Maladaptive central plasticity and suprathreshold hearing disorders in humans with sensorineural hearing loss and their relation to biomarkers of cochlear synaptopathy

项目4-项目摘要 听力障碍通常是从想要发出听不见的声音的角度来研究和治疗的 听得见。然而，三种最常见和最令人衰弱的成人听力投诉反映了相反的问题： 不是人们听不到的，而是他们无法停止听到的。老年人或有噪音史的人 暴露经常受到无法抑制的幻听（耳鸣）的感知，他们经历 中等强度的声音响亮，痛苦，甚至痛苦（听觉过敏），他们努力抑制 在听目标说话者说话时，对背景噪声源的感知。虽然年龄，噪音暴露， 听力状况是这些知觉障碍的危险因素，这种联系充其量是间接的， 关于可能更密切相关的干预神经过程的猜测。动物研究表明 这些疾病的根本原因可能源于耳蜗初级之间的对话出错， 传入神经元和大脑声音处理中心的神经元。尾椎神经变性 已经被证明可以触发中枢听觉通路的代偿性可塑性过程， 射击目标，使中枢听觉神经元过度活跃，过敏，超同步， 内部“噪音”。在许多动物物种和听力损失范例中发表的工作达成了广泛共识 表明，作为CND的结果而产生的适应不良的中枢可塑性在近端与 耳鸣、听觉过敏和噪声中选择性听力障碍的行为表现。这一假设 由于测量风险因素的挑战，难以在人类受试者中进行测试， 状态，中枢可塑性签名，以及这些听力障碍的详细行为表型， 科目在这里，通过在相同的环境中进行中枢神经、自主神经和心理物理测量， 受试者也经历了广泛的听觉周边测试项目3，我们已经开发了一个 创新和详尽的方法，把这一假设的测试在人类受试者。项目4的目标1将 使用新的EEG措施来检验假设，即更明显的估计CND（CNDe）水平是 与增加的神经增益、快速刺激时间特征的神经编码差和神经功能差相关。 抑制与任务无关的噪声源。目标2将利用新的自主措施，声音诱发 瞳孔扩张、皮肤电导、心率和微面部表情的变化，以检验以下假设： 在努力倾听的过程中，更明显的CNDe与异常强烈的自主神经募集有关 and in response响应to emotional情感evocating唤起sounds声音.目标3将联合收割机结合上述神经和自主措施 详细的行为表型使用因果中介分析，目标3将确定CNDe，中央 增益、时间编码、干扰噪声源抑制和情感声音处理具体涉及 一系列阈上听力障碍，如通过测量多说话者的言语所确定的， 可理解性、耳鸣心理声学、耳鸣负担、响度心理声学和听觉过敏负担。

Project 4 – Project Summary Hearing disorders are typically studied and treated from the perspective of wanting to make inaudible sounds audible. Yet three of the most common and debilitating adult hearing complaints reflect just the opposite problem: not what persons cannot hear, but what they cannot stop hearing. Older adults or persons with a history of noise exposure are often assaulted by the irrepressible perception of phantom sounds (tinnitus), they experience moderate intensity sounds as loud, distressing, or even painful (hyperacusis), and they struggle to suppress the awareness of background noise sources when listening to a target speaker. Although age, noise exposure, and hearing status are risk factors for these perceptual disorders, the connection is indirect at best, prompting much speculation about the intervening neural processes that may be more closely related. Animal research suggests that the underlying cause of these disorders may be rooted in a dialog gone wrong between cochlear primary afferent neurons and neurons in sound processing centers of the brain. Cochlear neural degeneration (CND) has been shown to trigger a compensatory plasticity process in the central auditory pathway that often over- shoots the mark, rendering central auditory neurons hyperactive, hypersensitive, hyper-synchronized, and internally ‘noisy’. A broad consensus from work published in many animal species and hearing loss paradigms suggests that maladaptive central plasticity that arises as a consequence of CND is proximally linked to the behavioral manifestation of tinnitus, hyperacusis, and selective difficulties hearing in noise. This hypothesis has been difficult to test in human subjects owing to the challenge of measuring risk factors, auditory peripheral status, central plasticity signatures, and detailed behavioral phenotyping of these hearing disorders in the same subjects. Here, by performing central neural, autonomic, and psychophysical measurements in the same subjects that have also undergone extensive auditory peripheral testing in Project 3, we have developed an innovative and exhaustive approach to put this hypothesis to the test in human subjects. Aim 1 of Project 4 will use novel EEG measures to test the hypothesis that more pronounced levels of estimated CND (CNDe) is associated with increased neural gain, poor neural encoding of rapid stimulus temporal features, and poor neural suppression of task-irrelevant noise sources. Aim 2 will utilize novel autonomic measures of sound-evoked changes in pupil dilation, skin conductance, heart rate, and micro facial expressions to test the hypothesis that more pronounced CNDe is associated with abnormally strong autonomic recruitment during effortful listening and in response to emotionally evocative sounds. Aim 3 will combine the neural and autonomic measures above with detailed behavioral phenotyping. Using causal mediation analysis, Aim 3 will determine how CNDe, central gain, temporal encoding, distractor noise source suppression, and affective sound processing specifically relate to a spectrum of suprathreshold hearing disorders, as identified by measurements of multi-talker speech intelligibility, tinnitus psychoacoustics, tinnitus burden, loudness psychoacoustics, and hyperacusis burden.