Abstract
Investigations of cochlear synaptopathy in living humans rely on proxy measures of auditory nerve function. Numerous procedures have been developed, typically based on the auditory brainstem response (ABR), envelope-following response (EFR), or middle-ear-muscle reflex (MEMR). Validation is challenging, due to the absence of a gold-standard measure in humans. Some metrics correlate with synaptic survival in animal models, but translation between species is not straightforward; measurements in humans are likely to reflect greater error and greater variability from non-synaptopathic sources. The present study assessed the reliability of seven measures, as well as testing for correlations between them. Thirty-one young women with normal audiograms underwent repeated measurements of ABR wave I amplitude, ABR wave I growth, ABR wave V latency shift in noise, EFR amplitude, EFR growth with stimulus modulation depth, MEMR threshold, and an MEMR across-frequency difference measure. Intraclass correlation coefficients for ABR wave I amplitude, EFR amplitude, and MEMR threshold ranged from 0.85 to 0.93, suggesting that such tests can yield highly reliable results, given careful measurement techniques. The ABR and EFR difference measures exhibited only poor-to-moderate reliability. No significant correlations, nor any consistent trends, were observed between the various measures, providing no indication that these metrics reflect the same underlying physiological processes. Findings suggest that many proxy measures of cochlear synaptopathy should be regarded with caution, at least when employed in young adults with normal audiograms.
Highlights
Seminal work in a mouse model demonstrated that noise exposure can destroy synapses between cochlear inner hair cells and auditory nerve (AN) fibers, without widespread hair-cell loss (Kujawa and Liberman, 2009)
Findings suggest that many proxy measures of cochlear synaptopathy should be regarded with caution, at least when employed in young adults with normal audiograms
The number of proxy measures of cochlear synaptopathy employed in humans has exploded in recent years, extending into double figures
Summary
Seminal work in a mouse model demonstrated that noise exposure can destroy synapses between cochlear inner hair cells and auditory nerve (AN) fibers, without widespread hair-cell loss (Kujawa and Liberman, 2009). Cochlear thresholds are left largely intact, yet auditory brainstem response (ABR) amplitudes are reduced at moderate-to-high stimulus levels (Hickox et al, 2017). Synaptopathy may preferentially affect the subset of AN fibers with low-to-medium spontaneous firing rates (low-SR fibers; Furman et al, 2013), which have high response thresholds (Liberman, 1978). The vast majority of studies have not employed histological techniques, relying instead on non-invasive proxy measures of cochlear synaptopathy. A wide variety of such measures are reported in the literature, generally based on the ABR, envelope-following response (EFR), or acoustic middle-ear-muscle reflex (MEMR)
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