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

项目摘要 在任何老龄化社会中，最常见的医疗条件之一是老年性耳聋，或与年龄相关的听力损失。 大约三分之一的美国成年人患有这种疾病，通常从中年开始， 70岁以上的成年人中约有一半患有严重的听力障碍。的机制之一 老年性耳聋发生在中枢神经系统，称为中枢性听力损失。老年人与中央 听力损失可能具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，即多个声源同时活动的情况，例如忙碌的 餐厅、公共场所或任何背景噪音活跃的场所。其主要原因 困难在于受影响的个体在感知上难以隔离感兴趣的声源（例如，的 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 执行这种计算的机制效率较低。我们提出了一个结合人类的主题， 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有关的 声音定位通路的变化，位于听觉脑干，这种现象。的 这一建议的首要假设是，在声音定位内神经活动的精确定时 随着年龄的增长，听觉通路功能下降，导致双耳听力和声音定位能力不太精确。我们 假设这些变化有助于降低复杂声学中的行为表现， 在人类和动物模型中的环境。对于人的部分，我们将测试声音 “年轻”和“老年”听众的噪声能力的定位和听力，并与行为减少有关 老年听众的表现，以降低声音定位中神经活动的时间精度 途径（目标1）。我们将证明，老年蒙古沙鼠重演这些与年龄有关的变化， 他们是研究这种人类状况的良好模型（目标2）。然后，我们将探索细胞机制背后的 神经活动的时间精确度降低（目的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疾病中的作用，将有助于诊断 中枢性听力损失的研究更客观，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。

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.