# Cochlear synaptopathy and audiometric measures from human temporal-bone cases of sensorineural hearing loss

> **NIH NIH P50** · MASSACHUSETTS EYE AND EAR INFIRMARY · 2024 · $575,200

## Abstract

Project 2 Summary - Abstract
 Since the inner ear cannot be biopsied, and clinical imaging cannot produce cellular-level
resolution, the only way to uncover the functionally important structural changes underlying
sensorineural hearing loss is the microscopic examination of post-mortem human temporal
bones. This P50 Center focuses on primary neural degeneration in the inner ear (i.e. the loss of
synaptic connections between surviving sensory cells and auditory nerve cells), and its
hypothesized role in limiting the ability to understand complex stimuli like speech and as a key
elicitor of tinnitus and hyperacusis.
 Over the past 5 years, Project 2 showed, as predicted from animal models, that the rate of
auditory nerve loss in normal-aging human ears out-paced the rate of hair cell loss by 2:1, and
that this neural loss was further accelerated in those with a history of noise exposure. A rigorous
statistical model showed that while the audiometric thresholds were well predicted by the
patterns of hair cell loss, the neural loss did not affect threshold but contributed to the
differences in word identification abilities among those with similar audiograms.
 Over the next 5 years, Project 2 builds on this foundation to explore a wider range of
acquired hearing loss etiologies, i.e. ototoxic antibiotics and chemotherapeutics, sudden
sensorineural hearing loss and Ménière’s disease. We choose this because they are common,
well represented in our temporal bone archives, and are often associated with tinnitus and
difficulties in speech discrimination. We are developing machine-learning approaches to
automate the acquisition of quantitative histopathological data, because we aim to grow the
number of cases analyzed as rapidly as possible. As we have now entered the era of clinical
trials for deafness therapeutics, there is a critical need for robust statistical models to accurately
predict the degree and pattern of cellular loss from the audiogram, word score, hearing loss
etiology, age and sex of a candidate patient.

## Key facts

- **NIH application ID:** 10896021
- **Project number:** 5P50DC015857-08
- **Recipient organization:** MASSACHUSETTS EYE AND EAR INFIRMARY
- **Principal Investigator:** M. Charles Liberman
- **Activity code:** P50 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $575,200
- **Award type:** 5
- **Project period:** 2017-08-02 → 2027-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10896021

## Citation

> US National Institutes of Health, RePORTER application 10896021, Cochlear synaptopathy and audiometric measures from human temporal-bone cases of sensorineural hearing loss (5P50DC015857-08). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10896021. Licensed CC0.

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