# Biomarkers of cochlear synaptopathy and their relation to suprathreshold hearing disorders in humans with sensorineural hearing loss

> **NIH NIH P50** · MASSACHUSETTS EYE AND EAR INFIRMARY · 2024 · $578,157

## Abstract

Project 3 Summary – Abstract
 Difficulty understanding speech in noisy backgrounds, reduced sound-level tolerance and tinnitus are the
most common complaints associated with noise- and age-related hearing loss. Parsing the sensory vs. neural
contributions to these impairments gained new traction from animal studies showing that hair cell death (and
the threshold shift it produces) is often preceded by loss of hair cell synapses with auditory nerve fibers. This
cochlear neural degeneration (CND) degrades auditory processing and may contribute to difficulties
understanding speech, especially in noisy environments, but has little effect on thresholds in quiet until it
becomes extreme. CND could also be a major contributor to the genesis of tinnitus and hyperacusis, via an
induction of central-gain adjustment secondary to the loss of auditory input to the central nervous system.
 Over the last grant period, we showed correlations between inferred measures of CND and word-
recognition performance in difficult listening environments among normal-hearing listeners. Over the next five
years, we broaden our focus to include those with threshold shifts. In Aim 1 we study high-tone hearing-loss,
because temporal bone studies show that CND will be worse, despite normal thresholds in the speech-
frequency region. In Aim 2 we study the flat hearing loss in late-stage Ménière's, because CND may be
particularly severe in this disorder. In both, we test the correlation of the word-score outcomes with a battery of
physiological measures chosen to probe the early stages of auditory processing, i.e. distortion product
otoacoustic emissions and high-frequency audiometry to evaluate OHC function, threshold-in-noise tests and
pitch-masking tasks to identify cochlear dead regions, and electrocochleography (including stacked ABRs),
envelope-following responses to rectangular envelopes and middle-ear-muscle reflexes to probe for CND and
assess its severity as a function of cochlear location. A medial olivocochlear reflex assay will evaluate the
potential for hyperresponsivity of brainstem circuits. In Aim 3, we test if CND is a major elicitor of tinnitus and
hyperacusis by assessing the relationships between our physiological estimates of CND, word-identification
tasks, and several psychophysical measures of tinnitus and sound level tolerance. In concert with Project 4,
which will further examine the same subjects, we will directly probe the relation between estimated CND and
central manifestations of neural hyperactivity, perceptual hypersensitivity and behavioral hyperreactivity.
 The successful completion of these Aims will determine if, and to what extent, markers consistent with
CND are associated with the speech intelligibility deficits observed in patients with SNHL and will clarify the
association between biomarkers of peripheral neural deficits with psychophysical measures of tinnitus and
sound-level intolerance. Given progress in the repair of noise-induced coch...

## Key facts

- **NIH application ID:** 10896024
- **Project number:** 5P50DC015857-08
- **Recipient organization:** MASSACHUSETTS EYE AND EAR INFIRMARY
- **Principal Investigator:** Stéphane F. Maison
- **Activity code:** P50 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $578,157
- **Award type:** 5
- **Project period:** 2017-08-02 → 2027-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10896024

## Citation

> US National Institutes of Health, RePORTER application 10896024, Biomarkers of cochlear synaptopathy and their relation to suprathreshold hearing disorders in humans with sensorineural hearing loss (5P50DC015857-08). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10896024. Licensed CC0.

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