# Cochlear Synaptopathy: Prevalence, Diagnosis and Functional Consequences

> **NIH NIH P50** · MASSACHUSETTS EYE AND EAR INFIRMARY · 2020 · $2,371,694

## Abstract

Overall Project Summary
 New insights from animal studies of noise-induced and age-related hearing loss suggest that the
most vulnerable elements in the inner ear are the synaptic connections between hair cells and sensory
neurons. This primary neural degeneration, also called cochlear synaptopathy, does not elevate
thresholds. Thus, it can be widespread in ears with intact hair cell populations and normal audiograms,
where it has been called “hidden” hearing loss. It likely contributes to difficulties understanding speech
in a noisy environment and may be an instigating factor in the generation of tinnitus and hyperacusis.
Cochlear synaptopathy may also be widespread in acquired sensorineural hearing loss of other
etiologies and degrees of hair cell damage. Thus, it may be a major contributor to the well-known
differences in auditory performance among people with identical audiometric patterns of “overt” hearing
loss.
 Our Research Center aims to take these paradigm-shifting ideas from animal models to human
subjects. Based on the synthesis of many research threads from the study of overt and hidden hearing
loss, we have devised a set of physiological, electrophysiological and psychophysical tests of hearing
and cochlear function that we believe are most powerful in the diagnosis and understanding of cochlear
synaptopathy in human subjects. In Project 1, we apply this test battery to gerbils exposed to noise or
ototoxic drugs and test their diagnostic power by directly measuring the underlying cochlear
histopathology in cases of overt or hidden hearing loss. In Project 2, we use immunostaining to directly
assess the prevalence of cochlear synaptopathy in human temporal bones from subjects with overt or
hidden hearing loss with a range of etiologies. In Project 3, we study hidden hearing loss in college
students by applying the test battery to subjects with normal audiograms but a broad range of reported
and measured sound exposures. In Project 4, we assess older adults with overt hearing loss by
applying the tests to a subject pool with carefully matched down-sloping audiograms and by
characterizing training-based improvements in speech-in-noise performance as reflected at different
peripheral, brainstem, midbrain and cortical levels.
 Our preliminary studies of young adults show clear signs of hidden hearing loss in a group with
repeated exposure to high-level music, suggesting the importance of this phenomenon to the public
health. The success of neurotrophin-based approaches to the treatment of cochlear synaptopathy in
animal models suggests that therapies may be on the horizon. Thus, the need for better understanding
of the prevalence, diagnosis and functional consequences of cochlear synaptopathy is clear.

## Key facts

- **NIH application ID:** 9987315
- **Project number:** 5P50DC015857-04
- **Recipient organization:** MASSACHUSETTS EYE AND EAR INFIRMARY
- **Principal Investigator:** Sharon G Kujawa
- **Activity code:** P50 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $2,371,694
- **Award type:** 5
- **Project period:** 2017-08-02 → 2022-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9987315

## Citation

> US National Institutes of Health, RePORTER application 9987315, Cochlear Synaptopathy: Prevalence, Diagnosis and Functional Consequences (5P50DC015857-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9987315. Licensed CC0.

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