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Physiological Signatures and Behavioral Correlates of Hidden Hearing Loss

隐性听力损失的生理特征和行为相关性

基本信息

批准号：
10318936
负责人：
Ramnarayan Ramachandran
金额：
$ 64.25万
依托单位：
VANDERBILT UNIVERSITY MEDICAL CENTER
依托单位国家：
美国
项目类别：
财政年份：
2018
资助国家：
美国
起止时间：
2018-01-10 至 2024-12-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10318936
关键词：
Acoustic Nerve Adult Affect Anatomy Animal Model Animals Attention Auditory Brainstem Responses Auditory Perception Auditory Threshold Behavior Behavioral Clinical Cochlea Code Communication Communication impairment Complex Control Animal Control Groups Cues Data Detection Diagnostic Environment Exposure to Fiber Genetic Hair Cells Hearing High Prevalence Histologic Histology Human Impairment Inner Hair Cells Macaca Masks Measurement Measures Methods Modeling Monkeys Nerve Fibers Noise Noise-Induced Hearing Loss Pattern Perception Performance Physiological Physiology Predisposition Prevalence Primates Process Process Measure Recovery Reflex action Research Rodent Rodent Model Severities Signal Transduction Speech Perception Stimulus Temporary Threshold Shift Testing Time Ursidae Family base behavior measurement cohort dosage ear muscle experimental study exposed human population hearing impairment hidden hearing loss histological studies middle ear neurophysiology noise exposure nonhuman primate normal hearing pressure programs response ribbon synapse sound species difference speech in noise speech processing stimulus processing

项目摘要

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 synaptopathy on auditory perception. Results of our coordinated research program will be used to develop reliable, clinically viable physiological and behavioral indicators of human synaptopathy.

摘要

项目成果

期刊论文数量（6）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Audiologic characterization using clinical physiological measures: Normative data from macaque monkeys.

DOI：
10.1016/j.heares.2022.108568
发表时间：
2022-10
期刊：
HEARING RESEARCH
影响因子：
2.8
作者：
Stahl, Amy N.;Mondul, Jane A.;Alek, Katy A.;Hackett, Troy A.;Ramachandran, Ramnarayan
通讯作者：
Ramachandran, Ramnarayan

An assessment of ambient noise and other environmental variables in a nonhuman primate housing facility.