first description by Kemp (1978), the measurements of TEOAEs have progressed from laboratory research to clinical application. Today it is universally accepted that OAE phenomena are of cochlear origin (Probst, 1991; Zurek, 1985). Nevertheless, the particular segments of the cochlear partition generate TEOAE in response to a stimulus with given frequency composition remain unresolved (Hilger et al., 1995; Kemp 1986; Tavartkiladze et al., 1993). This situation is due to the very complex structure of the TEOAE frequency spectrums and to the fact that not all frequencies evoke TEOAEs (Probst et al., 1986). Constructing TEOAE tuning curves under simultaneous tonal masking conditions can reveale information about the location of the cochlear partition vibration maximum. Unfortunately, only a few researchers have described the results of TEOAE simultaneous masking investigations (Kemp & Chum, 1980; Wilson, 1980).

3. Simultaneous-Masking Procedures

All our simultaneous masking experiments were performed with subjects who were 21 to 33 years of age, with audiometric thresholds less than 20 dB HL within the frequency range of 125-8000 Hz, with type A tympanograms, and no signs of otologic diseases during the investigation. Because spontaneous otoacoustic emissions (SOAEs) could modify TEOAE responses (Probst et al., 1986), the existence of SOAE or (synchronized) quasi-SOAEs was tested using an ILO 88 system (Otodynamics, Hatfield, UK).

TEOAEs were recorded with a custom-designed acoustic probe, consisting of a microphone (EA-1842) and two Knowles (Itasca, IL) electroacoustic transducers (ED-1913) (Fig. 1). The free field calibration of the probe microphone was carried out by short broadband clicks with initial rarefaction wave. The probe under calibration was placed close to the measuring microphone (4676, Bruel & Kjaer, Nram, Denmark) connected to a measuring amplifier (2235 noise meter, Bruel & Kjaer). Output of the measuring amplifier was used for calibration of the probe. (The frequency response of the probe-microphone channel is presented in the left bottom panel of Fig. 1).

During the experiments, probe-microphone output was amplified and fed to a Medelec "Sensor-3" clinical averager using an effective filter bandwidth of 300 Hz (6 dB per octave) to 6000 Hz (12 dB per octave). One of the electroacoustical transducers was used to deliver test stimuli, which were 60 and 500 microsecond clicks, and tone bursts of different frequencies with trapezoidal envelope: 1 cycle rise/fall, 1 cycle plateau for frequencies less than 1 kHz, and 2 cycles rise and fall, 3 cycles plateau for frequencies more than 1 kHz. To reduce inter-subject variability of TEOAE amplitude, the stimulus intensity was related to the subject's sensation level and set at 20 dB SL to provide selective excitation of the limited segment of cochlear partition. Test stimuli repetition rate was 20 Hz.

TEOAE-response waveforms were obtained with synchronous averaging of 2000 consecutive responses to test stimuli. The signal was then routed into two independent channels of averaging system. Thus, averaged responses to even and odd stimuli were obtained. The sum of these curves formed the TEOAE record, and the difference between them was used for noise-level estimation. The second electroacoustical transducer was employed to deliver masking tones of different frequencies. First, the subjective threshold of tone perception was determined for each frequency. After that, masking was continued with constant intensity during the averaging process. Any intensity changes were performed at least 1-2 min before the start of averaging. For masker-artifact cancellation, the reference masker was attenuated, phase-corrected, and electrically added to the probe-microphone output (Fig.1) before leading it to the averager. The degree of attenuation and phase correction angle were manually adjusted in such a way as to minimize amplitude of the signal at the averager input. The adjustment was necessary each time when the frequency or intensity of the masker tone were changed.

The results obtained were used for the construction of iso-suppression tuning curves. For each frequency of masking tone, the relation between the masker intensity (5-60 dB SL) and TEOAE amplitude was determined. Then the masking tone intensity necessary for 50% reduction of TEOAE amplitude was approx20uation was less than 50%, even under the highest levels of masking tone (50-60 dB SL), the masking tone of this frequency was not considered to produce TEOAE reduction and this intensity was marked by the arbitrary value of 180 dB.

Fig 1: Schematic drawing of the simultaneous masking experiments setup. Left bottom panel represents the probe-microphone frequency response

4. TEOAE-Amplitude Calculation

Linear component cancellation (Bray & Kemp, 1987; Kemp,et al., 1986) was not suitable for these experiments, because the method dramatically reduced the amplitude of TEOAE evoked by stimuli of a relatively low intensity (Frolenkov et al., 1995; Grandori & Ravazzani, 1993; Tavartkiladze et al., 1994). Instead, TEOAEs were recoeded by ordinary averaging. However, the linear component cancellation was used for the determination of time window of analysis. For this purpose, the control TEOAE recordings were made at different click intensities (0-46 dB SL), and for each subject the difference was obtained between TEOAE records to 30 dB SL click and to 20 dB SL click after multiplying the latter record by a 10 dB correction coefficient (Fig. 2). The difference consisted of non-linear TEOAE components only and was used to determine the analysis window (Fig. 2). Additionally, the appropriateness of the time window estimate was determined by the construction of input/output curves for the RMS amplitude of TEOAE in time intervals shorter than window chosen. Any time intervals that did not include non-linear TEOAE components were excluded from consideration. Hamming window function and Fast Fourier Transform (FFT) was performed. The amplitude of the TEOAE was calculated as the square root of the difference between the signal power and noise power in the frequency range where the spectrum of signal exceeded that of noise more than 3 dB.

5. TEOAE Tuning Properties

The TEOAEs were suppressed in all the experiments with simultaneous tonal masking. Fig. 3 shows typical TEOAEs recorded in response to 1.5-kHz tone bursts without masking and with masking tone of various intensities. In the experiments, the masking effect increased directly with the sensation level of the masking tone. With the tone at 40 dB SL, almost total suppression of TEOAE was observed. Such significant response suppression was found only at the masking-tone frequency equal or close to that of the tone burst (Fig. 3).

Fig.3: TEOAE reduction under simultaneous masking by 1.5-kHz tone of increasing intensity (indicated on the records). OAEs were evoked by 1.5-kHz, 20-dB SL tone bursts.

        Fig. 4 shows typical iso-suppression tuning curves of tone-burst and click-evoked OAEs. In all subjects and for all stimuli the tuning curve corresponded to the TEOAE frequency spectrum. In the case of tone-burst stimulation, locations of the maxima of the TEOAE and stimulus spectrum and tuning-curve tip were the same. The tuning properties of click-evoked OAE were different, and TEOAE spectral maxima, as well as TEOAE tuning-curves tips, did not correspond to the stimulus spectra. Indeed, clicks of various duration (60 microseconds and 500 microseconds) had quite different spectra . Irrespective of the click-stimuli spectra, the spectra of TEOAE were practically identical, and correspondingly similar TEOAE tuning-curves were obtained. In addition, the smaller difference between the tip and the low-frequency segment of the tuning curve with the 500 microseconds stimulus closely correlated to the existence of low-frequency TEOAE components which were not observed for the 60 microseconds click stimulation. In this subject tone burst stimulation with a frequency of 1.5 kHz was the most effective for the TEOAE excitation . The TEOAE evoked by this stimulus had in its spectrum essentially the same peaks that dominated in the spectra of TEOAE to broad-band stimulation . As a result, the tuning curve of the TEOAE to the 1.5 kHz tone burst was similar to the tuning curves of click-evoked OAEs (Fig.6-6). TEOAE spectra of all test subjects were characterized by the dominant peaks within the 1 to 2 kHz range, and the peaks strictly determined the tuning curves of both OAEs evoked by clicks of different duration and TEOAE to the tone burst of the most effective frequency. Nevertheless, this apparent independence of TEOAE-frequency composition and iso-suppression tuning curves from the stimuli spectra was only relative. When the stimulus energy was concentrated within the frequency range which did not comprise the frequencies of the dominant peaks of TEOAE to broad-band stimulation, the TEOAE with different frequency composition was observed . For example, OAEs evoked by 2.5 kHz tone bursts had the spectral peaks within the range of 1.8 to 2.6 kHz and the tuning curve with the tip located around 2.5 kHz (Fig. 4). Comparison of the tone-evoked OAE tuning curves showed that OAEs evoked with 2.5 kHz tone burst was characterized by a somewhat wider tuning curve than the TEOAEs to 1.5 kHz stimulation. This difference was not surprising considering the wider spectrum of TEOAE to the 2.5 kHz tone burst (Fig. 4). The tuning-curves shape with typical flat low frequency "plateau" and steep high frequency rise (Fig. 4) was observed in all subjects.

Fig. 4. Iso-suppression tuning curves (top) of OAEs evoked by clicks of different durations (A) and by tone bursts of different frequencies (B). Bottom records show from top to bottom: the spectra of stimuli and the spectra of corresponding TEOAEs. Stimuli intensity was 20 dB SL. Dashed lines indicate noise level.

The relation of TEOAE simultaneous-masking properties to the TEOAE-frequency composition was further explored by construction of tuning curves of the separate TEOAE frequency components (Fig. 5). It was found that the components were suppressed independently and had individual tuning curves with the typical shape (Fig. 4). The tips of the tuning curves were closely related to the frequency of separate components (Fig. 5). The intensities of masking tones that corresponded to the tuning curves tips tended to be higher for dominant peaks (Fig. 5). Usually the amplitudes of the TEOAE frequency components differed, and the tuning curve constructed from total TEOAE spectrum was determined by the contribution of TEOAE dominant spectral peaks (Fig. 5). Finally, the the independent suppression of the TEOAE frequency components was observed in all the subjects. Unfortunately, neither subjects had SOAEs, and it could not be determined how the presence of SOAEs could modify the suppression of TEOAE spectral constituents.

6. Ipsilateral Forward Masking of TEOAE

Neurons of the medial olivocochlear system (MOCS) can be effectively activated with both contralateral and ipsilateral sound (Liberman & Brown, 1986). Direct electrical stimulation of the crossed olivocochlear bundle (the subsystem of the MOCS presumably consisting of the ipsilaterally activating efferent fibers (Warren & Liberman, 1989) at the floor of the IV ventricle) has resulted in bilateral desensitization of the cochleas (Rajan, 1988, 1990), as well as in the suppression of the DPOAEs (Mountain, 1980). Therefore, it is reasonable to suggest some functional significance of the ipsilaterally activated olivocochlear feedback. Nevertheless, the latter reflex arc has received little attention in the literature. Evidence was presented for the involvement of efferent system in the ipsilateral forward-masking of the compound-action potential (Bonfils & Puel, 1987), and in the ipsilateral forward masking of TEOAE, demonstrated by the comparison between ipsilateral, contralateral, and binaural forward masking of TEOAE (Berlin et al., 1995). Nevertheless, the majority of the data related to the cochlear efferent physiology were obtained in experiments on the anesthetized animals, which may have changed reflex properties of the efferent neurons (Liberman & Brown, 1986). As a result, in an awake human being even the question about the latency of the contralateral activation of MOCS is still disputable (Lind, 1994). There are indications for the existence of the ipsilaterally activated efferent suppression of TEOAE in normal hearing subjects (Tavartkiladze et al., 1996). Comparison of the ipsilateral and contralateral efferent-mediated TEOAE suppressions in the same subject could be useful for the clinical testing of MOCS functioning.

7. Forward-Masking Experiment

As in the simultaneous-masking studies, subjects investigated were normal-hearing subjects with no history of otologic disease, with audiometric thresholds less than 20 dB within the frequency range of 125-8000 Hz, and type-A tympanograms. Absence of the spontaneous OAEs was proved by the ILO 88 analyzer (Otodynamics). Suppression of TEOAE by the continuous contralateral-noise stimulation is known to be of the same order of magnitude as the TEOAE spontaneous changes (Berlin et al., 1993) and slightly more than the TEOAE changes with directed attention (Froehlich et al., 1993). The TEOAE suppression by relatively short acoustic stimuli (clicks or broad-band noise no more than 30 ms duration) was investigated. This effect was expected to be somewhat smaller than the suppression associated with continuous noise presented contralaterally. To minimize baseline changes all TEOAE recordings were performed in one lengthy recording session without change of the probe’s position in the test ear.

The ILO88 system (with software version 3.94L) was set up with uniform (80-microseconds) linear clicks as stimulus 1 and quad-spaced clicks as stimulus 2. Stimulus 1 was routed to channel A as the ipsilateral acoustic stimulus. Stimulus 2 was fed to channel B. In click-to-click forward masking experiments, the latter stimulus was delivered ipsilaterally through the second electroacoustic transducer of ILO probe and was used as a masker. In noise-to-click forward masking experiments, output of the channel B triggered the general-purpose digital generator (HP33120A, Hewlett Packard). After appropriate attenuation (output attenuator of the Midimate 602 audiometer, Madsen Electronics) digitally generated broadband (bandwidth: 50-8000 Hz) noise bursts of 10 or 30 milliseconds duration were delivered ipsilaterally to the second electroacoustic transducer of the ILO probe or contralaterally to the TDH-39 headphone. Canceling of masking-signal artifact was observed in the course of averaging because the ILO system alternates the phase of every accepted stimulus and response. Before the execution of forward masking experiments, the TEOAE was also masked by continuous broad-band noise delivered contralaterally. In all forward masking experiments test clicks were delivered in sequence (inter-click interval 30 milliseconds) with the repetition rate of 3 Hz (Fig. 6). Such a low stimulation rate was used in order to guarantee a 200 milliseconds pause between the test series. This time was probably essential for the excitation decay in the olivocochlear reflex arc (Giraud et al., 1997; Warren & Liberman, 1989). Emission to each test click was stored separately. At least 1000 TEOAE responses were recorded without windowing. After averaging TEOAE responses in each software buffer (to different test clicks) were time-windowed (4-15 milliseconds) and their RMS amplitudes were calculated using ILO88 software. To trace baseline variations in response amplitude (see for example: (Berlin et al., 1993), TEOAE records were obtained alternatively: with and without contralateral or ipsilateral masking stimulation. Each TEOAE record in the presence of noise preceded the record without a masker. The mean differences (and their standard errors) of TEOAE amplitudes from these pairs (5 pairs per each point) were calculated. The time delay (D t) between the the onset of masker and the second test click in sequence was adjusted to be 1 to 30 milliseconds (Fig. 1). In noise-to-click forward masking experiments it was fixed at two predetermined values: 0 milliseconds (test A) or 15 milliseconds (test B). A tone-tailed test (t-test) was applied to determine the statistical significance of the TEOAE amplitude changes under masking conditions.

8. Contralateral Masking With Continuous Broad-Band Noise

Contralateral noise remarkably reduced the TEOAE amplitude. In one subject OAE evoked by the clicks of moderate intensity of 65.5 dB SPL (relating to subjective threshold it was 30 dB SL) were diminished by as much as 2.3 dB with the use of 60 dB SL contralateral noise. The effect was observed at the masker intensities up to 30 dB SL .

9. Ipsilateral Click-to-Click Forward Masking

TEOAEs were dramatically suppressed during the first ms after masking click delivery (Fig. 7). This suppression consisted in the overall decrease of emission-time components with maybe a more prominent reduction of long-latency emission. the amplitude of emission recovered to 90% of the control value in 5 milliseconds. Changes of emission amplitude at longer interstimulus intervals were not significant.

Fig.7. Changes of TEOAE amplitude with interstimulus time interval (D t) under click-to-click forward masking conditions. Filled circle indicates the control TEOAE amplitude (TEOAE amplitude to the first click in test sequence). Dashed line indicates noise level. Test click intensity = 20 dB SL; masking click intensity = 46 dB SL.

10. Contralateral Versus Ipsilateral Noise-To-Click Forward Masking

Contralateral broad-band noise burst stimulation with the intensity of 50 dB SL (65 dB nHL) evoked statistically significant reduction of TEOAE amplitude 15 milliseconds after masker onset (Fig.8). This effect became more prominent with the increase of noise duration up to 30 milliseconds. The same noise stimulation presented ipsilaterally, evoked similar effect at the intervals between masker and the test of more than 30 milliseconds (Fig. 8). These effects could not be related to the efferent feedback activation by the test sequence because there were no statistically significant changes in the amplitude of OAE evoked by different clicks in test sequence without masking (Fig. 8). The time course of ipsilateral and contralateral suppressions was practically identical. Nevertheless, the prominent ipsilateral suppression at the masker-stimulus onset delay of 15 milliseconds was also found. It corresponded to the 5 milliseconds difference between masker end and the stimulus delivery, and obviously related to the dramatic TEOAE suppression revealed in click-to-click forward masking experiment (Fig. 7).

Fig 8. Temporal dynamics of contralateral (A) and ipsilateral (B) suppression of TEOAE. Each point represents the mean difference of TEOAE amplitudes (5 pairs) recorded in masker-on and masker-off conditions. Open squares on B show the mean TEOAE amplitudes without masker. The latter amplitudes were related to the mean amplitude of TEOAE evoked by the first click in test sequence. Error bars indicate standard errors.

11. Middle-Ear Reflexes

In noise-to-click forward-masking experiments noise intensities as high as 50 dB SL were used. With the noise presented continuously, this value was found to be only slightly below the threshold of stapedial muscle reflex in this subject. Nevertheless, the middle-ear reflex threshold using short-noise bursts of the maximum for our experiments duration (30 milliseconds), was determined to be as much as 80 dB SL, which is 30 dB higher than the intensity used in masking experiments . To eliminate the possibility of the middle-ear reflexes which cannot be recorded with conventional impedance measurements, the sound pressure in the outer-ear canal during alternative presentation of contralateral noise was evaluated. There was no pressure excursion at the 40 to 110 milliseconds poststimulus time when the stapedial reflex could be observed (Fisch & Schulthess, 1963; Metz, 1951). The observation could not rule out the theoretical possibility of slowly developing reflex tension in the middle-ear muscles. In order to exclude this possibility, the TEOAE amplitudes were compared without masker and just before masker onset (it is a response to the first click in test sequence). No statistically significant differences were found (Tavartkiladze et al., 1997).

12. Efferent-Mediated Effects in Ipsilateral-TEOAE Suppression

The magnitudes of the TEOAE suppression caused by contralateral continuous noise (e.g., 0.6 dB with the contralateral noise at 30 dB SL in one subject were only slightly less than previously reported mean values for normal-hearing subjects (0.7 dB with the masker intensity of 20 dB SL) (Collet et al., 1990). Hence, the excitability of the olivocochlear reflex arc (at least from contralateral side) was unlikely to differ significantly from the typical one. The dramatic decrease of the TEOAE under click-to-click forward-masking conditions at the interstimulus intervals smaller than 5 ms (Fig. 7) could be attributed exclusively to the intracochlear processes due to the longer minimal latency of the medial olivo-cochlear neuron responses to the external sound. This latency was found to be at least 6-8 ms in cat (Liberman & Brown, 1986) and 7 milliseconds in guinea pig (Brown, 1989), and there is no reason to expect the significant reduction of this time in human beings. Moreover, practically complete TEOAE inhibition observed withing the first 5 ms poststimulus (Fig. 7) correlated well with the degree of the TEOAE suppression that was reported previously for the ipsilateral simultaneous TEOAE masking (Tavartkiladze et al., 1994). Hence, the TEOAE suppression observed 5 ms after the end of ipsilateral masking noise burst (Fig. 8) may have been mainly of cochlear origin.

It is known that short acoustic clicks with relatively low repetition rate are quite ineffective in eliciting efferent response (Liberman & Brown, 1986). Longer stimuli (i.e., tone bursts of 50 milliseconds) are capable of exciting the MOCS neurons (Brown, 1989). Accordingly, noise bursts presented contralaterally or ipsilaterally elicited a statistically significant TEOAE reduction 30 milliseconds and more after the end of noise stimulation (Fig. 8). The latency of this effect from the contralateral side was found to be less than 15 milliseconds (Fig. 8). This value differs somewhat from the previously reported estimate of the contralateral TEOAE-suppression latency (less than 40-140 milliseconds) (Lind, 1994) and from the latency of the efferent-mediated ipsilateral suppression of the compound-action potential in guinea pigs [30-40 milliseconds (Bonfils & Puel, 1987]. So far no systematic studies of this question have been performed. Moreover, at the 15 milliseconds interval between contralateral noise and test click the possibility that additional TEOAE suppression related to the intracochlear processes on the ipsilateral side cannot be exclude. The degree of acoustic isolation between the two ears was not greater than 40 dB, and attenuated noise could stimulate ipsilateral cochlea owing to crosstalk. Nevertheless, the effect at longer noise-to-click intervals appears to result from MOCS activation because (1) its duration was not explained by intracochlear suppression (Fig. 7 and 8) and (2) the suppression magnitude was similar from ipsilateral and contralateral sides. The long duration of the efferent-mediated inhibition of TEOAE (more than 80 milliseconds; see Fig. 8) did not contradict previously reported TEOAE forward masking data (Gobsch et al., 1992; Lind, 1994) and other studies of ipsilateral effects (Berlin et al., 1995).

The most striking result of our experiments was the close resemblance of the magnitudes and time courses of the efferent-mediated effects elicited from contralateral and ipsilateral sides (Fig. 8). Berlin, et al. (1995) compared forward masking of TEOAE by ipsilateral, contralateral and binaural noise. In full accordance with the data presented in this chapter, they found TEOAE suppression of approximately the same magnitude (about 0.5 dB) for both ipsilateral and contralateral noise stimulation. Binaural noise stimulation caused more prominent reduction of TEOAE amplitude (about 1-1.5 dB). Differences between ipsilateral and contralateral effects were not significant 20 to 100 milliseconds after noise stimulation (Berlin et al, 1995). These results appear to contradict the results of Liberman and Brown (1986) who reported that 59% of MOCS neurons are most sensitive to the ipsilateral stimuli, 29%, to the contralateral ones, and 11%, from both. Consequently one could expect some difference in the magnitude of the efferent-mediated TEOAE suppression evoked by contralateral and ipsilateral stimulation. This discrepancy may be related to the fact that the MOCS neuron excitability pattern depends on the level of general anesthesia. Indeed, it was speculated that percent of binaurally responding MOCS neurons can be higher in less anesthetized animals (Liberman & Brown, 1986). Moreover, in unanesthetized decerebrated cats, 60% of efferent units were reported to respond to both contralateral acoustic stimulation and ipsilateral electrical stimulation (Fex, 1962, 1965). Thus, in awake human beings, a significant portion of MOCS neurons can be expected to be bilaterally activated. This could explain the similar magnitudes of the efferent-mediated TEOAE suppressions evoked by contralateral and ipsilateral stimuli.

13. References

Aran J-M: Current perspectives on inner ear toxicity. Otolaryngol Head Neck Surg 1995; 112: 133-144.

Avan P, Bonfils P, Loth D et al.: Quantitative assessment of human cochlear function by evoked otoacoustic emissions. Hear Res 1991; 52: 99-112.

Berlin CI, Hood LJ, Cecola RP et al.: Does type I afferent neuron dysfunction reveal itself through lack of efferent suppression? Hear Res 1993; 65: 40-50.

Berlin CI, Hood LJ, Wen H, Szabo P et al.: Contralateral suppression of non-linear click-evoked otoacoustic emissions. Hear Res 1993; 71: 1-11.

Berlin CI, Hood LJ, Hurley AE et al.: Binaural noise suppresses linear click-evoked otoacoustic emissions more than ipsilateral or contralateral noise. Hear Res 1995; 87: 96-103.

Bonfils P, Puel J-L: Functional properties of the crossed part of the medial olivo-cochlear bundle. Hear Res 1987; 28: 125-130.

Bray P, Kemp DT: An advanced cochlear echo suitable for infant screening. Br J Audiol 1987; 21: 191-204.

Brown M.C. Morphology and response properties of single olivocochlear fibers in the guinea pig. Hear Res 1989; 40: 93-110.

Collet L: Use of otoacoustic emissions to explore the medial olivocochlear system in humans. Br J Audiol 1993; 27: 155-159.

Collet L, Kemp PT, Veuillet E et al.: Effect of contralateral auditory stimuli on active cochlear micromechanical properties in human subjects. Hear Res 1990; 43: 251-262.

Dallos P :Response characteristics of mammalian cochlear hair cells. J Neurosci 1985; 5: 1591-1608.

Durrant JD: Contralateral suppression of otoacoustic emissios: delay of effect? J Commun Disord 1998; 31: 485-488.

Elberling C, Parbo J, Johnsen NJ et al.: Evoked acoustic emissions: clinical application. Acta Oto-Laryngol (Stockh) 1985; Suppl 421: 77-85.

Fex J: Auditory activity in centrifugal and centripetal cochlear fibers in cat. Acta Physiol Scand 1962; Suppl 189: 2-68.

Fex J: Auditory activity in uncrossed centrifugal cochlear fibers in cat. Acta Physiol Scand 1965; 64: 43-57.

Fisch U, Schulthess G: Electromyographic studies on the human stapedial muscle. Acta Otolaryngol (Stockh) 1963; 56: 287-297.

Froehlich P, Collet L, Morgon A: Transient evoked otoacoustic emission amplitudes change with changes of directed attention. Physiol Behav 1993; 53: 679-682.

Frolenkov GI, Artamasov SV, Kruglov AV et al.: Time and frequency components of transient evoked otoacoustic emission: the input/output functions. Abstr. Eighteenth Midwinter Meet. Assoc. Res. Otolaryngol. 1995: 121.

Giraud AL, Collet L, Chery-Croze S: Suppression of otoacoustic emission is unchanged after several minutes of contralateral acoustic stimulation. Hear Res 1997; 109: 78-82.

Gobsch H, Kevanishvili Z, Gamgebeli Z et al.: Behaviour of delayed evoked otoacoustic emission under forward masking paradigm. Scand Audiol 1992; 21: 143-148.

Grandori F: Non-linear phenomena in click- and tone-burst- evoked otoacoustic emissions. Audiol 1985; 24: 71-80.

Grandori F, Ravazzani P: Non-linearities of click-evoked otoacoustic emissions and the derived non-linear technique. Br J Audiol 1993; 27: 97-102.

