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％的患者的听力阈值正常，但很难理解 噪音的讲话。了解噪声环境中的语音需要对上空的感知分析 声音功能与听力阈值相比，这是听众可以使用的最柔软声音的估计值 探测。这些上方的处理定义了正常的听力患者无法治疗 目前，因为他们在听觉途径中的基础尚未确定。承诺的解释是 人工耳蜗突触病，指内毛细胞突触丧失。突触病离开阈值 不受影响，但降低了通过听觉脑干来衡量的上空声音的编码 反应（ABR），并改变听觉途径中的兴奋性抑制平衡，这是必需的 编码空间和临时声音功能。人类文学的佐证证据来自 研究形式表明，正常的听力受试者显示出很大的个体差异 空间和临时处理的神经生理和行为量度。特别是双耳 在具有此特征的患者中，ABR的相互作用成分（BIC）受到损害。重要的是，BIC可能 这些引人入胜的链接 在远处的处理缺陷和突触病的神经生理作用之间，没有 突触病引起感知的直接证据。这很大，因为突触病只能是 通过验证后的人工耳蜗组织学验证，并且很少在动物研究中使用感知措施 突触病。此外，对突触病的研究仅使用了啮齿动物，这与priment不同 抑制性神经传递以及空间和临时处理的感知测量。这样的差异 可能使神经生理学和行为发现为诊断和治疗的翻译变得复杂 创新。正是由于这些原因，我们建议使用我们的非人类私人模型 突触病，将突触病的解剖学，神经生理和感知作用联系起来。我们建议 研究突触病对临时和空间处理的影响以建立突触病的感知 效果（AIM 1），并将这些效果与空间听力的神经生理相关性联系起来 - ABR（AIM 2）。临时处理和空间处理都将在检测和歧视范式中进行研究， 有了期望，歧视任务将显示出最大的缺陷，该突触性疾病和 降解的BIC将与这些缺陷相关。这些链接将提供有关突触病的解释 它的神经后果会导致正常听力受试者的缺陷，并将成为 人类突触性疾病的无创诊断测试。