# Suprathreshold processing and binaural interaction in rhesus macaques with cochlear synaptopathy

> **NIH NIH F31** · VANDERBILT UNIVERSITY · 2021 · $31,266

## Abstract

ABSTRACT
As many as 15% of patients in audiology clinics have normal hearing thresholds, but struggle to understand
speech in noise. Understanding speech in noisy environments requires perceptual analysis of suprathreshold
sound features, in contrast to audiometric threshold, which is an estimate of the softest sound a listener can
detect. These suprathreshold processing deficits that normal hearing patients exhibit cannot be treated
currently because their basis in the auditory pathway is not well established. A promising explanation is
cochlear synaptopathy, which refers to inner hair cell synapse loss. Synaptopathy leaves thresholds
unaffected, but degrades the encoding of suprathreshold sounds as measured by the auditory brainstem
response (ABR), and alters excitatory-inhibitory balance in the auditory pathway, which is required for
encoding spatial and temporal sound features. Corroborating evidence from the human literature comes in the
form of studies showing that normal hearing subjects display substantial individual differences in
neurophysiological and behavioral measures of spatial and temporal processing. In particular, the binaural
interaction component (BIC) of the ABR is compromised in patients with this profile. Importantly, the BIC may
depend on subcortical inhibition, which is compromised by synaptopathy. Despite these compelling links
between suprathreshold processing deficits and the neurophysiological effects of synaptopathy, there is no
direct evidence that synaptopathy causes perceptual deficits. This is largely because synaptopathy can only be
verified via post-mortem cochlear histology, and perceptual measures have rarely been used in animal studies
of synaptopathy. Moreover, studies of synaptopathy have only used rodents, which differ from primates in their
inhibitory neurotransmission, and perceptual measures of spatial and temporal processing. Such differences
could complicate the translation of neurophysiological and behavioral findings into diagnostic and therapeutic
innovations. It is for these reasons that we propose using our nonhuman primate model of cochlear
synaptopathy to link anatomical, neurophysiological, and perceptual effects of synaptopathy. We propose
studying the effects of synaptopathy on temporal and spatial processing to establish synaptopathy's perceptual
effects (Aim 1), and linking those effects with a neurophysiological correlate of spatial hearing – the BIC of the
ABR (Aim 2). Both temporal and spatial processing will be studied in detection and discrimination paradigms,
with the expectation the discrimination tasks will show the largest deficits, and that synaptopathy, and
degraded BIC, will correlate with these deficits. These links will provide an explanation of how synaptopathy
and its neural consequences can cause deficits in normal hearing subjects, and will form the basis for
noninvasive diagnostic tests for synaptopathy in humans.

## Key facts

- **NIH application ID:** 10386444
- **Project number:** 1F31DC019823-01A1
- **Recipient organization:** VANDERBILT UNIVERSITY
- **Principal Investigator:** Chase Mackey
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $31,266
- **Award type:** 1
- **Project period:** 2021-09-01 → 2024-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10386444

## Citation

> US National Institutes of Health, RePORTER application 10386444, Suprathreshold processing and binaural interaction in rhesus macaques with cochlear synaptopathy (1F31DC019823-01A1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10386444. Licensed CC0.

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