Journal article
Non-Invasive Assays of Cochlear Synaptopathy – Candidates and Considerations
Neuroscience, Vol.407, pp.53-66
05/21/2019
DOI: 10.1016/j.neuroscience.2019.02.031
PMCID: PMC6513698
PMID: 30853540
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.
•Animal models show that noise exposure and age can cause cochlear synaptopathy not seen in standard clinical tests.•Non-invasive assays for synaptopathy have been suggested in mice, but human studies have yielded mixed results.•Here, we illustrate six extraneous sources of variability in these non-invasive assays that may limit human results.•Using strategies that mitigate extraneous variables, we show that three assays exhibit across-individual correlations.•The wideband middle-ear muscle reflex is promising as a quick measure correlated with synaptopathy.
Details
- Title: Subtitle
- Non-Invasive Assays of Cochlear Synaptopathy – Candidates and Considerations
- Creators
- Hari M Bharadwaj - Purdue University West LafayetteAlexandra R Mai - Purdue University West LafayetteJennifer M Simpson - Purdue University West LafayetteInyong Choi - University of IowaMichael G Heinz - Purdue University West LafayetteBarbara G Shinn-Cunningham - Carnegie Mellon University
- Resource Type
- Journal article
- Publication Details
- Neuroscience, Vol.407, pp.53-66
- DOI
- 10.1016/j.neuroscience.2019.02.031
- PMID
- 30853540
- PMCID
- PMC6513698
- NLM abbreviation
- Neuroscience
- ISSN
- 0306-4522
- eISSN
- 1873-7544
- Publisher
- Elsevier Ltd
- Grant note
- DOI: 10.13039/100000002, name: NIH; DOI: 10.13039/100002046, name: Hearing Health Foundation
- Language
- English
- Date published
- 05/21/2019
- Academic Unit
- Communication Sciences and Disorders; Iowa Neuroscience Institute
- Record Identifier
- 9984258847502771
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