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

摘要 听力测试，或对语音理解至关重要的频率的阈值测试，是最常见的和 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到， 严重的内耳损伤，阈值测量没有发现，听力受损的人 个体在听力的功能指标上可能会有很大的差异，例如在噪音中甚至 有相似阈值且没有耳蜗后病理证据的个体。这些发现有 引起了人们对“隐性听力损失”的极大兴趣，“隐性听力损失”的特点是内耳损伤未被发现 通过门槛措施。现在有猜测说，传入突触的丢失可能是噪音听力的基础。 听力障碍、听觉过敏症和耳鸣。然而，功能性缺陷的证据是什么？这些缺陷是从哪里产生的？ 赤字开始了吗？令人惊讶的是，目前没有证据表明有任何重大的功能缺陷与 在动物中存在突触，而在人类中没有令人信服的证据。因此，至关重要的是要确定 与隐性听力损失相关的功能缺陷何时开始的临界界限。建立 内毛细胞(IHC)或突触丢失等特定耳蜗性损伤模式之间的关系 而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，并对早期发病或未发现的听力损失进行干预。 这项建议的总体目标是评估功能性听力障碍的动物模型 噪声暴露或选择性耳毒性丧失内毛细胞对传入突触的降解作用 没有相应的门槛高程。具体地说，这种“隐藏的”但意义重大的影响是什么？ 噪声中听、强度辨别、前掩蔽、耳鸣和生理学的耳蜗病理学 功能性听力的相关因素？这些赤字是什么时候开始的？完成后，这项工作将明确定义 功能缺陷包括由噪音暴露或卡铂引起的“隐性听力损失”。 这些数据将提供迫切需要的证据，以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，增强病变诊断的位置，并揭示 用于康复目的的隐性功能缺陷目标。

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.