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，最常见的疾病之一是老年性耳聋，即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，而且 在70岁以上的成年人中，约有一半患有严重的听力障碍。其中一种机制是 老年性耳聋发生在中枢神经系统，被称为中枢性听力损失。老年人患有中枢神经 听力损失可能有正常或接近正常的听力图，但在进行对话方面存在问题 复杂环境，即多个声源同时处于活动状态的情况，例如忙音 餐厅、公共场所或任何背景噪音活跃的场合。这其中的主要原因 困难在于受影响的个人难以感知地隔离感兴趣的声音来源(例如， 他们想听的说话者的声音)有效地来自其他来源，想必是因为神经 执行这种计算的机制效率较低。我们提出了一个综合的人类研究对象和 动物模型研究来解决这个问题。具体地说，我们建议研究与年龄相关的 位于听觉脑干的声音定位通路的变化对这一现象的影响。这个 这一建议的首要假设是声音定位内神经活动的准确时间 通路随着年龄的增长而下降，导致双耳听力和声音定位能力较差。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。对于人工组件，我们将测试声音 “青年”和“老年”听者噪声能力的定位和听力，并与行为能力下降有关 老年听者对声音定位中神经活动时间精确度降低的表现 途径(目标1)。我们将展示年迈的蒙古沙鼠概括了这些与年龄相关的变化，使 它们是研究这一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(目标3)。这项研究的预期结果将有所帮助 确定声音定位通路在这种常见医学状况中的作用，将有助于诊断 中枢性听力损失更加客观，将直接为未来医学的发展提供机制建议 干预措施，并将有助于解决健康老龄化的一个关键挑战。

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.