Effects of Sensorineural Hearing Loss on Robust Speech Coding

描述（由申请人提供）：感觉神经性听力损失（SNHL）的重要感知和生理方面仍然“隐藏”在标准的临床诊断中（即纯音听力学，测量耳朵在安静时的灵敏度）。在许多SNHL患者中，即使在正常听力学阈值的频率上，时间处理的阈上缺陷也会发生。此外，严重的永久性耳蜗突触病变（高达50%的损失）可能发生在“只”经历暂时阈值移位的噪声暴露的耳朵中。目前的建议提供了一种系统的方法来直接联系暂时性和永久性阈值转移情况下噪声引起的听力损失的生理和行为影响。这些实验的设计是基于听觉神经的证据，即SNHL引起的时间编码的生理缺陷可能隐藏在安静的条件下，窄带和宽带声音可能不同，并且可能在缓慢变化的声音波动（“时间包络”）中比在快速变化的“精细结构”中更突出。具体目标1是量化永久性噪声性听力损失对腹侧耳蜗核时间编码的影响，腹侧耳蜗核是上行听觉脑干通路的第一个处理站，也是所有听觉神经纤维的强制性突触。通过记录麻醉龙猫耳蜗腹侧单个神经元对宽带噪声的响应，测量其精细结构/包膜强度和张力性的平衡。神经测量分析将量化听力损失对包络调制检测和判别阈值的影响，以及调制深度和背景噪声水平。具体目的2是量化暂时阈值移位后突触病变对听神经和腹侧耳蜗核反应的影响。免疫组织化学技术将用于量化突触病变，并评估对耳蜗突触丧失的非侵入性生理检测的敏感性。与Aim 1中相同的单神经元测量将用于突触病变和非突触病变噪声暴露。具体目标3是将噪音暴露的行为和生理后果联系起来。龙猫将接受训练，在背景噪音中执行检测和识别任务。将测量音调检测，强度识别和包络调制检测和识别。将比较心理测量（目标3）和神经测量（目标1和2）阈值。我们假设毛细胞功能障碍和耳蜗突触病比精细结构编码更能改变包膜，并且这种时间编码的不平衡将在与噪声听力相关的低调制深度下感知相关。无论这一假设是否被支持或驳斥，这些基础数据将对联系感音神经性听力损失的生理和感知效应非常有用。通过与研究噪音暴露后人类感知缺陷的合作者密切协调这些行为和生理测量，我们最大限度地将我们的动物结果转化为人类隐性听力损失的诊断和流行测量。

DESCRIPTION (provided by applicant): Significant perceptual and physiological aspects of sensorineural hearing loss (SNHL) remain "hidden" from standard clinical diagnostics (i.e., pure tone audiometry, which measures the ear's sensitivity in quiet). Suprathreshold deficits in temporal processing occur in many listeners with SNHL, even at frequencies with a normal audiometric threshold. Furthermore, significant permanent cochlear synaptopathy (up to 50% loss) can occur in noise-exposed ears that "only" experience a temporary threshold shift. The current proposal provides a systematic approach to directly link physiological and behavioral effects of noise-induced hearing loss in cases of both temporary and permanent threshold shift. These experiments were designed based on evidence from the auditory nerve that physiological deficits in temporal coding due to SNHL may be hidden in quiet conditions, may be different for narrowband vs. broadband sounds, and may be more prominent in the slowly varying fluctuations in sound ("temporal envelope") than in the rapidly varying "fine-structure." Specific Aim 1 is to quantify the effects of permanent noise-induced hearing loss on temporal coding in the ventral cochlear nucleus, which is the first processing station of the ascending auditory brainstem pathway and an obligatory synapse of all auditory-nerve fibers. The balance of fine-structure/envelope strength and tonotopicity will be measured from responses to broadband noise recorded from single neurons in the ventral cochlear nucleus of anesthetized chinchillas. Neurometric analyses will quantify the effects of hearing loss on envelope modulation detection and discrimination thresholds, vs. modulation depth and background-noise level. Specific Aim 2 is to quantify the effects of synaptopathy following temporary threshold shift on auditory-nerve and ventral-cochlear- nucleus responses. Immunohistochemical techniques will be used to quantify synaptopathy and to evaluate sensitivity of non-invasive physiological assays to cochlear-synapse loss. The same single-neuron measures as in Aim 1 will be made for both synaptopathic and non-synaptopathic noise exposures. Specific Aim 3 is to relate behavioral and physiological consequences of noise exposure. Chinchillas will be trained to perform detection and discrimination tasks in background noise. Tone detection, intensity discrimination, and envelope modulation detection and discrimination will be measured. Psychometric (Aim 3) and neurometric (Aims 1 and 2) thresholds will be compared. We hypothesize that hair-cell dysfunction and cochlear synaptopathy will alter envelope more than fine-structure coding, and that this imbalance in temporal coding will be perceptually relevant at low modulation depths associated with listening in noise. No matter whether this hypothesis is supported or refuted, these fundamental data will be extremely useful for linking physiological and perceptual effects of sensorineural hearing loss. By closely coordinating these behavioral and physiological measures with collaborators studying human perceptual deficits after noise exposure, we maximize the potential for translating our animal results to diagnostic and prevalence measures of hidden hearing loss in humans.