Noise-Induced Cochlear Neuronal Degeneration and Its Perceptual Consequences

描述 CDA-1建议的目的是为Naomi BramHall博士提供必要的支持和指导，使其从噪声性听力损失的基础科学研究过渡到临床研究。布拉姆霍尔博士之前的研究重点是遗传性听力损失和毛细胞再生，但作为一名注册听力学专家，她渴望转向临床听力研究。这项提案将为布拉姆霍尔博士提供从事临床研究和生成数据所需的工具和经验，这些数据将用于申请未来的资金，如CDA-2，将指导她作为临床研究人员走向独立的道路。她这项提议的主要导师是道恩·康拉德-马丁博士，M·查尔斯·利伯曼博士是共同导师。在服兵役期间经常会经历巨大的噪音暴露，听力损失是退伍军人中第二常见的与服役相关的残疾。听力损失和言语辨别能力差的人通常在 助听器，因为放大声音提高了语音信号的可听性，而不是清晰度。强噪声暴露不仅会对外毛细胞造成损害，还会导致听神经细胞退化。神经损伤会导致单词识别能力下降(Schuknecht，1994)，这可能解释了为什么许多退伍军人的语音辨别能力比预期的要差，这是基于他们检测音调的能力，特别是在嘈杂的环境中。小鼠表现出听神经外周终末的快速退化，随后在噪声暴露后的几个月内螺旋神经节神经元缓慢退化，即使它们的纯音听觉阈值完全恢复(Kujawa和Liberman 2009)。最容易受到噪声影响的神经元亚群由低自发频率的纤维组成(Furman等人。2013)，它们具有较高的灵敏度阈值，并对较高强度的声音做出反应。这种神经元的丧失与听性脑干反应(ABR)第一波的幅度降低有关。在人类中已经证实了与年龄相关的波I的幅度降低(Konrad-Martin等人)。2012年)，并与显示听神经元随年龄增长而丧失的颞骨研究一致(Makary等人。(2011)，这表明听觉神经元存活的这一指标也适用于人类。以前，由于在测量人类听神经元丢失方面的局限性，量化听觉神经元存活对语音理解的影响一直是困难的，这只能通过死后的颞骨研究来完成。该建议的主要目的是利用电生理学方法1)确定ABR波I波幅降低是否与人类的噪声暴露有关；2)研究噪声暴露和波I波幅降低对听觉感知的影响。我们的假设是，噪声暴露将与波I幅度降低相关，这与动物研究一致，并且这种变化将与高声水平下语音识别能力下降、在背景噪声存在下难以理解语音以及对大声声音的耐受性下降相关。发展利用现有临床工具评估听觉神经元存活的能力，并促进我们对神经元丧失导致的特定听觉感知缺陷的理解，将有助于指导未来听力损失退伍军人的治疗选择。

DESCRIPTION The purpose of this CDA-1 proposal is to provide Dr. Naomi Bramhall with the support and mentorship necessary to make the transition from basic science research to clinical research of noise-induced hearing loss. Dr. Bramhall's previous research has focused on hereditary hearing loss and hair cell regeneration, but as a certified audiologist, she is eager to shift to clinical hearing research. This proposal will provide Dr. Bramhall with the tools and experience necessary to engage in clinical research and generate data which will be used in applying for future funding such as the CDA-2, will guide her path towards independence as a clinical researcher. Her primary mentor for this proposal is Dr. Dawn Konrad-Martin and Dr. M. Charles Liberman is a co-mentor. Loud noise exposure is routinely experienced during military service and hearing loss is the second most common service-related disability among Veterans. Individuals with hearing loss and poor speech discrimination ability often have little success with hearing aids because amplifying sound improves the audibility, but not the clarity, of the speech signal. Loud noise exposure may result not only in damage to outer hair cells, but also lead to auditory neuronal degeneration. Neural loss can result in decreased word recognition (Schuknecht 1994) and may explain why many Veterans have poorer speech discrimination than would be expected based on their ability to detect tones, particularly in noisy environments. Mice show rapid degeneration of auditory nerve peripheral terminals followed by a slow degeneration of spiral ganglion neurons over a period of several months following loud noise exposure, even when their pure tone auditory thresholds recover completely (Kujawa and Liberman 2009). The subpopulation of neurons most vulnerable to noise exposure consists of the low spontaneous rate fibers (Furman et al. 2013), which have a high sensitivity threshold and respond to higher intensity sounds. This neuronal loss is correlated with a decrease in the amplitude of the first wave of the auditory brainstem response (ABR). Age-related reduction in the amplitude of wave I has been demonstrated in humans (Konrad-Martin et al. 2012) and is consistent with temporal bone studies showing auditory neuronal loss with age (Makary et al. 2011), suggesting this metric of auditory neuronal survival is also applicable to humans. Previously, quantification of the degree to which auditory neuronal survival influences speech understanding has been difficult due to limitations in measuring auditory neuronal loss in humans, which could only be accomplished through post-mortem temporal bone studies. The main objectives of this proposal are to use electrophysiological methods to 1) determine if decreased ABR wave I amplitude is associated with noise exposure in humans and 2) examine the impact of noise exposure and decreased wave I amplitude on auditory perception. Our hypothesis is that noise exposure will be associated with decreased wave I amplitude, consistent with animal studies, and that this change will be correlated with decreased speech recognition at high sound levels, difficulty understanding speech in the presence of background noise, and decreased tolerance to loud sounds. Developing the ability to assess auditory neuronal survival with existing clinical tools and advancing our understanding of the specific auditory perceptual deficits resulting from neuronal loss will help guide future treatment options for Veterans suffering from hearing loss.