Hauser R, Probst R, Lohle E: Click- and tone-burst-evoked otoacoustic emissions in normally hearing ears and in ears with high-frequency sensorineural hearing loss. European Arch Oto-Rhino-Laryngol 1991; 248: 345-352.

Hilger AW, Furness DN, Wilson JP: The possible relationship between transient evoked otoacoustic emission and organ of Corti irreguliarities in the guinea pig. Hear Res 1995; 84: 1-11.

Hill JC, Prasher DK, Luxon LM: Latency of contralateral sound-evoked auditory efferent suppression of otoacoustic emissions. Acta Otolaryngol (Stockh) 1997; 117: 343-351.

Kemp DT: Stimulated acoustic emissions from within the human auditory system. J Acoust Soc Am 1978; 64: 1368-1391.

Kemp DT: Towards a model for the origin of cochlear echoes. Hear Res 1980; 2: 533-548.

Kemp DT: Otoacoustic emissions, traveling waves and cochlear mechanisms. Hear Res 1986; 22: 95-104.

Kemp DT, Chum RA: Properties of the generator of stimulated acoustic emissions. Hear Res 1980; 2: 213-232.

Kemp DT, Bray P, Alexander L et al.: Acoustic emission cochleography: practical aspects. In Cianfrone G, Grandori F (eds): Cochlear Mechanics and Otoacoustic Emissions: Scand Audiol 1986; Suppl. 25: 71-95.

Kossl M, Russell IJ: The phase and magnitude of hair cell receptor potentials and frequency tuning in guinea pig cochlea. J Neurosci 1992; 12: 1575-1586.

Kubo T, Sakashita T, Hachikawa K et al.: Frequency analysis of evoked otoacoustic emissions. Acta Oto-Laryngol 1991; Suppl. 486: 73-77.

Liberman MC, Brown MC: Physiology and anatomy of single olivocochlear neurons in the cat. Hear Res 1986; 24: 17-36.

Lind O: Contralateral suppression of TEOAE. Attempts to find a latency. Br J Audiol 1994; 28: 219-225.

Lonsbury-Martin BL, Martin GK, Probst R et al.: Spontaneous otoacoustic emissions in nonhuman primate. II. Cochlear anatomy. Hear Res 1988; 33: 69-94.

Martin GK, Lonsbury-Martin BL, Probst R et al.: Spontaneous otoacoustic emissions in a nonhuman primate. I. Basic features and relations to other emissions. Hear Res 1988; 33: 49-68.

Norton SJ, Neely ST: Tone-burst-evoked otoacoustic emissions from normal-hearing subjects. J Acoust Soc Amer 1987; 81: 1860-1872.

Metz O: Studies on the contraction of the tympanic muscles as indicated by changes in the impedance of the ear. Acta Otolaryngol (Stockh) 1951; 39: 397-405.

Mountain DC: Changes in endolymphatic potential and crossed olivocochlear bundle stimulation alter cochlear mechanics. Science 1980; 210: 71-72.

Probst R, Coats AC, Martin GK et al.: Spontaneous, click-, and toneburst-evoked otoacoustic emissions from normal ears. Hear Res 1986; 21: 261-275.

Probst R: Otoacoustic emissions: An overview. In Pfaltz CR (ed): New aspects of cochlear mechanics and inner ear pathophysiology. Adv Otorhinolaryngol, 44: pp 1-91. Karger, Basel, 1990.

Probst R: A review of otoacoustic emissions. J Acoust Soc Am 1991; 89: 2027-2067.

Rajan R: Effect of electrical stimulation of the crossed olivocochlear bundle on temporary threshold shifts in auditory sensitivity. I Dependence on electrical stimulation parameters. J Neurophysiol 1988; 60: 549-567.

Rajan R: Functions of the efferent pathways to the mammalian cochlea. In Rowe M, Aitkin L (eds): Information processing in mammalian auditory and tactile systems, pp 81-96. Wiley Liss, New York, 1990.

Tavartkiladze GA, Frolenkov GI, Kruglov AV: On the site of the evoked otoacoustic emission generation. In Proc. XII Biennal Symposium of the International Electric Respons audiometry Study Group, (Terme Di Comano (TN) - Italy, September 25-29, 1991), 1991: 58.

Tavartkiladze GA, Frolenkov GI, Kruglov AV: Delayed evoked otoacoustic emission and mechanisms of its generation. Sensory Systems 1993; 7: 85-99.

Tavartkiladze GA, Frolenkov GI, Kruglov AV et al.: Ipsilateral suppression effects on transient evoked otoacoustic emission. Br J Audiol 1994; 28: 193-204.

Tavartkiladze GA, Frolenkov GI, Artamasov SV: Ipsilateral suppression of transient evoked otoacoustic emission: role of the medial olivocochlear system. Acta Otolaryngol (Stockh) 1996; 116: 213-218.

Tavartkiladze GA, Frolenkov GI, Kruglov et al.: Ipsilateral suppression of transient evoked otoacoustic emissions. In Robinette MS, Glattke TJ (eds): Otoacoustic Emissions: Clinical Applications, chapt.6, pp 110-129. Thieme, New-York-Stuttgart, 1997.

Veuillet E, Collet L, Duclaux R: Effect of contralateral acoustic stimulation on active cochlear micromechanical properties in human subjects: Dependence on stimulus variables. J Neurophysiol 1991; 65: 724-735.

Veuillet E, Collet L, Morgon A: Differential effects of ear-canal pressure and contralateral acoustic stimulation on evoked otoacoustic emissions in humans. Hear Res 1992; 61: 47-55.

Warren EH, Liberman MC: Effects of contralateral sound on auditory-nerve responses. I. Contributions of cochlear efferents. Hear Res 1989; 37: 89-104.

Wilson JP: Evidence for a cochlear origin for acoustic re-emissions, threshold fine-structure and tonal tinnitus. Hear Res 1980; 2: 233-252.

Wilson JP, Sutton GJ: Acoustic correlates of tonal tinnitus. In Tinnitus: Ciba Foundation symposium, pp 82-107. Pitman Books, London: 1981.

Zurek PM: Spontaneous narrowband acoustic signals emitted by human ears. J Acoust Soc Amer 1981; 69: 514-523.

Zurek PM: Acoustic emissions from the ear: A summary of results from humans and animals. J Acoust Soc Am 1985; 78: 340-344.

[email protected], Ph.D

ENT-Department, Technical University Munich, Germany

         Due to their non-linear transmission characteristics and corresponding intermodulation distortion, outer hair cells evoke intermodulation vibrations in cochlear micromechanics and fluid when stimulated by two tones f₁ and f₂ (f₂ > f₁) of neighboring frequencies. In humans, the 2f₁-f₂ distortion product (DPOAE) has the highest amplitude and is therefore primarily used for diagnosing cochlear dysfunction. There are two main problems when using DPOAEs as a probe for monitoring loss of sensitivity and loss of compression of the outer hair cell amplifiers.

Fig. 1. Schematic drawing of how to evoke DPOAEs within the cochlea and how to measure them in the outer ear canal. The sound probe consists of two loudspeakers for applying the primary tones with frequencies f₁ and f₂ and levels L₁ and L₂, and one microphone for measuring acoustic signals in the outer canal. DPOAEs are generated within the region of overlap of the traveling waves of the two primary tones close to the f₂ place. The level L_dp of the 2f₁-f₂ DPOAE and the related noise floor (average of 6 spectral lines around 2f₁-f₂) are measures for determining DPOAE amplitude and signal-to-noise ratio.

1. First problem: How to elicit DPOAEs?

DPOAE amplitude is known to depend on the frequency ratio and level ratio of the two primary tones. If we want to use DPOAEs as a probe for monitoring changes in outer hair cell function we need to ensure that DPOAE generation is restricted to a distinct place in the cochlea. The question is: what is the best parameter setting for eliciting DPOAEs?  Intermodulation distortion originates in the cochlear region where the travelling waves of the two primary tones overlap. Due to the steeper slope of the travelling wave towards cochlear apex, the maximum interaction site is close to the f₂ place in the cochlea. Thus, the outer hair cells of the f₂ place contribute most to DPOAE generation (Fig. 1). The number of outer hair cells contributing to DPOAE generation depends on the size of the overlapping region which is determined by the levels L₁ and L₂ and the frequency ratio f₂/f₁ of the primary tones. To preserve the overlapping region at low primary tone levels for eliciting DPOAEs near the hearing threshold, a primary tone level setting has to be used that accounts for the different compression of the two primary tones at the DPOAE generation site, at f₂. When using such a paradigm, the level and frequency of the higher primary tone (L₂ and f₂) are decisive for the generation of DPOAEs in the cochlea. Thus, when plotting the DPOAE level L_dp as a function of L₂ (DPOAE I/O-function) DPOAEs reflect the compressive sound processing of the cochlea at the f₂-place.

2. Using the scissor paradigm for eliciting DPOAEs.

How must a parameter setting look like that accounts for the different compression of the two primary tones? Whitehead et al. (1995a) and our group (Janssen et al., 1995a,b; Kummer et al., 2000) have proposed a primary tone level setting in which the difference between L₁ and L₂ increases with decreasing stimulus level. Using this paradigm, instead of the common used equilevel paradigm, DPOAE growth reflects the compressive nonlinear cochlear sound processing known from direct measurements of basilar membrane motion in animal experiments (Ruggero et al., 1997; Boege and Janssen, 2002). Fig. 2 shows the influence of the primary tone level difference on DPOAE level. As one can see not the L₁=L₂ condition yields the highest DP level, but the scissor pradigm. At high primary tone levels, L₁ and L₂ are equal. However, with lower stimulus levels the difference between L₁ and L₂ has to be increased using the formular L₁=0.4L₂+39 (with f₂/f₁=1.2). This so called scissor paradigm (in German: “Pegelschere”, Janssen et al., 1995 a,b) varies only slightly with f₂ (Kummer et al., 2000). Thus, the formular L₁=0.4L₂+39 can be used nearly independent of f₂. It should be emphazised, that this formular is only true for the sound probe (ER-10C, Etymotic Research, USA) and the sound pressure calibration method (in-the-ear calibration, see Whitehead et al., 1995b) used during the development of the scissor paradigm. Thus, when using different sound probes and/or different calibration methods a new scissor paradigm has to be determined. This is also true when measuring DPOAEs in different mammalian ears (for guinea-pigs, see Michaelis et al., to be published in Hearing Res).

L1 L2

65 65

63  60

61   55

59    50

57     45

55      40

53       35

51        30

49         25

47          20

Fig. 2. Scissor paradigm (left). DPOAE level L_dp for different L₁, L₂ combinations. DPOAEs when elicited by the scissor paradigm yielded highest levels (see projection on the floor). Dashed line on the floor indicates equilevel primary tone setting (after Janssen et al., 1995 a,b; Kummer et al., 2000).

3. Second problem: How to measure DPOAEs at near-to-threshold primary tone levels?

At near-to-threshold primary tone levels either no DPOAEs or DPOAEs with unsufficient signal-to-noise ratios can be measured. Therefore, when plotting the DPOAE level L_dp as a function of  f₂ (DP-gram) the DPOAEs often do not reflect cochlear hearing thresholds. How to overcome the problem? The idea is as follows. If we can not reliably measure DPOAEs at close-to-threshold primary tone levels, then we have to estimate the DPOAEs at threshold. A simple way to estimate DPOAEs at threshold is to extrapolate DPOAE I/O-functions. For extrapolating DPOAE I/O-functions we need to know the relationship between the DPOAE level L_dp and the primary tone level L₂

4. Using extrapolated DPOAE I/O-functions for estimating DPOAEs at threshold.

Using the scissor paradigm L₁=0.4L₂+39dB in most of the DPOAE I/O-functions recorded in normal-hearing human ears a logarithmic dependency of the distortion product sound pressure level L_DPon the sound pressure level L₂ of the f₂ primary tone can be found (Boege and Janssen, 2002). In normal-hearing ears, in the low primary tone level range the slope amounted to about 1 dB/dB whereas in the high primary tone level range the slope amounted to about 1/3 dB/dB. With increasing hearing loss the slope continously increases (see Janssen et al., 1998; Kummer et al., 1998 for mean slope values in normal-hearing and cochlear impaired subjects). With that, DPOAE growth is similar to that what has been found in basilar membrane responses (Ruggero et al., 1997). Thus, DPOAE I/O-functions are able to reflect the compressive sound amplification in the cochlea at the outer hair cell level.

Fig. 3. DPOAE I/O-function in a semi-logarithmic scale  at f₂ = 1709 Hz in a human cochlear hearing loss ear (upper panel) and log-log scale (lower panel). Solid line shows the fitted linear function. The vertical bar marks the estimated DPOAE threshold. Filled circles indicate DPOAEs, open triangles noise floor (after Boege and Janssen, 2002).

The logarithmic dependency of the DPOAE sound pressure level on the primary tone sound pressure level results in a linear dependency between the DPOAE sound presure p_DP and the primary tone sound pressure level L₂. In Fig. 3 the DPOAE sound pressure p_DP (top panel) and the DPOAE sound pressure level L_DP (bottom panel) of the same DPOAE I/O-function are plotted as a function of the primary tone level L₂. The linear fit to the data (solid line) proves the logarithmic dependency of p_DP on p₂ or Ldp on L₂. The correlation coefficient r²gives a measure of the accuracy of the linear fit. The vertical bar marks the intersection point of the regression line with the primary tone level axis which serves as an estimate of the cochlear pure-tone thresholdin both panels. (The estimated cochlear pure-tone threshold L_EDPTis the extrapolated value equivalent to the primary tone level L₂ that would give a zero DPOAE sound pressure (p_DP =0).)

5. Correlation between estimated DPOAE threshold and behavioral threshold.

In our clinical data set we found a close correspondence between the estimated cochlear pure-tone threshold and the behavioral threshold which was recorded with the same sound probe.  

Fig. 4. Behavioral pure-tone threshold L_T is plotted across estimated DPOAE threshold level L_EDPT for 4236 DPOAE I/O-functions of 30 normal-hearing and 119 cochlear hearing loss ears fullfillung linear regression criteria (left). Distribution of the difference between between pure-tone threshold L_T and estimated DPOAE threshold level L_EDPT  (right) (after Boege and Janssen, 2002).

When comparing the behavioral pure-tone threshold L_T and the estimated cochlear pure-tone threshold L_EDPT for 4236 DPOAE I/O-functions of 30 normal-hearing and 119 cochlear hearing loss ears that fulfill linear regression criteria (for detail see Boege and Janssen, 2002) a significant correlation is present. Moreover, there is almost a 1:1 relationship between the subjective and the objective measures. This means that there is a direct quantitative relationship between the estimated cochlear pure-tone threshold and the behavioral pure-tone threshold (Fig. 4, left). When calculating the difference for all 6182 as well as for the 4236 I/O-functions fulfilling the criteria the mean difference amounted to 2.2 and 2.5 dB, respectively. The standard deviations were 12.7 and 10.9 dB, respectively (Fig. 4, right). 

Recently, Gorga et al. (2003) extended our method by increasing the primary tone level (up to 85 dB SPL) and changing the criteria for accepting I/O-functions. They also evaluated the effects of the primary tone frequency. The authors essentially replicated our results (Boege and Janssen, 2002) when using the same stimulus conditions and linear regression criteria. Taking measurements for a wider range of levels and slightly altering the inclusion criteria Gorga et al. achieved an improvement in test performance. They found prediction errors not to be uniformly distributed across test frequency. Best performance was observed for mid-to-high frequencies. In a retrospective study on our data using weighted extrapolated DPOAE I/O-functions we got similar results and attributed the frequency dependent estimation error to problems with in-the-ear-canal sound pressure calibration (Oswald and Janssen, 2003). Therefore, further efforts are necessary to improve the sound pressure calibration in the outer ear canal for applying definite sound pressure at the ear drum and hence improving cochlear pure-tone threshold estimation.

6. Using the slope of the DPOAE I/O-functions for estimating cochlear compression.

Besides the estimation of pure-tone thresholds, DPOAE I/O-functions provide an additional measure. That is the slope of the I/O-function, which is able to estimate the compression of outer hair cell amplifiers. This was shown for guinea pigs in which the outer hair cells were impaired using acute furosemide intoxication (Mills and Rubel, 1996) and for humans suffering from cochlear hearing loss (Janssen et al., 1998; Kummer et al., 1998; Boege and Janssen, 2002; Neely et al., 2003). In these studies the slope of the DPOAE I/O-function increases with increasing hearing loss revealing loss of compression of outer hair cell amplifiers.

7. Potential clinical applications of extrapolated DPOAE I/O-functions

An important problem in neonatal hearing screening is to interpret the effect of middle-ear status on the measures. Recently, we applied extrapolated DPOAE I/O-functions in human neonates to estimate cochlear pure-tone threshold and compression (Janssen et al., 2003). The estimated pure-tone threshold was found to be increased within the early postnatal period (average age: 3 days), predominantly at the higher frequencies, and to be normalised in a follow-up measurement (after four weeks). However, the slope of DPOAE I/O-functions obtained in the first and second measurement was unchanged revealing normal cochlear compression. Consequently, we interpret the findings as temporary sound conductive hearing loss due to amniotic fluid and/or Eustachian tube dysfunction. Thus, we conclude that newborn hearing screening, especially during the first days of life, may lead to false positive results due to a temporary sound conductive hearing loss. In order to avoid unnecessary and time consuming audiological testings we propose to use the slope of DPOAE I/O-functions in neonatal hearing screening to differentiate between (temporary) middle ear and (persisting) cochlear disorders.

We believe that extrapolated DPOAE I/O-functions give more information for diagnostical purposes than those of DP-grams or transitory evoked OEAs (TEOAEs). Beside the assessment of middle-ear status we suggest our method to be able to quantify loss of cochlear sensitivity and compression especially in newborns and children. Consequently, our future targets are to implement extrapolated DPOAE I/O-functions in a hand-held hearing screening device to provide frequency-specific and quantitative information on hearing loss and to  estimate whether there is a sound conductive or cochlear hearing loss. Another potential application of extrapolated DPOAE I/O-functions is to objectively adjust hearing aids in children. Since DPOAE I/O-functions are reported to be correlated with loudness (Neely et al. 2003), DPOAE would also offer the potentiality of basic hearing aid adjustment (Müller and Janssen, in preparation).

References:

• Boege P, Janssen T (2002) Pure-tone threshold estimation from extrapolated distortion product otoacoustic emission I/O-functions in normal and cochlear hearing loss ears. J Acoust Soc Am 111 (4) 1810-1818
• Gorga MP, Neely ST, Dorn PA, Hoover BM (2003) Further efforts to predict pure-tone thresholds from distortion product otoacoustic emission input/output functions. J Acoust Soc Am 113 (6) 3275-3284
• Janssen T, Kummer P, Arnold W (1995a) Wachstumsverhalten der Distorsionsproduktemissionen bei kochleären Hörstörungen. Otorhinolaryngol NOVA 5:34-46
• Janssen T, Kummer P, Arnold W (1995b) Wachstumsverhalten der Distorsions­produktemissionen bei normaler Hörfunktion. Otorhinolaryngol NOVA 5:211-22
• Janssen T, Kummer P, Arnold W (1998) Growth behavior of the 2f1-f2 distortion product otoacoustic emission in tinnitus. J Acoust Soc Am Vol 103 (6):3418-3430
• Janssen T, Klein A, Gehr D. (2003) Automatische Hörschwellenbestimung bei Neugeborenen mit extrapolierten DPOAE-Wachstumsfunktionen. Eine neue Hörscreening-Methode. HNO (to be published in December)
• Kummer P, Janssen T, Arnold W (1998) The level and growth behavior of the 2f1-f2 distortion product otoacoustic emission and its relationship to auditory sensitivity in normal hearing and cochlear hearing loss.J Acoust Soc Am Vol 103 (6):3431-3444
• Kummer P, Janssen T, Hulin P, Arnold W (2000) Optimal L1-L2 primary tone level separation remains independent of test frequency in humans. Hearing Research 146: 47-56
• Michaelis CE, Gehr DD, Deingruber K, Arnold W, Lamm K. Optimum primary tone level setting for measuring high amplitude DPOAEs in guinea pigs (to be published in Hearing Res)
• Mills DM, Rubel ED (1996). Developement of the cochlear amplifier. J Acoust Soc Am Vol 100:  428-441
• Müller J, Janssen T. Similarity in loudness and distortion product otoacoustic emission input/output functions: Implications for an objective hearing aid adjustment (in preparation)
• Neely ST, Gorga MP, Dorn PA (2003) Cochlear compresion estimates from measurements of distortion-product otoacoustic emissions. J Acoust Soc Am Vol 114: 1499-1507

• Oswald JA, Janssen T (2003) Weighted DPOAE I/O-functions: A tool for automatically assessing hearing loss in clinical application. Z Med Physik 13: 93-9

• Ruggero MA, Rich NC, Recio A, Narayan SS (1997) Basilarmembrane responses to tones at the base of the chinchilla cochlea. J Acoust Soc Am Vol 101: 2151-2163
• Whitehead ML, McCoy MJ, Lonsbury-Martin BL, Martin GK (1995a) Dependence of distortion-product otoacoustic emissions in primary tone level in normal and impaired ears. I. Effects of decreasing  L2 below L1. J Acoust Soc Am 97: 2346-2358
• Whitehead ML, Stagner BB, Lonsbury-Martin BL, Martin GK (1995b) Effects of era-canal standing waves on measurements of distortion-product otoacoustic emissions. J Acoust Soc Am 98: 3202-3214

1.  Introduction

       Hearing screening in newborns and infants was first performed in Poland in the 60's. During these years hearing tests were performed in infants and toddlers, using mainly behavioral techniques and in a few hospitals rather in a broad scale. In the 90's the tests were conducted under the supervision of the Institute of Pathology and Physiology of Hearing within a context of a governmental project. Selected clinics and hospitals participated in that project, using different screening models (high risk groups or universal), different protocols and techniques (OAE-AABR, AABR-AABR). Despite these efforts the implementation of a large-scale hearing screening in newborns was not realistic. There are approximately 380,000 children born a year in Poland nowadays. If we assume a 3:1000 prevalence of binaural sensorineural hearing loss then we can expect to have approximately 1200 hearing impaired newborns each year.

        The possibility of implementing a universal newborn hearing screening in Poland appeared in 2001 with the initiative of "The Great Orchestra of Christmas Charity" Foundation.

       The Foundation was established in 1993 and in 2001 its members, decided to collect money for a newborn hearing screening project. The result was very successful more than 6 million dollars were collected on the 7th of January, 2001.

        A team of experts was put together having as members neonatologists, otolaryngologists, audiologists, speech-therapists and engineers. All the members worked on a voluntary basis. Their task was (1) to elaborate the details and the implementation of a national universal newborn hearing screening program, which would be based on the general guidelines published previously (European Consensus, 1998; Joint Committee on Infants Hearing Position Statement, 2000) and (2) take into account specific, local conditions. International experts such as Dr. Ferdinado Grandori (Italy), and Dr. Karl White (USA) contributed as consultants to the project.

The team of experts set the following program goals

1. Every newborn will be offered a hearing screening test in a neonatology department. The newborns which are not tested (for a variety of reasons) will be offered a hearing test in audiology departments.

2. Every child who will not pass the hearing test will be referred to an audiology department. Full diagnosis will be completed by the end of third month of life.

3. Every infant with confirmed hearing loss will receive appropriate intervention by the sixth month of life.

4. Infants with late on-set, progressive or acquired hearing loss will be diagnosed and receive appropriate intervention as soon as possible.

5. A computerized system that would maintain current information on hearing screening and any eventual follow-ups would be created. In this context, the safety of data could be guarantied.

6. A surveillance and a evaluation system would be created to assure that contact with infants who need intervention could be continuous and the quality of the program could be systematically improved.

Different local conditions were considered in connection to the program's goals, among others:

· The Time of newborns' discharge from the participating hospitals.

· Any previous neonatal staff's experience in hearing screening.

· How the tasks related to screening could affect the work organization in the various neonatology departments

· The Costs of medical equipment required for both neonatology and audiology departments.

· The Costs of the program's implementation and any additional running costs.

        Till 2001, babies were screened in many hospitals by the staff of the audiology depts, therefore only 17 out of 441 neonatology departments declared that their staff performed hearing screening on their own before. Taking this factor into consideration, the group of experts decided that the Polish program would be based on a two-stage OAE screening protocol. In order to avoid missing infants with late on-set hearing loss and auditory neuropathy, which is observed mainly in the high risk neonatal group, every infant with risk factors confirmed, would be referred to further observation despite the outcome of the screening result. The precise period of follow-up depended on the total number and type of risk factors.

         The Foundation bought screening devices for all neonatology departments (EroScan, by Maico), and diagnostic devices, which supplemented actual equipment of the audiology departments. The testing was conducted with computer terminals, which enable data acquisition and transmission to the central server, where all data is stored in the main database.

        A variety of informational printed material was prepared: instructions for the personnel conducting the screening, questionnaires, and brochures for parents. All printing-costs were covered by the Foundation.

        At the end of May 2002 a pilot program in 36 neonatal departments started. The aim of this pilot study was to check the efficiency of the personnel training, the proper data flow and the identification of any problems that might occur during the program. Based on this pilot project, a two stages training program for approximately 2000 nurses and doctors started in the autumn of 2002. By the end of November 2002 all neonatal and audiological departments joined the national UNHS program.

2. Model and protocol

       The UNHS is conducted in public hospitals (441), but a number of private hospitals is expected to join soon.

        In Poland, newborns are typically released after 48 hours. Every child is offered the hearing test before discharge from the neonatology department. Mothers are informed about hearing loss and its consequences. They receive full information about the screening methodology and any additional services. Although there is no obligatory legislation related to newborn hearing screening until now, almost 100% of born babies are screened.

        The hearing screening result is reported in each child's "Health Book". Newborns who do not need follow-up receive a "blue" information, while the referred cases receive the "yellow" information.

