Age and hearing loss effects on subcortical neural encoding

项目摘要 言语识别困难在老年人和年龄相关性听力损失（ARHL）患者中很常见， 特别是在复杂的环境中。中枢听觉系统的适应不良性过度兴奋， 中枢增益，是已知的发生与年龄和听力损失，并可能有助于改变时间处理 以及随后的噪声中语音（SIN）缺陷。对人类中枢增益的研究通常集中在大脑皮层 过度活跃，但研究表明，皮层下过度活跃，特别是夸大的声音编码， 起始点和低频幅度调制包络（如语音中常见的包络）可能存在于 老年人和听力受损的成年人的听觉中脑，并发挥更大的影响SIN的困难， 以前认为。然而，我们目前缺乏一个清晰的理解的背景下，皮层下 多动存在于年龄和ARHL以及它如何与行为相关。这使长期努力复杂化， 开发药物和行为干预，以改善SIN缺陷。的首要目标 拟议的研究是表征如何超敏刺激起始和调制包络 定位于听觉中脑的是（1）老年人比年轻人更普遍，（2）与下丘脑有关。 丘结构，（3）预测老年人听力损失（与年龄无关），（4）与 SIN缺陷。实验使用电生理学，结构神经成像， 源定位以表征由皮层下发生器部位（例如，下 丘）在安静和噪音。为了量化中脑相对于外周的高反应性， 下丘反应是标准化的听觉神经反应。目的1检查多动症是否是 相对于年轻人，老年人更普遍，无论耳蜗压缩是否减少， 与ARHL导致增强信封编码在安静，并评估如何中脑微结构 与GABA能变化相关的特征（例如纵向弛豫时间，R1）涉及 过敏和潜在的介导年龄效应。目的2探讨中脑超敏反应如何预测 行为，测试更大的超敏性有利于安静时的感知的假设（例如，较佳振幅 安静时的调制（AM）辨别）而不是噪声中的感知（例如，SIN测试性能较差， 噪声中的AM辨别力较差）。结果可以促进我们对信封的背景的理解， 和声音起始高反应性存在于皮层下听觉系统，如何最好地量化它， 它是有利于感知还是阻碍感知。研究结果将为未来的皮层下神经元的研究提供信息。 多动，不仅提高了我们对老年人SIN困难的理解，而且还确定了 临床干预需要考虑皮质下结构和功能下降的程度。与 随着老龄化（和听力受损）人口的逐年增长，这项研究具有很高的

PROJECT SUMMARY Speech recognition difficulties are common for older adults and those with age-related hearing loss (ARHL), particularly in complex environments. Maladaptive hyperexcitability in the central auditory system, a form of central gain, is known to occur with age and hearing loss and may contribute to altered temporal processing and subsequent speech-in-noise (SIN) deficits. Studies of central gain in humans often focus on cortical hyperactivity, yet research suggests that subcortical hyperactivity, notably exaggerated encoding of sound onsets and low-frequency amplitude modulation envelopes (like those common in speech), may be present in the auditory midbrain of older and hearing-impaired adults and exert a larger influence on SIN difficulties than previously thought. However, we currently lack a clear understanding of the contexts in which subcortical hyperactivity exists in age and ARHL and how it relates to behavior. This complicates long-term efforts to develop pharmaceutical and behavioral interventions to ameliorate SIN deficits. The overarching goal of the proposed research is to characterize how hypersensitivities to stimulus onsets and modulation envelopes localized to the auditory midbrain are (1) more prevalent for older than younger adults, (2) related to inferior colliculus structure, (3) predicted by hearing loss in older adults (independently of age), and (4) associated with SIN deficits. Experiments use an innovative combination of electrophysiology, structural neuroimaging, and source localization to characterize neural responses arising from subcortical generator sites (e.g. inferior colliculus) in both quiet and noise. To quantify hyperresponsivities in the midbrain relative to the periphery, inferior colliculus responses are normalized auditory nerve responses. Aim 1 examines whether hyperactivity is more prevalent in older adults relative to younger adults, whether diminished cochlear compression associated with ARHL leads to enhanced envelope encoding in quiet, and assesses how midbrain microstructural characteristics that have been associated with GABAergic changes (e.g. longitudinal relaxation time, R1) relate to hypersensitivity and potentially mediate age effects. Aim 2 examines how midbrain hypersensitivity predicts behavior, testing the hypothesis that greater hypersensitivity benefits perception in quiet (e.g., better amplitude modulation (AM) discrimination in quiet) but not perception in noise (e.g., poorer performance on SIN tests, poorer AM discrimination in noise). Results can advance our understanding of the contexts in which envelope and sound onset hyperresponsivities are present in the subcortical auditory system, how best to quantify it, and whether it alternately benefits or impedes perception. Findings will inform future studies of subcortical neural hyperactivity and not only improve our understanding of SIN difficulties of older adults, but also determine the extent to which clinical interventions need to consider declines in subcortical structure and function. With the aging (and hearing-impaired) population growing yearly, this research has high