Cochlear Synaptopathy: Prevalence, Diagnosis and Functional Consequences

整体项目总结 对噪音引起的和年龄相关的听力损失的动物研究表明，大多数 内耳中的脆弱因素是毛细胞和感觉神经元之间的突触连接。 这种初级耳蜗神经变性(CND)不会提高阈值，因此，它可以在 毛细胞群完整的耳朵，可以“隐藏”在正常的听力图后面。它可能有助于 在嘈杂的环境中理解语言有困难，可能是导致 耳鸣和听力亢进。CND也可能是广泛的，在获得性疾病中甚至更严重 感音神经性听力损失(SNHL)，即毛细胞受损和阈值升高。因此，它可能是一个 相同者在听觉表现上的众所周知差异的主要原因 显性听力损失的测听模式。 我们的研究中心旨在将这些范式转换的想法从动物模型转移到人类受试者身上。 在综合多条研究思路的基础上，我们设计了一套生理、心理和生理的 我们认为耳蜗功能和听力的行为分析在诊断CND和CND方面最有效 了解其对阈值上听力的影响。在项目1中，我们将电生理测试应用于 暴露在噪声或耳毒性药物下的动物，验证它们在预测潜在CND方面的有效性，并应用 评估CND在耳鸣和听力亢进中作用的行为学方法。在项目2中，我们 研究SNHL患者的尸检材料以直接评估CND的患病率和模式 并评估它在降低单词识别分数方面的作用以及作为耳鸣的风险因素。在……里面 项目3，我们对SNHL患者进行研究，以表征CND的影响，这是从“自下而上”推断的。 外周听觉功能电生理检测对听力困难患者单词辨认的影响 并探讨CND在耳鸣和听力亢进发生中的作用。在项目4中，我们 进一步研究相同的对象，探讨CND对中枢通路神经功能亢进的影响，以及其 “自上而下”对对声音的高反应性的影响，这是耳鸣和耳鸣的临床负担 听觉亢进。 在我们的研究中心，我们利用P50机制来结合来自听觉的研究视角 神经科学和听力学对SNHL最不利方面的协调研究。取得的进展 了解CND的影响以及如何有效地诊断它，随着 毛细胞和耳蜗神经元再生疗法的进展从实验室进入临床试验。

Overall Project Summary Insights from animal studies of noise-induced and age-related hearing loss suggest that the most vulnerable elements in the inner ear are the synaptic connections between hair cells and sensory neurons. This primary cochlear neural degeneration (CND) does not elevate thresholds, thus, it can be widespread in ears with intact hair cell populations and can “hide” behind a normal audiogram. It likely contributes to difficulties understanding speech in a noisy environment and may be an instigating factor in the generation of tinnitus and hyperacusis. CND may also be widespread, and even more severe, in cases of acquired sensorineural hearing loss (SNHL) where there is hair cell damage and threshold elevation. Thus, it may be a major contributor to the well-known differences in auditory performance among people with identical audiometric patterns of overt hearing loss. Our Research Center aims to take these paradigm-shifting ideas from animal models to human subjects. Based on the synthesis of many research threads, we have devised a set of physiological, psychophysical and behavioral assays of cochlear function and hearing that we believe are most powerful in diagnosing CND and understanding its effects on suprathreshold hearing. In Project 1, we apply electrophysiological tests to animals exposed to noise or ototoxic drugs and validate their utility in predicting the underlying CND and apply behavioral approaches to assess the role of CND in generating tinnitus and hyperacusis. In Project 2, we study human autopsy material from subjects with SNHL to directly assess the prevalence and patterns of CND in humans and to evaluate its role in compromising word-recognition scores and as a risk factor for tinnitus. In Project 3, we study patients with SNHL to characterize the effects of CND, as inferred from “bottom-up” electrophysiological measures of peripheral auditory function, on word identification in difficult listening environments and to probe the role of CND in the generation of tinnitus and hyperacusis. In Project 4, we further study the same subjects, probing the effects of CND on neural hyperactivity in central pathways, and its “top-down” effects on the hyper-reactivity to sound that dominates the clinical burden of tinnitus and hyperacusis. In our Research Center, we leverage the P50 mechanism to combine research perspectives from auditory neuroscience and audiology in a coordinated study of the most handicapping aspects of SNHL. Progress in understanding the effects of CND and how to effectively diagnose it, are of increasing importance as the progress in regenerative therapies for hair cells and cochlear neurons move from laboratories to clinical trials.