        Every parent, regardless of the screening result, receives a brochure that provides general guidelines for the expected baby's reactions to sound and the baby's speech development at various developmental milestones.

         Babies with at least one ear REFERRED and/or with confirmed hearing-loss risk factors are referred to 53 audiological departments.

         Those infants with confirmed hearing loss are referred to one of nine audiological centers, where an early intervention program is introduced. The rehabilitation is carried to the center which is closer to the residential area of the child.

3. Data Tracking and Surveillance System

       All data is registered both electronically and on paper. Due to the lack of common transmission and connection solutions among the participating hospitals and the issue of data security, a unique data transmission system was elaborated. The computer terminals are equipped with GSM (GPRS) modems communicating in a separate, dedicated network. The team of computer scientists monitors the proper system performance and upgrades the software according to newly develop requirements. The medical coordinator in the "The Children's Memorial Health Institute" (in Warsaw) supervises the entire system. A data analysis and reporting system was also created, in order to follow the progress made by each child at any level of the program.

4. Current outcomes

         From the beginning of the program 120,000 newborns were tested, which corresponds to an the average rate of 1500 daily hearing tests country-wise. Due to the positive results of hearing screening, less than 7% of newborns were referred to audiological departments, out of which 60% failed in only one ear. Children with risk factors account for less than 5% of the population, however about 70% of them resulted as PASS. As a result 11% of all newborns were referred to the second level centers. The number of children referred to next level constantly decreases. No important problems, associated with the follow up visits, have occurred so far.

5. Actual problems

         Although the program is not supervised by the government, the screening tests are now free of charge. All the running costs (except for the staff) are covered by the foundation and the personnel of the participating clinics conducts the tests as a part of their daily routine, without getting any additional payment. The audiological diagnosis costs are covered by the state, but unless some law regulations are settled, they might be insufficient for 2003. An emerging problem is the reimbursement for the hearing aid costs. The present system (partial reimbursement from different sources, relatively long time needed for administrative tasks) makes it difficult to obtain hearing aids before turning 6 months of age. So far all the children with confirmed hearing loss were equipped with hearing aids. The Foundation has undertaken certain actions to provide such a possibility to each newborn with detected hearing loss. The newborns' rehabilitation takes place basing on already existing speech therapy centers. Certain actions were undertaken in order to build up new network of centers specializing in newborn rehabilitation, which would be supervised by 16 local coordinators (one per district) and the general coordinator. The first workshops for speech therapists were organized. The work on including rehabilitation centers into the database system have already begun and the team of experts has considered advantageous that these centers should also be equipped with computer terminals running customized software.

1.  Introduction

       The East is always a region with great diversity in terms of politics, economies and the sociocultural life of its countries. It contains the world most populous country, China with its 1.28 billion people, and many small Southeast Asian countries. The diversity is also evident in the availability and provision of hearing care personnel and resources to the people in the region. Information on deafness and hearing loss is still very scanty and not often comparable among many countries in Southeast Asia¹. With this backdrop, it is reasonable to see various OAE related activities in some Asian countries such as China, Japan and Korea; and not much or even no OAE information in others, where OAEs is still a little-known topic.

2. The geographical distribution of OAE papers

       The major countries or economies in Asia include: China, Japan, Korea, India, Singapore, Indonesia, Malaysia, the Philippines, Thailand, Hong Kong and Taiwan. A MEDLINE search of OAE articles recorded in PubMed reveals that relevant research work has originated from China, Japan, Korea, Singapore, Hong Kong and Taiwan. It is not surprising to find insufficient OAE tempo in the other countries, where audiological services are in a different evolutionary status.

        Publications written by researchers and clinicians in China and Japan comprise the greatest proportion of works done in the region. However, most if not all, appear in local journals written in their own languages. In China, OAE articles can be easily found in local medical journals like Lin Chuang Er Bi Yan Hou Ke Za Zhi [Journal of Clinical Otorhinolaryngology (Wu-Han Shih)] and Zhonghua Er Bi Yan Hou Ke Za Zhi [Chinese Journal of Otorhinolaryngology (Beijing)]. Whereas in Japan, Nippon Jibiinkoka Gakkai Kaiho [Journal of the Otorhinolaryngological Society of Japan (Tokyo)] publishes most of the OAE related works done in its country.

        On the other hand, OAE related works done in smaller cities or countries like Hong Kong, Korea, Singapore and Taiwan usually can be found in English journals, and therefore more assessable to interested parties worldwide. The published work is scattered in international journals such as Audiology, Acta Otolaryngologica (Stockholm), Hearing Research, Journal of Audiological Medicine and the International Journal of Pediatric Otorhinolaryngology; and regional journals such as Asia Pacific Journal of Speech, Language and Hearing, and the Journal of Singapore Paediatric Society.

3. OAEs and Neonatal Hearing Screening

       The existence of many successful newborn auditory screening programs using OAEs worldwide has undoubtedly caught the attention of many clinicians in the East. It is a reliable, objective and quick procedure that can cover huge populations. It is also a relatively inexpensive clinical tool and can be performed by trained personnel like the nureses and audiological technicians apart from audiologists. All these features seem to be tailor-made for many Asian countries with their large population size and inadequate audiological personnel.

        Earlier published works done in China ^2,3 and Japan ⁴ focused on targeted neonates or infants (like those with high risk factors or those suspected to have hearing loss) and reported favourable results. The first generation of the OAE devices, such as the Otodynamics ILO-88, were employed because they provided the flexibility of a relatively fast screening as well a detailed analysis of the TEOAE data. Recent published works^5,6 consider the possibility of establishing universal screening schemes. Researchers have started evaluating the effectiveness of OAE automated screeners, such as the GSI 70 from Grason-Stadler. "Establishing local neonatal screening programmes are becoming common in the more affluent cities, such as Hong Kong and Shanghai, in China", says Bradley McPherson, Associate Professor of the Divison of Speech and Hearing Sciences in the University of Hong Kong. "And OAE has been trialed in preparation for universal screening and rehabilitation programmes". Readers who are interested in this material can refer to articles describing other Asian screening projects using OAEs in Singapore⁷, Thailand⁸ and Hong Kong⁹.

4. OAEs as a Research Tool

         Although OAEs as used in neonatal screening have very much been established, there are many things we have not clarified about its nature. On the other hand, there are still numerous possibilities in how we use OAEs as a diagnostic tool. Audiologists, ENT specialists, biologists and engineers in Asia see these opportunities and diversify their OAE researches. The first two groups of researchers usually focus their investigations on the clinical application of OAEs. Many reseach groups in many different Asian countries find common interest in establishing OAE norm data from their native young population^10-18, varying OAE parameters or conditions to increase clinical accuracy^19-30, and assessing the applicability of measuring OAEs in different groups of patients^31-49. Apart from clinics and hospitals, quite a number of biology and engineering laboratories devote their efforts to OAE research. Their reseach projects include developing different kinds of animal models^50-57 and investigating new measurement protocols^58-60.

        Taking all these past diversed experiences together, the final question is "What is the direction of OAE related works in the East?" "I foresee the Asian OAE researchers in the near future will be mainly focussed on consolidating our clinical knowledge, asking questions concerning the screening effectiveness of various OAE procedures, and in developing new means to clearly measure the OAE responses," comments McPherson.

5. References

1. Rafei UM. Work of WHO in SEAR from 1 July 1999 to 30 June 2000. Retrieved on 10 January 2003 from here.

2. Xia Z, Li B. (1998) DPOAE in high-risk neonatal screening for hearing. Lin Chuang Er Bi Yan Hou Ke Za Zhi. 12(7):306-8.

3. Guo Y, Yao D. (1996) The application of otoacoustic emissions in paediatric hearing screening. Zhongguo Yi Xue Ke Xue Yuan Xue Bao. 18(4):284-7.

4. Matsumura M, Chida E, Kashiwamura M, Fukuda S, Satoh N, Inuyama Y. (1999) Transient evoked otoacoustic emission measurement in infants. Nippon Jibiinkoka Gakkai Kaiho. 102(11):1234-41.

5. Lin HC, Shu MT, Chang KC, Bruna SM. (2002) A universal newborn hearing screening program in Taiwan. Int J Pediatr Otorhinolaryngol. 63(3):209-18.

6. Matsumura M, Chida E, Suto S, Fukuda S, Kashiwamura M, Kuroda T, Ohwatari R, Inuyama Y. (2001) Utility of OAE screener (GSI 70) for the evaluation of distortion product otoacoustic emissions. Nippon Jibiinkoka Gakkai Kaiho. 104(7):721-7.

7. Ng J, Yun HL. (1992) Otoacoustic emissions (OAE) in paediatric hearing screening--the Singapore experience. J Singapore Paediatr Soc. 34(1-2):1-5.

8. Jariengprasert C, Sriwanyong S, Kasemsuwan L, Supapannachart S. (2002) Early identification of hearing loss in high-risk newborns and young children in Thailand by using transient otoacoustic emissions (TEOAEs). Asia Pacific J of Speech, Language and Hearing. 7:1-9

9. Yu KY. (2002) Effects of DPOAE pass/ refer criteria on outcome of neonatal hearing screening. Dissertation of M.Sc. in Audiology. The University of Hong Kong.

10. Wang YF, Wang SS, Tai CC, Lin LC, Shiao AS. (2002) Hearing screening with portable screening pure-tone audiometer and distortion-product otoacoustic emissions. Zhonghua Yi Xue Za Zhi (Taipei). 65(6):285-92.

11. Chan JCY, McPherson B. (2001) Spontaneous and transient evoked otoacoustic emissions: a racial comparison. J of Audiological Medicine. 10:20-32.

12. Dan H, Ni D, Li F. (1998) Distortion product otoacoustic emissions in normally hearing young humans. Zhongguo Yi Xue Ke Xue Yuan Xue Bao. 20(3):207-11.

13. Liu A, Cui Y, Huang H. (1998) A research for basic properties of distortion product otoacoustic emissions in normally hearing subjects. Lin Chuang Er Bi Yan Hou Ke Za Zhi. 12(10):435-8.

14. Chida E, Satoh N, Kawanami M, Kashiwamura M, Sakamoto T, Fukuda S, Inuyama Y. (1997) Relationship between distortion product otoacoustic emissions and pure tone thresholds in normal and hearing-impaired ears. Nippon Jibiinkoka Gakkai Kaiho. 100(4):436-43.

15. Qian J, Jiang W, Wang L. (1994) The frequency-domain analysis of TEOAE in neonates and youths. Zhonghua Er Bi Yan Hou Ke Za Zhi. 29(6):362-5.

16. Fuse T, Aoyagi M, Suzuki T, Koike Y. (1993) Clinical application of transiently evoked otoacoustic emissions in screening for auditory dysfunction. Nippon Jibiinkoka Gakkai Kaiho. 96(7):1125-32.

17. Shi Y. (1989) Evoked otoacoustic emissions from normal-hearing young Chinese. Zhonghua Er Bi Yan Hou Ke Za Zhi. 24(6):349-51, 385.

18. Xu L. (1989) Measurement of evoked otoacoustic emissions in normal-hearing adults. Zhonghua Er Bi Yan Hou Ke Za Zhi. 24(6):352-4, 385.

19. Chan RH, McPherson B. (2000). Test-retest reliability of tone burst evoked otoacoustic emissions. Acta Otolaryngologica (Stockholm). 120:825-834

20. Kuroda T, Fukuda S, Chida E, Kashiwamura M, Matsumura M, Oowatari R, Inuyama Y, Sato N. (2000) Influence of spontaneous otoacoustic emission (SOAE) on transiently evoked otoacoustic emission (TEOAE). Nippon Jibiinkoka Gakkai Kaiho. 103(10):1135-40.

21. Lee J, Kim J. (1999) The maximum permissible ambient noise and frequency-specific averaging time on the measurement of distortion product otoacoustic emissions. Audiology. 38(1):19-23

22. Chida E. (1998) Distortion product otoacoustic emissions for the assessment of auditory sensitivity. Nippon Jibiinkoka Gakkai Kaiho. 101(11):1335-47.

23. Qian J, Jiang W. (1997) Distortion product otoacoustic emissions on neonates. Lin Chuang Er Bi Yan Hou Ke Za Zhi. 11(1):3-5.

24. Shi Y, Jiang S, Gu R. (1997) Effects of short-term tone exposure on DPOAEs. Zhonghua Er Bi Yan Hou Ke Za Zhi. 32(1):41-4.

25. Wang H, Zhong N. (1997) A study on the contralateral suppressive effects of distortion product otoacoustic emissions. Lin Chuang Er Bi Yan Hou Ke Za Zhi. 11(11):489-92.

26. Wang H, Zhong N. (1997) Effects of selective attention on distortion product otoacoustic emissions. Lin Chuang Er Bi Yan Hou Ke Za Zhi. 11(12):543-5.

27. Inoue T. (1994) Practical study of evoked otoacoustic emissions concerning individual variation of noise susceptibility. Nippon Jibiinkoka Gakkai Kaiho. 97(1):75-83.

28. Sawaki M, Hattori T, Niwa H. (1994) Forward masking of transiently evoked otoacoustic emissions. Nippon Jibiinkoka Gakkai Kaiho. 97(4):688-95.

29. Kashiwamura M, Satoh N, Fukuda S, Kawanami M, Chida E, Inuyama Y. (1993) Changes in human spontaneous otoacoustic emissions with contralateral acoustic stimulation. Nippon Jibiinkoka Gakkai Kaiho. 96(6):922-30.

30. Abe T, Tsuiki T, Ito S, Endo Y, Suzuki K, O-Uchi T. (1990) Suppression of evoked otoacoustic emissions by contralateral noise exposure in humans. Nippon Jibiinkoka Gakkai Kaiho. 93(11):1890-7.

31. Yeo SW, Park SN, Park YS, Suh BD. (2002) Effect of middle-ear effusion on otoacoustic emissions. J Laryngol Otol. 116(10):794-9.

32. Lee JS, McPherson B, Yuen KC, Wong LL. (2001) Screening for auditory neuropathy in a school for hearing impaired children. Int J Pediatr Otorhinolaryngol. 19;61(1):39-46.

33. Park MS, Park SW, Choi JH. (2001) Distortion product otoacoustic emissions in diabetics with normal hearing. Scand Audiol Suppl. 52:148-51.

34. Sakashita T, Kubo T, Kyunai K, Ueno K, Hikawa C, Shibata T, Yamane H, Kusuki M, Wada T, Uyama T. (2001) Changes in otoacoustic emission during the glycerol test in the ears of patients with Meniere's disease. Nippon Jibiinkoka Gakkai Kaiho. 104(6):682-93.

35. Chang SO, Jang YJ, Rhee CK. (1998) Effects of middle ear effusion on transient evoked otoacoustic emissions in children. Auris Nasus Larynx. 25(3):243-7.

36. Cui X, Jiang S, Chen H. (1998) The relationship between loudness recruitment phenomenon and distortim product otoacoustic emission and their clinical significance. Zhonghua Er Bi Yan Hou Ke Za Zhi. 33(5):294-6.

37. Li H, Zhong N. (1998) Analysis of spectral history of distort-product otoacoustic emissions in subjects of transient vertebrobasilar ischemic vertigo. Lin Chuang Er Bi Yan Hou Ke Za Zhi. 12(5):217-20.

38. Wang H, Zhong N. (1998) A study on DPOAE in patients with diabetes mellitus. Lin Chuang Er Bi Yan Hou Ke Za Zhi. 12(11):483-6.

39. Hashimoto Y. (1997) Effect of intravenous injection of lidocaine HCl on evoked otoacoustic emissions in tinnitus case. Nippon Jibiinkoka Gakkai Kaiho. 100(7):747-53.

40. Liang F, Liu C, Liu B. (1997) Otoacoustic emission and auditory efferent function testing in patients with sensori-neural hearing loss. Chin Med J (Engl). 110(2):139-41.

41. Kashiwamura M, Ohwatari R, Satoh N, Kawanami M, Chida E, Sakamoto T, Fukuda S, Inuyama Y. (1996) Otoacoustic emissions of full-term and preterm neonates. Nippon Jibiinkoka Gakkai Kaiho. 99(1):103-111.

42. Liu B, Liu C, Song B. (1996) Otoacoustic emissions and tinnitus. Zhonghua Er Bi Yan Hou Ke Za Zhi. 31(4):231-3.

43. Tanaka Y. (1996) Relationship between distortion product otoacoustic emissions and frequency discrimination in normal-hearing and hearing-impaired ears. Nippon Jibiinkoka Gakkai Kaiho. 99(1):65-78

44. Takahashi S, Ikeda K, Kobayashi T, Takasaka T, Ohyama K, Wada H. (1996) Effect of aging on distortion product otoacoustic emissions. Nippon Jibiinkoka Gakkai Kaiho. 99(7):978-84.

45. Yokoyama K, Nishida H, Noguchi Y, Komatsuzaki A. (1996) Assessment of cochlear functions of patients with acoustic neuromas. Nippon Jibiinkoka Gakkai Kaiho. 99(4):586-93.

46. Kawanami M, Sato N, Kashiwamura M, Chida E, Sato M, Terakura N, Ishikawa K, Inuyama Y. (1993) Evoked oto-acoustic emissions in patients with secretory otitis media. Nippon Jibiinkoka Gakkai Kaiho. 96(9):1423-9.

47. Ke XM. (1993) Analysis of evoked otoacoustic emissions in patients with high frequency cochlear hearing loss. Zhonghua Er Bi Yan Hou Ke Za Zhi. 28(5):268-70, 313.

48. Shi YB. (1993) Evoked otoacoustic emission behavior in clinical sensorineural hearing loss. Zhonghua Er Bi Yan Hou Ke Za Zhi. 28(1):22-5, 59.

49. Wang ZM. (1992) Distorsion-products otoacoustic emissions in acoustic neuroma. Zhonghua Er Bi Yan Hou Ke Za Zhi. 27(6):337-9, 381-2.

50. Li K, Wang Z, Cao K. (1998) The effect of calcium ion in perilymphatic fluid on guinea pig's distortion product otoacoustic emissions. Zhonghua Er Bi Yan Hou Ke Za Zhi. 33(2):75-7.

51. Li K, Wang Z, Ni D. (1998) The effection of obstructing OCB with strychnine on the guinea pig's DPOAE. Lin Chuang Er Bi Yan Hou Ke Za Zhi. 12(8):368-9.

52. Liang Y, Zhong N. (1998) Determination of normal values and analysis of their relation for distortion product otoacoustic emission in guinea pigs. Lin Chuang Er Bi Yan Hou Ke Za Zhi. 12(3):124-7.

53. Wang L, Jiang W, Jiang P. (1998) Changes in distortion product otoacoustic emissions and hair cells after noise exposure in guinea pigs. Lin Chuang Er Bi Yan Hou Ke Za Zhi. 12(8):364-7.

54. Fujimura K, Yoshida M, Makishima K. (1997) Suppression tuning characteristics of the 2f1-f2 distortion product in cochlear microphonics and otoacoustic emissions. Nippon Jibiinkoka Gakkai Kaiho. 100(8):839-45.

55. Wang L, Jiang W, Jiang P. (1997) Effect of perilymphatic fistula on distortion product otoacoustic emissions in guinea pigs. Zhonghua Er Bi Yan Hou Ke Za Zhi. 32(3):160-2.

56. Kumagai S. (1995) Distortion-product otoacoustic emissions in kanamycin-treated guinea pig cochlea. Nippon Jibiinkoka Gakkai Kaiho. 98(3):368-79.

57. Ueda H, Yamamoto Y, Arai M, Saito I, Nakata S. (1993) Evoked otoacoustic emissions: a comparison between responses from humans and guinea pigs. Nippon Jibiinkoka Gakkai Kaiho. 96(12):2065-72.

58. Yang LP, Young ST, Kuo TS. (2002) Effects of noise on transient-evoked oto-acoustic emission pass/fail criteria. Med Biol Eng Comput. 40(3):278-81.

59. Yang LP, Young ST, Ku TS. (2002) Modification of the wavelet method used in transiently evoked otoacoustic emission pass/fail criterion to increase its accuracy. Med Biol Eng Comput. 40(1):34-40.

60. Zheng L, Yang F, Ye D. (1998) Location of cochlear defect by AR spectrum analysis of TEOAE. Zhongguo Yi Liao Qi Xie Za Zhi. 22(4):187-91.

1.  Introduction

       In this second part of our editorial devoted to Auditory Neuropathy/Dys-Synchrony (AN/AD), we would like to address several issues regarding its management. As it is not until recently that this specific kind of deafness was identified, several aspects of its management are still under investigation. However, the follow-up of dozens of patients seen at Kresge Lab allows us to give some insights about the main directions that need to be taken.

2. Background Information

       AN/AD patients have:

 

(1) evidence of poor auditory function, with difficulty hearing in at least some situations or for some stimuli;

 

(2) evidence of poor auditory neural function, with absent or elevated auditory brain-stem reflexes (either middle ear muscle reflex or olivocochlear reflex) and an abnormal auditory brainstem response (ABR);

 

(3) evidence of normal outer hair cell function, demonstrated by the presence of either or both otoacoustic emissions (OAEs) and cochlear microphonic (CM). A patient with this hearing disorder can have an audiogram of 90dBHL but still have OAEs. Alternately, a patient with AN/AD can have an audiogram in which all thresholds fall within the normal range of hearing, yet have no ABR.

       In AN/AD patients the exact site of the problem cannot be specified. Based on audiologic test results, the anatomic site of lesion of AN/AD lies somewhere in the auditory pathway between the outer hair cells and the afferent neurons of the auditory nerve. Locating the exact site of lesion is complicated by the likelihood that AN/AD has more than one etiology and by the tendency for secondary degenerative effects to occur as a result of damage to one part of the peripheral auditory system (Harrison, 2001).

       First of all, it is important to know that neither "correcting the audiogram" nor predicting hearing and speech behaviors based on ABR is useful for such patients. The ABR, while required for identification, is not predictive of future speech and language development in these patients. Some AN/AD patients develop speech and language skills despite the lack of an ABR. Also, pure tones do not give an accurate reflection of hearing in AN/AD patients. Pure tone test results may fluctuate, and range from normal thresholds to profound loss with many configurations. The predictive value of the pure tone results merits further study in terms of prognosis for the patient. There is also no significant correlation between CM amplitude and the presence or absence of transient evoked otoacoustic emissions (TEOAEs) with the degree of pure tone hearing loss (Starr et al., 2001).

3. Hearing Aids

       The potential benefit from hearing aids appears limited for most patients with AN/AD. Hearing aids may provide greater awareness to environmental sounds, and observation as well as aided sound field audiograms can reflect this. However, the experiences of the patients known to Kresge Lab indicate that hearing aids do not help in development of auditory communication or language acquisition, and this is a primary reason that we do not routinely recommend the use of hearing aids for AN/AD patients. Most patients with AN/AD reject the amplification of a dys-synchronous signal that can create a frustrating listening condition.

       If patients or professionals feel that a hearing aid trial is necessary for newly identified AN/AD patients, one ear can be aided and the OAEs of the other ear can be monitored to follow the status of AN/AD (Berlin, 1998).

4. Cochlear Implants

         Cochlear implants were not considered at first for AN/AD patients because of the suspected abnormality of the eighth nerve, which seemed counterintuitive for cochlear implant management. Given appropriate family and patient history, cochlear implants are a viable management option for AN/AD patients. Children usually show significant improvements in speech perception abilities, communication skills, and sound detection. A few adults with AN/AD have also been implanted.

We now make our decision on a case-by-case basis, looking at the history of the patient and the desires for future outcomes of the patient and family. Not knowing how a patient will develop makes it difficult to offer a single management plan. Therefore, the age of the patient, current language ability, and extent to which the condition is affecting their life should be considered. Implants are not the only management option but rather may be a strong possibility after careful consideration of the individual's background.

5. Changes over time

         Over time, AN/AD may improve, remain unchanged, or become worse. In a few rare cases, the condition seems to have improved over time. In our sample group of 100, seven patients began to develop age appropriate speech and language without amplification, and further intervention was not required for them to function in the hearing and speaking world (Berlin et al., 2001). However, they still no showed no synchronous ABR. Those infants that worsen tend to lose their emissions and become indistinguishable from sensory hearing loss patients. In these cases, early identification can be helpful; it may assist in understanding future behaviors such as sporadic evidence of hearing seen by good prosody, vocal monitoring, word use, awareness to environmental sounds, or a strong rejection of hearing aids.

      Berlin et al. (2001) suggested that AN/AD encompasses a continuum of possible outcomes from living in Deaf culture to only minimal difficulty hearing in noise. AN/AD is not limited to children; adults have also been diagnosed with it, though it is not known if the condition developed late, gradually grew worse, or was present but unidentified since infancy. To date, there is no means to accurately predict which course an AN/AD patient may take, whether improving, remaining the same, or progressively worsening.

The variation in AN/AD is particularly represented in adult patients. Some of those seen at Kresge Lab have been able to manage quite well with visual input such as lip reading, closed captioning or by using their own compensation strategies. Some AN/AD adults obtain success with cochlear implants, while others function well in the Deaf community and use sign language as their primary means of communication. A few patients show only mild functional effects of the AN/AD.

6. Other considerations

         With the development of newborn screening programs many AN/AD patients are identified at a young age. From the sample of 100 AN/AD patients (Berlin et al., 2001), the largest group was two years old or younger. For infants, management can mean watchful waiting. While this can seem frustrating for parents, it is necessary to ensure the best course of action. During the waiting period, visual language in the form of cued speech and some method of signs (e.g., baby signs, signed English, ASL) should be used with the infant to avoid language delays (Berlin et al., 2002).

The watchful waiting period can vary, though a general guideline used at the Kresge Lab is no more than 18-24 months of age. During this time, methods of visual language training are used, and the child should be monitored for presence of emissions, synchrony in the ABR, and development of language. The family should determine what they want for the child's future in terms of functioning in the hearing world.

