Little is known about how outer hair cell loss interacts with noise-induced and age-related auditory nerve degradation (i.e., cochlear synaptopathy) to affect auditory brainstem response (ABR) wave characteristics. Given that listeners with impaired audiograms likely suffer from mixtures of these hearing deficits and that ABR amplitudes have successfully been used to isolate synaptopathy in listeners with normal audiograms, an improved understanding of how different hearing pathologies affect the ABR source generators will improve their sensitivity in hearing diagnostics. We employed a functional model for human ABRs in which different combinations of hearing deficits were simulated and show that high-frequency cochlear gain loss steepens the slope of the ABR Wave-V latency versus intensity and amplitude versus intensity curves. We propose that grouping listeners according to a ratio of these slope metrics (i.e., the ABR growth ratio) might offer a way to factor out the outer hair cell loss deficit and maximally relate individual differences for constant ratios to other peripheral hearing deficits such as cochlear synaptopathy. We compared the model predictions to recorded click-ABRs from 30 participants with normal or high-frequency sloping audiograms and confirm the predicted relationship between the ABR latency growth curve and audiogram slope. Experimental ABR amplitude growth showed large individual differences and was compared with the Wave-I amplitude, Wave-V/I ratio, or the interwaveI–W latency in the same listeners. The model simulations along with the ABR recordings suggest that a hearing loss profile depicting the ABR growth ratio versus the Wave-I amplitude or Wave-V/I ratio might be able to differentiate outer hair cell deficits from cochlear synaptopathy in listeners with mixed pathologies.

4The perceptual consequences of cochlear synaptopathy are presently not well understood as a direct 5 quantification of synaptopathy is not possible in humans. To study its role for human hearing, recent studies 6 have instead correlated changes in basic supra-threshold psychoacoustic tasks with individual differences in 7 subcortical EEG responses, as a proxy measure for synaptopathy. It is not clear whether the reported 8 missing relationships between the psychoacoustic quantities and the EEG are due to the adopted methods, 9 or to a minor role of synaptopathy for sound perception. We address this topic by studying the theoretical 10 relationship between subcortical EEG and psychoacoustic methods for different sensorineural hearing deficits. 11 1 Introduction 12The role of cochlear synaptopathy (i.e., the loss of inner-hair-cell auditory-nerve fiber synapses due to noise 13 exposure or aging; or hidden hearing loss) for supra-threshold hearing has been heavily contested in recent 14 human studies [1, 2, 3, 4] even though animal studies show clear histological evidence for synaptopathy [5, 6, 7]. 15It is not clear whether the cause of the missing correlations between subcortical EEG measures, as a non-16 invasive tool to quantify synaptopathy, and the suprathreshold psychoacoustic tasks stems from methodological 17 confounds. It might be that the adopted subcortical EEG methods (e.g. the envelope-following response, EFR 18 and auditory brainstem response, ABR) are not sensitive markers of synaptopathy in humans, or, that the EEG 19 methods are not targeting the same mechanisms involved in the psychoacoustic task, resulting in differential 20 effects of synaptopathy on both measures. To address these issues, we study the theoretical relationship between 21 the EFR and two common supra-threshold hearing tasks: tone-in-noise (TiN) and amplitude-modulation (AM) 22 detection for different degrees of sensorineural hearing loss. We employ a computational model of the human 23 auditory periphery that simulates neural responses to quantify psychoacoustic detection cues and subcortical 24 EEG metrics [8]. We simulate how different aspects of sensorineural hearing loss (synaptopathy, cochlear gain 25 loss and combinations) affect the theoretical relationship between the EFR and psychoacoustic metrics to assess 26 their sensitivity in quantifying synaptopathy in humans. 27Verhulst et al., p. 2 2 Methods 28Participants were informed according to the ethical guidelines at Oldenburg University and paid for participa-29 tion. TiN detection: 11 normal-hearing (NH; 24±4.4 yrs, 9 females) subjects with normal audiograms (Auritec 30 AT900) and 9 hearing-impaired (HI; 63 ± 6, 7 females) participants with a high-frequency sloping hearing loss 31 (≤40 dB HL up to 6 kHz, with a 20 to 25 dB HL loss at 4 kHz). AM detection: 12 NH listeners (26±4, 7 32 females) with flat audiograms and a max. 15 dB HL threshold at 4 kHz. 8 HI listeners (70±5, 5 females) with 33 sloping audiograms and a 4-kHz threshold between 20 and 40 dB HL. 34Psycho...

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