# Maladaptive central plasticity and suprathreshold hearing disorders in humans with sensorineural hearing loss and their relation to biomarkers of cochlear synaptopathy

> **NIH NIH P50** · MASSACHUSETTS EYE AND EAR INFIRMARY · 2024 · $578,395

## Abstract

Project 4 – Project Summary
Hearing disorders are typically studied and treated from the perspective of wanting to make inaudible sounds
audible. Yet three of the most common and debilitating adult hearing complaints reflect just the opposite problem:
not what persons cannot hear, but what they cannot stop hearing. Older adults or persons with a history of noise
exposure are often assaulted by the irrepressible perception of phantom sounds (tinnitus), they experience
moderate intensity sounds as loud, distressing, or even painful (hyperacusis), and they struggle to suppress the
awareness of background noise sources when listening to a target speaker. Although age, noise exposure, and
hearing status are risk factors for these perceptual disorders, the connection is indirect at best, prompting much
speculation about the intervening neural processes that may be more closely related. Animal research suggests
that the underlying cause of these disorders may be rooted in a dialog gone wrong between cochlear primary
afferent neurons and neurons in sound processing centers of the brain. Cochlear neural degeneration (CND)
has been shown to trigger a compensatory plasticity process in the central auditory pathway that often over-
shoots the mark, rendering central auditory neurons hyperactive, hypersensitive, hyper-synchronized, and
internally ‘noisy’. A broad consensus from work published in many animal species and hearing loss paradigms
suggests that maladaptive central plasticity that arises as a consequence of CND is proximally linked to the
behavioral manifestation of tinnitus, hyperacusis, and selective difficulties hearing in noise. This hypothesis has
been difficult to test in human subjects owing to the challenge of measuring risk factors, auditory peripheral
status, central plasticity signatures, and detailed behavioral phenotyping of these hearing disorders in the same
subjects. Here, by performing central neural, autonomic, and psychophysical measurements in the same
subjects that have also undergone extensive auditory peripheral testing in Project 3, we have developed an
innovative and exhaustive approach to put this hypothesis to the test in human subjects. Aim 1 of Project 4 will
use novel EEG measures to test the hypothesis that more pronounced levels of estimated CND (CNDe) is
associated with increased neural gain, poor neural encoding of rapid stimulus temporal features, and poor neural
suppression of task-irrelevant noise sources. Aim 2 will utilize novel autonomic measures of sound-evoked
changes in pupil dilation, skin conductance, heart rate, and micro facial expressions to test the hypothesis that
more pronounced CNDe is associated with abnormally strong autonomic recruitment during effortful listening
and in response to emotionally evocative sounds. Aim 3 will combine the neural and autonomic measures above
with detailed behavioral phenotyping. Using causal mediation analysis, Aim 3 will determine how CNDe, central
gain, temporal en...

## Key facts

- **NIH application ID:** 10896026
- **Project number:** 5P50DC015857-08
- **Recipient organization:** MASSACHUSETTS EYE AND EAR INFIRMARY
- **Principal Investigator:** Daniel B. Polley
- **Activity code:** P50 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $578,395
- **Award type:** 5
- **Project period:** 2017-08-02 → 2027-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10896026

## Citation

> US National Institutes of Health, RePORTER application 10896026, Maladaptive central plasticity and suprathreshold hearing disorders in humans with sensorineural hearing loss and their relation to biomarkers of cochlear synaptopathy (5P50DC015857-08). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10896026. Licensed CC0.

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