AN/AD is not limited to the pediatric population. Some patients do not discover that they have AN/AD until later in life when difficulty in school or work is encountered. Some of these patients may also have associated conditions such as Charcot-Marie-Tooth disease, other neurological degenerative conditions, or visual deficits that require careful scrutiny. Current language level and function should be examined in this population. Even though language may develop, our experience is that AN/AD patients have little or minimal word or sentence recognition in the presence of competing noise. This can have a significant effect on educational and vocational achievement.

7. Conclusions

         The evolution of AN/AD continues to present a challenge to audiologists and other professionals because there are many variables to consider in its diagnosis and management. Rather than one path, AN/AD presents many facets and several possible outcomes for patients. The use of physiologic tests, MEMRs, ABR, OAEs, are critical to an accurate diagnosis. Age is not a limiting factor in the identification of new AN/AD patients. Rather than treating the audiogram, audiologists should match the management with the physiology and the needs of the patient and the family. This may mean not recommending hearing aids even though the audiogram might suggest that they are appropriate. In terms of outcome, there are many variations on the theme of AN/AD, which complicates the choices that families must make. Options should be explored based on patient history, including birth history and the possibility of peripheral neuropathy, and whether there is a desire to enter the hearing and speaking world. Cochlear implants have been found to be successful in many patients with AN/AD, and are one, though not the only, option. With the proliferation of screening programs using ABR, the detection of AN/AD is likely to increase markedly. Therefore we recommend watchful waiting so long as the patient's speech and language develops on target.

8. References

Berlin, C.I., Hood, L.J., Cecola, P., Jackson, D.F., & Szabo, P. (1993). Does type I afferent neuron dysfunction reveal itself through lack of efferent suppression? Hearing Research, 65, 40-50.

Berlin, C.I., Hood, L.J., Hurley, A., & Wen, H. (1996). Hearing aids: Only for hearing impaired patients with abnormal otoacoustic emissions. In C.I. Berlin (Ed.), Hair cells and hearing aids. San Diego: Singular Publishing Group, Inc., 99-111.

Berlin, C.I., (1998). Auditory Neuropathy. Current Opinions in Otolaryngology & Head and Neck Surgery, 6, 325-329.

Berlin, C. (1999). Auditory neuropathy: Using OAEs and ABRs from screening to management. Seminars in Hearing, 20(4), 307-315.

Berlin, C.I., Taylor-Jeanfreau, J., Hood, L.J., Morlet, T., Keats, BJ (2001). Managing and renaming auditory neuropathy (AN) as part of a continuum of auditory dys-synchrony (AD). Abstracts of the 24th Annual Midwinter Research Meeting ,Association for Research in Otolaryngology, 486, 137.

Berlin, C., Hood, L., & Rose, K. (2001). On renaming auditory neuropathy as auditory dys-synchrony. Audiology Today, 13, 15-17.

Berlin, C.I., Li, L., Hood, L.J., Morlet, T., Rose, K., & Brashears, S. (In press,2002). Auditory Neuropathy/Dys-synchrony: After the diagnosis, then what? Seminars in Hearing.

Deltenre, P., Mansbach, A.L., Bozet, C., Christiaens, F., Barthelemy, Pl, Paulissen, D., & Renglet, T., (1999). Auditory neuropathy with preserved cochlear microphonics and secondary loss of otoacoustic emissions. Audiology, 38, 187-195.

Harrison, R.V. (1998). An animal model of auditory neuropathy. Ear & Hearing, 19, 355-361.

Harrison, R. (2001). Models of auditory neuropathy based on inner hair cell damage. In Y. Sininger & A. Starr (Eds.), Auditory Neuropathy: A new perspective on Hearing Disorders (pp. 51-66). San Diego, CA: Singular Publishing Group, Inc.

Hood, L.J., Berlin, C.I., Morlet, T., Brashears, S., Rose, K., & Tedesco, S. (In press, 2002). Considerations in the Clinical Evaluation of Auditory Neuropathy/Auditory Dys-synchrony. Seminars in Hearing.

Rance, G., Beer, D.E., Cone-Wesson, B., Shepherd, R.K., Dowell, R.C., King, A.M. Rickards, F.W., & Clark, G.M. (1999). Clinical findings for a group of infants and young children with auditory neuropathy. Ear and Hearing, 20, 238-252.

Rogers, R. Kimberling, W.J., Starr, A., Kirschhofer, K., Cohn, E., Keyon, J.B., & Keats, B. (2001). The genetics of audiory neuropathy. In Y. Sininger & A. Starr (Eds.), Auditory Neuropathy: A new perspective on Hearing Disorders (pp. 15-35). San Diego, CA: Singular Publishing Group, Inc.

Sawada, S., Mori, N., Mount, R.J., & Harrison, R.V. (2001). Differential vulnerability of inner and outer hair cell systems to chronic mild hypoxia and glutamate ototoxicity: insights into the causes of auditory neuropathy. The Journal of Otolaryngology, 30(2), 106-114.

Shallop, J.K., Peterson, A., Facer, C.W., Fabry, L.B., Driscoll, C.L. (2001). Cochlear implants in five cases of auditory neuropathy: postoperative findings and progress. Laryngoscope, 111, 555-62.

Sininger, Y., & Oba, S. (2001). Patients with auditory neuropathy: Who are they and what can they hear? In Y. Sininger & A. Starr (Eds.), Auditory Neuropathy: A new perspective on Hearing Disorders (pp. 15-35). San Diego, CA: Singular Publishing Group, Inc.

Starr, A., Picton, T.W., Siniger, Y., Hood, L.J., & Berlin, C.I. (1996). Auditory neuropathy. Brain. 119, 741-753.

Starr, A., Sininger, Y., Nguyen, T., Michalewski, H.J., Oba, S., & Abdala, C. (2001). Cochlear receptor (microphonic and summating potentials, otoacoustic emissions) and auditory pathway (auditory brain stem potentials) activity in auditory neuropathy. Ear and Hearing, 22, 91-99.

Starr, A., Picton, T., & Kim, R. (2001). Pathophysiology of auditory neuropathy. In Y. Sininger & A. Starr (Eds.), Auditory Neuropathy: A new perspective on Hearing Disorders (pp. 67-82). San Diego, CA: Singular Publishing Group, Inc.

8. For more information

lhood@%20lsuhsc.edu or [email protected]?subject=%20From%20the%20OAE%20Portal :
Kresge Hearing Research Laboratory of the South
Department of Otolaryngology and Biocommunication
Louisiana State University Health Science Center
533 Bolivar Street New Orleans, LA 70112-2234, USA

1.  Introduction

        This month’s editorial is dedicated to a recently described new type of hearing impairment, Auditory Neuropathy/Dys-Synchrony (AN/AD). It is not until recently that this specific kind of deafness was identified by experienced audiologists and scientists using new techniques of exploration of the auditory system such as otoacoustic emissions (OAEs).
We will address first the definition of AN/AD and the necessary diagnostic tools and, in a future editorial, we will address the question of its management.

2. What is Auditory Neuropathy / Dys-Synchrony?

        AN/AD is a type of hearing impairment that is characterized by:

• absence of auditory brainstem responses (ABRs) associated with the presence of a cochlear microphonic.
  
  
• presence of evoked OAEs (transient OAEs or distortion product OAEs)
  
  
• a pure tone audiogram that varies from normal to profound.
  
  
• disturbed speech perception inconsistent with audiogram and particular difficulty with speech in competing signals.
  
  
• absence of middle ear reflexes
  
  
• no efferent suppression of OAEs.

It is noteworthy to notice that a patient with AN/AD can have an audiogram of 90dBHL but still have OAEs and, alternately, a patient with AN/AD can have an audiogram in which all thresholds fall within the normal range of hearing, yet have no ABRs.

While cases with the symptoms of AN/AD were reported in the literature in the early 1980s (Worthington & Peters, 1980, Lenhardt, 1981, Kraus et al., 1984), the use of the term auditory neuropathy did not become prevalent until over a decade later (Starr et al., 1996). With hindsight we realize that we saw our first AN/AD patient at Kresge Hearing Research Laboratory in 1982. A boy of 14 years presented with no synchronous ABR, nearly normal though fluctuating pure tone thresholds, and relatively normal speech and language development. There were no neurological or motor deficits, and the patient’s complaints mimicked those of a patient with a central auditory processing disorder. His primary complaint was difficulty hearing in background noise or the presence of any competing signal. OAEs were not available in 1982 to further define his hearing ability, and he remained largely a mystery until several years later when additional patients with similar symptoms were identified.

Figure 1 shows the TEOAEs recorded in the right ear of a 10-year-old child and Figure 2 the ABR recordings. For the ABR, the two upper traces (in red) clearly show absence of any identifiable neural components, but the inversion of the polarity of the click stimulus reveal the presence of a long ringing cochlear microphonic that could have been improperly associated with a neural response if only one polarity of the click had been used.

Figure 1: TEOAE response


Figure 2: ABR recording

Patients with results that were seemingly just as incongruous were identified by several facilities in the United States and Canada. These patients were reminiscent of those with inexplicably absent ABRs and normal pure tones (Worthington & Peters, 1980, Kraus et al., 1984).

Once AN/AD was defined as a hearing disorder, some basic criteria for making the diagnosis could be established. Sininger and Oba (2001) suggest that patients must have all of the following to be considered as having AN/AD: (1) evidence of poor auditory function, with difficulty hearing in at least some situations or for some stimuli, (2) evidence of poor auditory neural function, with absent or elevated auditory brain-stem reflexes (either middle ear muscle reflex or olivocochlear reflex) and an abnormal ABR, and (3) evidence of normal hair cell function, demonstrated by the presence of OAEs and/or cochlear microphonic (CM).

3. What is the CM?

         An electrical response from the cochlea, the cochlear microphonic (CM) reflects a combination of inner and outer hair cell function. The CM can be identified by comparing auditory evoked potential averages obtained with both rarefaction and condensation clicks. Because the CM is a stimulus following response, it will reverse in phase with changes in the stimulus polarity from rarefaction to condensation (Ferraro & Krishnan, 1997). The appearance is that the waves "flip" or invert. For click and high frequency tone bursts, neural responses do not invert with stimulus polarity changes while the CM does. This comparison can also be used to distinguish wave I of the ABR from the CM because wave I may shift slightly in latency but does not invert. The CM in AN/AD patients has been noted to often be large and extend over a considerable time period. In some cases it may extend for several milliseconds and have the "appearance" of an ABR response (Berlin et al., 1998; Deltenre et al., 1999). This enhanced CM seems to be more pronounced with younger patients. Starr et al. (2001) found that the amplitude of the CM in AN/AD cases was greater in patients aged 10 years or younger when compared to normal hearing subjects. When a patient is suspected of having AN/AD, we recommend that a set of tests be administered first for proper classification of the hearing loss: middle ear muscle reflexes (MEMRs), OAEs, and ABRs with two polarities (Berlin, 1999). Notice that the presence of AN/AD does not rule out the possibility of cochlear loss or of a conductive component, and there can be several confounding factors that may make the diagnosis more difficult.

4. Can OAEs be absent in some cases of AN/AD?

         Yes. Absence of OAEs can be found when a conductive problem exists. If OAEs are attempted but not obtained in this case, then the status of outer cell function remains unknown. Obtaining accurate results in ABR or ECochG in these cases is important in identifying the presence of hair cell responses. In patients with conductive components, sound must travel through a compromised middle ear system to reach the cochlea, and any resultant OAEs must return through the same system. Cochlear microphonics are measured via electrodes on the scalp and thus spared the return trip through a compromised middle-ear system, making it possible to obtain CM in some patients where OAEs are absent (Hood et al., 2002). For surface recorded responses, insert earphones can help reduce stimulus artifact and aid in identification of the CM. Also, another factor that can confound the diagnosis of AN/AD is hearing aid use. OAEs may be absent or greatly reduced in patients who have worn hearing aids over a period of time. Since some AN/AD patients naturally lose their emissions over time, use of hearing aids in both ears makes it more difficult to tell whether absence of OAEs is occurring naturally or as a result of hearing aid use and excess amplification. We have followed a number of patients who had robust OAEs at birth or when they were first identified as AN/AD but later lost their emissions. Such patients who otherwise meet the criteria of having AN/AD but have no OAEs have been reported by others as well (Deltenre et al., 1999; Rance et al., 1999). Recently, a study of transient otoacoustic emissions (TEOAEs), CMs, and summating potentials in 33 AN/AD subjects found that eight had absent TEOAEs bilaterally and three had absent TEOAEs unilaterally (Starr et al., 2001). From this group, nine had present TEOAEs on prior tests and all were prior hearing aid users. CMs were present in all the ears with absent TEOAEs.

5. What is the exact cause of AN/AD?

         In AN/AD patients the exact site of the problem is not yet specified. Based on audiologic test results, the anatomic site of lesion of AN/AD lies somewhere in the auditory pathway between the outer hair cells and the afferent neurons of the auditory nerve. Locating the exact site of lesion is complicated by the likelihood that AN/AD has more than one etiology and by the tendency for secondary degenerative effects to occur as a result of damage to one part of the peripheral auditory system (Harrison, 2001). Proposed causes of AN/AD have been: (1) a disorder of the auditory nerve with normal outer hair cell function (such as peripheral hereditary motor-sensory neuropathy, Charcot-Marie-Tooth disease) (2) a disorder of the inner hair cells, or (3) a disorder of the synapse between inner hair cells and the eighth nerve dendrites (Berlin et al., 1993; Harrison, 1998; Starr et al., 1996, 2001). As more data are collected, it may be possible to define different types of AN/AD with varying prognostic and managerial implications.

Thorough birth and family histories can also provide insight into the diagnosis of AN/AD. Many patients identified with AN/AD have complicated birth histories, often having spent some time in the neonatal intensive care unit. In our first sample of 100 patients, we saw the following in birth histories of AN/AD patients: elevated bilirubin levels, prematurity, ototoxic medications, exchange transfusions, and oxygen deprivation requiring use of a vent. Mitochondrial disorders and neurological conditions such as cerebral palsy were also noted (Berlin et al., 2001).

The number of AN/AD patients with elevated bilirubin levels is not disproportionate to the number of babies with elevated bilirubin who do not develop hearing loss. More notable is the number of infants with AN/AD who have had exchange transfusions (Hood et al., 2002). From the sample of 100 patients reviewed by Berlin et al. (2001), 30 patients had jaundice while 25 had other complicating medical conditions such as cerebral palsy. However, many in this sample had no other complicating condition aside from AN/AD. This is interesting when compared to the group presented in the Starr et al. (1996) paper in which most patients did have some form of peripheral neuropathy. While AN/AD may occur in conjunction with a peripheral neuropathy, it is important to note that it can occur without any co-existing medical factors.

6. Can all newborn hearing screenings detect AN/AD?

         The answer is no. Because AN/AD subjects have OAEs (and newborns do not wear hearing aids), any newborn hearing screening using ONLY OAEs (TEOAEs or DPOAEs) as an assessment tool will not be able to identify AN/AD. Notice also that when ABRs are used without inversion of click polarities, a long and large CM might be misread as an ABR response and an AN/AD case missed. OAE use in screening has the advantage of being a fast and low-cost technique to operate in a nursery. If OAEs can not be used in conjunction with ABRs for all well-babies, we recommend however that at least babies with at least one risk factor for hearing (as described by international committees) been checked using both techniques. If this procedure is followed, then it must still be realized that some AN/AD cases –those with no risk factors- will be missed.

7. References

• Berlin, C.I., Hood, L.J., Cecola, P., Jackson, D.F., & Szabo, P. (1993). Does type I afferent neuron dysfunction reveal itself through lack of efferent suppression? Hear. Res. 65, 40-50.
  
  
• Berlin, C.I., Hood, L.J., Hurley, A., & Wen, H. (1996). Hearing aids: Only for hearing impaired patients with abnormal otoacoustic emissions. In C.I. Berlin (Ed.), Hair cells and hearing aids. San Diego: Singular Publishing Group, Inc., 99-111.
  
  
• Berlin, C.I., Bordelon, J., St. John, P., Wilensky, D., Hurley, A., Kluka, E., & Hood, L.J. (1998). Reversing click polarity may uncover auditory neuropathy in infants. Ear Hear. 19, 37-47.
  
  
• Berlin, C. (1999). Auditory neuropathy: Using OAEs and ABRs from screening to management. Seminars in Hearing, 20(4), 307-315.
  
  
• Berlin, C.I., Taylor-Jeanfreau, J., Hood, L.J., Morlet, T., Keats, BJ (2001). Managing and renaming auditory neuropathy (AN) as part of a continuum of auditory dys-synchrony (AD). Abstracts ARO, 486, 137.
  
  
• Berlin, C., Hood, L., & Rose, K. (2001). On renaming auditory neuropathy as auditory dys-synchrony. Audiology Today, 13, 15-17.
  
  
• Deltenre, P., Mansbach, A.L., Bozet, C., Christiaens, F., Barthelemy, Pl, Paulissen, D., & Renglet, T., (1999). Auditory neuropathy with preserved cochlear microphonics and secondary loss of otoacoustic emissions. Audiol. 38, 187-195.
  
  
• Ferraro, J.A., & Krishnan, G. (1997). Cochlear Potentials in clinical audiology. Audiol. Neuro-Otol. 2, 214-256.
  
  
• Harrison, R.V. (1998). An animal model of auditory neuropathy. Ear Hear. 19, 355-361.
  
  
• Harrison, R. (2001). Models of auditory neuropathy based on inner hair cell damage. In Y. Sininger & A. Starr (Eds.), Auditory Neuropathy: A new perspective on Hearing Disorders (pp. 51-66). San Diego, CA: Singular Publishing Group, Inc.
  
  
• Hood, L.J., Berlin, C.I., Morlet, T., Brashears, S., Rose, K., & Tedesco, S. (In press, 2002). Considerations in the Clinical Evaluation of Auditory Neuropathy/Auditory Dys-synchrony. Seminars in Hearing.
  
  
• Kraus, N. Ozdamar, O., Stein, L., & Reed, N. (1984). Absent auditory brain stem response: Peripheral hearing loss or brain stem dysfunction? Laryngoscope, 94, 400-406.
  
  
• Lenhardt, M. (1981). Childhood central auditory processing disorder with brainstem evoked response verification. Arch. Otolaryngol. 107, 623-625.
  
  
• Rance, G., Beer, D.E., Cone-Wesson, B., Shepherd, R.K., Dowell, R.C., King, A.M. Rickards, F.W., & Clark, G.M. (1999). Clinical findings for a group of infants and young children with auditory neuropathy. Ear Hear. 20, 238-252.
  
  
• Sininger, Y., & Oba, S. (2001). Patients with auditory neuropathy: Who are they and what can they hear? In Y. Sininger & A. Starr (Eds.), Auditory Neuropathy: A new perspective on Hearing Disorders (pp. 15-35). San Diego, CA: Singular Publishing Group, Inc.
  
  
• Starr, A., Picton, T.W., Siniger, Y., Hood, L.J., & Berlin, C.I. (1996). Auditory neuropathy. Brain. 119, 741-753.
  
  
• Starr, A., Sininger, Y., Nguyen, T., Michalewski, H.J., Oba, S., & Abdala, C. (2001). Cochlear receptor (microphonic and summating potentials, otoacoustic emissions) and auditory pathway (auditory brain stem potentials) activity in auditory neuropathy. Ear Hear. 22, 91-99.
  
  
• Worthington, D., & Peters, J. (1980). Quantifiable hearing and no ABR: Paradox or error? Ear Hear. 5, 281-285.
  
  

8. For more information

lhood@%20lsuhsc.edu or [email protected]?subject=%20From%20the%20OAE%20Portal :
Kresge Hearing Research Laboratory of the South
Department of Otolaryngology and Biocommunication
Louisiana State University Health Science Center
533 Bolivar Street New Orleans, LA 70112-2234, USA

1.  Introduction

        This article presents a brief review of current knowledge and issues regarding the fundamental mechanisms of distortion-product otoacoustic emission (DPOAE) generation. Before discussing the specifics of the relevant DPOAE research, a more general framework, from which DPOAEs can be viewed with regard to the other otoacoustic emission (OAE) subtypes, is presented.

        The traditional categorization of OAEs often divides them simply into two categories based upon the stimulus parameters needed to evoke the specific classes of OAEs (Probst et al 1991). For example, spontaneous OAEs (SOAEs) are in a class of their own in that no stimulus is required to evoke these emissions. Transient-evoked OAEs (TEOAEs), stimulus-frequency OAEs (SFOAEs), and DPOAEs are placed in the other category referred to as the stimulus-evoked emissions in that all these OAEs are elicited by applying deliberate acoustic stimulation to the ear. A major limitation of this simple classification scheme is that little information is provided about the mechanisms of generation for the unique subtypes of OAEs. Generally, under this schema, all OAEs are assumed to arise from the same nonlinear mechanical workings that underlie cochlear processing (eg, Kemp 1978; Kemp & Brown 1983). Recently, Shera and Guinan (1999) presented a taxonomy for mammalian OAEs that can be experimentally verified (Kalluri & Shera 2001). In this conceptualization, Shera and Guinan (1999) proposed that OAEs arise from two fundamentally different mechanisms. Thus, there are OAEs that arise by linear reflection and those that are generated by nonlinear distortion. This distinction [see Fig 10 in Shera & Guinan (1999)] forms a 'family tree' of OAEs in which TEOAEs, SFOAEs, and SOAEs are based upon linear reflections, whereas DPOAEs are produced mainly from nonlinearities acting as emission sources. This classification system is extremely useful in that OAEs can be categorized based upon their mechanisms of generation. Thus, the familiar click-evoked TEOAEs come from reflection off of pre-existing micromechanical impedance perturbations, distributed along the organ of Corti, which might include such conditions as disorganized outer hair cell (OHC) arrays (eg, Lonsbury-Martin et al 1988), that are unique to each cochlea. On the other hand, DPOAEs arise primarily from nonlinear elements in the cochlea that are stimulated by the in-coming traveling waves. What is most important to realize is that OAEs recorded in the ear canal, especially in humans, are rarely due purely to one form or the other, but represent a mixture of the two emission sources. This point will be further addressed, below when the locations along the cochlear partition, from which DPOAEs appear to originate, are discussed. But, first, DPOAEs generated by nonlinear distortion, without any components attributable to linear reflection, are considered.

2. Cochlear Mechanics

       For the moment, we will consider the cochlea simply as a black box and the ear-canal signal as representing the output of this system. Into this black box, two pure tones are applied which, traditionally, are referred to as the f1 and f2 primaries (f1<f2). If the cochlea acts in a linear manner, then we would expect that the output frequencies would be the same as the input frequencies. In other words, the function relating the input to the output signal is a straight line representing a linear function. However, if the function relating the input of the two sinusoids to the output is not a straight line, that is, the input/output (I/O) function is nonlinear, then new frequencies will be generated at the output. I/O functions that are typically used to represent the basilar membrane (BM) response are described in Fig 3 in Fahey et al (2000). One of these I/O plots (Fig 3b) is highly similar in shape to the hair cell receptor voltage versus stereocillia displacement function measured earlier by Hudspeth and Corey (1977) and Russell et al (1986). These types of nonlinear I/O functions obtained from various cochlear structures are relevant to the discussion of physical mechanism(s) within the cochlea that are capable of generating DPOAEs. If such functions exhibit both even- and odd-order symmetry, then all the DPOAEs that can be found in the ear-canal signal will be observed. Thus, combinations of the primaries that result in even-order DPOAEs, such as the simple difference tone, f2-f1, and many odd-order DPOAEs, the largest and most commonly studied one being the 2f1-f2 frequency, will be measured. Other DPOAEs often seen are the lower odd-order sideband 3f1-2f2 and the upper odd-order sideband DPOAE at the 2f2-f1 frequency.

        When the f1 and f2 primaries are presented to the ear canal, the first constraints that must be placed upon DPOAE generation can be appreciated from observations of the underlying BM mechanics [for a recent excellent review, see Robles and Ruggero, (2001)]. Presentation of a pure tone to the ear canal results in the well-known traveling wave of displacement on the BM, that peaks at its characteristic frequency (CF), and then rapidly dies out at more apical points that are lower in frequency. This displacement pattern defines the place on the BM where DPOAEs must be generated. That is, the only place where f1 and f2 can mix in the nonlinearity (often assumed to be based in the OHCs--see below) is in the tail of the BM displacement of the f1 primary. If f2 is placed at a much higher frequency, then, because of the steep apical cutoff of BM displacement, f2 cannot substantially interact with f1. Consequently, on theoretical grounds, DPOAEs must be produced at, or near to, the f2 place, where the two primaries can physically interact on the BM.

        This theoretical prediction is borne out by findings from suppression studies in which a third tone (f3) is used to interfere with DPOAE generation. By sweeping f3 in level and frequency, suppression tuning curves (STCs) can be produced, with their tips typically tuned near the f2 place for the 2f1-f2 DPOAE (eg, Brown & Kemp 1984; Martin et al 1998a). Much of this requirement also accounts for the much studied f2/f1 ratio effect, in which DPOAE levels decrease on either side of an optimum ratio value. In humans, this ideal f2/f1 ratio is approximately 1.22, and DPOAEs are largest at this ideal separation of the two primary tones. Some of this ratio effect, as the primary f1 and f2 tones come closer together, may be due to mutual suppression or interaction of multiple DPOAEs (Stover et al 1996a). It has also been proposed that this phenonmenon can be explained by a second-filter effect (Brown et al 1992).

        When DPOAEs are produced in the cochlea, they can be seen on the BM, and they propagate just as if they were external tones introduced into the ear canal (Robles & Ruggero, 2001). Because the 2f1-f2 is lower in frequency than the f2 place where it is generated, this combination tone will not be perceived, if someone is deaf at this lower frequency. Such an outcome occurs because the 2f1-f2 DPOAE travels to its characteristic place, where it then acts like an external tone.

