The contributions of age related changes in the sound localization pathway to central hearing loss

声音定位路径中与年龄相关的变化对中枢性听力损失的贡献

• 批准号: 10164754
• 负责人: Achim Klug
• 金额: $ 57.81万
• 依托单位: UNIVERSITY OF COLORADO DENVER
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-06-07 至 2024-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10164754
• 关键词: Acoustic Nerve; Acoustics; Address; Adult; Affect; Age; Aging; American; Animal Model; Animals; Area; Audiology; Auditory; Auditory Threshold; Axon; Behavioral; Binaural; Biological Models; Brain; Brain Stem; Cell Nucleus; Central Hearing Loss; Cessation of life; Clinical; Cochlea; Cochlear nucleus; Complex; Crowding; Data; Demyelinations; Development; Diagnosis; Elderly; Electrophysiology (science); Environment; Future; Gerbils; Glycine Receptors; Goals; Hair Cells; Health; Hearing; Hearing Tests; Human; Impairment; Individual; Intervention; Kinetics; Link; Location; Measurement; Measures; Medial; Medical; Minor; Modeling; Neuraxis; Neurons; Noise; Output; Pathway interactions; Patients; Performance; Positioning Attribute; Presbycusis; Property; Research; Restaurants; Rodent; Role; Sensorineural Hearing Loss; Series; Societies; Sound Localization; Source; Speed; Structure; Study models; Synapses; Testing; Therapeutic; Time; Trapezoid bone structure; Voice; age related; aged; auditory pathway; base; behavior test; binaural hearing; brain stem auditory evoked potentials; experimental study; healthy aging; hearing impairment; human model; human subject; interest; lateral superior olive; middle age; nerve damage; neuromechanism; relating to nervous system; sound; speech in noise; therapy development

Project Summary One of the most common medical conditions in any aging society is presbycusis, or age-related hearing loss. Approximately one third of American adults suffer from this condition typically starting at middle age, and about half of adults over 70 years have a substantial hearing impairment. One of the mechanisms of presbycusis happens in the central nervous system and is termed central hearing loss. Older adults with central hearing loss may have normal or near normal audiograms yet have problems carrying on a conversation in complex environments, i.e. situations where multiple sound sources are active at the same time, such as a busy restaurant, a public place, or any situation where background noises are active. The main reason for this difficulty is that affected individuals have trouble perceptually isolating sound sources of interest (e.g., the voice of the speaker they want to listen to) effectively from other sources, presumably because the neural mechanisms that perform this computation are less effective. We propose a combined human subjects and animal model study to tackle this issue. Specifically, we propose to study the contribution of age-related changes in the sound localization pathway, located in the auditory brain stem, to this phenomenon. The overarching hypothesis of this proposal is that precise timing of neural activity within the sound localization pathway declines with age, leading to less precise binaural hearing and sound localization abilities. We hypothesize that these changes contribute to decreased behavioral performance in complex acoustic environments in both humans and animal models. For the human component, we will test the sound localization and hearing in noise abilities of “young” and “old” listeners, and relate decreased behavioral performance in older listeners to decreased temporal precision of neural activity in the sound localization pathway (aim 1). We will show that aged Mongolian gerbils recapitulate these age-related changes, making them good models to study this human condition (aim 2). We will then explore cellular mechanisms behind the decreased temporal precision of neural activity (aim 3). The expected results from this study will help determine the role of the sound localization pathway in this common medical condition, will help diagnose central hearing loss more objectively, will directly suggest mechanisms for the development of future medical interventions, and will help resolve a key challenge to healthy aging.

项目摘要 任何老龄化社会中最常见的医疗状况之一是老年人或与年龄有关的听力损失。 大约三分之一的美国成年人通常从中年开始遭受这种疾病，并且 大约一半的成年人超过70年，有很大的听力障碍。一种机制之一 长老会发生在中枢神经系统中，被称为中央听力损失。中央老年人 听力损失可能具有正常的或接近正常的听力图，但在对话中进行对话问题 复杂的环境，即多个声源同时处于活动状态的情况，例如忙碌 餐厅，公共场所或背景噪音活跃的任何情况。主要原因 困难的是，受影响的个体在感知上孤立了感兴趣的声音源（例如， 他们想从其他来源有效听的说话者的声音，大概是因为中立 执行此计算的机制效率较低。我们提出了一个合并的人类主题， 动物模型研究以解决此问题。具体而言，我们建议研究与年龄相关的贡献 在听觉脑干中的声音定位途径的变化到这种现象。这 该提议的总体假设是声音本地化中神经活动的精确时机 途径随着年龄的增长而下降，导致双耳听力和声音定位能力降低。我们 假设这些变化有助于复杂声学的行为表现降低 人类和动物模型的环境。对于人类组成部分，我们将测试声音 “年轻”和“老”听众的噪音能力的本地化和听力，并提高了行为 在较老的听众中的表现降低了声音定位中神经活动的临时精度 途径（目标1）。我们将表明，老年蒙古的沙鼠概括了这些与年龄有关的变化，从而使 他们可以研究这种人类状况的良好模型（AIM 2）。然后，我们将探索后面的细胞机制 神经活动的临时精度降低（AIM 3）。这项研究的预期结果将有助于 确定声音定位途径在这种常见的医疗状况中的作用，将有助于诊断 中央听力损失更具客观地，将直接提出开发未来医学的机制 干预措施，将有助于解决健康衰老的关键挑战。