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

项目总结 不对称外周功能障碍的后果在听觉系统中尤其深刻，在那里 耳蜗感受器细胞在空间上没有组织。因此，听觉空间信息是唯一可用的 通过对双耳信号进行中央处理。不对称听力损失(AHL)，这是最严重的 常见形式的听力障碍，严重扰乱空间听力和相关功能，如 在噪声中区分空间分离的信号(SIN)。值得注意的是，跨听力领域的残疾 AHL患者通常比同等情况下的对称性听力损失(SHL)更严重，而且更多 比预期的外周功能障碍严重。这些残疾进一步加剧了有问题的 下游结果包括耳鸣、认知障碍和生活质量下降。渐增 对与AHL相关的严重残疾的认识引起了人们对彻底了解其 中枢性后果，特别是初级听觉皮质(ACTx)水平的重组。双耳皮质 传统上，塑性是通过特征频率(CF)估计的变化来评估的，这些估计是从 受损耳朵的对侧半球。一般情况下，从受损耳朵获得的CFS向 存活的耳蜗细胞的频率。尽管之前的研究集中在光谱的变化上 为了理解神经，需要对替代反应特征的变化进行处理、评估 在AHL患者中观察到严重的语音处理缺陷和SIN基础。而且，虽然 理解罪恶的困难，例如在嘈杂环境中的言语，构成了最大的临床挑战。 在AHL中，以前没有研究直接研究SIN在中枢听觉通路中的处理，或在 受控动物行为实验。在这种准备过程中获得的知识可以产生新的 对这种衰弱状况背后的机制的洞察，并极大地促进新的 临床干预。考虑到这些目标，我们建议对改变的罪进行多方面的分析 使用转基因小鼠模型研究急性淋巴细胞性白血病后的加工和皮质感受野改变。我们会 使用频域感受场增强经典纯音反应指标，如CF和阈值 (STRF)参数，包括激发-抑制(E-I)比和时间处理能力，它们是 对言语和罪过的感知至关重要。我们将进一步提供中断的皮质犯罪的详细描述 在AHL中通过在一系列竞争背景中呈现语音通信信号元素来进行处理 噪音水平。我们将把这些结果与SIN处理的小鼠的行为缺陷进行比较 听觉辨别任务。这种方法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，临床上 研究人员将配备新的和更明确的AHL中央生物标记物，促进 制定改进的康复战略。

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.