        Basilar-membrane mechanics also explain why DPOAE are more effectively produced at lower primary-tone levels, when the level of f2, ie, L2, is lower than the level of f1, ie, L1. This is the familiar unequal-level primary tones protocol, typically 65/55 dB SPL, that is almost universally advocated in the clinical literature (Stover et al 1996b) for obtaining DPOAEs in humans. The rationale for lowering L2 is to equate the amplitudes of the vibration of the traveling waves representing the two primaries, where they interact on the BM. Because the BM response is highly compressive at the CF, assumed to be f2 for DPOAEs, and linear at the off-CF frequency of f1, then lowering the level of f2, where it is 'amplified' at low stimulus levels, helps to equate the two stimuli, where they interact at the f2 place [see Fig 4 in Kummer et al (2000) for a superb explanation of this phenomenon]. As primary-tone levels become higher, this L1-L2 difference is no longer needed to equate the two stimuli, a point often not appreciated in the clinical literature (Whitehead et al 1995).

3. DPOAE Generation Mechanisms

        In short, DPOAEs are produced when the primary tones interact on the BM to stimulate nonlinear elements in the cochlea. There is now very convincing evidence that the OHCs are the site of this nonlinearity (Brownell 1990). Specifically, it has been proposed that OHC electromotility, first described by Brownell et al (1985), is the source of the 'cochlear amplifier'. That is, it is assumed that the OHC electromotility-based cochlear amplifier is responsible for the compressive BM response at CF, and the associated sharpness of nerve-fiber tuning seen in physiologically healthy preparations, but absent in damaged or dead animals (Robles & Ruggero 2001), along with the nonlinearity responsible for producing DPOAEs. However, other sources have been proposed for the cochlear amplifier including stereocillia motility (Martin et al 2000). Ultimately, it will probably be discovered that DPOAEs originate from a variety of nonlinear sources, besides OHC electromotility, that participate in the OHC-transduction process including opening and closing of transduction channels (Patuzzi 1998), nonlinearities in stereocillia-bundle motion (Jaramillo et al 1993), and asymmetries in stereocillia stiffness (Khanna & Hao 1993).

        Related to the question of how DPOAEs are generated is the issue of where do DPOAEs originate from with respect to a point(s) along the cochlear partition. As discussed above, it is generally assumed that DPOAEs come from the f2 place. However, once created, DPOAEs also propagate as traveling waves along the BM. Consequently, it is possible for a propagated DPOAE to stimulate the DPOAE place, ie, the 2f1-f2 frequency place, where other OAEs can be further produced by the mechanism of linear-coherent reflection (eg, Heitmann et al 1998; Kalluri & Shera 2001). These two sources (ie, the DPOAE generated at the f2 place and the emissions reflected from the 2f1-f2 DPOAE place) then mix to form the final ear-canal signal.

        Evidence also exists for basal DPOAE sources that may also contribute to the final DPOAE signal. These basal sources are revealed as secondary regions of suppression or enhancement above f2 during the collection of the STCs mentioned above. Such regions of suppression/enhancement are observed at frequencies that are more than an octave above f2 (Martin et al 1999; Mills 2000), where it is unreasonable for the f3, due to the steep apical cutoff of the traveling wave, to affect the f2 place. One possible explanation for these phenomena is that a harmonic of f1 (ie, 2f1) interacts with f2 to produce a simple difference-tone DPOAE. This emission will always have the same frequency as the 2f1-f2, so, depending upon the phase of the difference tone, either suppression or enhancement could result (Fahey et al 2000). Another possibility is that f3 acts as a catalyst to produce difference-tone DPOAEs by more complicated routes that can then interact with the 2f1-f2 DPOAE. Evidence for both possibilities seems to be present in the data.

        Another difficult-to-explain finding is the observation that the upper sideband 2f2-f1 DPOAE appears to originate from its characteristic place on the BM (Martin et al 1998b). As discussed above, this finding contrasts with the notion that all DPOAEs must be generated at the f2 place, where the two traveling waves representing f1 and f2 optimally interact. One possibility is that the 2f2-f1 observed in the ear canal comes largely from a difference-tone DPOAE based upon the interaction of a harmonic of f2 (ie, 2f2) and f1, which of course, will be at the 2f2-f1 frequency.

        A final issue that must be discussed regarding DPOAEs is the notion that there are 'active' versus 'passive' DPOAEs. This conceptualization originated from earlier studies like Norton and Rubel (1990) and Whitehead et al (1992a,b). In these investigations, administration of loop diuretics, such as ethacrynic acid or fursosemide, eliminated low-level DPOAEs, while DPOAEs evoked by high-level tones remained relatively unaffected [see Fig 3 in Whitehead et al (1992)]. Results like these led to the notion that DPOAEs evoked by high-level tones were not relevant to cochlear function, and many clinical studies focused on low-level primaries in the 55- to 65-dB SPL range. However, early studies in humans (Lonsbury-Martin et al 1990) clearly indicate that 75/75 dB SPL equilevel primaries can accurately track the pattern of hearing loss in individuals with impaired hearing. More recently, studies in mice with age-related hearing loss (Jimenez et al 1999) indicate that all levels of primaries accurately follow the progressive degeneration of high-frequency OHCs observed in these animals. Similarly, a brief exposure to damaging levels of noise will affect, not only low-level DPOAEs, but high-level DPOAEs as well (Howard et al 2001). Thus, more recent thinking assumes that there are not two sources of DPOAEs, that is, a low-level 'active' one along with a high-level 'passive' source. Rather, low-level DPOAEs are based upon a functional cochlear amplifier, whereas high-level DPOAEs arise when stimulation is sufficient to move the BM without amplification, in turn, stimulating remaining nonlinear elements to evoke DPOAEs.

4. Summary

In summary, it is clear that we know considerably more regarding DPOAEs generation than when DPOAEs were originally described over 20 years ago (Kemp 1979). In fact, we now have enough confidence in DPOAEs to use them to tell us about the functional status of the cochlea, which now is routinely done in a number of clinical applications including newborn hearing-screening programs. However, we now also realize that DPOAEs measured in the ear canal are considerably more complex than originally envisioned. The newly appreciated complexity of DPOAEs, however, should not be viewed negatively but, rather, should be seen as a further opportunity to extract more information about cochlear function, that will ultimately improve the utility of these emissions as a clinical test.

5. References

• Brown AM, Kemp DT (1984): Suppressibility of the 2f1-f2 stimulated acoustic emissions in gerbil and man. Hear Res 13:29-37.
  
  
• Brown AM, Gaskill SA, Williams DM (1992): Mechanical filtering of sound in the inner ear. Proc Roy Soc Lond B 250:29-34.
  
  
• Brownell WE (1990): Outer hair cell electromotility and otoacoustic emissions. Ear Hear 11:82-92.
  
  
• Brownell WE, Bader CR, Bertrand D, Ribaupierre Y (1985): Evoked mechanical responses of isolated outer hair cells. Science 227:194-196.
  
  
• Fahey PF, Stagner BB, Lonsbury-Martin BL, Martin GK (2000): Nonlinear interactions that could explain distortion product interference response areas. J Acoust Soc Am 108:1786-1802.
  
  
• Heitmann J, Waldmann B, Schnitzler H-U, Plinkert PK, Zenner H-P (1998): Suppression of distortion product otoacoustic emissions (DPOAE) near 2f1-f2 removes DP-gram fine structure--Evidence for a secondary generator. J Acoust Soc Am 103:1527-1531.
  
  
• Howard MA, Stagner BB, Lonsbury-Martin BL, Martin GK (2002): Effects of reversible noise exposure on the suppression tuning of rabbit distortion-product otoacoustic emissions. J Acoust Soc Am 111:285-296.
  
  
• Hudspeth AJ, Corey DP (1977): Sensitivity, polarity, and conductance change in the response of vertebrate hair cells to controlled mechanical stimuli. Proc Natl Acad Sci USA 74:2407-2411.
  
  
• Jaramillo F, Markin VS, Hudspeth AJ (1993): Auditory illusions and the single hair cell. Nature 364:527-529.
  
  
• Jimenez AM, Stagner BB, Martin GK, Lonsbury-Martin BL (1999): Age-related loss of distortion-product otoacoustic emissions in four mouse strains. Hear Res 138:91-105.
  
  
• Kalluri R, Shera CA (2001): Distortion-product source unmixing: A test of the two-mechanism model for DPOAE generation. J Acoust Soc Am 109:622-637.
  
  
• Kemp DT (1978): Stimulated acoustic emissions from within the human auditory system. J Acoust Soc Am 64:1386-1391.
  
  
• Kemp DT (1979): Evidence of mechanical nonlinearity and frequency selective wave amplification in the cochlea. Arch Otorhinolaryngol 224:37-45.
  
  
• Kemp DT, Brown AM (1983): An integrated view of cochlear mechanical nonlinearities observable from the ear canal. In: Mechanics of Hearing, E de Boer, MA Viergever (Eds). Delft, Delft Univ Pr, pp75-82.
  
  
• Khanna SM, Hao LF (1999): Nonlinearity in the apical turn of living guinea pig cochleap. Hear Res 135:89-104.
  
  
• Kummer P, Janssen T, Hulin P, Arnold W (2000): Optimal L1-L2 primary tone level separation remains independent of test frequency in humans. Hear Res 146:47-56.
  
  
• Lonsbury-Martin BL, Martin GK, Probst R, Coats AC (1988): Spontaneous otoacoustic emissions in a nonhuman primate: II. Cochlear anatomy. Hear Res 33:69-94.
  
  
• Lonsbury-Martin BL, Harris FP, Hawkins MD, Stagner BB, Martin GK (1990): Distortion-product emissions in humans: I. Basic properties in normally hearing subjects. Ann Otol Rhinol Laryngol 99, Suppl 147:3-13.
  
  
• Martin GK, Jassir D, Stagner BB, Lonsbury-Martin BL (1998a): Effects of loop diuretics on the suppression tuning of distortion-product otoacoustic emissions in rabbits. J Acoust Soc Am 104:972-983.
  
  
• Martin GK, Jassir D, Stagner BB, Whitehead ML, Lonsbury-Martin BL (1998b): Locus of generation for the 2f1-f2 vs 2f2-f1 distortion-product otoacoustic emissions in normal-hearing humans revealed by suppression tuning, onset latencies, and amplitude correlations. J Acoust Soc Am 103:1957-1971.
  
  
• Martin GK, Stagner BB, Jassir D, Telischi FF, Lonsbury-Martin BL (1999): Suppression and enhancement of distortion-product otoacoustic emissions by interference tones above f2: I. Basic findings in rabbits. Hear Res 136:105-123.
  
  
• Martin P, Mehta AD, Hudspeth AJ (2000): Negative hair-bundle stiffness betrays a mechanism for mechanical amplification by the hair cell. Proc Natl Acad Sci USA 97:12026-12031.
  
  
• Mills DM (2000): Frequency responses of two- and three-tone distortion product otoacoustic emissions in Mongolian gerbils. J Acoust Soc Am 107:2586-2602.
  
  
• Norton SJ, Rubel EW (1990): Active and passive ADP components in mammalian and avian ears. In: Mechanics and Biophysics of Hearing, P Dallos, CD Geisler, JW Matthews, MA Ruggero, CR Steele (Eds). New York: Springer-Verlag, pp219-226.
• Patuzzi R (1998): A four-state kinetic model of the temporary threshold shift after loud sound based on inactivation of hair cell transduction channels. Hear Res 125:39-70.
  
  
• Probst R, Lonsbury-Martin BL, Martin GK (1991): A review of otoacoustic emissions. J Acoust Soc Am 89:2027-2067.
  
  
• Robles L, Ruggero MA (2001): Mechanics of the mammalian cochlea. Physiol Rev 81:1305-1352.
  
  
• Russell IJ, Cody A, Richardson G (1986): The responses of inner and outer hair cells in the basal turn of the guinea pig cochlea and in the mouse cochlea grown in vitro. Hear Res 22:199-216.
  
  
• Shera CA, Guinan JJ Jr (1999): Evoked otoacoustic emissions arise by two fundamentally different mechanisms: A taxonomy for mammalian OAEs. J Acoust Soc Am 105:782-798.
  
  
• Stover LJ, Neely ST, Gorga MP (1996a): Latency and multiple sources of distortion product otoacoustic emissions. J Acoust Soc Am 99:1016-1024.
  
  
• Stover LJ, Gorga MP, Neely ST, Montoya D (1996b): Toward optimizing the clinical utility of distortion product otoacoustic emission measurements. J Acoust Soc Am 100:956-967.
  
  
• Whitehead ML, Lonsbury-Martin BL, Martin GK (1992a): Evidence for two discrete sources of 2f1-f2 distortion-product otoacoustic emission in rabbit: I. Differential dependence on stimulus parameters. J Acoust Soc Am 91:1567-1607.
• Whitehead ML, Lonsbury-Martin BL, Martin GK (1992b): Evidence for two discrete sources of 2f1-f2 distortion-product otoacoustic emission in rabbit: II. Differential physiological vulnerability. J Acoust Soc Am 92:2662-2682.
  
  
• Whitehead ML, McCoy MJ, Lonsbury-Martin BL, Martin GK (1995): Dependence of distortion-product otoacoustic emissions on primary levels in normal and impaired ears: I. Effects of decreasing L2 below L1. J Acoust Soc Am 97:2346-2358.

5. Contributing Author

Glen K Martin, Ph.D.
Department of Otolaryngology (B205)
University of Colorado Health Sciences Center
4200 East Ninth Ave, Denver CO 80262
303-315-1568 (voice)
303-315-8787 (fax)

1.  Introduction

        Cisplatin (cis-diamminedichloroplatinum (II); PtCl2(NH3)2) is one of the most potent cytotoxic drugs currently available for cancer chemotherapy, and is especially effective in the treatment of advanced and metastatic forms of solid tumours such as testicular, ovarian and head-and-neck carcinomas. Its clinical efficacy, however, is limited by severe side effects, which include renal injury, peripheral neuropathies, hearing impairment, nausea and vomiting, visual impairment, and myelosuppression. Of these, nephrotoxicity, peripheral neurotoxicity and ototoxicity are potentially the major dose-limiting factors, in that they are cumulative and in general only partially reversible with discontinuation of therapy. Several attempts have been made to reduce the toxic side effects of cisplatin. Although vigorous pre- and post-hydration and mannitol-induced diuresis are now included routinely in cisplatin chemotherapy, these techniques have proven to be only partially successful, since renal failure still occurs, especially after repeated administration of cisplatin. It has also been attempted to reduce the toxic side effects of cisplatin by concomitant administration of so-called rescue agents (usually sulfur-containing ligands; cf., Reedijk and Teuben, 1999), but many of these compounds seem not only to reduce the nephrotoxicity and ototoxicity but the antitumour effect of cisplatin as well. Cisplatin-induced ototoxicity in humans is generally manifested as tinnitus and sensorineural hearing loss. This hearing impairment is dose-related, cumulative, bilateral, usually permanent and is initially characterized by a high-frequency deficit, but in patients receiving repeated doses of cisplatin progressively extends toward frequencies that are important for speech perception.

2. Histological changes

        Histologically, the most prominent change seen in the cochlea after chronic administration of cisplatin is degeneration of the organ of Corti, consisting of loss of the outer hair cells (OHCs) and the inner hair cells (IHCs) as well as a disturbance of the organ of Corti's typical microarchitecture. Hair cell loss follows a specific topographical pattern similar to that observed after chronic aminoglycoside administration or acoustic overstimulation. Initially, OHC loss is present predominantly in the basal cochlear turn, with the first row of OHCs being more vulnerable than the other OHC rows and the IHCs. In more severely damaged cochleas loss of both OHCs and IHCs is found along the entire basilar membrane. These findings correlate with the permanent, frequency-dependent elevation in the auditory thresholds and with the irreversible suppression of both the cochlear microphonics and compound action potential. Post-treatment degeneration of the organ of Corti, frequently observed during aminoglycoside-induced ototoxicity, has never been observed in cisplatin-intoxicated cochleas. In fact, recent studies indicate that functional and morphological recovery of the guinea-pig organ of Corti may be possible after cessation of cisplatin administration (Stengs et al., 1997; Cardinaal et al., 2000a), suggesting that an intrinsic regenerative mechanism is present in the organ of Corti. This finding may have clinical implications, especially since recovery of cisplatin-induced hearing loss has been reported to occur occasionally in patients. Equally important is the finding that concomitant administration of the neuroprotective ACTH(4-9) analogue (melanocortin) ORG 2766, which has been proven not to interfere with the antitumour effect of cisplatin, significantly reduces cisplatin-induced loss of OHCs (Smoorenburg et al., 1999; Cardinaal et al., 2000b). However, these phenomenological findings require more insight into the cellular mechanism(s) of cisplatin ototoxicity in order to further develop the protection and recovery potentials.

3. The Mechanisms of Ototoxicity

         Although the ototoxic effect of cisplatin has been extensively studied during the past decades, the cellular mechanism(s) by which cisplatin induces loss of OHCs and subsequent degeneration of the organ of Corti remain elusive. Furthermore, it is unclear if the degenerative changes in the organ of Corti and the functional and morphological changes in the stria vascularis in cisplatin-intoxicated cochleas occur by the same mechanism(s). This is mainly due to the fact that the cellular sites of cisplatin uptake and accumulation in the cochlea have not been properly identified. Although [195mPt]-labelled cisplatin could be detected in homogenated samples of the organ of Corti and the stria vascularis (Schweitzer, 1993), ultrastructural X-ray microanalysis studies have failed to localize cisplatin in OHCs (Maruyama et al., 1993; Saito and Aran, 1994; Welb, 1995). Electrophysiological studies have demonstrated that cisplatin interferes with the mechano-electric transduction process, either directly by blocking the transduction channels in the apical membranes of the OHCs or indirectly by a blockage of the voltage-sensitive calcium-channels in the basolateral membranes of the OHCs. However, one must bear in mind that most of these data have been obtained with in vitro models and may not resemble actual physiological alterations in the intact cochlea. In the absence of proof, we will assume that the cellular mechanism(s) underlying cisplatin-induced ototoxicity, which involves damage to terminally-differentiated, post-mitotic OHCs, are identical to the toxic action of cisplatin in tumour cells, which are more susceptible for damage by cytotoxic agents than non-proliferating cells.

         It is generally thought that the free (dichloro) form of cisplatin is passively transported across the plasma membrane of both normal and tumour cells. The lower chloride concentration of the cytoplasm and the lower cytosolic pH favour aquation of the dichloro form and successive deprotonation, which yields positively charged aquated species of the drug. These reactive species are potent electrophilics that will react with the nucleophilic groups of nucleic acids (DNA and RNA) and the sulfhydryl moieties of peptides (e.g., glutathione), proteins (e.g., metallothionein) as well as other cellular macromolecules (for a review, see Reed et al., 1996). It is commonly accepted that binding of cisplatin to DNA results in the formation of cisplatin-DNA adducts, which produce severe local distortions in the DNA double helix, and that this so-called DNA-platination is an essential first step in the cytotoxic action of cisplatin. The cellular consequences of cisplatin-induced DNA damage and the mechanism by which these adducts cause cell death, however, are less well-understood.

         One potentially important way by which cisplatin-DNA adducts may kill cells is by the induction of programmed cell death or apoptosis. Despite a large volume of literature describing the ability of cisplatin to induce apoptosis in various tumour cells and the recent observation that the ototoxic aminoglycoside antibiotic amikacin induces apoptosis in OHCs in the neonatal rat cochlea (Vago et al., 1998), reports presenting evidence for cisplatin-induced apoptosis of OHCs in the adult mammalian cochlea remain sparse (Alam et al., 2000). Moreover, in most ultrastructural studies, morphological features typical of apoptosis, such as nuclear condensation and segmentation, cell fragmentation and apoptotic bodies, were never observed in the organ of Corti of cisplatin-intoxicated cochleas. However, in cisplatin-intoxicated kidneys, and also in dorsal root ganglia, high levels of cisplatin-DNA adducts and cisplatin-induced apoptosis have been demonstrated. Since most nephrotoxic drugs usually exhibit ototoxic activity and nephroprotective agents also ameliorate cisplatin ototoxicity, it cannot be excluded that cisplatin induces OHC loss by apoptotic cell death subsequently to the formation of cisplatin-DNA adducts.

         Although genomic DNA is generally accepted as the critical cellular target of cisplatin, there is evidence that other cellular targets may also be involved, such mitochondrial DNA, cytosolic proteins, cell membrane phospholipids and cytoskeletal proteins, and hence, alternative cellular mechanisms might be involved in cisplatin-induced OHC loss. X-ray microanalysis studies of cisplatin-intoxicated kidneys have demonstrated that cisplatin is internalized through an endocytotic process and is accumulated in lysosomes in the proximal tubular epithelial cells (Makita et al., 1982; Berry et al., 1985), and it has been suggested that subsequent release of the lysosomal contents into the cytoplasm provokes cellular necrosis. In addition, a role of glutathione has been implicated. Alterations in the activity of anti-oxidant enzymes and depletion of cochlear glutathione levels have been demonstrated after cisplatin administration and this suggests a role for reactive oxygen species in cisplatin-induced ototoxicity (Rybak and Somani, 1999). Depletion of glutathione levels are associated with the generation of reactive oxygen species, and these can cause not only DNA strand breaks but also lipid peroxidation and aberrant expression of membrane-bound enzymes, which can alter the cell's ability to maintain ionic gradients. Most experimental data indicate that the ototoxic effect of cisplatin is a multi-target phenomenon, involving not only the organ of Corti but also in the stria vascularis, both at the physiological and morphological level (Schweitzer, 1993). Cisplatin administration results in a marked decrease in the endochlear potential, which is generated in the stria vascularis (Klis et al., 2000; Tsukasaki et al., 2000), but this decrease is not permanent, contrary to the elevated auditory thresholds. Histologically, cisplatin-induced strial changes, which consist of blebbing of the marginal cells, intermediate cell atrophy and strial oedema, are dose-related and resemble those observed after administration of loop diuretics. More evidence for an effect on the stria vascularis derives specifically from the finding that cisplatin inhibits strial adenylate cyclase activity, which is present predominantly in the basolateral membranes of the marginal cells and seems to be involved in electrolyte and solute transport in the stria vascularis. This is supported by the observation that both sodium and potassium concentrations in the endolymph are increased after cisplatin administration, probably due to changed passive transport of solutes. Furthermore, recent studies suggest that cisplatin also may affect the auditory neurons (Zheng and Gao, 1996; Gabaizadeh et al., 1997) and the spiral ganglion cells (Cardinaal et al., 2000b). If, and how, OHC loss and subsequent degeneration of the organ of Corti are related to the strial changes and the changes in the spiral ganglion is as yet unknown. A precise localization of the cellular site(s) of uptake and accumulation of cisplatin in the cochlea as well as proper identification of the cellular mechanisms involved in drug-induced OHC degeneration may shed more light onto this issue and this will be helpful in the development and implementation of more sophisticated treatment protocols to prevent the ototoxic side effects of cisplatin.

4. References

• Alam, S.A., Ikeda, K., Oshima, K., Suzuki, M., Kawase, T., Kikuchi, T. and Takasaka, T. (2000) Cisplatin-induced apoptotic cell death in Mongolian gerbil cochlea. Hearing Res. 141: 28-38.
  
  
• Berry, J.P., Brille, P., LeRoy, A.F., Gouveia, Y., Ribaud, P., Galle, P. and Mathé, G. (1985) Experimental ultrastructural and X-ray microanalysis study of cisplatin in the rat: Intracellular localization of platinum. Cancer Treatment Rep. 66: 1529-1533.
  
  
• Cardinaal, R.M., De Groot, J.C.M.J., Huizing, E.H., Veldman, J.E. and Smoorenburg, G.F. (2000b) Dose-dependent effect of 8-day cisplatin administration upon the morphology of the albino guinea pig cochlea. Hearing Res. 144: 135-146.
  
  
• Cardinaal, R.M., De Groot, J.C.M.J., Huizing, E.H., Veldman, J.E. and Smoorenburg, G.F. (2000a) Cisplatin-induced ototoxicity: Morphological evidence of spontaneous outer hair cell recovery in albino guinea pigs? Hearing Res. 144: 147-156
  
  
• Gabazaideh, R., Staecker, H., Liu, W., Kopke, R., Malgrange, B., Lefebvre, P.P. and Van de Water, T.R. (19970 Protection of both auditory hair cells and auditory neurons from cisplatin induced damage. Acta Otolaryngol. (Stockh.) 117: 232-238.
  
  
• Klis, S.F.L., O'Leary, S.O., Hamers, F.P.T., De Groot, J.C.M.J. and Smoorenburg, G.F. (2000) reversible cisplatin ototoxicity in the albino guinea pig. NeuroReport 11: 623-626.
  
  
• Makita, T., Hakoi, K. and Ohokawa, T. (1982) X-ray microanalysis and elctron microscopy of platinum complex in the epithelium of proximal renal tubules of the cisplatin-administered rabbit. Cell Biol. Int. Rep. 10: 447-454.
  
  
• Maruyama, T., Furuya, N. and Daimon, T. (1993) Distribution of platinum in the inner ear of guinea pigs treated with cisplatin. J. Otolaryngol. Jpn. 96: 1758-1759.
  
  
• Reed, E., Dabholkar, M. and Chabner, B.A. (1996) Platinum analogues. In: Chabner, B.A. and Longo, D.L. (Eds.) Cancer Chemotherapy and Biotherapy, 2nd Edition. Lippincott-raven Publishers, Philadelphia, pp. 357-378.
  
  
• Reedijk, J. and Teuben, J.M. (1999) Platinum-sulfur interactions involved in antitumour drugs, rescue agents and biomolecules. In: Lippert, B. (Ed.) Cisplatin. Chemistry and Biochemistry of A Leading Anticancer Drug. Wiley-VCH, Weinheim, pp. 339-362.
  
  
• Rybak, L.P. and Somani, S. (1999) Ototoxicity. Amelioration by protective agents. Ann. NY Acad. Sci. 884: 143-151.
  
  
• Saito, T. and Aran, J.-M. (1994) X-ray microanalysis and ion microscopy of guinea pig cochlea and kidney after cisplatin treatment. ORL 56: 310-314.
  
