Non-Invasive Assays of Cochlear Synaptopathy - Candidates and Considerations.

Abstract:

:Studies in multiple species, including in post-mortem human tissue, have shown that normal aging and/or acoustic overexposure can lead to a significant loss of afferent synapses innervating the cochlea. Hypothetically, this cochlear synaptopathy can lead to perceptual deficits in challenging environments and can contribute to central neural effects such as tinnitus. However, because cochlear synaptopathy can occur without any measurable changes in audiometric thresholds, synaptopathy can remain hidden from standard clinical diagnostics. To understand the perceptual sequelae of synaptopathy and to evaluate the efficacy of emerging therapies, sensitive and specific non-invasive measures at the individual patient level need to be established. Pioneering experiments in specific mice strains have helped identify many candidate assays. These include auditory brainstem responses, the middle-ear muscle reflex, envelope-following responses, and extended high-frequency audiograms. Unfortunately, because these non-invasive measures can be also affected by extraneous factors other than synaptopathy, their application and interpretation in humans is not straightforward. Here, we systematically examine six extraneous factors through a series of interrelated human experiments aimed at understanding their effects. Using strategies that may help mitigate the effects of such extraneous factors, we then show that these suprathreshold physiological assays exhibit across-individual correlations with each other indicative of contributions from a common physiological source consistent with cochlear synaptopathy. Finally, we discuss the application of these assays to two key outstanding questions, and discuss some barriers that still remain. This article is part of a Special Issue entitled: Hearing Loss, Tinnitus, Hyperacusis, Central Gain.

journal_name

Neuroscience

journal_title

Neuroscience

authors

Bharadwaj HM,Mai AR,Simpson JM,Choi I,Heinz MG,Shinn-Cunningham BG

doi

10.1016/j.neuroscience.2019.02.031

subject

Has Abstract

pub_date

2019-05-21 00:00:00

pages

53-66

eissn

0306-4522

issn

1873-7544

pii

S0306-4522(19)30142-3

journal_volume

407

pub_type

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