On the Use of Envelope Following Responses to Estimate Peripheral Level Compression in the Auditory System

Hearing impairment is a common and increasingly frequent problem among elderly people. The success of restoration or compensation therapies is strongly dependent on the development of reliable diagnostic methods for individual patients. The ability to compress the large level range of incoming sounds into a smaller range of vibration amplitudes on the basilar membrane (BM) is an important property of the healthy auditory system. Sensorineural hearing impairment typically leads to a decrease in sensitivity to sound and a reduction of the amount of compression observed in BM input-output functions in the cochlea. While sensitivity loss can be measured efficiently via audiometry, no measure has yet been provided that represents fast and reliable compression estimates in the individual listener. This would be useful to disentangle outer hair cells (OHC) from inner hair cells (IHC) damage. In the present study, magnitude-level functions obtained from envelope following response (EFR) to four simultaneously presented amplitude modulated tones were measured in normal hearing (NH) and sensorineural hearing impaired (HI) listeners. The slope of part of the EFR magnitude-level function was used to estimate level compression as a proxy of peripheral compression. The median values of the compression estimates in the group of NH listeners were found to be consistent with previously reported group-averaged compression estimates based on psychoacoustical measures and group-averaged distortion-product otoacoustic emission magnitude-level functions in human listeners. They were also similar to BM compression values measured invasively in non-human mammals. The EFR magnitude-level functions for the HI listeners were less compressive than those for the NH listeners. This is consistent with a reduction of BM compression. Given the numerical concordance between EFR-based compression estimates and group-averaged estimates from other methods, the frequency-specific (on-characteristic frequency (CF)) nature of BM compression was analysed through computer modelling. A computer model of the auditory nerve (AN) was used to simulate EFR magnitude-level functions at the level of the AN. The recorded EFRs were considered to represent neural activity originating mainly from the auditory brainstem-midbrain rather than a direct measure of AN activity. Nonetheless, the AN model simulations could account for the recorded data. The model simulations revealed that the growth of the EFR magnitude-level function might be highly influenced by contributions from off-CF neural populations. This compromises the possibility to estimate on-CF (i.e., frequency-specific or “local”) level compression with EFRs. Furthermore, the model showed that, while the slope of the EFR magnitude-level function is sensitive to a loss of BM compression observed in HI listeners due to OHC dysfunction, it is also sensitive to IHC dysfunction. Overall, it is concluded that EFR magnitude-level functions may not represent frequency-specific level compression in the auditory system. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement This work was supported by the Oticon Centre of Excellence for Hearing and Speech Sciences (CHeSS) and the Novo Nordisk Foundation grant NNF17OC0027872 at the Technical University of Denmark (DTU). ### Author Declarations All relevant ethical guidelines have been followed; any necessary IRB and/or ethics committee approvals have been obtained and details of the IRB/oversight body are included in the manuscript. Yes All necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable. Yes The data reported in this article are publicly available in a Zenodo repository.