Suprathreshold processing and binaural interaction in rhesus macaques with cochlear synaptopathy

耳蜗突触病恒河猴的阈上处理和双耳相互作用

• 批准号: 10468047
• 负责人: Chase Mackey
• 金额: $ 0.78万
• 依托单位: VANDERBILT UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-09-01 至 2022-10-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10468047
• 关键词: Acoustic Nerve; Acoustics; Anatomy; Animals; Audiology; Auditory; Auditory Brainstem Responses; Auditory Threshold; Autopsy; Behavioral; Behavioral Assay; Binaural; Biological Markers; Brain; Chinchilla (genus); Clinic; Clinical; Cochlea; Complex; Data; Deafferentation procedure; Detection; Diagnostic; Diagnostic tests; Discrimination; Environment; Equilibrium; Exhibits; Frequencies; Future; Head; Histology; Human; Impairment; Individual Differences; Inner Hair Cells; Knowledge; Laboratories; Link; Literature; Macaca; Macaca mulatta; Measures; Modeling; Monkeys; Neurons; Noise; Oryctolagus cuniculus; Patients; Performance; Peripheral; Persons; Phylogenetic Analysis; Physiological; Population; Primates; Property; Rattus; Reporting; Rodent; Signal Transduction; Speech; Stimulus; Synapses; Task Performances; Testing; Therapeutic; Translations; Work; auditory pathway; base; behavior measurement; binaural hearing; cochlear synaptopathy; expectation; hearing impairment; hidden hearing loss; innovation; neurophysiology; neurotransmission; noise exposure; nonhuman primate; noninvasive diagnosis; normal hearing; relating to nervous system; response; sound; species difference; speech in noise; translational study

ABSTRACT As many as 15% of patients in audiology clinics have normal hearing thresholds, but struggle to understand speech in noise. Understanding speech in noisy environments requires perceptual analysis of suprathreshold sound features, in contrast to audiometric threshold, which is an estimate of the softest sound a listener can detect. These suprathreshold processing deficits that normal hearing patients exhibit cannot be treated currently because their basis in the auditory pathway is not well established. A promising explanation is cochlear synaptopathy, which refers to inner hair cell synapse loss. Synaptopathy leaves thresholds unaffected, but degrades the encoding of suprathreshold sounds as measured by the auditory brainstem response (ABR), and alters excitatory-inhibitory balance in the auditory pathway, which is required for encoding spatial and temporal sound features. Corroborating evidence from the human literature comes in the form of studies showing that normal hearing subjects display substantial individual differences in neurophysiological and behavioral measures of spatial and temporal processing. In particular, the binaural interaction component (BIC) of the ABR is compromised in patients with this profile. Importantly, the BIC may depend on subcortical inhibition, which is compromised by synaptopathy. Despite these compelling links between suprathreshold processing deficits and the neurophysiological effects of synaptopathy, there is no direct evidence that synaptopathy causes perceptual deficits. This is largely because synaptopathy can only be verified via post-mortem cochlear histology, and perceptual measures have rarely been used in animal studies of synaptopathy. Moreover, studies of synaptopathy have only used rodents, which differ from primates in their inhibitory neurotransmission, and perceptual measures of spatial and temporal processing. Such differences could complicate the translation of neurophysiological and behavioral findings into diagnostic and therapeutic innovations. It is for these reasons that we propose using our nonhuman primate model of cochlear synaptopathy to link anatomical, neurophysiological, and perceptual effects of synaptopathy. We propose studying the effects of synaptopathy on temporal and spatial processing to establish synaptopathy's perceptual effects (Aim 1), and linking those effects with a neurophysiological correlate of spatial hearing – the BIC of the ABR (Aim 2). Both temporal and spatial processing will be studied in detection and discrimination paradigms, with the expectation the discrimination tasks will show the largest deficits, and that synaptopathy, and degraded BIC, will correlate with these deficits. These links will provide an explanation of how synaptopathy and its neural consequences can cause deficits in normal hearing subjects, and will form the basis for noninvasive diagnostic tests for synaptopathy in humans.

抽象的 听力学诊所中多达 15% 的患者听力阈值正常，但难以理解 噪声中的语音。理解噪声环境中的语音需要对超阈值进行感知分析。 声音特征，与听力阈值相反，听力阈值是对听者能听到的最柔和声音的估计 正常听力患者表现出的这些阈上处理缺陷无法治疗。 目前，因为它们在听觉通路中的基础尚未建立，一个有希望的解释是。 耳蜗突触病，是指内毛细胞突触缺失阈值。 不受影响，但会降低听觉脑干测量的阈上声音的编码 响应（ABR），并改变审计通路中的兴奋-抑制平衡，这是 编码空间和时间声音特征的证据来自人类文献。 研究表明，听力正常的受试者在以下方面表现出显着的个体差异 空间和时间处理的神经生理学和行为测量。 具有这种特征的患者的 ABR 相互作用成分 (BIC) 会受到损害，重要的是，BIC 可能会受到损害。 尽管有这些引人注目的联系，但依赖于皮质下抑制，而突触病会损害这种抑制。 在阈上处理缺陷和突触病的神经生理学效应之间，不存在 直接证据表明突触病导致知觉缺陷，这很大程度上是因为突触病只能是。 通过死后耳蜗组织学进行验证，感知测量很少用于动物研究 此外，突触病的研究仅使用啮齿类动物，其与灵长类动物的不同之处在于。 抑制性神经传递以及空间和时间处理的感知测量。 可能会使神经生理学和行为学发现转化为诊断和治疗变得复杂 正是出于这些原因，我们建议使用我们的非人类灵长类动物耳蜗模型。 我们提出将突触病的解剖学、神经生理学和知觉效应联系起来。 研究突触病对时间和空间处理的影响，以建立突触病的感知 效应（目标 1），并将这些效应与空间听觉的神经生理学相关性（BIC）联系起来 ABR（目标 2）。将在检测和区分范式中研究时间和空间处理， 预计辨别任务将显示出最大的缺陷，并且突触病和 退化的 BIC 将与这些缺陷相关联，这些联系将解释突触病是如何发生的。 其神经后果可能会导致正常听力受试者的缺陷，并将构成听力障碍的基础 人类突触病的无创诊断测试。