The Search for a Diagnostic Indicator of Cochlear Deafferentation: Predicting Age and Veteran Status from Auditory Evoked Potential Measures

Objectives: Cochlear synaptopathy, a type of cochlear deafferentation that occurs with aging and following loud noise exposure, is expected to be common in humans and to have negative impacts on auditory perception. However, there is currently no means for diagnosing cochlear deafferentation in living humans. Auditory brainstem response (ABR) wave I amplitude and the envelope following response (EFR) are auditory evoked potentials that have been proposed as potential non-invasive indicators of cochlear deafferentation. However, these measures may be impacted by outer hair cell (OHC) dysfunction, making them difficult to interpret. One potential method for estimating the degree of deafferentation in individual patients is to combine evoked potential and distortion product otoacoustic emission (DPOAE) measurements with a computational model of the auditory periphery (CMAP). The goal of this study was to evaluate the ability of auditory evoked potentials, with and without the CMAP, to predict risk factors for cochlear synaptopathy (age and history of military noise exposure). Design: In a population of military Veterans and non-Veterans with up to a mild sensorineural hearing loss, a CMAP was used with Bayesian regression to predict synapse numbers across cochlear frequency (synaptograms) for individual human participants based on their ABR, EFR, and/or DPOAE measurements. Linear regression models were then used to evaluate the ability of the synaptograms and various ABR wave I amplitude, EFR magnitude, and DPOAE measurements to predict age and Veteran status. All Veterans were assumed to have at least some history of military noise exposure. Results: High frequency (4 and 5.6 kHz) ABR wave I amplitude measurements and synaptograms generated from high frequency ABR wave I amplitudes performed the best at predicting participant age. Accounting for OHC function (as indicated by DPOAEs) in the generation of the synaptograms or by including DPOAEs in the linear regression models had limited impact on the ability of ABR wave I amplitudes to predict age. DPOAEs were highly predictive of Veteran status, making it difficult to isolate the ability of the auditory evoked potentials to predict Veteran status. Conclusions: High frequency ABR wave I amplitudes and synaptograms generated from high frequency ABR wave I amplitudes were able to predict participant age within approximately 6 years, with or without incorporating DPOAE measurements. This suggests that high frequency ABR wave I amplitude measurements are good candidates for non-invasive diagnosis of age-related cochlear deafferentation and it may not be necessary to use the CMAP or measure DPOAEs to predict deafferentation in individual patients. Unfortunately, specific recommendations for predicting noise-induced cochlear deafferentation could not be ascertained from this study due to confounding related to OHC dysfunction.