# Physiological Signatures and Behavioral Correlates of Hidden Hearing Loss

> **NIH NIH R01** · VANDERBILT UNIVERSITY MEDICAL CENTER · 2021 · $671,920

## Abstract

ABSTRACT
Noise-induced hearing loss affects more than 25 million adults, with the majority of these cases suspected to
be the result of exposure to environmental sounds. Importantly, some humans with no overt indications of
hearing loss have extraordinary difficulty processing speech in noisy environments, but only recently has a
potential explanation emerged. Noise exposure at sound pressure levels that cause a temporary threshold
shift but no permanent threshold shift results in a loss of ribbon synapses (synaptopathy) without any hair cell
loss, and a reduction in the amplitude of auditory brainstem response (ABR) Wave I. Low spontaneous rate
(LSR) auditory nerve fibers (ANFs) seem particularly susceptible to this loss. While these effects are well
described in rodents, it is not clear that they occur in humans. It is impossible to demonstrate synaptopathy
directly in humans. We propose to bridge this gap by performing parallel experiments in humans and an
animal model that shares great similarity, both anatomically and mechanistically, with humans: macaques.
Our recently developed macaque model of synaptopathy shares some features with the established rodent
model, but also reveals differences in susceptibility, which may also be present in other primates such as
humans. We propose parallel experiments in control and noise-exposed macaques (without and with
synaptopathy, respectively) and in two groups of humans with normal hearing thresholds: a control group and
a noise-exposed human cohort. Our overarching hypothesis is that synaptopathy caused by noise exposure
impairs temporal processing, resulting in deficits in physiological (Aim1) and behavioral (Aims 2) metrics of
suprathreshold stimulus processing, and these deficits will be correlated with the amount of synaptopathy,
which will be verified by histology and ANF recordings in macaques (Aim 3). We predict that physiological
measures of processes that involve LSR fibers (including coding of modulation in suprathreshold sounds and
masked sounds, middle ear muscle reflexes, and recovery from forward masking) will be impaired in subjects
with synaptopathy relative to normal subjects (Aim 1). We predict that behaviors that require temporal cues to
process simple stimuli (detection of amplitude modulation, suprathreshold masked detection, forward
masking thresholds, and the contribution of temporal cues to the detection of suprathreshold tones in noise)
and complex stimuli (speech-in-noise and spatial-attention tasks, and release from masking) will be impaired
in subjects with synaptopathy (Aim 2). The synaptopathy will be histologically verified and its ANF correlates
(loss of LSR fibers) verified directly in macaques (Aim 3). The results of these studies will reveal sensitive
physiological and behavioral markers of synaptopathy, validated by histological and neurophysiological
findings in macaques. These parallel studies in humans and macaques will elucidate the functional
consequences of ...

## Key facts

- **NIH application ID:** 10074559
- **Project number:** 5R01DC015988-04
- **Recipient organization:** VANDERBILT UNIVERSITY MEDICAL CENTER
- **Principal Investigator:** Ramnarayan Ramachandran
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $671,920
- **Award type:** 5
- **Project period:** 2018-01-10 → 2022-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10074559

## Citation

> US National Institutes of Health, RePORTER application 10074559, Physiological Signatures and Behavioral Correlates of Hidden Hearing Loss (5R01DC015988-04). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10074559. Licensed CC0.

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