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.

项目摘要 噪声中的听力是一项复杂的听觉任务，对于在存在的情况下来说对于有效沟通至关重要 竞争的声音。几种神经元的机制和电路有助于偿听的能力，包括 编码上部信号，神经元反应适应和中间的神经元亚群 耳肌和内侧橄榄石反射（MEMR，MOCR）。许多寻求听力护理报告的患者 听力很难在噪音中，但听力正常（即“隐藏的听力损失”）。人工耳蜗 突触病（SYN；内部毛细细胞色带突触的丧失）是一种内耳病，被认为有助于 在没有毛细细胞损伤的情况下，毫无疑问的缺陷和听力阈值不佳 在标准听力测试电池中很容易确定。在啮齿动物中，Syn破坏突触信号，该信号传导 改变神经元的适应并导致听觉神经纤维的损失，尤其是声音高的纤维 编码噪声信号并为MEMR和MOCR提供输入的阈值。自Syn降解以来 支持噪声听力的神经元机制可能会导致毫无障碍的听力缺陷。 但是，很少有研究直接评估SYN对噪声或感知中信号编码的影响 毫无听力的能力。可疑同步的佐证在人类中受到限制和 尚未建立噪音的能力和SYN，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非常适合评估Syn在 毫无听力，并提供啮齿动物和人类研究之间的翻译桥梁。补充 生理和心理物理措施将用于评估噪声编码和听力的信号 已知导致同步的噪音暴露之前和之后的猕猴的噪声能力。中央 假设是SYN后，噪声中编码和听力能力的信号将受到损害，更大 在突触损失较大的受试者中观察到的缺陷。在AIM 1中，噪声中信号的编码将是 使用传统非侵入性临床测定的变体进行了研究，包括听觉脑干反应 （ABR），失真产物耳声发射（DPOAES），MEMR和MOCRS，以有或没有的方式测量 同侧和对侧噪声，以探测支持噪声听力的神经元机制。在 AIM 2，将在引起不同的掩盖条件下测量噪声中的心理物理信号检测 毫无听力的神经元适应性。受试者内比较（前与暴露后） 与人工耳蜗组织学表征突触损失的回归将评估关系 在耳蜗完整性和听觉功能之间。这种多模式在生理上和感知上 测量具有组织学验证的噪声引起的SYN的非人类灵长类动物中的听力能力 导致新型生物标志物用于SYN。提高听力障碍鉴别诊断的敏感性 由于隐藏的听力损失对于人类听力损失的快速治疗方法至关重要。