Effects of Age-related Cochlear Synaptopathy on Speech-in-noise Intelligibility: A Cross-species Approach

年龄相关的耳蜗突触病对噪声中语音清晰度的影响：跨物种方法

• 批准号: 10360725
• 负责人: Aravindakshan Parthasarathy
• 金额: $ 19.12万
• 依托单位: UNIVERSITY OF PITTSBURGH AT PITTSBURGH
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-03-01 至 2025-02-28
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10360725
• 关键词: ATPase inhibitory protein; Acoustic Nerve; Address; Adult; Affect; Age; Age-Years; Aging; Anatomy; Animal Experimentation; Animal Model; Animals; Auditory; Auditory Threshold; Autopsy; Behavioral; Biological Markers; Birth; Clinic; Clinical; Cochlea; Code; Cognitive; Communication; Complex; Cues; Data; Development; Diagnostic; Diagnostic tests; Dose; Elderly; Electrophysiology (science); Exhibits; Frequencies; Future; Gerbils; Goals; Hearing; Hearing Tests; Hearing problem; Histologic; Human; Individual; Infusion procedures; Inner Hair Cells; Intervention; Labyrinth; Lead; Link; Measurement; Measures; Methods; Nerve; Nerve Fibers; Ouabain; Patients; Performance; Peripheral; Phase; Presbycusis; Quality of life; Research; Rodent Model; Role; Specimen; Speech; Speech Intelligibility; Speech Perception; Stimulus; Structure; Synapses; Testing; Therapeutic Intervention; Translations; age effect; age related; auditory pathway; base; cochlear synaptopathy; comorbidity; design; efficacy testing; experience; experimental study; hearing impairment; hearing range; help-seeking behavior; hidden hearing loss; human model; indexing; innovation; juvenile animal; middle age; normal hearing; novel diagnostics; preclinical study; programs; relating to nervous system; response; response biomarker; speech in noise; translational approach

Project Summary Age-related hearing loss is exceedingly common, with an estimated 60% of individuals over 70 years of age having hearing loss significant enough to interfere with communication and affect quality of life. However, increasing evidence suggests that the overt loss of hearing thresholds alone fails to capture real-world hearing difficulties experienced by older adults. One hitherto undiagnosed cause of hearing deficits could be the progressive loss of synapses between the inner hair cell and the auditory nerve with age, termed cochlear synaptopathy. Cochlear synaptopathy is thought to affect speech intelligibility under complex listening conditions, yet it goes undetected by the threshold audiogram, remaining ‘hidden’. While the functional consequences of cochlear synaptopathy are still unclear, emerging evidence suggests that it is associated with deficits in representation of timing cues in the auditory periphery. This may differentially affect the encoding of rapid stimulus temporal fine structure (sTFS) cues in speech, which are critical for listening in noisy conditions. Establishing the effects of cochlear synaptopathy on decreased speech-in-noise intelligibility cannot be accomplished in a single species. Perceptual deficits observed in humans cannot be attributed directly to cochlear synaptopathy, because anatomical synaptopathy is only verifiable in post-mortem specimens. Rodent models offer the means to directly measure cochlear synaptic integrity but are limited in their potential to serve as models of human speech perception under real-world settings. This proposal addresses these translational challenges by integrating research in humans and animal models, with non-invasive electrophysiological responses measured under near identical conditions in both humans and animal models acting as the translational bridge. Experiments in Aim 1 will use a battery of behavioral and electrophysiological methods in humans to test the hypothesis that degradations in speech-in-noise intelligibility with age are accompanied by altered neural coding of sTFS cues. In Aim 2, the role of age-related cochlear synaptopathy in degraded sTFS processing will be studied in an animal model whose hearing range is sensitive to human speech frequencies, using the electrophysiological biomarkers of sTFS processing validated in humans. Aim 3 will isolate contributions of cochlear synaptopathy to the neural coding of sTFS cues from possible confounding age-related effects by inducing graded synaptopathy in young animals and evaluating the same electrophysiological and immunohistological markers used in Aim 2. The completion of this project has the potential to result in a single biomarker that links cochlear synaptopathy to deficits in speech-in-noise intelligibility. The project will further establish an integrated research pipeline that can accelerate the translation of pre-clinical studies to early human trials for future biomarkers or interventional therapies. Finally, the data obtained here will form the basis for future studies that will follow this translational approach to explore the interactions between age-related cochlear synaptopathy, peripheral threshold sensitivity, and compensatory plasticity in the central auditory pathway.

项目总结