Physiological and Perceptual Assessment of Hearing in Noise in Nonhuman Primates Following Noise-Induced Cochlear Synaptopathy

噪声引起的耳蜗突触病后非人类灵长类动物噪声听力的生理和知觉评估

• 批准号: 10312287
• 负责人: Jane Ann Mondul
• 金额: $ 6.93万
• 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: 2021-06-01 至 2023-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10312287
• 关键词: Acoustic Nerve; Acoustics; Address; American; Anatomy; Animals; Auditory; Auditory Brainstem Responses; Auditory Threshold; Biological Assay; Biological Markers; Caring; Clinical; Cochlea; Communication; Complex; Contralateral; Data; Detection; Diagnostic; Diagnostic Sensitivity; Diagnostic tests; Differential Diagnosis; Ear; Elements; Frequencies; Functional disorder; Genetic; Growth; Hair Cells; Hearing; Hearing problem; Histologic; Human; Impairment; Injury; Inner Hair Cells; Ipsilateral; Knowledge; Labyrinth; Link; Macaca; Masks; Measures; Medial; Mediating; Modeling; Monkeys; Nerve Fibers; Neurons; Noise; Outer Hair Cells; Pathology; Patients; Performance; Phylogeny; Physiological; Physiology; Predisposition; Proxy; Psychophysics; Reflex action; Reporting; Reproducibility; Research; Risk; Rodent; Signal Transduction; Stimulus; Synapses; Test Result; Testing; Therapeutic; Training; Uncertainty; Variant; Work; behavior measurement; cell injury; cochlear synaptopathy; ear muscle; experience; hearing impairment; hidden hearing loss; improved; middle ear; multimodality; neuron loss; nonhuman primate; normal hearing; novel marker; otoacoustic emission; relating to nervous system; response; ribbon synapse; sound; speech in noise; stimulus interval

PROJECT SUMMARY Hearing in noise is a complex auditory task that is critical for effective communication in the presence of competing sounds. Several neuronal mechanisms and circuits contribute to hearing-in-noise abilities, including neuronal subpopulations that encode suprathreshold signals, neuronal response adaptation, and the middle ear muscle and medial olivocochlear reflexes (MEMR, MOCR). Many patients seeking audiologic care report difficulties hearing in noise, but have normal hearing sensitivity (i.e. `hidden hearing loss'). Cochlear synaptopathy (SYN; the loss of inner hair cell ribbon synapses) is an inner ear pathology thought to contribute to hearing-in-noise deficits, in the absence of hair cell damage and poor hearing thresholds that are more readily identified in the standard audiologic test battery. In rodents, SYN disrupts synaptic signaling, which alters neuronal adaptation and leads to loss of auditory nerve fibers, especially those with high sound-evoked thresholds that encode signals in noise and provide input to the MEMR and MOCR. Since SYN degrades neuronal mechanisms that support hearing-in-noise, SYN may result in concomitant hearing-in-noise deficits. However, few studies have directly assessed the effect of SYN on encoding of signals in noise or perceptual hearing-in-noise abilities. Corroboration of suspected SYN is limited in humans and the relationship between hearing-in-noise abilities and SYN has not been established, leading to translational uncertainty. Our nonhuman primate model of noise-induced SYN is uniquely suited to assess the consequences of SYN on hearing-in-noise and provide a translational bridge between rodent and human research. Complementary physiological and psychophysical measures will be used to assess signal in noise encoding and hearing-in- noise abilities of macaque monkeys before and after noise exposure known to cause SYN. The central hypothesis is that signal encoding and hearing abilities in noise will be impaired following SYN, with greater deficits observed in subjects with greater synapse loss. In Aim 1, encoding of signals in noise will be investigated using variants of traditional noninvasive clinical assays, including auditory brainstem responses (ABRs), distortion product otoacoustic emissions (DPOAEs), MEMRs, and MOCRs, measured with and without ipsilateral and contralateral noise, in order to probe neuronal mechanisms that support in hearing-in-noise. In Aim 2, psychophysical signal detection in noise will be measured under masking conditions that elicit different kinds of neuronal adaptation involved in hearing-in-noise. Within-subject comparisons (pre- vs. post-exposure) and regressions with cochlear histological characterization of synapse loss will assess the relationship between cochlear integrity and auditory function. This multimodal approach to physiologically and perceptually measure hearing-in-noise abilities in nonhuman primates with histologically verified noise-induced SYN could result in novel biomarkers for SYN. Improving the sensitivity of differential diagnosis of hearing disorders such as hidden hearing loss is critically important with the rapid approach of therapeutics for human hearing loss.

项目概要 噪音中的听力是一项复杂的听觉任务，对于在有噪音的情况下进行有效沟通至关重要 竞争的声音。几种神经元机制和电路有助于噪声中的听觉能力，包括 编码阈上信号、神经元反应适应和中间信号的神经元亚群 耳肌和内侧橄榄耳蜗反射（MEMR、MOCR）。许多寻求听力护理的患者报告 在噪音中听力困难，但听力敏感度正常（即“隐性听力损失”）。人工耳蜗 突触病（SYN；内毛细胞带状突触丧失）是一种内耳病理学，被认为是导致 噪声中的听力缺陷，在没有毛细胞损伤和听力阈值较差的情况下， 在标准听力测试电池中很容易识别。在啮齿类动物中，SYN 会破坏突触信号传导，从而 改变神经元适应并导致听觉神经纤维损失，尤其是那些具有高声音诱发的神经纤维 对噪声中的信号进行编码并向 MEMR 和 MOCR 提供输入的阈值。由于 SYN 降级 支持噪声中听力的神经机制，SYN 可能会导致伴随的噪声中听力缺陷。 然而，很少有研究直接评估 SYN 对噪声或感知信号编码的影响。 噪音中的听力能力。对可疑 SYN 的证实在人类中是有限的，并且两者之间的关系 噪声中的听力能力和 SYN 尚未建立，导致翻译不确定性。我们的 噪声引起的 SYN 的非人类灵长类动物模型特别适合评估 SYN 对 噪声中的听觉并在啮齿动物和人类研究之间提供转化桥梁。补充 生理和心理物理测量将用于评估噪声编码和听力中的信号 猕猴在暴露于已知会导致 SYN 的噪声之前和之后的噪声能力。中央 假设信号编码和噪音中的听力能力在 SYN 后会受到损害，并且影响更大 在突触损失较多的受试者中观察到的缺陷。在目标 1 中，噪声中的信号编码为 使用传统非侵入性临床检测的变体进行研究，包括听觉脑干反应 (ABR)、失真产物耳声发射 (DPOAE)、MEMR 和 MOCR，使用和不使用测量 同侧和对侧噪声，以探究支持噪声中听力的神经元机制。在 目标 2，噪声中的心理物理信号检测将在引发不同的掩蔽条件下进行测量 与噪音中的听觉有关的神经元适应类型。受试者内比较（暴露前与暴露后） 突触损失的耳蜗组织学特征回归将评估这种关系 耳蜗完整性和听觉功能之间的关系。这种生理和感知上的多模式方法 通过组织学验证的噪声诱导 SYN 测量非人类灵长类动物的噪声听力能力 产生新的 SYN 生物标志物。提高听力障碍等听力障碍鉴别诊断的灵敏度 由于隐性听力损失对于人类听力损失的快速治疗方法至关重要。