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

项目总结 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进行有效的沟通至关重要 相互竞争的声音。几种神经元机制和电路有助于提高噪声中的听觉能力，包括 编码阈值以上信号的神经元亚群、神经元反应适应和中间 耳肌和内侧橄榄耳蜗肌反射(MEMR，MOCR)。许多寻求听力护理的患者报告 在噪声中听力有困难，但听力敏感度正常(即“隐性听力损失”)。耳蜗骨 突触病(SYN；内毛细胞带状突触的丢失)是内耳的一种病理现象 在没有毛细胞损伤和听力阈值较差的情况下，噪音中的听力障碍 在标准听力学测试电池中很容易识别。在啮齿动物中，SYN扰乱突触信号，这是 改变神经元的适应性并导致听神经纤维的丢失，特别是那些高声诱发的听神经纤维 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障碍。 然而，很少有研究直接评估SYN在噪声或知觉中对信号编码的影响 在噪音中的听力能力。疑似SYN的佐证在人类中有限，两者之间的关系 噪声中的听力和SYN尚未建立，导致翻译的不确定性。我们的 非人灵长类动物噪声性SYN模型是唯一适合于评估SYN对 在噪音中听力，并在啮齿动物和人类研究之间提供了一座转换的桥梁。互补性 将使用生理和心理物理措施来评估噪声编码和听觉中的信号。 猕猴在噪声暴露前后的噪声能力，已知会导致SYN。中环 假说是SYN后，信号编码和听力在噪声中的能力会受到损害， 在突触丢失较大的受试者中观察到的缺陷。在目标1中，噪声中的信号编码将是 使用传统非侵入性临床测试的变体进行研究，包括听性脑干反应 (ABR)、失真产物耳声发射(DPOAE)、MEMR和MOCRS，在有和没有测量的情况下 同侧和对侧噪声，以探索在噪声中听力支持的神经元机制。在……里面 目标2，在噪声中的心理物理信号检测将在不同的掩蔽条件下被测量 噪声中听觉涉及的神经元适应的种类。受试者内部比较(曝光前和曝光后) 与突触缺失的耳蜗学组织学特征的回归将评估两者之间的关系 耳蜗完整性和听觉功能之间的关系。这种从生理上和感知上的多模式方法 用组织学证实的噪声诱导的SYN测量非人灵长类动物在噪声中的听力 结果产生了SYN的新生物标志物。提高听力障碍鉴别诊断的敏感性 随着人类听力损失治疗方法的快速发展，隐蔽性听力损失变得至关重要。

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.