Supra-threshold psychoacoustics and envelope-following response relations: normal-hearing, synaptopathy and cochlear gain loss

Abstract

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...

Applicability of subcortical EEG metrics of synaptopathy to older listeners with impaired audiograms

“…The relationship between synaptopathy and auditory 10 evoked potentials has opened avenues to diagnose synaptopathy in humans and to study the 11 relationship between synaptopathy and sound perception. 12 In humans, a stronger reduction of EFR strength with decreasing stimulus modulation depth was 13 found to go along with worse ITD detection thresholds as well as degraded AM detection and 14 poorer selective attention performance in listeners with otherwise normal audiograms 15 (Bharadwaj et al, 2015). Reduced perceptual temporal encoding abilities may thus be 16 diagnosed using this relative EFR slope metric.…”

“…However, some aspects of hearing impairment, especially those 9 reported by people with normal-hearing thresholds, are not sufficiently characterised by the 10 audiogram alone (Hind et al, 2011;Kobel et al, 2017;Kumar et al, 2007; Lobarinas et al, 11 2017). These so-called suprathreshold hearing deficits, in the presence of normal sound 12 detection, are a topic of intensive investigation as the underlying cause of these deficits may 13 explain why two individuals with the same audiogram can have very different speech 14 intelligibility scores (Festen and Plomp, 1983). 15 One possible cause for suprathreshold hearing deficits in the presence of normal hearing 16 sensitivity is cochlear synaptopathy or neuropathy.…”

“…The quantification and isolation of cochlear synaptopathy from other 10 coexisting contributors of hearing loss is therefore still a major unsolved problem in hearing 11 diagnostics (Hickox et al, 2017;Kobel et al, 2017;Plack et al, 2016;Verhulst et al, 2016). 12 As a first step to disentangle peripheral hearing deficits from a single electrophysiological 13 metric, we investigated whether existing ABR/EFR metrics for synaptopathy diagnosis in a young 14 NH (yNH) group (25±4.1 years) follow the same trends for an older hearing impaired (oHI) group 15 (65±7.9 years) with high-frequency sloping audiograms. The latter group has OHC deficits as 16 verified using the audiogram and distortion-product otoacoustic emission (DPOAE) thresholds 17 (Chen et al, 2008) and is expected to suffer from synaptopathy on the basis of recent studies 18 relating normal ageing to synaptopathy expression (Parthasarathy and Kujawa, 2018; 19 Sergeyenko et al, 2013;Wu et al, 2018).…”

“…Wu et al, 2018). We investigate the 12 following hypotheses which are motivated by extending the NH synaptopathy results to an 13 older HI group with high-frequency hearing loss and a suspected high degree of synaptopathy. 14 15 1) Reduced EFR amplitudes: 16 On the basis of animal-synaptopathy findings (Parthasarathy and Kujawa, 2018; Shaheen et al, 17 2015) and reduced temporal envelop encoding ability (Bharadwaj et al, 2014) we expect that 18 the EFR strength is reduced in the oHI group.…”

“…6 4) Shallower ABR amplitude slopes: 7 If synaptopathy is the driving force behind the ABR amplitude as a function of stimulus level 8 increases (i.e., the ABR amplitude slope), we expect a shallower slope for the oHI group. 9 However, a potential loss of cochlear compression due to OHC deficits would yield steeper ABR 12 relatively stronger contributions of the intact apical portion of the basilar membrane. If 13 synaptopathy drives the ABR amplitude metric, we expect to see shallower ABR slopes which do 14 not relate to the ABR latency slope, expected to reflect OHC loss.…”