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)的重要知觉和生理方面仍然对标准的临床诊断(即纯音测听，它测量耳朵在安静状态下的敏感度)仍然是“隐藏的”。在SNHL的许多听者中，即使在听力阈值正常的频率上，也会出现听阈上的时间加工缺陷。此外，显著的永久性耳蜗性突触病变(高达50%的丢失)可能发生在噪声暴露的耳朵中，这些耳朵“只是”经历了暂时的阈值漂移。目前的建议提供了一种系统的方法，在暂时性和永久性阈值漂移的情况下，直接将噪声引起的听力损失的生理和行为影响联系起来。这些实验是基于来自听神经的证据设计的，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，对于窄带和宽带声音可能不同，并且在声音的缓慢变化的波动(“时间包络”)中可能比在快速变化的“精细结构”中更加突出。具体目标1是量化噪声导致的永久性听力损失对耳蜗腹核内时间编码的影响，腹侧核是上行听性脑干通路的第一个处理站，也是所有听神经纤维的必备突触。精细结构/包膜强度和紧张性的平衡将由麻醉的龙猫耳蜗腹核单个神经元对宽带噪声的反应来测量。神经计量学分析将量化听力损失对包络调制检测和分辨阈值的影响，以及与调制深度和背景噪声水平的关系。具体目标2是量化暂时性阈值漂移后突触对听神经和腹侧耳蜗核反应的影响。免疫组织化学技术将被用来量化突触，并评估非侵入性生理学检测对耳蜗突触丢失的敏感性。对于突触病理性和非突触病理性噪声暴露，将进行与目标1相同的单神经元测量。具体目标3是将噪声暴露的行为和生理后果联系起来。将训练栗鼠在背景噪音中执行检测和辨别任务。将测量音调检测、强度辨别以及包络调制检测和辨别。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性突触病变将更多地改变包络，而不是精细结构编码，并且这种时间编码的不平衡将在与在噪声中收听相关的低调制深度感知上相关。无论这一假说是被支持还是被驳斥，这些基本数据对于将感音神经性听力损失的生理和知觉效应联系起来将是非常有用的。通过与研究噪声暴露后人类感知缺陷的合作者密切协调这些行为和生理指标，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指标。

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.