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Cortical reorganization and signal-in-noise processing following asymmetric hearing loss

不对称听力损失后的皮质重组和噪声处理

基本信息

批准号：
10063506
负责人：
James Bigelow
金额：
$ 7.26万
依托单位：
UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
依托单位国家：
美国
项目类别：
财政年份：
2018
资助国家：
美国
起止时间：
2018-12-01 至 2021-11-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10063506
关键词：
Adult Affect Anesthesia procedures Animals Auditory Auditory area Auditory system Behavioral Binaural Biological Markers Cells Characteristics Clinical Cochlea Communication Comprehension Contralateral Data Set Development Disabled Persons Discrimination Disease Ear Elements Environment Evaluation Exhibits Exposure to Foundations Frequencies Functional disorder Future Genetic Goals Hearing Human Impaired cognition Impairment Interneuron function Interneurons Intervention Intuition Knowledge Link Measures Mind Mus Neurons Noise Outcome Parvalbumins Pathology Patients Performance Peripheral Preparation Property Quality of life Receptor Cell Recovery Research Research Personnel Resources Role Signal Transduction Sound Localization Speech Speech Perception Stimulus Testing Tinnitus Training Transgenic Mice Underserved Population asymmetric hearing loss auditory discrimination auditory pathway awake behavioral impairment behavioral response disability experimental study extracellular functional restoration hearing impairment improved indexing inhibitory neuron insight interest mouse model normal hearing novel optogenetics receptive field rehabilitation strategy relating to nervous system response speech processing tool

项目摘要

PROJECT SUMMARY The consequences of asymmetric peripheral dysfunction are especially profound in the auditory system, where cochlear receptor cells are not spatially organized. Thus, auditory spatial information is available exclusively through central processing of binaural signals. Asymmetric hearing loss (AHL), which is one of the most common forms of hearing impairment, profoundly disrupts spatial hearing and related functions such as differentiating spatially-separated signals in noise (SIN). Remarkably, disabilities across hearing domains are generally more severe in AHL patients than in equivalent cases of symmetric hearing loss (SHL), and more severe than predicted by peripheral dysfunction. These disabilities are further compounded by problematic downstream outcomes including tinnitus, cognitive impairment, and reduced quality of life. Increasing recognition of the severe disabilities associated AHL has generated interest in a thorough understanding of its central consequences, especially reorganization at the level of primary auditory cortex (ACtx). Binaural cortical plasticity is traditionally assessed by shifts in characteristic frequency (CF) estimates obtained from the hemisphere contralateral to the impaired ear. In general, CFs obtained from the impaired ear shift toward frequencies of surviving cochlear cells. Although previous research has focused on shifts in spectral processing, evaluation of changes in alternative response characteristics are needed to understand the neural basis of the profound deficits in processing speech and SIN observed in AHL patients. Moreover, although difficulties understanding SIN, such as speech in noisy environments, constitutes the largest clinical challenge in AHL, no previous studies have directly investigated SIN processing in the central auditory pathway, or in controlled animal behavioral experiments. The knowledge obtained in such preparations could generate novel insights into the mechanisms underlying this debilitating condition and greatly facilitate the development of new clinical interventions. With these goals in mind, we propose to conduct a multifaceted analysis of altered SIN processing and cortical receptive field alteration following AHL using a transgenic mouse model. We will augment classic pure-tone response metrics such as CF and threshold with spectrotemporal receptive field (STRF) parameters including excitation-inhibition (E-I) ratio and temporal processing capabilities, which are critical for perception of speech and SIN. We will further provide a detailed description of disrupted cortical SIN processing in AHL by presenting elements of vocal communication signals in a range of competing background noise levels. We will compare these outcomes to behavioral deficits in SIN processing in mice performing an auditory discrimination task. The wealth of new insights made possible by this approach are capable of resolving numerous outstanding questions regarding central reorganization in AHL. As a result, clinical researchers will be equipped with new and better-defined central biomarkers of AHL, facilitating the development of improved rehabilitation strategies.

项目摘要非对称性外周功能障碍的后果在听觉系统中尤其严重，耳蜗感受器细胞不是空间组织的。因此，听觉空间信息是唯一可用的通过双耳信号的中央处理。非对称性听力损失（AHL），这是一个最重要的常见形式的听力障碍，严重破坏空间听觉和相关功能，如区分噪声中的空间分离信号（SIN）。值得注意的是，听力领域的残疾 AHL患者通常比对称性听力损失（SHL）的同等病例更严重，比外周功能障碍预测的严重。这些残疾因问题而进一步加剧，下游结果包括耳鸣、认知障碍和生活质量下降。增加认识到与AHL相关的严重残疾，中枢后果，特别是初级听觉皮层（ACtx）水平的重组。双耳皮质可塑性传统上是通过特征频率（CF）估计值的变化来评估的，受损耳朵的对侧半球。一般来说，从受损耳获得的CF向存活耳蜗细胞的频率。虽然以前的研究集中在光谱的变化，处理，评估替代反应特征的变化，以了解神经系统的变化。这是基于在AHL患者中观察到的言语处理和SIN的严重缺陷。而且虽然理解SIN的困难，例如在嘈杂环境中的语音，构成了最大的临床挑战在AHL中，以前的研究没有直接研究过中枢听觉通路中的SIN处理，或者受控动物行为实验在这种制备中获得的知识可以产生新的深入了解这种衰弱状况的机制，大大促进了新的临床干预。考虑到这些目标，我们建议对改变的SIN进行多方面的分析使用转基因小鼠模型，观察AHL后大脑皮层的加工和皮层感受野的改变。我们将用谱时感受野增强经典纯音反应指标，如CF和阈值（STRF）参数，包括兴奋-抑制（E-I）比和时间处理能力，其是对言语和SIN的感知至关重要。我们将进一步提供一个破坏皮质SIN的详细描述通过在一系列竞争背景中呈现语音通信信号的元素来处理AHL noise levels.我们将比较这些结果与在小鼠中SIN处理的行为缺陷，听觉辨别任务这种方法所带来的丰富的新见解能够解决有关AHL中央重组的许多悬而未决的问题。因此，临床研究人员将配备新的和更好定义的AHL中心生物标志物，制定更好的康复战略。