Place and Time Processing of Pitch in the Context of Cochlear Dysfunction

耳蜗功能障碍背景下音调的地点和时间处理

• 批准号: 10680120
• 负责人: Andrew Sivaprakasam
• 金额: $ 5.27万
• 依托单位: PURDUE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-01-01 至 2025-12-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10680120
• 关键词: Acoustic Nerve; Acoustic Trauma; Adult; Affect; Age; American; Anatomy; Animal Model; Animals; Auditory; Auditory system; Behavioral; Biological Assay; Categories; Chinchilla (genus); Cochlea; Cochlear Hearing Loss; Cochlear Nerve; Code; Communication; Complex; Cues; Data; Diagnosis; Diagnostic; Differential Threshold; Discrimination; Electrophysiology (science); Emotions; Experimental Designs; Frequencies; Functional disorder; Hair Cells; Health; Hearing; Human; Impairment; Individual; Individual Differences; Inner Hair Cells; Intuition; Investigation; Knowledge; Laboratories; Link; Literature; Measures; Modeling; Music; Nerve Fibers; Neurological Models; Outcome; Outer Hair Cells; Pathology; Pathway interactions; Pattern; Perception; Periodicity; Peripheral; Physicians; Physiological; Physiology; Pitch Discrimination; Pitch Perception; Play; Process; Protocols documentation; Psychoacoustics; Recording of previous events; Reflex action; Research; Research Training; Role; Scientist; Self-Help Devices; Sensorineural Hearing Loss; Statistical Models; Stimulus; Synapses; Synaptic Transmission; Tail; Techniques; Testing; Time; Treatment Protocols; Variant; Voice; Work; animal data; base; behavior measurement; cell injury; cellular transduction; clinical predictors; clinically relevant; cochlear synaptopathy; design; ear muscle; experimental study; falls; hearing impairment; human data; human subject; improved; individual variation; innovation; insight; middle age; middle ear; nervous system disorder; neural; neural correlate; neurophysiology; normal hearing; otoacoustic emission; response; skills; sound; synaptic function; theories

Abstract: Sensorineural hearing loss occurs in 15% of American adults and current treatment protocols are often guided by limited and archaic diagnostics. Not all types of sensorineural hearing loss are identical in physiology and a major priority of current auditory research is to innovate in the space of precision auditory diagnostics and treatments. Understanding how specific patterns of damage to the cochlea or auditory nerve variably impair the perception of different sound features is critical to improve treatments for hearing-impaired individuals. The history of auditory research has led to considerable insight as to how anatomic components of the auditory periphery, namely inner hair cells (IHCs), outer hair cells (OHCs), and the cochlear synapse function together to transduce, amplify, and code simple sounds. However, there exists considerable gaps in our knowledge of how these peripheral components are responsible for maintaining the fidelity of more complex auditory phenomena and perception. Pitch, the perceived “highness” or “lowness” of a given sound, is an example of a complex psychoacoustic phenomenon. Pitch cues are used to listen to and compose music and to process vowels, identify talkers, and convey emotion. Without intact pitch perception, conversation becomes emotionless, a symphony becomes a cacophony. While pitch has been extensively studied perceptually, our knowledge of the underlying neurophysiology of pitch remains mostly hypothetical. Three categories of pitch theories attempt to explain pitch coding in terms of the tonotopic organization of our auditory system (place), the temporal information present in neural firing patterns (time), or a combination of these (place-time). We plan to assess these theories in the context of cochlear pathologies that are expected to differentially alter place and timing cues, hence developing a more comprehensive understanding of pitch. Based on the literature, our central hypothesis is that deficits in time and place coding both affect the neural coding and perception of pitch, but with distorted place coding playing a stronger role. We will test this hypothesis by using animal models of OHC, IHC, cochlear synapse damage, and Distorted Tonotopy to investigate SNHL effects on pitch-related electrophysiology (Aim 1). OHC damage primarily disrupts place cues, while IHC and cochlear synapse damage alter timing cues. We will then compare this animal electrophysiology to identical measures in humans with normal and impaired hearing, evaluating the implications on behavioral pitch discrimination (Aim 2). Finally, we will develop four statistical models to identify how variations in pitch coding and perception are predicted by non-invasive assays of hearing loss and profiles of SNHL (Aim 3). This cross-species approach moves the field forward by testing well- established pitch theories in the context of SNHL and by opening doors to better identifying the functional consequences of individual variations in hearing ability. Overall, the cross-species design of the proposed work will develop my potential as a physician-scientist, strengthening my ability to design translational experiments that use ideal laboratory models of neurological disorders to predict clinically relevant outcomes.

抽象的： 15% 的美国成年人患有感音神经性听力损失，目前的治疗方案通常是指导性的 通过有限且陈旧的诊断。并非所有类型的感音神经性听力损失在生理学上都是相同的，并且 当前听觉研究的首要任务是在精确听觉诊断和领域进行创新 治疗。了解耳蜗或听觉神经损伤的特定模式如何不同程度地损害 对不同声音特征的感知对于改善听力障碍患者的治疗至关重要。这 听觉研究的历史使我们对听觉的解剖学组成部分有了相当多的了解。 外周细胞，即内毛细胞 (IHC)、外毛细胞 (OHC) 和耳蜗突触共同发挥作用 转换、放大和编码简单的声音。然而，我们对于如何 这些外围组件负责维持更复杂的听觉现象的保真度 和感知。音高，即给定声音的感知“高”或“低”，是复杂的一个例子 心理声学现象。音高提示用于聆听和创作音乐以及处理元音、识别 说话者，传达情感。如果没有完整的音高感知，谈话就会变得毫无感情，就像一首交响乐 变成刺耳的声音。虽然音高已经在感知上得到了广泛的研究，但我们对底层的了解 音调的神经生理学仍然主要是假设的。三类音高理论试图解释音高 根据我们听觉系统（地点）的音调组织进行编码，存在于 神经放电模式（时间）或这些模式的组合（地点-时间）。我们计划评估这些理论 耳蜗病理的背景预计会不同地改变位置和时间线索，从而发展 对音调有更全面的了解。根据文献，我们的中心假设是 时间和地点编码都会影响神经编码和音调感知，但地点编码会失真 发挥更强有力的作用。我们将通过使用 OHC、IHC、耳蜗突触的动物模型来检验这一假设 损伤和扭曲音调来研究 SNHL 对音高相关电生理学的影响（目标 1）。 OHC 损伤主要破坏位置线索，而 IHC 和耳蜗突触损伤则改变时间线索。我们随后将 将这种动物电生理学与听力正常和受损的人类的相同测量进行比较， 评估对行为音调歧视的影响（目标 2）。最后，我们将制定四种统计方法 确定如何通过非侵入性听力检测来预测音调编码和感知变化的模型 SNHL 的损失和概况（目标 3）。这种跨物种方法通过良好的测试推动了该领域的发展 在 SNHL 背景下建立了音高理论，并为更好地识别功能性打开了大门 听力能力个体差异的后果。总体而言，拟议工作的跨物种设计 将开发我作为一名医师科学家的潜力，增强我设计转化实验的能力 使用神经系统疾病的理想实验室模型来预测临床相关结果。