  
• Schweitzer, V.G. (1993) Cisplatin-induced ototoxicity: Effect of pigmentation and inhibitory agents. Laryngoscope Suppl. 59.
  
  
• Smoorenburg, G.F., De Groot, J.C.M.J., Hamers, F.P.T. and Klis, S.F.L. (1999) Protection and spontaneous recovery from cisplatin-induced hearing loss. Ann. NY Acad. Sci. 884:192-210
  
  
• Stengs, C.H.M., Klis, S.F.L., Huizing, E.H. and Smoorenburg, G.F. (1997) Cisplatin-induced oto-oxicity: Electrophysiological evidence of spontaneous recovery in the albino guinea pig. Hearing Res. 111: 103-113.
  
  
• Tsukasaki, N., Whitworth, C.A. and Rybak, L.P. (2000) Acute changes in cochlear potentials due to cisplatin. Hearing Res. 149: 189-198.
  
  
• Vago, P., Humert, G. and Lenoir, M. (1998) Amikacin intoxication induces apoptosis and cell proliferation in rat organ of Corti. NeuroReport 9: 431-436.
  
  
• Welb, R. (1995) Experimentelle Studie über die Wirkung von Cisplatin auf das Innenohr. Ph.D. Thesis, Heinrich-Heine-Universität, Düsseldorf, Germany.
  
  
• Zheng, J.L. and Gao, W.Q. (1996) Differential damage to auditory neurons and hair cells by ototoxins and neuroprotection by specific neurotrophins in rat cochlear organotypic cultures.Eur. J. Neurosci. 8: 1897-1905.
  
  

5. Contributing Author

John De Groot, Ph.D.
Hearing Research Laboratories (Histology Unit), Department of Otorhinolaryngology,
University Medical Center Utrecht, Room G.02.531,
P.O. Box 85.500, NL-3508 GA Utrecht,
The Netherlands

1.  Introduction

        All around the world, the issue regarding the newborn hearing screening has been discussed among different kinds of professionals, and the hope lies on the early detection, diagnosis and intervention of hearing loss in very young children.

        The past decade in Brazil was of great importance for the development of newborn hearing screening. The Brazilian Task Force on Universal Newborn Hearing Screening – Grupo de Apoio a Triagem Auditiva Neonatal (GATANU) - was founded in 1998 and an important step was given towards the implementation of screening programs in hospitals. Also, in October 1998, it was created the Brazilian Committee on Infant Hearing (Comitê Brasileiro sobre Perdas Auditivas Na Infância 2000) with members from the Brazilian Societies of Otolaryngology, Pediatrics, Speech Pathology/Audiology and other national organizations. In November 1999 the Committee finished the first consensus about the newborn hearing screening (NHS) program. It was recommended that all newborns should be screened for hearing loss before hospital discharge, or at most by 3 months of age.

        Brazil has approximately 170.000.000 inhabitants (IBGE,2000). A developing and huge country with several economical and political particularities and regional diversities. If we consider the estimated number of 3.500.000 live births per year (FUNASA, 2000), and the prevalence of bilateral sensorineural hearing loss in this population as 3:1000, we will have around 10.500 new hearing impaired babies every year. Also, some local studies have showed that the diagnosis of congenital hearing loss is made after 24 months of age. These facts are sufficient to make us move on… We got a lot of work to do!!!

        Nowadays, universal newborn hearing screening (UNHS) program is not required by law in any State, but it is performed routinely in many of them. Some cities have laws which demand that every child born must have his hearing tested, but not every hospital in these counties perform the screening yet. In the year of 2001 we acknowledged 75 NHS programs in 16 different states, and 39 of them are located in Sao Paulo. Last year we had half of the amount of programs. The distribution of these programs among the states , taken from the web site www.gatanu.org is shown in Fig. 1.

Figure1:

2. Protocols and Testing Results

         Who pays the cost of the Newborn Hearing Screening Programs? Most of the programs are supported by parents who are in charge of their baby hearing screening. Very few Health Insurance Cos covers the neonatal hearing screening. This cost varies from US$ 16,00 to 40,00 dollars, deppending on the hospital policies. Very few hospitals offer the screening without charging the parents.

        The professional team in NHS programs in Brazil involves audiologists, pediatricians and otolaryngologists. Many of these programs are coordinated by audiologists, and some by pediatricians or otolaryngologists. The audiologists are responsible for choosing and performing the protocols, parents counseling and orientation, and also for the follow-up in case of failure in the hearing screening.
        The screening test is generally accomplished prior to the hospital discharge, within 48 hours of birth, unless the babies are admitted in the neonatal intensive care unit (NICU).

        Two types of tests are commonly used: otoacoustic emissions (OAEs) and auditory brainstem response (ABR). Typically, screening programs use a two-stage screening approach (OAE-OAE, OAE-ABR or ABR-ABR).

        Children who fail in-hospital screening tests usually are asked to return to the hospital in order to be re-screened after 4 weeks after discharge. Positive results are usually validated by combination of otolaryngologic and audiologic examinations, before the age of 3 months. The Brazilian Committee endorses the recommendation(s) of the Joint Committee on Infant Hearing (2000) that infants with confirmed hearing loss should receive intervention before 6 months of age. This is our real challenge, to guarantee the necessary follow up and intervention that should follow the screening test.

        The first hospital to perform a newborn hearing screening was Hospital Israelita Albert Einstein, in São Paulo, Brazil. Below we report partially some results (taken from Chapchap and Segre, 2001) "From September 1996 to August 1999, 4631 babies were born at the maternity of Hospital Israelita Albert Einstein and 4196 (90,6%) had a hearing screening performed on the 2nd or 3rd day for the well-baby population, and before discharge for the NICU population. The TEOAE were recorded with an ILO88 OAE Analyser, software version 4.2, using the non-linear technique and "quickscreen" mode (time-window from 2.5 to 12 ms). A 2 stages protocol was used as shown in Fig. 2 and Fig. 3. The pass criteria chosen was the presence of 3 out 4 frequency bands evaluated with signal to noise ratio >= 3 dB for the 1.6 kHz or reproducibility >=50% and signal to noise ratio >=6 dB for the 2.4, 3.2 and 4.0 kHz or reproducibility >= 70%; total repro>=50%; probe stability > 70%. The considered stimulus level varied among 78 and 85 dB SPL. A minimum of 50 low noise sweeps was required. The software HI*screen and Hi*track were used for data collecting, management and analysis. The parents were personally informed by the audiologists about the program routine and after the hearing screening was performed, they received a written result of the test.

Figure 2:


Figure 3:

Results: From the 4196 babies tested, 4123 (98.2%) had a normal test and 73 (1.8%) failed at the first stage screening. The follow up was done in 60 (82%) of those 73 babies and 10 (2.3--1000 live births) had a confirmed hearing loss, 3 of which without any hearing risk factors.

Figure 4: Results of screening

3. The Future

         Health professionals in Brazil have a new challenge– the implementation of Universal Newborn Hearing Screening. Our goal of detection, diagnosis and intervention with hearing impaired children before the age of 6 months has not been achieved yet. Education, information and awareness about the need of early diagnosis and intervention is still necessary and mandatory in order to increase the number of programs in hospitals and maternities involving all the newborns and not only high-risk ones. We believe that the first step was already taken... But we still have a long way to go!!

4. References and Readings

• AMERICAN ACADEMY OF PEDIATRICS, Task Force on Newborn and Infant Hearing, Pediatrics Vol. 103, No. 2 : 527-530, February, 1999.
  
  
• APPUZZO,ML & YOSHINAGA-ITANO,C, Early Identification of Infants with Significant Hearing Loss and the Minnesota Child Development Inventory, Seminars in Hearing, Vol. 16, No. 2 : 124-139, may, 1995
  
  
• Chapchap MJ and Segre CM. Universal newborn hearing screening and transient evoked otoacoustic emission: new concepts in Brazil. Scand Audiol Suppl, 2001, (53) 33-6
  
  
• Comitê Brasileiro sobre Perdas Auditivas Na Infância - Recomendação 01--99. Jornal do CFFa 2000; 5: 3-7.
  
  
• DOWNS, MP, The Case for Detection and Intervention at Birth, Seminars in Hearing, Vol. 15, No. 2 :70-83, may, 1994.
  
  
• GRANDORI, F & LUTMAN,M, The European Consensus Development Conference on Neonatal Hearing Screening – Milan, May 15-16, 1998, Am J Audiol, 8(1) : 19-20, Jun, 1999.
  
  
• JOINT COMMITTEE ON INFANT HEARING, Year 2000 Position Statement: Principles & Guidelines for Early Hearing Detection & Intervention Programs, Audiology Today, Special Issue : 1-23, August, 2000.
  
  
• NATIONAL INSTITUTES OF HEALTH, Early identification of Hearing Impairment in Infants and Young Children – National Institutes of Health Consensus Development Conference Statement, 1-3; 11(1) :1-24, march, 1993.
  
  
• PARVING, A, The need for Universal Neonatal hearing screening – some aspects of epidemiology and identification, Acta Paediatr Suppl, 88(432) : 69-72, dec, 1999.
  
  
• SPIVAK,LG, Universal Newborn Hearing Screening, New York, Thieme, 1998.

1.  Introduction

        A number of handbooks introducing us in the world of sound, are stating that sound has three main characteristics time, frequency and intensity. My intention here is to give an introduction to these terms as deeply as necessary and then to proceed further to the more sophisticated topic of time frequency (TF) analysis and its interpretation in the context of TEOAEs.

        Time and frequency are somewhat connected terms. In a mathematical or engineering context it might be said that the information carried by a sound signal can be represented in one of two equivalent forms - in a time-domain or in a frequency-domain. Although the time-domain representation is the natural form, one can transform the information to the frequency domain and back to the time domain without any loss of information. This transformation considers only the mathematical properties of information in the signal. However, for very simple periodic signals, the transition to the frequency domain allows a better signal inspection than the natural time representation. On the other hand, if a source emits acoustic signals of variable frequency or there are transient segments in the acoustic signal, the frequency representation has only a formal and technical value. In this case, the spectrum of the signal, being the frequency domain representation, helps in evaluating the properties of the acoustic signal.

2. Properties of a simple periodic acoustic signal

        Let us go back to the considerations about the fundamental features of sound that is the time, intensity and frequency. I would like to focus only on practical aspects of these phenomena from the "engineering" point of view. And this approach will be particularly difficult if we try to describe time. A lot has been written about the term "time" in philosophical and physical aspects (i.e. theory of relativity), however these descriptions and subtleties have little practical meaning in consideration of the otoacoustic emission signals. It is more practical to follow a mathematical approach and say that time is a primitive term. For us, the most important feature of time is that it "runs" permanently.

        As the time "runs" we can observe the changes around us. For the otoacoustic emissions, our observations consist in the recording of acoustic pressure changes produced by the activity of the outer hair cells in the inner ear. As the movement of the cells has two phases, in the process of expansion and contraction, the acoustic pressure changes its sign being once positive then negative. It should be noted that in this example we are referring to the instantaneous values of the otoacoustic emission signals, as they are commonly presented in the "Waveform" panels of the majority of commercial software packages which run the acquisition of the OAE responses.

        The instantaneous value represents either the temporary phase of pressure or the intensity of the otoacoustic emission. We are going to separate these two aspects and focus only on the intensity. In evaluating the intensity, the "signal envelope" and "signal amplitude" terms are very helpful. In order to introduce definitions of these terms, we need to start with an easy case from the class of simple periodic signals. For these signals, nor the envelope neither the amplitude changes in time. The envelope consists of two straight parallel lines limiting all possible values of the signal. The upper line links all maximum values (peaks) of the waveform and the lower line links the minima. The reason why for simple signals both lines are straight is that nothing changes in the signal except of the phase of vibration. Amplitude is defined as the one half of the difference between the upper and lower line level of the envelope. For a large class of the simple periodic signals, the upper line is the mirror reflection of the lower line as both of them are symmetrically placed around the time axis. The otoacoustic emission signals roughly satisfy this condition. Anyway, in such cases, we can define the amplitude as the distance of the upper envelope line from the baseline.

3. More complex acoustic signals

        The above definition of the envelope is consistent only for less-complicated waveforms. If one tries to apply these definitions on a wider, general class of signals, he will meet a lot of difficulties. One of the problems appears in the case for which many oscillations appear inside one period of the signal. Examples of these class of signals include the glottal vibrations or the simpler arterial pressure waveform with its dichotic notch. These are examples of quasi periodic signals, where many positive and negative peaks exist in the segment covering one period. Which peak is important for the envelope calculation? The answer is suggested in the statement defining the problem. If we know what is the period of the oscillations, we can take one maximum in the range of the period for the upper level line of the envelope and one minimum for the lower line. The two extreme deviations, positive and negative, are important in this concept.

        The above method provides single points from particular periods as data for the signal's envelope. At this point certain questions arise: What about the rest of the continuous time scale? Are the values for the rest of the time scale important and how they can be evaluated? In order to find the answers to the above questions, let us recall that our intention is to get information about the sound intensity. The points which we are estimating, from the sequence of peaks of acoustic pressure, belong to a small subset of intensity samples. The full evaluation of the signal's envelope requires special processing methods.

        Through an evaluation of the sound intensity we aim to reconstruct the energetic characteristics of the vibrational source. For example, in a pendulum, the temporary angle of swing changes. Despite these variations there is continuous mutual exchange in the form of the energy. In the lowest position, the pendulum ball has the largest speed and maximal kinetic energy. In contrary, when the ball reaches highest position the kinetic energy is equal to zero because all energy is accumulated as potential one in gravitational field. The key property of this phenomenon is that the balance, being the sum of both forms of energy, is preserved, athough the ball position changes in a continuous oscillation format. The total energy stored in the vibrating object is a good measure of the intensity of the oscillations.

        The analogy with hair cells is direct, but in this context the oscillations have an active nature. This means, that vibrations are stimulated and energy is continuously provided to the cells. Here, the energy balance, calculated for a longer time period shows that the provided energy compensates any friction losses. We believe that the energy emitted from the hair cell vibrations is approximately proportional to the current energy of the cells. The observed otoacoustic emission differs from that emitted through some transformations occurring on the way between the source (cochlea) and external canal. Again we believe that these transformations are passive and that they modify the OAE signal slightly. If so, by investigating the energy of the "emitted wave" we can get access to the information about the current intensity of the vibration of the source. In the ideal pendulum, the energy (intensity) of the oscillations is constant and single measurement provides all characteristic of the phenomenon. The energy of vibrations of OAE source (or sources) depends on many factors and changes in time. The changes are the key goal of our experimental interest. The amplitude of vibrations, as we defined it above, reflects directly instantaneous power of the signal that is the intensity of OAE. The reconstruction of the amplitude variations in time is an important task leading indirectly to the knowledge about intensities of source sound vibrations.

4. Signal processing methods

        Considering the statements above, we can say that the information carried by the sequence of peak values is important and… fragmentary. In the paragraphs below, we are going to review methods to fill the gaps between the peaks creating the envelope and the amplitude. The most popular and traditional method is called peak rectification. The method derives from a former radio broadcasting technique, when the signals were coded using amplitude modulation. The radio transmitter modulated the carrier of constant frequency by changing the intensity of the emitted radio waves. The task of the receiver was to reconstruct the amplitude and in this way to get information about the intensity. The analogy with our task is vary close, the hair cells are the transmitters and our probe-microphones are the receiver. Because the envelope is symmetrical, it is enough to take only positive part of the waveform (rectification) and connect peaks of such signal. To perform such a connection, the device uses memorizing elements (capacitors) to store value of the last peak.

        The estimation of the instantaneous power offers more likelihood reflection of the amplitude. Values of the signal are squared (squared rectification), then the components being side-product of the highest rate of changes are removed by low-pass filtering. The resulted waveform is transformed by square rooting. For a signal obtained this way one can scale it to get the measure of the intensity.

        The first method, peak rectifier, is similar to hand made determination of the amplitude which one can perform on paper connecting successive peaks with a straight line or slowly decaying line. This method does not give smooth waveform and the accuracy of the method is not high. The second method using gives a smoother but not ideal representation. The dilemma arises how to select the cutting frequency of the low-pass filter. If we "cut" too low the high frequency components, we will get false ripples. If we "cut" too much, we will get inertial effects and the result will be slower then real changes of intensity.

        Another method of estimation of amplitude is the reconstruction of the analytical signal using Hilbert filtration. In the above sentence we have introduced two new terms - Hilbert filtration and analytical signal. In order to explain them we need to go back to the pendulum analogy. Let us recall that in the pendulum there are two forms of energy , the kinetic related to movement and the potential related to position. Sound has also two forms of the energy but by using microphones we record one of them called sound-velocity or pressure. In order to evaluate the energy of the acoustic signal one needs to know both forms of energy. One solution would be to use a second type of microphone, however such an approach is not very efficient. Instead of conducting complicated measurements, we can use a mathematical transformation to get the dual form of the signal. The transformation is called Hilbert filtration. A pair of signals consisted of real measured waveforms, obtained from the filtration, can be used to create a complex signal called analytical form. The amplitude of the analytical signal is calculated as the square root of instantaneous power of both components. Using this method the estimated amplitude provides a correct information about the source of the signal, but only in cases when the signal is simple. Mathematical proofs have verified that the envelope, determined by the amplitude of the analytical signal, passes through all peaks of the real component. So it satisfies the assumption from which we started - it crosses the amplitude peaks. The advantage of this method is that there is no questions on how to cut the high frequency oscillations because the this method has no inertia.

        However, the Hilbert filtration has limitations. If the signal has many peaks in the range of the period then the envelope will automatically pass through all such peaks. And in such cases the method will give a lot of false ripples. The method is limited only to simple signals.

5. Frequency

        Lets try to define a term which we can call as the "frequency component". But first few words about "frequency". The frequency is just reciprocal of the time length of the signal period - this fragment of the waveform which regularly repeats in the signal. Not all signals are periodic, which means that we cannot characterize all signals with frequency. To extend our consideration we will define a class of signals with variable frequency, where the period changes more or less systematically in time. The most popular example of such signal is what we call a "chirp" showed in the Figure 1. Although the amplitude and frequency of the chirp change in time, for this signal we can attribute values of amplitude and frequency. The simplest case of frequency component is the sinusoidal tone. However a waveform of similarly constant frequency and amplitude but not sinusoidal shape is for us a composed signal with harmonics. In turn, each harmonic having frequency being an integer multiplication of a fundamental frequency belongs to the class of frequency components.

Figure 1: TF representation of a Chirp signal

        Now we have a couple of terms which will allow us to determine the objective of time-frequency (TF) analysis. The goal of TF methods is to provide a picture of the signal as a set of frequency components. For each frequency component, we are interested in the evaluation of its amplitude and frequency variations. We assume that a particular frequency component may derived from a particular source or may be a harmonic So, we believe that performing a TF analysis of a signal like a TEOAE we are getting information about the sources or emission generators of the signal.

        The result of the TF analysis has a form where signal intensities are mapped on the plane in time and frequency coordinates. In theory we have a lot of variants of methods dedicated for TF analysis. However, the spectrogram called Short Term Fourier Transform (STFT) is the most popular and natural method introduced by Gabor. The distribution is created using traditional spectral analysis for sliding, short segments of the signal. For successive time instants, a segment of the signal is gated around a given point in the time scale. The spectrum calculated for this time instant shows how power is distributed over frequencies. The time scale is scanned by sliding the gating window.

        The STFT approach is very natural and has good physical interpretation. Unfortunately, the STFT gives results with low resolution. The time resolution is determined by the width of the sliding window and the obtained spectrum is averaged for the time period of "gated" segment. On the other hand, if one shortens the segment in order to increase the time resolution, he would lose frequency resolution. The uncertainty rule says that frequency resolution is reciprocal of the time resolution and vice versa. For such short signal as a TEOAE, dividing it into shorter segments results in very smeared image of the energy distribution. A distribution using the wavelet transform offers the possibility to get such image that time resolution is higher for high frequency components and lower for low frequency components. Generally like in spectrograms, however, the similar trade-off both domains exists here.

        We can increase the resolution two times by applying the so-called Wigner-Ville distribution (WVD). The "cost" of WND generating such over-natural effect consists in that false components, called cross-terms, appear in the image. Additionally, the values of the energy distribution is not positive everywhere, and this introduces difficulties in the interpretation of results.A typical TF represenation from a pre-term neonate is shown in Figure 2, generated with a custom-made software package, which will be soon be available in the OAE Portal site .

Figure 2: TF represenation of a TEOAE response, showing a large number of cross-terms

        Various methods of smoothing have been proposed in order to lessen the effect of cross-terms. This concept has lead to the Cohen class of smoothing distributions. In this family, the most prominent position is taken by the exponential distribution named as Choi-Williams. The majority of studies which have used time-frequency analyses have pointed out that each class of signals requires an optimal selection of a specific distribution, which yields optimal results for that class of signal. The first reason is the necessity to select the resolution to fit the particular characteristics of the studied signal. The most fundamental reason is that a given "waveform" may have more than one time-frequency representations. For example, a signal with variable amplitude and constant frequency may be interpreted (and generated) as a signal with amplitude modulation, or as the superposition of two tones with close frequency and constant amplitudes. The same waveform may be generated one way or another and one distribution may give an image consistent with the first generator and another distribution may be consistent with other one. The usefulness of a particular method of analysis depends on that how well it matches the original signal.

6. TEOAEs and TF analyses

       For TEOAE TF analysis I personally prefer to use the Wigner-Ville method modified with a specially fitted technique of regional smoothing. The method does not belong to the Cohen class of distributions because the smoothing is applied selectively to (a) regions where the energy is negative and (b) to the borders of such negative energy contours. With this method we can obtain significant improvements in the quality of the results, without losing significant portions of resolution. We know also the disadvantages of such an approach. When the cross-terms are located on the same places as the real components, the smoothing is not efficient enough to emphasize such information. Generally, though the smoother WVD method gives good results for the TEOAE signals.

        An example of the Wigner-Ville distribution with regional smoothing is shown in Figure 3.

Figure 3: The TF representation of Figure 2, smoothed 500 times

        Data from a recent study we have conducted on neonatal subjects have indicated that on the time-frequency plane one can distinguish several categories of components, such as:

• Horizontal lines with almost constant frequencies
  
  
• Almost vertical lines covering broad band of frequencies and short time period
  
  
• Lines with decreasing (falling) frequencies.
  
  

Figure 4: Various types of TEOAE components in a TF representation

        Our interpretation of these results leads to the conclusion that every component category might be generated by a different cochlear mechanism. The horizontal lines are related to spontaneous emission. We have observed that the dominant frequencies of these lines overlap with the peak frequencies of the spectrum of spontaneous emissions. We suspect that the vertical lines are traces of the acoustic artifact the click produced by stimulus reflections. We have not clear explanations yet, about the decreasing frequency-components. We hypothesize that these component could reflect distortion product otoacoustic emissions, an argument which needs additional investigations.

I am very glad to announce that all the  Educational material (PowerPoint presentations and White Papers) have been transferred to the new platform. Next,  we have scheduled to transfer the rest of the material from the Guest Editorials from 2001 to 2004.

The topics of emphasis for the next few months will be: (i)  TEOAE signal processing and Time Frequency analyses ; (ii) Post Screening Intervention policies (mainly in the Cochlear Implant area). For the latter we have observed an increased interest from the Portal visitors and as such we are evaluating the creation of a dedicated FORUM space with various arguments. Most probably what is of interest to everybody is the experience of families who have children implanted , after the initial experience of hearing screening.  These issues will be tackled later on this year, as we need to liaison with Sponsors and affiliated Institutions.

Introduction

Understanding the origin of spontaneous otoacoustic emissions (SOAEs) in mammals has been a challenge for more than three decades. Right from the beginning two mutually exclusive concepts were explored. After 30 years this has now resulted in two well established but incompatible theories, the global standing-wave theory and the local oscillator theory. The outcome of this controversy will be important for our understanding of inner ear functions, because local tuned oscillators in the cochlea would indicate the possibility of frequency analysis via local resonance also in mammals. In a recent investigation of this controversy, Braun (2013) gained new information from cases of high-multiple SOAEs in human ears. These cases, with 12 to 32 SOAEs per ear, presented large numbers of adjacent small frequency intervals. It was found that the distribution of frequency intervals of SOAEs shows no above-chance probability of multiples of the preferred minimum distance (PMD) between SOAEs. This result, together with several simulations of random-generated SOAE spacing, and a comparison of high-multiple with low- and medium-multiple SOAEs, indicated that the typical frequency spacing of human SOAEs may be due to a stochastic distribution of emitters along the cochlea plus a graded probability of mutual close-range suppression between adjacent emitters. After publication of the results, an argument was put forward that multiples of PMD in SOAE spacing might have been disguised by overlapping distribution peaks of higher-order intervals. Here, also the distribution of 2nd- and 3rd-order intervals from the same group of 18 ears with ≥ 15 SOAE per ear was analyzed. It was found that the distribution peaks were located far off from PMD multiples and that at the points of PMD multiples on the x-axis nothing of interest appeared. In conclusion, also 2nd- and 3rd-order spacing of SOAEs is consistent with the local oscillator theory of SOAE generation, and thus with intrinsic tuning of cochlear outer hair cells.

1. Background

   The global standing-wave theory (GST) and the local oscillator theory (LOT) of SOAE generation have been extensively described and discussed (recently in: Wit and van Dijk 2012). Here the two concepts are only outlined very briefly. The GST, based on concepts of Kemp (1979), Zweig and Shera (1995), and Shera (2003), proposes coherent reflections of basilar membrane (BM) traveling waves between the stapes and points of slight functional irregularities along the cochlear duct, in analogy with the coherent wave reflections in the optical cavity of a laser. Part of the energy of the BM standing wave vibrates the stapes, and via backward middle ear transmission sound is emitted into the ear canal. The standing wave is sustained by energy input from elements of the cochlear amplifier, in particular the outer hair cells (OHC). The LOT, based on concepts of Johannesma (1980), Bialek and Wit (1984), and van Hengel et al. (1996), proposes that the same elements of the cochlear amplifier behave as local oscillators without being coupled to a standing wave. They transmit part of their vibrational energy directly through cochlea and middle ear to the ear canal.

