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: 10394729
• 负责人: Achim Klug
• 金额: $ 54.09万
• 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/10394729
• 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.

项目概要 在任何老龄化社会中，最常见的疾病之一是老年性耳聋，或与年龄相关的听力损失。 大约三分之一的美国成年人通常从中年开始患有这种疾病，并且 大约一半 70 岁以上的成年人有严重的听力障碍。其机制之一是 老年性耳聋发生在中枢神经系统，称为中枢性听力损失。患有中枢神经系统的老年人 听力损失的人可能有正常或接近正常的听力图，但在进行对话时存在问题 复杂环境，即多个声源同时处于活动状态的情况，例如繁忙的环境 餐厅、公共场所或任何有背景噪音的场所。造成这种情况的主要原因 困难在于受影响的个体难以在感知上隔离感兴趣的声音源（例如， 他们想听的说话者的声音）有效地从其他来源，大概是因为神经 执行此计算的机制效率较低。我们提出了一个组合的人类受试者和 动物模型研究来解决这个问题。具体来说，我们建议研究与年龄相关的贡献 位于听觉脑干的声音定位通路的变化导致了这种现象。这 该提案的总体假设是声音定位中神经活动的精确计时 通路随着年龄的增长而衰退，导致双耳听力和声音定位能力的精确度降低。我们 假设这些变化导致复杂声学中行为表现的下降 人类和动物模型中的环境。对于人体部分，我们将测试声音 “年轻”和“年长”听众的噪音能力的定位和听力，并将行为下降联系起来 老年听众的声音定位中神经活动的时间精度下降 途径（目标 1）。我们将展示老年蒙古沙鼠重现这些与年龄相关的变化，使得 它们是研究人类状况的良好模型（目标 2）。然后我们将探索背后的细胞机制 神经活动的时间精度降低（目标 3）。这项研究的预期结果将有助于 确定声音定位通路在这种常见疾病中的作用，将有助于诊断 中枢性听力损失更客观，将直接提示未来医学发展的机制 干预措施，并将有助于解决健康老龄化的关键挑战。