Damage to auditory-nerve-ber synapses (i.e. cochlear synaptopathy) degrades the neural coding of sound and is predicted to impair sound perception in noisy listening environments. However, establishing a causal relationship between synaptopathy and speech 15 intelligibility is di cult because we have no direct access to synapse counts in humans. Hence, we rely on the quality of noninvasive auditory-evoked potential (AEP) markers developed in rodent studies of histologically-veri ed synaptopathy. However, there are a number of reasons which render the interpretation of these markers in humans di cult. To bridge this translational gap, we apply a multi-method approach to enable a meaningful interpretation of the relationship 20 between the histopathology of sensorineural hearing loss (SNHL) and speech perception. We rst selected a synaptopathy-sensitive AEP marker and veri ed its sensitivity (i) in an animal model using a Kainic-acid induced synaptopathy, and (ii), via auditory model simulations which connect the histopathology of SNHL to the source generators of AEPs. Secondly, we restricted the frequency content of the speech-material to ensure that both AEP and speech metrics targeted 25 similar cochlear frequency regions and associated auditory coding mechanisms. Following this approach, we studied the relative contribution of AEP markers of synaptopathy and hearing sensitivity to speech recognition thresholds in 44 listeners (24 women) of di erent ages and SNHL pro les. Our analysis shows that synaptopathy plays an important role for speech intelligibility in noise, but that outer-hair-cell integrity predicts performance in the absence of 30 noise. Our results corroborate conclusions from animal studies regarding the prevalence of age-related synaptopathy, and its occurrence before outer-hair-cell loss damage.
Signi cance StatementTemporal-bone histology demonstrates that cochlear synaptopathy, i.e. damage to inner-hair-cell 35 auditory-nerve ber synapses, sets in before sensory cell damage and associated hearing threshold elevation. Clinical practice assesses hearing status on the basis of audiometric thresholds, and is hence overlooking a -likely prevalent-aspect of sensorineural hearing damage given that ageing, noise exposure or ototoxic drugs can cause synaptopathy. We present a multi-method approach to study the relationship between synaptopathy and speech intelligibility and address an important 40 1 of 40 unresolved issue in hearing science, namely why speech-intelligibility-in-noise degrades as we age, even when hearing sensitivity remains normal. Our study outcomes have important implications for hearing diagnostics and treatment.
AbbreviationsAN(F) -auditory nerve ( ber); 45 BB -broadband; CF -characteristic frequency; CN -cochlear nucleus; DPOAE -distortion product otoacoustic emission; EEG -electroencephalography; 50 EFR -envelope following response; H/M/LSR bers -high/medium/low spontaneous rate bers; HI -hearing-impaired; HP -highpass ltered; IC -inferior colliculus; 55 IHC -inner hair cell; IQR...