   Of the many qualities of SOAEs that the two theories have to account for, perhaps the most complex and demanding one is the observed spacing order of multiple SOAEs in one ear. Schloth (1983) and Dallmayr (1985; 1986) reported a preferred minimum distance (PMD) between spectrally neighboring SOAEs, which appears as outstanding mode in interval histograms. Later studies replicated this result, and Braun (1997) determined on the basis of a pool of 5245 intervals of human SOAEs that the mean PMD amounts to almost exactly 1 semitone (ST) = 1/12 of an octave (recently reviewed in: Wit and van Dijk, 2012).

   According to the GST, “the characteristic SOAE spacing can be traced to the value of the wavelength of the traveling wave” (Shera 2003, p. 259). In other words, the GST assumes a general standing wave system that self-stabilizes as the best fit to multiple sites of irregularities. By doing so, it amplifies multiple frequencies simultaneously, leading to multiple SOAEs with a characteristic, wavelength dependent, frequency spacing.

   Concerning the LOT, van Hengel et al. (1996) used a mathematical cochlear model to test the effect of frequency distance on mutual interaction of SOAEs. They concluded that “the resulting suppression profile leads to natural minimal distances of effective emissions, without any necessity of additional assumptions about the mechanics of the cochlea” (p. 3570).

   Thus, for the LOT the PMD is a short-range effect of mutual interaction of oscillators, whereas for the GST it is a long-range effect of the wavelength of the BM traveling wave. This conflict has the advantage that it can be resolved by experimental data. The simple empirical question was, can the predicted short-range and/or long-range effects be observed in measured SOAE data?

   High-multiple SOAEs (>10) in each ear of normal hearing human subjects are occasionally found in large screenings. Indications that SOAE mechanisms might vary according to emission numbers per ear had not been found, and there were no known reasons to expect such a variation. Therefore high-multiple SOAEs could reasonably be regarded as representative for all human SOAEs. Because of their large number of adjacent small SOAE intervals, ears with high-multiple SOAEs provided a unique and previously unexploited opportunity to examine the question of SOAE spacing order, and thus also the question of SOAE generation.

   The results of the new investigations (Braun, 2013) led to the following conclusions. The distribution of frequency intervals of human SOAEs shows no above-chance probability of multiples of the PMD. The size of PMD is related to SOAE density. The variation in size between adjacent small intervals is not significantly different in random-generated than in measured data. Each of these three results appeared to be in conflict with the predictions of the global standing-wave theory (GST) but in agreement with the local oscillator theory (LOT) of SOAE generation. After publication of the results an argument was put forward that multiples of PMD might have been disguised by overlapping distribution peaks of higher-order intervals. Therefore, also the distribution of 2nd- and 3rd-order intervals from the same group of 18 ears with ≥15 SOAE per ear was analyzed.

2. Results

   Fig.1 corresponds to Fig.3B of Braun (2013). Added are the distributions of 2nd- and 3rd-order intervals. 2nd-order intervals are intervals between an SOAE frequency and the frequency of its second next neighbor. 3rd-order intervals are intervals between an SOAE frequency and the frequency of its third next neighbor.

   The distribution of 2nd-order intervals shows a plateau-like peak between 170 and 270 Cent. The distribution of 3rd-order intervals shows a flat peak between 330 and 350 Cent. Most importantly, both added distributions again show no relation to multiples of PMD, such as 200, 300, 400, and 500 Cent.

   The right-shift of the new peaks relative to the expected locations at 200 and 300 Cent was examined further. It seemed reasonable to expect such right-shifts, in case there was a size correlation of neighboring intervals. For example, if an interval of 115 Cent has a neighbor also of 115 Cent, the 2nd-order interval is 230 Cent. In order to test this hypothesis, from the 18 ears two groups intervals were considered, >110 Cent and <90 Cent. Next, all intervals neighboring the grouped ones were extracted, separately for low-frequency and for high-frequency neighbors.

          Figure 1
  
   Fig.2 shows the distribution of the four groups of neighboring intervals. The groups of intervals >110 Cent have an outstanding chance to have a neighbor of ca 110 Cent, and the groups of intervals <90 Cent have an outstanding chance to have a neighbor of ca 90 Cent. The distributions of the four subgroups in Fig.2 were compared with the respective off-group distributions for the bins 50 to 180 Cent, and the differences were tested on significance by the paired t-test. For each of the two <90 Cent groups, the difference was significant on the 0.001 level. For >110 Cent, the low-side group showed a significant difference on the 0.05 level, whereas the high-side group did not reach significance. Overall, the size correlation of neighboring interval has turned out to be highly significant, and thus the right-shift of the peaks in the 2nd-and 3rd-order interval distributions (Fig.1) has found a plausible explanation.

   The rationale for the assumption of size correlation of intervals was based the mechanism of close-range suppression of a weak emitter by a stronger one, which is a necessary component of the LOT. If a strong emitter only permits neighboring emitters in a distance of >110 Cent, it is likely that this effect occurs both on the low- and the high-frequency side. This leads to a tendency of interval correlation, as seen in Fig.2. A corresponding effect can be expected for a weaker suppressor that permits neighbors in a distance of < 90 Cent.

 
          Figure 2
  
   The LOT also predicts a frequency dependence of interval size. Fig.4 of Braun (2006) shows that SOAE level in humans has a clear trend of a monotonous decrease from 1000 to 4000 Hz. Over this distance of two octaves the mean SOAE level decreased from ca –3 to ca –13 dB SPL. In other words, high-frequency SOAEs tend to have lower levels and thus less strength to suppress neighbors. This prediction could be tested by comparing the mean frequencies of the two groups described above. For each interval the mean of its two frequencies was calculated. Then the grand mean per group was determined. For the group of intervals >110 Cent the grand mean was 1992 Hz. For the group of intervals <90 Cent the grand mean was 2659 Hz. According to the data in Fig.4 of Braun (2006) the lower frequency corresponds to a mean level of ca –7.5 dB SPL, and the higher one to a mean level of ca –10 dB SPL. Thus, interval size is correlated with emission strength, and the prediction of the LOT has been confirmed.
   

References

Bialek W,Wit HP (1984) Quantum limits to oscillator stability: theory and experiments on acoustic emissions from the human ear. Phys Lett 104A:173-178.

Braun M (1997) Frequency spacing of multiple spontaneous otoacoustic emissions shows relation to critical bands: A large-scale cumulative study. Hear Res 114:197-203.

Braun M (2006) A retrospective study of the spectral probability of spontaneous otoacoustic emissions: Rise of octave shifted second mode after infancy. Hear Res 215:39-46.

Braun M (2013) High-multiple spontaneous otoacoustic emissions confirm theory of local tuned oscillators. SpringerPlus 2:135. http://www.springerplus.com/content/2/1/135

Dallmayr C (1985) Spontane oto-akustische Emissionen: Statistik und Reaktion auf akustische Störtöne. Acustica 59:67-75.

Dallmayr C (1986) Stationäre und dynamische Eigenschaften spontaner und simultan evozierter oto-akustischer Emissionen. Dissertation, Technische Universität München.

Johannesma PIM (1980) Narrow band filters and active resonators. Comments on papers by DT Kemp and RA Chum, and HP Wit and RJ Ritsma. In: van den Brink G, Bilsen FA (eds) Psychophysical, Physiological, and Behavioural Studies in Hearing. Delft University Press, Delft, pp 62-63.

Kemp DT (1979) The evoked cochlear mechanical response and the auditory microstructure - Evidence for a new element in cochlear mechanics. Scand Audiol Suppl 9:35-47.

Schloth E (1983) Relation between spectral composition of spontaneous otoacoustic emissions and fine-structure of threshold in quiet. Acustica 53:250-256.

Shera CA (2003) Mammalian spontaneous otoacoustic emissions are amplitude-stabilized cochlear standing waves. J Acoust Soc Am 114:244-262.

van Hengel PWJ, Duifhuis H, van den Raadt MPMG (1996) Spatial periodicity in the cochlea: The result of interaction of spontaneous emissions? J Acoust Soc Am 99:3566-3571.

Wit HP, van Dijk P (2012) Are human spontaneous otoacoustic emissions generated by a chain of coupled nonlinear oscillators? J Acoust Soc Am 132:918-926.

Zweig G, Shera CA (1995) The origin of periodicity in the spectrum of evoked otoacoustic emissions. J Acoust Soc Am 98:2018-2047.

About the Author

As a neurobiologist and a composer, [email protected] is specialized on investigating music related auditory physiology. Since 1993 he has published original research on inner ear function, otoacoustic emissions, pitch processing in the auditory midbrain, neurophysiology of acoustical sensory consonance, precognitive absolute pitch, and the physiology of octave circularity of pitch. From 2000 he works for the independent research organization Neuroscience of Music near Karlstad in Sweden.

We have dedicated a considerable time to the solution regarding the issue of the OAE FORUM. We have received numerous responses regarding the usefulness of a FORUM , considering that the majority of visitors can access the various communications channels of the Portal easily. A lot of users have suggested to eliminate the FORUM , due to the high levels of Spam, and to focus only on a communication between users and members of the OAE Portal. My personal opinion is that the FORUM provides a service, even when the user has resolved the issues he has been troubled with. That is, that experience can be shared with others facing similar problems. The majority of the Portal editorial board agreed to follow this direction.

In the last few months we have laid the design foundations for the FORUM, and from this month you can find a FRESH new Forum under the appropriate MENU. There is a problem though, we cannot transfer efficiently the old messages because the OLD and the NEW software structures are not compatible. So the obvious solution , at least for the next 6 months, is to have access to the OLD Forum . In addition we are considering the task of importing the messages from a generic email account , so that new users can utilize the information presented.

   We will do some experiments this month and we hope that you can provide some feedback.

Telehealth, or telemedicine, is the provision of health care services using a telecommunications medium (American Speech-Language-Hearing Association, 2005; Ricketts, 2000; Wootton, 2001). Specifically, telehealth indicates that practitioner services are provided to patients using an electronic medium such as a computer network, the telephone, satellite or two way radio (Mun & Turner, 1999; Stanberry, 2000).Telehealth services are used to serve people with limited healthcare access who typically live in rural or inner city communities. 

Applications have advanced substantially since the first telehealth services were explored. Also, it is likely that the most important telehealth advancements have occurred in the past decade spurred by lower interactive video costs and the advent of powerful but affordable personal computers. In addition, the greater accessibility to cost effective Internet services, and rapid computerization of medical devices are important contributing factors leading to telehealth service development.

A pdf version of the editorial is also available

Terminology.

Although telehealth is a common term, similar terms are often used today. These terms include telemedicine, e-care, e-health, telepractice, and telecare. Telemedicine is frequently used to describe physician and other medical services. In contrast, telehealth is more broadly defined to include those services provided by allied health-care professionals and by physicians alike. This view led to the Comprehensive Telehealth Act of 1997 in the United States in which all health care services provided over a telecommunications system were defined as telehealth.  It is with this perspective that the term, telehealth , will be used for the remainder of the paper.

A brief history of telehealth.

Telehealth is over a century old (Stamm, 1998; Stanberry, 2000). While the first telehealth service was not documented, it was probably conducted using a telephone (or the telegraph) and was likely a consultation. In the early 1900’s, maritime telehealth services were provided to sailors on ships from land based physicians using two-way radio. It is interesting that similar maritime telehealth services continue today even though the transmissions are likely satellite based in most cases. In the 1960’s, the National Aeronautics and Space Administration (NASA) used telehealth technology with astronauts to measure vital signs and radiation exposure while in space. Because of the continued need to provide care to individuals in remote locations, telehealth services are commonly used in many professions, including cardiology, radiography, otology, pediatrics, pharmacology, psychology, psychiatry, and speech-language pathology (Blackham, Eikelboom, & Atlas, 2004; Krumm & Sims, 2011; Nickelson, 1998; Perednia & Allen, 1996; Spooner, Gotlieb, & the Steering Committee on Clinical Information Technology and Committee on Medical Liability, 2004; Stamm, 1998).

Telehealth models.

Telehealth services can be delivered by synchronous (real-time) or asynchronous (store and forward) methods. Synchronous data communication is typically conducted via interactive video and can be augmented by information sent in an asynchronous mode. In contrast, asynchronous telehealth services require that patient data has been recorded first at the patient site and then, after some period of time, sent electronically to the clinician for interpretation. Asynchronous procedures are commonly employed when there is inadequate bandwidth for synchronous procedures. In addition, asynchronous applications may be utilized when time is less of a concern regarding the diagnosis or when the clinician is unavailable to conduct services. Finally, analog equipment which cannot be used for remote computing purposes, often can be gainfully configured for asynchronous applications. For example, an old tympanometer, which can only print out immittance results, can still be used for asynchronous applications by scanning patient immittance results into a computer and sending the data (via email attachment) to an audiologist for interpretation.

Asynchronous telehealth technology. 

Asynchronous data transfer is probably used by audiologists today and may in fact be a common practice. Specifically, this form of telehealth technology is utilized when information such as tympanograms, audiograms, auditory brainstem response recordings, or video-otoscopy images are transmitted via E-mail or by fax (see Figure 1).

                                       Figure 1. Modes of asynchronous services.

Asynchronous studies have been published evaluating the efficacy of telehealth with  tympanometry, video-nystagmography (VNG), and video-otoscopy (Birkmire-Peters et al, 1999; Yates and Campbell, 2005).  In addition, E-mail communication was used to deliver cognitive-behavioral therapy for tinnitus treatment (Kaldo-Sandström et al, 2004) and for counseling new hearing aid users (Laplante-Lévesque et al, 2006).

One appealing asynchronous application is self-assessment of hearing sensitivity. Presently, self-assessment procedures involving hearing testing online appear to suffer from questionable calibration, poor validation, and the lack of control over environmental noise levels. Nevertheless, as this is an emerging area of audiology telehealth, it is likely problems associated with self-assessment will be solved in the future.

Synchronous services.

Synchronous services are characterized by the clinician delivering services to clients in real time or “live” (See Figure 2). Such services may include the use of online chat, the telephone, interactive video, or remote computing technology. Interactive video is typically utilized with synchronous services to observe client responses to stimuli and to assure clinicians that audiometric equipment (transducer, probes, and electrodes) are properly placed. Interactive video may be provided by a laptop Webcam or by a dedicated camera system that is interfaced directly to the computer network. While interactive video can require substantial bandwidth, the benefits are obvious, providing the clinician and patient with services that are essentially “face-to-face”. High costs have limited routine use of interactive video but it is increasingly available and affordable in rural communities.

Audiologists may use two models of synchronous telehealth models. The first model is the traditional model used in other professions. This model requires the extensive use of high-quality interactive video in which the clinician supervises testing by a technician at the remote site. Once the technician obtains patient data, the clinician will typically provide a diagnosis and recommend management. This model has already been used successfully by Marincovich (M. Marincovich, personal communication, April 5, 2009) to provide hearing evaluations and hearing aid fittings in a rural region of California in the USA. For this model to be effective, the technician must be trained well enough to administer, but not necessarily interpret, audiology test results. Rather, interpretation and counseling is done by the audiologist. This is an effective solution when the technician turnover is low and ongoing technician training is possible. Also, the traditional model has the benefit of comparatively modest technology requirements.

                                     Figure 2. Synchronous services using interactive video

Another form of synchronous audiology services incorporates remote-control in so that clinicians can test patients at distant sites. This is a reasonable telehealth strategy to consider as many audiology systems are computerized, utilizing a Windows platform; and as a result can be incorporated for remote computing applications.  Consequently, a clinician at one site can control computerized audiology equipment at a distant site using application sharing software through a network, modem or the Internet. The greatest advantage to this method is that a technician is not required to do testing at the patient site. However, a technician is still required to do tasks such patient basic instructions, transducer placement, otoscopy, and have some skills in running the computer at the patient site.  Figures 3 and Figure 4 show the equipment that is typically used with a synchronous program.

Figure 3. The clinician equipment configuration for an audiologist administering telehealth services. Note only a computer (with remote computing software) and a webcam is required at the clinician site.

1.     Using this paradigm, investigators have employed synchronous protocols to administer a variety of common hearing tests to subjects including pure tone, speech, otoacoustic emissions and the auditory brainstem evoked response (Choi, Lee, Park, Oh, & Park, 2007; Givens & Elangovan, 2003; Krumm, Ribera & Klich, 2007; Ribera, 2005; Swanepoel,  Koekemoer & and  Clark, 2010,Towers, Pisa, Froelich, & Krumm, 2005).

            Figure 4. Equipment required at the patient site. For remote computing purposes, a computer, web cam or dedicated camera, computerized audiometric equipment (an audiometer is pictured), video-otoscopy, immittance (not shown) and a LAN connection would permit basic audiology telehealth services.

In addition, synchronous technology has been utilized to program cochlear implants (Franck, Pengelly & Zerfoss. 2006;Ramos et al., 2008), program and verify hearing aids functioning (Fabry, 2004; Ferrari & Bernardez-Braga, 2009;Wesendahl, 2003) and to provide neural response/telemetry assessment (Shapiro, Huang, Shaw, Roland & Lalwani, 2008).  This telehealth technique presently requires further validation but been used successfully to administer hearing tests over considerable distances (Krumm, Ribera & Klich, 2007; Ribera, 2005; Towers, Pisa, Froelich, & Krumm, 2005).

The hybrid model.

While the sole use of asynchronous or synchronous technology appears to be reasonable in some circumstances, audiologists should consider the most efficient system to deliver telehealth services. In many cases, a combination of synchronous and asynchronous technology will yield the best solution for hearing health-care services. This combination of technology is considered a hybrid model and is regularly used in many telehealth programs.

Telehealth services and otoacoustic emissions in adults. Evoked otoacoustic emissions (EOAEs) have obvious applications for hearing assessment and, therefore, it is not surprising that investigators incorporated EOAEs in early audiology telehealth research. The first of these studies was a master thesis written by Schmiedge (1997) assessing the validity of DPOAEs recordings using synchronous methods. In this investigation, an Apple (Power PC) computer system was interfaced to a computer peripheral capable of generating and recording DPOAEs (Virtual Systems model 330, version 1.9). Timbuktu desktop remote computing software was installed on the computer controlling the DPOAEs for remote computing (synchronous) purposes. 

Subjects assessed in this study were college aged students who exhibited normal hearing sensitivity and no significant history of hearing loss. These subjects were tested in a sound treated booth equipped with the Virtual DPOAEs system connected to a high speed computer network and to a modem. An audiologist (in the same building as the subjects) operated another Power PC computer equipped similarly as the subject computer and, therefore could control the subject DPOAE system using the computer network or modem. Subjects’ DPOAE amplitudes were obtained and compared in the following conditions: face-to-face in a “typical” clinical condition with an audiologist; through a modem connection capable of achieving a 33,600 baud/second connection; and through a high speed local area network (LAN) connection. DPOAE recordings were obtained in 1/3 octave intervals in the frequency range of 1000-4000 Hz using an f1/f2 ratio of 1.21and a stimulus presentation of 65/55 dB SPL. 

Results of this study revealed high agreement of DPOAE means and standard deviations between face-to-face, modem and LAN conditions. The outcome of these data suggested that DPOAE recordings could be accurately measured using telehealth technology with “off the shelf” otoacoustic emissions system hardware and desktop remote computing software. However, in this study there were problems with recording DPOAE data. Computer recordings of DPOAE data would were somewhat unstable during both telehealth conditions and would periodically result in corrupt DPOAE recordings. A caveat is that corrupt data is always possible and should remain a concern.

            Following this work by Schmiedge,a paper was published by Elangovan (2005), describing a customized otoacoustic emissions system developed for synchronous telehealth applications. Elangovan found that this system produced comparable distortion product otoacoustic emission DPOAEs results for five adult subjects when telehealth and face-to-face comparisons were made. Although the outcomes for the otoacoustic emissions systems were impressive, the investigators made their measurements in the same location of the subjects. Consequently, further validation was needed at a distance to determine the value of the system described by Elangovan.

            The first research which demonstrated that EOAEs could be measured at a substantial distance was published by Krumm at. al (2007). In their study Krumm et al. (2007) utilized an off-the-shelf computerized Biologic Scout EOAEs system and a low cost video-conferencing system to record DPOAEs in 30 adult subjects. The EOAEs system was interfaced to a PC connected to a LAN at the subject test site. A second PC was used to provide telehealth services at approximately 1000 Kilometers (Km) away from the subjects. PCs at both sites, running the Windows 2000 operating system, were configured with an interactive video system (VIGO, Emblaze-Vcon, Hackensack, New Jersey) bundled with Meeting Point 4.6 video conferencing software. Remote computing was made possible by application sharing software bundled within the Meeting Point program.  A schematic of this system is found in Figure 5. Results of this suggested that the synchronous measurement of DPOAEs over long distances was feasible as telehealth and face-to-face DPOAE measurements were equal. Further, no technical problems occurred that were described earlier by Schmiedge (1997).

Figure 5. A schematic of the DPOAE system used by the author for synchronous DPOAE research over a distance. 

Telehealth and DPOAEs measurements in Infants.  In all likelihood, EOAEs in telehealth will be used with infant and young children involved in an early hearing detection and intervention (EDHI) program.  But EDHI program goals can be difficult to achieve due to inadequate professional expertise, lack of program planning and insufficient funding ((Mencher, Davis, Devoe, Bereford & Bamford, 2001). Also an EDHI program should exhibit continuity of services up-to-date information, operate as a community-based health program, and provide accurate tracking information for newborns requiring further screeing or assessment (Mencher et al., 2001).  O’Neil, Finitzo, and Littman (2000) addressing similar EDHI issues suggested new paradigms should be developed to insure that each infant is provided needed services regardless of circumstances.

            Such a paradigm may incorporate telehealth services.  Telehealth has been an effective medium of providing medical expertise to isolated communities and is a common practice in many health care professions.

            One intriguing nature of EOAE systems is that many of these systems are commonly operated through desktop personal computers (PCs). Consequently, many EOAE systems can be employed for synchronous telehealth applications including remote computing. Further, remote computing applications for infant hearing assessment seem to have at least three advantages over asynchronous applications. For example, when hearing screenings cannot be accomplished face-to-face, a hearing heath care professional could conduct hearing screening from another location. Also, once personnel are trained to conduct infant hearing assessment in underserved area, these individuals can be mentored and supervised by a hearing health care professional in real time while testing clients. Remote computing also allows observation at distant centers for quality control purposes to achieve appropriate referral rates deterring referrals with excessive false positives.

Finally, diagnostic hearing assessment can be accomplished by hearing health care professionals using remote computing technology. This consideration is important as research indicates that infants with hearing loss require appropriate amplification and aural habilitation before reaching six months of age. Even under ordinary circumstances it can be difficult to conduct follow-up screening, comprehensive hearing assessment and a hearing aid fitting in this time frame unless the infant is precisely managed. In comparison, an infant in an isolated community requiring services at distant medical centers may ultimately suffer from the lack of continuity of care resulting in untimely intervention. Hearing assessment completed remotely by a competent hearing health care professional could serve to reduce the lack of continuity of care and hasten the diagnostic and hearing aid fitting process if needed.

A few papers have been published concerning telehealth and EOAEs in pediatric populations. The first which paper discussed pediatric applications of telehealth and otoacoutic emissions, was by Krumm, Ribera and Schmiedge (2005). This paper provided rationale, models and pilot data supporting the use of telehealth technology with infant hearing screening programs.  Additionally, described some of the issues associated with creating a telehealth service including establishing connectivity at the clinic site, use of a VPN to provide patient privacy, and the need to work collaboratively with computer network personnel who do not necessarily share an enthusiasm for telehealth procedures. 

In 2008, Krumm, Huffman, Dick and Klichdescribed a study in which they used remote computing technology to record DPOAEs and automated auditory brainstem audiometry response (AABR) data with infants. Specifically, 30 infants ranging in age from 11–45 days (with an average age of 16 days) were seen for this study. Subjects recruited for this study did not pass prior DPOAEs screening at birth and were being seen for re-screening at their regional medical hospital.

The Biologic ABAER  system ( Natus, San Carlos, California, USA) was used to conduct all automated ABR (AABR) and DPOAE measurements. The ABAER system was interfaced to a computer and interactive video system in the same manner described previously Krumm et al. (2007). This system was interfaced to a personal computer (PC) running the Windows 2000 operating system and connected to a LAN at the subjects’ site. A second PC was utilized by the audiologist conducting telehealth measurements 200 Km away from the subjects. PCs at both sites were configured with a VCON Vigo desktop videoconferencing system and vPoint software which was used for remote computing applications. Consequently, the audiologist conducting synchronous testing could control both DPOAE and ABR applications at the subject site using the Internet and a broadband connection.  A screen capture of a remote session utilizing remote computing technology to measure DPOAEs in a young subject is found in Figure 5. A virtual private network (VPN) connection was provided by the hospital at which the infant hearing re-screening was conducted to protect subject data transmission over the Internet. In addition, immittance and video-otoscopy images were sent from the subject site after being scanned into a computer system to simulate a complete infant telehealth hearing screening service.

Data analysis of this study indicated that DPOAE and AABR screening results were essentially equal when telehealth and face-to-face trials were compared. Figure 6 displays DPOAE representative results obtained in this study by telehealth and face-to-face methods.

As might be expected, most of the subjects passed the follow-up rescreening in this study.  However, some subjects were judged to need further referral. Specifically, one infant was referred on the basis of both DPOAE and AABR screening. Two other infants were referred by the AABR screening, probably as a result of excessive movement, but passed DPOAE screening. Hence, 29/30 infants passed DPOAE screening and 27/30 infants passed AABR screening in this study. Therefore, this study displayed some promise of providing ABR and DPOAE hearing screenings by remote computing to infants over the Internet.

Figure 6. Screen capture of a remote computing session in which DPOAEs are being measuring in a young child.

