Effect of Inner Hair Cell Loss and Afferent Damage on Functional Hearing

摘要 听力测定或对言语理解至关重要的频率进行阈值测试是最常见和最常见的方法。 普遍接受的听力健康指标。然而，从动物研究中可以清楚地看出， 是阈值测量未检测到的严重内耳损伤以及听力受损者 个体的听力功能指标可能存在很大差异，例如在噪音中的听力，甚至 具有相似阈值且没有耳蜗后病理证据的个体。这些发现有 对“隐性听力损失”产生了极大的兴趣，其特征是内耳损伤未被发现 通过阈值措施。现在有人猜测传入突触的丧失可能是噪音听力的原因 缺陷、听觉过敏和耳鸣。然而，功能缺陷的证据是什么？这些证据在哪里？ 赤字开始？令人惊讶的是，目前没有证据表明任何与此相关的重大功能缺陷 动物突触病，但在人类中没有令人信服的证据。因此，有必要确定 与隐性听力损失相关的功能缺陷何时开始的关键界限。建立 耳蜗损伤的特定模式之间的关系，例如内毛细胞 (IHC) 或突触的丧失 阈值未检测到的相应功能缺陷对于理解风险因素至关重要， 早期发现并干预早期发病或未被发现的听力损失。 该提案的总体目标是评估动物模型中的功能性听力障碍 使用噪声暴露或选择性耳毒性损失内毛细胞来降解传入突触 缺乏相应的阈值升高。具体来说，这种“隐藏”但显着的效果是什么？ 关于噪声听力、强度辨别、前向掩蔽、耳鸣和生理的耳蜗病理学 功能性听力的相关性？这些赤字何时开始？完成后，这项工作将明确定义 噪音暴露或卡铂引起的“隐性听力损失”中包含的功能缺陷。 这些数据将提供迫切需要的证据来指导听觉监测计划的潜在变化 推荐作为听力保护计划的最佳实践，增强病变诊断部位，并揭示 用于康复目的的隐藏功能缺陷目标。

ABSTRACT Audiometry, or threshold testing at frequencies essential for speech understanding, is the most common and universally accepted metric for hearing health. However, it is becoming clear from animal studies that there can be significant inner ear damage that is undetected by threshold measures and among hearing impaired individuals there can be substantial variability in functional metrics of hearing such as hearing in noise even across individuals with similar thresholds and no evidence of retrocochlear pathology. These findings have generated tremendous interest in “hidden hearing loss” characterized by inner ear damage that is undetected by threshold measures. There is now speculation that loss of afferent synapses may underlie hearing-in-noise deficits, hyperacusis, and tinnitus. However, what is the evidence for functional deficits and where do these deficits begin? Surprisingly, there is no current evidence of any significant functional deficits associated with synaptopathy in animals and there is no compelling evidence in humans. Thus, it is essential to determine the critical boundaries for when functional deficits associated with hidden hearing loss begin. Establishing the relationship between specific patterns of cochlear damage such as loss of inner hair cells (IHC) or synapses and the corresponding functional deficits undetected by thresholds are critical in understanding risk factors, early detection, and intervention for early onset or undetected hearing loss. The overall aims of this proposal is to evaluate functional hearing impairment in an animal model with degradation of afferent synapses using noise-exposure or selective ototoxic loss of inner hair cells in the absence of corresponding threshold elevations. Specifically, what is the effect of this “hidden” but significant cochlear pathology on hearing-in-noise, intensity discrimination, forward masking, tinnitus and physiological correlates of functional hearing? When do these deficits begin? When completed, this work will explicitly define the functional deficits encompassed within “hidden hearing losses” induced by noise exposure or carboplatin. These data will provide the evidence urgently needed to guide potential changes to auditory monitoring plans recommended as best practice in hearing conservation programs, enhance site of lesion diagnosis, and reveal hidden functional deficit targets for rehabilitative purposes.