Animal models suggest that cochlear afferent nerve endings may be more vulnerable than sensory hair cells to damage from acoustic overexposure and aging. Because neural degeneration without hair-cell loss cannot be detected in standard clinical audiometry, whether such damage occurs in humans is hotly debated. Here, we address this debate through co-ordinated experiments in at-risk humans and a wild-type chinchilla model. Cochlear neuropathy leads to large and sustained reductions of the wideband middle-ear muscle reflex in chinchillas. Analogously, human wideband reflex measures revealed distinct damage patterns in middle age, and in young individuals with histories of high acoustic exposure. Analysis of an independent large public dataset and additional measurements using clinical equipment corroborated the patterns revealed by our targeted cross-species experiments. Taken together, our results suggest that cochlear neural damage is widespread even in populations with clinically normal hearing.
Multiple animal models have robustly shown the effects of noise-exposure and aging can have on the afferent synapses between the cochlea and the auditory nerve. This cochlear synaptopathy can affect responses to suprathreshold stimuli while leaving audiometric thresholds intact. However, currently, there is much debate on whether these same changes occur in humans with significant noise-exposure or with middle age. Our study examined two different physiological responses in which these afferent synapses are a crucial component, the auditory brainstem response (ABR) and the middle ear muscle reflex (MEMR). Versions of these measures were completed in both a clinical setting and a laboratory. Responses to both measures in both testing environments demonstrated significant age and noise-exposure effects. Moreover, these effects remained significant even after statistically accounting for variability in audiometric sensitivity and otoacoustic emissions, suggesting that despite clinically normal audiograms, cochlear synaptopathy may be a widespread occurrence in humans with both acoustic-overexposure and normal aging. Finally, our results suggest that a battery combining ABR and MEMR measures may be viable as a non-invasive assay of synaptopathy and can help examine the perceptual sequelae of such damage.
The nervous system adapts in many ways to changes in the statistics of the inputs it receives. An example of such plasticity observed in animal models is that central auditory neurons tend to retain their driven firing rate outputs despite reductions in cochlear input due to hearing loss or deafferentation. The perceptual consequences of such “central gain” are unknown; pathological versions of such gain are often hypothesized to underlie tinnitus and hyperacusis. To investigate central gain in humans, we designed an electroencephalogram (EEG)-based paradigm that concurrently elicits robust separable responses from different levels of the auditory pathway. Using this measure, we find that cortical responses are relatively invariant despite a large monotonic decrease in auditory nerve responses with age, and that this central gain is also associated with perceptual deficits in co-modulation processing. We then applied the same measures to a cohort of individuals with persistent tinnitus and to a third cohort where a week-long monaural conductive hearing loss was induced using silicone earplugs. Overall, our results suggest that central gain is ubiquitous in response to reduced peripheral input and may affect auditory scene analysis, but does not in itself account for tinnitus perception.
Animal models suggest that cochlear afferent nerve endings may be more vulnerable than sensory hair cells to damage from acoustic overexposure and aging, but that such damage cannot be detected in standard clinical audiometry. Co-ordinated experiments in at-risk humans and a chinchilla model using two distinct physiological assays suggest that cochlear neural damage exists even in populations without clinically recognized hearing loss.
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