A rating scale was administered to the parents immediately following all infant hearing screenings to assess their satisfaction with telehealth services. One parent of each infant was provided a rating scale to complete. Twenty-six of thirty parents completed the rating scale. Four surveys were not answered as one parent was erroneously not offered a rating scale, and three declined to answer the rating scale.  The parents ages ranged from 20-34 years of age and respondents were mostly female (female n=19; male n=7). Parents rated telehealth screening results as excellent (n=22), very good (n=3), or acceptable (n=1). Concerning privacy of infant testing over the Internet, five parents were unsure about privacy, while others were a little concerned (n=8) or not concerned (n=13) about privacy. Although there seemed to be some parental ambivalence about privacy of screening results, all but one parent (n=25) indicated they would permit further telehealth infant hearing screenings.

Figure 7. A comparison of infant DPOAEs recording obtained by telehealthtechnology (top) and face-to-face by a clinician (bottom).

Although the outcome of this study was generally positive, it should be recognized there were a number of limiting factors to this study. First of all, the small n size of this study means that comparatively few infants with hearing loss were identified. Consequently, further studies are needed to determine the validity of the telehealth system described in this study on the basis of sensitivity and specificity measurements.  No such data has been published in a juried source at this time.

In addition, this study was conducted with one audiologist on-site to provide face-to-face assessments and a second audiologist provided telehealth services at a distance. The fact that testing face-to-face and via telehealth was done by audiologists probably resulted in the high agreement between the telehealth and face-to-face conditions describe in this study. Obviously, assistants at distant sites must apply EOAE probes, ear phones and electrodes to newborns or infants when actual hearing screenings are conducted by telehealth. Also, assistants must be trained to adjust malfunctioning or improperly fitting screening probes, electrodes or earphones during hearing screenings. So, further investigation examining the use of a trained assistant is necessary in future audiology telehealth studies.  Again, no such data has been reported in a juried source. Fortunately, the equipment used in this study provides the capacity to monitor AABR electrode application and DPOAE ear probe placements online when conducting remote computing sessions. Therefore, clinicians can identify and inform screening assistants to correct mechanical problems when infant hearing screenings are provided

There was one notable problem in this study concerning connectivity.  Although Internet connections between subject site and investigator site normally exceeded 384 Kilobits per second (Kbs), on two occasions the bandwidth was compromised by Internet congestion resulting in the loss of interactive video between sites. Even so, remote computing measurement could be continued and hearing screening results were successfully recorded using bandwidth below 100 Kbs. It is interesting that the parents did not respond negatively to the lack of interactive video other than indicating that the testing seemed slow.

Results and conclusions.

Although preliminary telehealth results are encouraging for infant hearing screening, additional investigation with telehealth procedures is needed to validate synchronous procedures with greater numbers of infants exhibiting hearing loss. The federal government in the United States has funded several telehealth projects for infant hearing screening and assessment. However, the results of these studies have not appeared in scientific journals.    

In addition to synchronous research, asynchronous and hybrid telehealth models should also be studied for EDHI screening, diagnostic and intervention services in rural communities. For example,in Northern Ohio (USA) one audiologist used asynchronous technology to measure DPOAEs with preschool children during hearing screenings (B. Whitford,personal communication, September 4, 2008). Further, clinicians providing direct EDHI services may consider the need to implement different newborn hearing screening protocols proposed in the literature to reduce false positives and follow-up visits (Gravel, White & Johnson et al.,2005; Lieu, Karzon, &Mange, 2005). These protocols include auditory brainstem response (ABR) testing at the time when newborns fail initial screenings; simultaneous use of both AABR and EOAE screenings at newborn screenings; and detecting middle ear disorders through high frequency tympanometry measurements. An audiologist could employ telehealth technology to provide some of these services.

Remote computing might also prove valuable as a means to provide ongoing instruction to hearing screening assistants established in rural areas. Specifically, clinicians can mentor and monitor assistants using remote computing applications while viewing newborn hearing screenings in real time. These services would be dispensed with the goal to enhance personnel expertise for newborn hearing screenings.

For clinicians contemplating telehealth applications, a few issues need to be reviewed. First of all, additional licensure or other clinician certification, may be needed to provide services in different regions and certainly countries. Also, informing the proper licensing authorities that telehealth services are being considered is sensible even if the clinician license permits such services.  Reimbursement for telehealth services may be unclear so funding sources must be clearly identified before telehealth services are initiated. Also, while it has been the experience of the author that most computerized audiology systems work well for remote computing applications, clinicians must prototype prospective computerized audiology systems for the remote computing and asynchronous applications to be assured that the telehealth technology will work as desired. 

Remote computing software is abundant. However, web-based conferencing software may be faster and just as cost effective as PC based video-conferencing software. Programs such as Teamviewer, Skype and DimDim may be used to provide low cost means to remote computing services but privacy must be assured through encryption or through a virtual private network (VPN). Teamviewer offers good encryption capabilities. Skype has offered encryption under paid plans. So, video/data encryption  or the use of a VPN must be carefully considered. Finally, the author would also advise clinicians to conduct telehealth services at distant sites first in which there is enthusiastic support. Even though telehealth is powerful, it is of no value if key personnel at the distant clinical site do not support new service methods.

In conclusion, while telehealth technology seems reasonable to use for screening and diagnostic services, the author recommends cautious validation and program review. Questionnaires should be provided to consumers who are served through telehealth services. Also, planning committees consisting of consumers, administrators and clinicians should be formed to assure proper procedures are developed for EDHI telehealth services.  Following the establishment of these mechanisms, clinicians could implement substantial telehealth strategies to bolster rural community services for parents and their hearing impaired infants.

On-line Examples

Tele-Audiology from the Tester side: https://ksutube.kent.edu/playback.php?playthis=4oup7d12r


Tele-Audiology from the patient/assistant site:  https://ksutube.kent.edu/playback.php?playthis=ys5yj2z6i

References

American Speech-Language-Hearing Association, (2005). Audiologists providing clinical services via telepractice: Technical report. Available from www.asha.org/policy.

Birkmire-Peters, D.P., Peters, L.J. & Whitaker, L.A. (1999). A usability evaluation for telemedicine medical equipment: a case study. Telemed J, 5(2):209–212.

Blackham, R., Eikelboom, R. H. & Atlas, M.D. (2004). Assessment of utilisation of ear, nose and throat services by patients in rural and remote areas. Australian Journal of Rural Health, 12, 150–151.

Choi, J., Lee, H., Park, C., Oh, S. & Park, K. (2007). PC-Based Tele-Audiometry. Telemed J E Health, 13(5):501–508.

Elangovan, S. (2005). Telehearing and the Internet. Semin Hear, 26:19–25.

Ferrari, D.V. & Bernardez-Braga G.R. 2009. Remote probe microphone measurement to verify hearing aid performance. J Telemed Telecare, 15, 122-124.

Franck, K., Pengelly, M. & Zerfoss S. (2006). Telemedicine offers remote cochlear implant programming. Volta Voices, 13(1):16–19.

Givens, G. & Elangovan, S. (2003). Internet application to tele-audiology-"nothin' but net." Am J Audiol, 12:50–65.

Gravel, J., White, K., Johnson, J., et al. (2005). A Multisite study to examine the efficacy of the otoacoustic emission/automated auditory brainstem response newborn hearing screening protocol: recommendations for policy, practice, and research. Am J Audiol2005; 14: S217–S228

Kaldo-Sandström,V., Larsen, H.C. & Andersson, G. (2004). Internet-based cognitive-behavioral self-help treatment of tinnitus: clinical effectiveness and predictors of outcome. Am J Audiol, 13(2):185–192.

Krumm, M., Huffman, T., Dick, K. & Klich, R. (2008). Providing infant hearing screening using OAEs and ABR using telehealth technology. J Telemed Telecare, 14(2):102–104.

Krumm, M., Ribera, J. & Klich R. (2007). Providing basic hearing tests using remote computing technology. J Telemed Telecare, 13(8):406–410.

Krumm, M., & Sims, M. (2011). Teleaudiology. Otolaryngol Clin North Am, 44 (8). 1297- 1304.

Laplante-Lévesque, A., Pichora-Fuller, M.K. & Gagné, J.P. (2003). Providing an internet-based audiological counselling programme to new hearing aid users: a qualitative study. Int J Audiol, 45:697–706.

Lieu, J., Karzon, R. &Mange C. (2006). Hearing screening in the neonatal intensive care unit: follow-up of referrals. Am J Audiol 2006; 15: 66–74

Mackert, M. & Whitten, P. (2007). Successful adoption of a school-based telemedicine program. J Sch Health, 77(6):327–330.

Mencher, G., Davis, A., Devoe, S., Bereford, D. & Bamford, J. (2001). Universal neonatal screening: past, present, and future. Am J Audiol, 10:3–12

Mun, S. & Turner, J. (1999). Telemedicine: emerging e-medicine. Ann Rev Biomed Eng 1:589–610.

O’Neal, J., Finitzo, T. & Littman, T. Neonatal hearing screening: followup and diagnosis. In: Roeser RJ, Valente M, Hosford-Dunn H, eds. Audiology Diagnosis. New York, NY: Thieme Medical Publishers, 2000; 527–44

Nickelson, D. (1998). Telehealth and the evolving health care system: Strategic opportunities for professional psychology. Professional Psychology: Research & Practice, 29, 527–535.

Perednia, D. & Allen A. (1996). Telemedicine technology and clinical applications. J Am Med Assoc, 273:483–488.

Ramos, A., Rodriguez, C., Martinez-Beneyto P., Perez D., Gault A., Falcon J.C. & Boyle P. (2009). Use of telemedicine in the remote programming of cochlear implants. Acta Otolaryngol, 129, 533-540.

Ricketts, T. (2000). The changing nature of healthcare. Annual Review of Public Health, 21, 639–657.

Ribera, J. (2005). Interjudge reliability and validation of telehealth applications of the Hearing in Noise Test. Semin Hear, 26:13–18.

Spooner, A.S., Gotlieb, E., & Steering Committee on Clinical Information Technology and Committee on Medical Liability, (2004). Telemedicine: pediatric applications. Pediatrics, 113:e639–e643.

Shapiro, W., Huang,T., Shaw, T., Roland, J. & Lalwani, A. (2008). Remote intraoperative monitoring during cochlear implant surgery is feasible and efficient. Otology & Neurotology,29:495-498.

Swanepoel, D.,  Koekemoer, K., &  Clark , J.,(2010). Intercontinental hearing assessment

        – a study in tele-audiology. J Telemed Telecare, 16 (5) 248-252

Stamm, B.H. (1998). Clinical applications of telehealth in mental health care. Prof Psychol Res Pr, 29:536–542

Standberry, B. (2000). Telemedicine: barriers and opportunities in the 21st century. J Intern Med, 247:615–627.

Towers, A.D., Pisa, J., Froelich, T.M. & Krumm M.  2005. The reliability of click-evoked and frequency-specific auditory brainstem response testing using telehealth technology. Semin Hear, 26, 19-25.

Wesendahl, T. (2003). Hearing aid fitting: application of telemedicine in audiology. International Tinnitus Journal, 9(1), 56-8.

Wootton, R. (2001).  Recent advances: telemedicine. Br J Med, 60:557–560.

Yates J.T. & Campbell, K.H. (2005). Audiovestibular education and services via telemedicine technologies. Semin Hear, 26:35–42.

About the Author

[email protected] is an associate professor in the School of Speech Pathology and Audiology at Kent State University in Kent, Ohio (USA).  He has been involved with telehealth applications for over a decade and has published a number of papers describing audiology telehealth use with pure tone audiometry, otoacoustic emissions, immittance, video-otoscopy and the auditory brainstem response (ABR). Dr. Krumm has also chaired the American Speech Language and Hearing Association (ASHA) committee on Telepractice and is presently the co-chair of the American Academy of Audiology (AAA) task force on telehealth.

We have dedicated a considerable time to the solution regarding the issue of the OAE FORUM. We have received numerous responses regarding the usefulness of a FORUM , considering that the majority of visitors can access the various communications channels of the Portal easily. A lot of users have suggested to eliminate the FORUM , due to the high levels of Spam, and to focus only on a communication between users and members of the OAE Portal. My personal opinion is that the FORUM provides a service, even when the user has resolved the issues he has been troubled with. That is, that experience can be shared with others facing similar problems. The majority of the Portal editorial board agreed to follow this direction. So for the next few months we will be trying to implement a FORUM that is free of SPAM .

This month with the guest-editorial we present the work of Dr. Mark Krumm on the important issue of  TeleHeath (Editorial April-September 2013: Pediatric Applications of Tele-Health technology and evoked otoacoustic emissions). A companion white paper on the same topic, by  will be published in May 2013.  Dr. Krumm has also promised us a video showing how the technology behaves. The streaming version of the video will be on-line next month as well.

Notes:

[2] Data used for illustration in this paper were collected with the approval of the Indiana University Bloomington Campus Committee

   About the Author  ( Lauren Shaffer Ph.D.)

Current Position:  Assistant Professor of Audiology, Ball State University
 
2000  Ph.D.  Hearing Science   Purdue University
1991  M.S.   Biology                Ball State University
1986  B.A.    Biology                Wilmington College

Electrically Evoked Otoacoustic Emissions (EE-OAEs)

Jiefu Zheng and Yuan Zou

1. Introduction

Electrically evoked otoacoustic emissions (EEOAEs) are acoustic signals emitted from the cochlea to the external ear canal when alternating current is delivered into the cochlea (Hubbard and Mountain, 1983; Mountain and Hubbard, 1989; Murata et al., 1991; Ren and Nuttall, 1995). Unlike acoustically evoked OAEs, the EEOAEs are considered "non-natural" because the cochlea is under the artificial situation stimulated with electrical currents rather than sounds. In addition, due to the need to open the bulla and place stimulation electrodes into/onto the cochlea, the procedures for EEOAE measurement are invasive. In general, there are two ways to apply current injection, one being the intracochlear and the other being the extracochlear stimulation. To our knowledge, the published reports of EEOAE measurements were conducted on animals. Animal species used for EEOAE research include gerbil, guinea pigs, chinchilla, lizards and chicken (Hubbard and Mountain, 1983; Nuttall and Ren, 1995; Sun et al., 2000; Manley 2001; Chen et al., 2001). The EEOAEs can always be obtained in normal ears.

 

The EEOAEs occur at the same frequency as that of the electrical stimulus as a result of fast electromotile responses of the outer hair cells (OHCs) that underlie the reverse transduction process (i.e., electrical-to mechanical transduction) (Mountain and Hubbard, 1989; Nuttall and Ren, 1995). They are reduced or absent in animals in which OHCs are damaged after treatment with ototoxic drugs or by acoustic injury (Ren and Nuttall, 2000; Reyes et al., 2001; Zheng et al., 2001; Nakajima et al., 1996). Experiments on basilar membrane (BM) motion induced by electrical stimulation indicate that OHCs undergoing electrically evoked motion are capable of producing high-fidelity, high frequency mechanical energy. The electrically evoked intracochlear energy results in conventional traveling waves within the cochlea, as well as emissions of sound from the cochlea (Xue et al., 1995; Nuttall and Ren, 1995). It is a consensus that the EEOAEs are generated at the location near the stimulation electrode. However, the mechanisms of EEOAE generation differ with methods for current delivery. It is thought that electrical currents delivered to the scala media (SM) pass through the transduction channels. Thus the EEOAEs are generated or modulated by mechanisms related to cochlear transduction (Yates and Kirk, 1998). In contrast, current delivered into the scala tympani (ST) (directly or from round window stimulation) may extracellularly stimulate the OHCs by directly affecting the transmembrane voltage of OHCs, resulting in voltage-dependent OHC motion (Ren and Nuttall, 1995; Nuttall and Ren, 1995; Nuttall et al., 2001). 

 

SM-applied current is thought to stimulate a spatially well-defined population of OHCs due to the confining effect of the SM space constant, which is estimated to be 1.5 to 4 mm (Xue et al., 1993; Nakajima et al., 1994). The space constant is frequency-dependent and as such it could be significantly shorter than 1.5 mm in the cochlear basal turn. The magnitude transfer functions (i.e., the magnitude of emissions as a function of the frequency) are relatively narrow band or low-pass functions and the slope of the phase-versus-frequency function of the emission (the group delay) is related to the tonotopic location of the SM electrode (Murata et al., 1991; Nakajima et al., 1994; Kirk and Yates, 1996) (see Figures 1 and 2). Similarly, currents applied in the ST result in emissions with tonotopically organized band-pass bandwidth properties as well (Nuttall et al., 2001) (Figure 3). In contrast, EEOAE transfer functions from passing current onto the round window (RW) are considerably broader in frequency (being from 60 Hz to 50 kHz in guinea pigs) with a group delay apparently consistent with the expected reverse propagation time from cochlear locations near the round window (Ren and Nuttall, 1995; Nuttall et al., 2001) (Figure 3).

When sweeping the electrical current with small frequency steps the resultant EEOAE transfer function shows peaks and notches in magnitude, the appearance being termed as ?fine structure?, which is similar to that has been observed in the DPOAE gram (Figure 3). Unlike the acoustically evoked OAEs, the EEOAE input-output function is generally linear even in sensitive cochlea (Figure 4), though nonlinearity could be observed in certain conditions (Ren and Nuttall, 1995; Nakajima et al., 1998). Nevertheless, simultaneously applied electrical currents at two frequencies (f1 and f2) are able to evoke DPOAEs as what are evoked by acoustic primaries (Ren et al., 1996)

EEOAEs can be modulated by an acoustic stimulus. It was firstly reported by Mountain and Hubbard and then by others that a simultaneously presented sound could enhance the EEOAEs evoked by currents applied into the SM (Mountain and Hubbard, 1989; Xue et al., 1993; Nakajima et al., 1994; Kirk and Yates, 1996) (see Figure 1). The enhancement is largest when the acoustic frequencies are near the characteristic frequency (CF) of the current injection location (Xue, et al., 1993). This enhancement is hypothesized as being the result of the opening of the negative feedback loop of the cochlear amplification by acoustic stimulation that causes reduction of the forward transduction. The ?opening? of the feedback loop, in this hypothesis, removes the suppression of the mechanical response and consequently results in an increased amplitude of the EEOAEs (Mountain and Hubbard, 1989). However, data inconsistent with this hypothesis were reported by others (Kirk and Yates, 1996). In round window evoked EEOAE study, it was observed that a high sound level acoustical tone enhanced the EEOAE fine structure at frequencies below that of the acoustical stimulus, and suppressed the overall level of the EEOAEs at frequencies above the acoustical frequency. The acoustic modulations on the EEOAEs was most efficient for frequencies approximately one half octave lower than the acoustical frequencies (Ren and Nuttall, 1998). The underlying mechanisms for these modulations were hypothesized to be the interaction between the electrically and acoustically evoked basilar membrane motions and/or the acoustical stimulus induced basilar membrane impedance discontinuity at its CF location that leads to a change of the electrically evoked traveling waves (Ren and Nuttall, 1998).

There is increasing evidence in favor of the hypothesis that the EEOAEs recorded in the ear canal have more than one origin on the BM. By using multiple component analysis method, a long delay component (LDC) and a short delay component (SDC) of EEOAEs were identified (Ren and Nuttall, 2000; Zou et al, 2003) (Figure 5). By observing the effects of furosemide, quinine, and other pathophysiological cochlear conditions on the multiple components of EEOAEs (Ren and Nuttall, 1998, 2000; Zheng et al, 2001), it was found that the LDC of the EEOAEs is closely related to the cochlear sensitivity and is vulnerable to cochlear damage. It was also found that the fine structure of EEOAEs was a feature of sensitive cochlea and depended on the presence of the LDC. The fine structure is postulated to result from the cancellation/enhancement effects of multiple sound waves in healthy cochlea. In contrast, the overall magnitude of EEOAEs is mainly related to the SDC and is relatively less sensitive to cochlear damage. Therefore, it is hypothesized thatelectrical currents delivered into the cochlea result in OHC motion and hence the basilar membrane vibration at the site near the stimulation electrode, giving rise to energy propagation to both forward (to apical) and backward (to basal) directions. The energy propagating backwards to the oval window results in stapes vibration, giving rise to the SDC. Whereas, the energy propagating forward will reflect from its own CF location, forming the LDC (Ren and Nuttall, 2000; Zou et al, 2003) (Figure 6).

2. Methods of EEOAE measurement

Experimental animals need to be anesthetized. A microphone is coupled to the ear canal to measure the acoustic signal generated in the cochlea by the electrical stimulation. In order to expose the cochlea for placement of the stimulation electrodes the bulla needs to be opened. The middle ear muscle tendons should be sectioned to avoid electrically evoked muscle contractions. The stimuli are usually sinusoidal constant currents delivered through an optically-isolated constant-current source. The acoustic signals in the ear canal are recorded in terms of magnitude and phase at the frequency of the electrical current.

Two approaches for electrical current stimulation are used to evoke the OAEs: (1) Intracochlear stimulation. Holes are made in the cochlea and electrodes are placed into the cochlea to deliver the current stimuli. According to the location of the electrode placement, there are two types of intracochlear stimulation, the scala media stimulation and scala tympani stimulation. (2) Extracochlear stimulation. The electrode is placed in the round window niche so that the current is delivered through the round window membrane into the scala tympani. The cochlea is kept intact in this situation.

 Scala media stimulation: A glass microelectrode is inserted into the scala media through the lateral wall or the basilar membrane (Figure 7). Constant current is injected into the scala media using the microelectrode. The tip diameter of the electrode is approximately 5 mm and the microelectrode is filled with 0.16 M, 1 M, or 3 M KCl. A Ag/AgCl wire is inserted into the neck muscles to serve as the current return electrode. The intensity of the currents could range from 1 to 50 mA peak-to-peak.

Scala tympani stimulation: A platinum-iridium wire is usually used (50-75 mm in diameter) for electrical current stimulation. The electrode is placed into the scala tympani (Figure 8). For monopolar electrode configuration, the Ag/AgCl wire (serving as the return electrode) is inserted into the neck muscles. For bipolar electrode configuration, a second platinum-iridium wire is placed into the scala tympani (or scala vestibuli) as the return electrode. The intensity of the currents could be 10 to 50 mA rms.

Extracochlear (round window) stimulation: The electric current is delivered to the scala tympani through a platinum-iridium electrode in the round window niche. The Ag/AgCl wire in the neck serves as the return electrode (Figure 9). The electric current level could be from 10 to 300 mA rms.

3. Data analysis and presentation

Magnitude and phase transfer functions

Magnitude and phase are essential information for EEOAEs research. The magnitude transfer function curve is obtained by plotting the magnitude as a function of the frequency, which provides information of the frequency response or bandwidth features (Figure 1 and Figure 3). As that has been mentioned in the Introduction, the EEOAE magnitude transfer function presents a feature of ?fine structure? in sensitive cochlea. While the overall level of the EEOAEs rises as the current intensity increase, the amplitude of fine structure (the peaks and notches in magnitude transfer function) tends to decrease with the increasing mean EEOAE level. When the phase (in degree or radian) is plotted against the frequency the phase transfer function curve will be obtained in that group delay could be calculated from the slope (see Figure 2 and Figure 3).

Input-output function

By plotting the magnitude of EEOAEs as a function of the electrical current intensity the input-output function (I/O function) is obtained. The I/O function of the EEOAEs is generally linear (see Figure 4).

Multiple component analysis

The presence of the fine structure suggests the existence of multiple sources of the EEOAEs and consequently, multiple components of the recorded emissions. A method of multiple component analysis (MCA) has been developed (Ren and Nuttall, 2000) in that the real part of the emission is calculated from the magnitude and phase  spectra and then the multiple components are extracted. By using the MCA for EEOAE data analysis, long delay component (LDC) and short delay component (SDC) are observed (Figure 5 and Figure 10).

 

4. Hearing sensitivity and EEOAEs

It has been demonstrated that the OHCs are the origin of the EEOAEs. Thus the EEOAEs provide a tool for the study of in vivo OHC electromotility. The magnitude and the fine structure (in the magnitude-frequency transfer function) of the EEOAEs are associated with the cochlear sensitivity. Any kind of insult to the cochlea that inhibits the OHC function will result in EEOAEs fine structure diminution and/or magnitude reduction. The fine structure is a feature of the sensitive cochlea and is very vulnerable to any damage on the OHCs whereas the overall mean magnitude of EEOAEs is relatively less sensitive to the damage. In fact, the reduction of the EEOAE magnitude is not proportional to the cochlear sensitivity loss. Even in the case when the animal is dead and the fine structure is abolished, the overall magnitude of EEOAEs is reduced by only about 15-20 dB, and residual EEOAEs still can be observed. Moreover, total loss of hair cells further reduces the EEOAE magnitude but generally residual emissions are still seen.

References:

Chen L, Sun W, Salvi RJ., Electrically evoked otoacoustic emissions from the chicken ear. Hear Res. 2001 Nov;161(1-2):54-64.

Hubbard, A.E., Mountain, D.C., 1983. Alternating current delivered into the scala media alters sound pressure at the eardrum. Science, 222, 510-512.

Kirk, D.L., Yates, G.K., 1996. Frequency tuning and acoustic enhancement of electrically evoked otoacoustic emissions in the guinea pig cochlea. J. Acoust. Soc. Am. 100, 3714-3725.

Mountain, D.C., Hubbard, A.E., 1989. Rapid force production in the cochlea. Hear. Res. 42, 195-202.

Manley, GA., 2001. Evidence for an active process and a cochlear amplifier in nonmammals. J. Neurophysiol. 86(2), 541-9. (Review)

Murata, K., Moriyama, T., Hosokawa, Y., Minami, S., 1991. Alternating current induced otoacoustic emissions in the guinea pig. Hear. Res. 55, 201-214.

Nakajima, H.H. and Olson, E.S., 1994. Electrically evoked otoacoustic emissions from the apical turns of the gerbil cochlea. J.Acoust. Soc. Am. 96 (2), 786-794.