Noise-Induced Cochlear Neuronal Degeneration and Its Perceptual Consequences

噪声引起的耳蜗神经元变性及其感知后果

• 批准号: 8781370
• 负责人: Naomi Bramhall
• 金额: --
• 依托单位: PORTLAND VA MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-08-01 至 2016-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8781370
• 关键词: Acoustic Nerve; Address; Age; Aircraft; Animals; Auditory; Auditory Brainstem Responses; Auditory Perception; Auditory Threshold; Basic Science; Cavia; Clinical; Clinical Research; Communication; Data; Electrophysiology (science); Environment; Esthesia; Fiber; Firearms; Funding; Future; Goals; Growth; Hearing; Hearing Aids; Human; Hyperacusis; Individual; Inherited; Lead; Loudness; Loudness Perception; Measures; Mentors; Mentorship; Methods; Military Personnel; Mus; Nerve Degeneration; Nerve Fibers; Neurons; Noise; Noise-Induced Hearing Loss; Outer Hair Cells; Output; Performance; Peripheral; Prevention; Recording of previous events; Research; Research Personnel; Risk; Services; Signal Transduction; Speech; Speech Discrimination; Temporal bone structure; Training; Veterans; Work; age related; base; combat; disability; experience; hair cell regeneration; hearing impairment; improved; neuron loss; neuronal survival; public health relevance; relating to nervous system; research study; sound; speech recognition; spiral ganglion; success; tool

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.

描述 CDA-1 提案的目的是为 Naomi Bramhall 博士提供必要的支持和指导，以实现噪声性听力损失从基础科学研究向临床研究的过渡。 Bramhall 博士之前的研究重点是遗传性听力损失和毛细胞再生，但作为一名经过认证的听力学家，她渴望转向临床听力研究。该提案将为 Bramhall 博士提供参与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 CDA-2 等未来资金，并将指导她作为临床研究人员走向独立之路。她这项提案的主要导师是 Dawn Konrad-Martin 博士，M. Charles Liberman 博士是共同导师。 在服兵役期间经常会遇到噪音，而听力损失是退伍军人中第二大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很难成功 助听器，因为放大声音可以提高语音信号的可听度，但不能提高清晰度。暴露在大声的噪音中不仅可能导致外毛细胞受损，还会导致听觉神经元变性。神经损失会导致单词识别能力下降（Schuknecht 1994），并且可以解释为什么许多退伍军人的语音辨别能力比根据他们检测音调的能力所预期的要差，尤其是在嘈杂的环境中。小鼠在暴露于大声噪音后的几个月内会表现出听觉神经末梢的快速退化，随后螺旋神经节神经元的缓慢退化，即使它们的纯音听觉阈值完全恢复（Kujawa 和 Liberman 2009）。最容易受到噪音影响的神经元亚群由低自发率纤维组成（Furman et al. 2013），它们具有高灵敏度阈值并对较高强度的声音做出反应。这种神经元损失与听觉脑干反应（ABR）第一波振幅的降低相关。 I 波振幅与年龄相关的降低已在人类身上得到证实（Konrad-Martin 等人，2012 年），并且与显示听觉神经元随年龄增长而丧失的颞骨研究相一致（Makary 等人，2011 年），表明听觉的这一指标神经元的生存也适用于人类。此前，由于测量人类听觉神经元损失的局限性，量化听觉神经元存活对言语理解的影响程度一直很困难，这只能通过死后颞骨研究来完成。 该提案的主要目标是使用电生理学方法来 1) 确定 ABR 波 I 幅度降低是否与人类噪声暴露有关，2) 检查噪声暴露和 I 波幅度降低对听觉感知的影响。我们的假设是，噪声暴露与 I 波振幅降低有关，这与动物研究一致，并且这种变化与高声级语音识别能力下降、背景噪声存在下难以理解语音以及对环境的耐受性降低有关。响亮的声音。开发利用现有临床工具评估听觉神经元存活率的能力，并加深我们对神经元损失导致的特定听觉感知缺陷的理解，将有助于指导患有听力损失的退伍军人未来的治疗选择。