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

感音神经性听力损失患者的适应不良中枢可塑性和阈上听力障碍及其与耳蜗突触病生物标志物的关系

• 批准号: 10641781
• 负责人: Daniel B. Polley
• 金额: $ 57.84万
• 依托单位: MASSACHUSETTS EYE AND EAR INFIRMARY
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-08-02 至 2027-07-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10641781
• 关键词: Adult; Affective; Afferent Neurons; Age; Aging; Animal Experimentation; Animals; Area; Arousal; Auditory; Auditory Perception; Auditory Threshold; Awareness; Behavior assessment; Behavioral; Biological; Biological Markers; Brain; Categories; Clinical; Cochlea; Code; Consensus; Coupling; Cues; Data; Diagnosis; Diameter; Digit structure; Disease; Disinhibition; Distress; Ear; Elderly; Electroencephalography; Emotional; Equilibrium; Exhibits; Face; Facial Expression; Functional disorder; Galvanic Skin Response; Grant; Growth; Hearing; Hearing problem; Heart Rate; Human; Hyperactivity; Hyperacusis; Hypersensitivity; Individual; Laboratories; Link; Loudness; Maps; Measurement; Measures; Mediation; Mydriasis; Nerve Degeneration; Nervous System; Neurons; Noise; Outcome; Pain; Peptide Initiation Factors; Perception; Perceptual Disorders; Peripheral; Persons; Phenotype; Physiological; Prevalence; Process; Process Assessment; Protocols documentation; Psychoacoustics; Psychophysics; Publishing; Pupil; Questionnaires; Randomized, Controlled Trials; Recording of previous events; Research; Research Priority; Risk Factors; Sensorineural Hearing Loss; Sensory; Series; Source; Speech Intelligibility; Speech Perception; Stimulus; Structure; Testing; Tinnitus; Training; Work; arm; assault; auditory pathway; auditory processing; behavioral outcome; behavioral phenotyping; cochlear synaptopathy; cognitive load; experience; hearing impairment; human subject; improved; innovation; neural; noise exposure; normal hearing; novel; novel strategies; recruit; response; sound; speech in noise

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.

项目4 - 项目摘要 听力障碍通常是研究的，并且从想要发出听不清的声音的角度进行治疗 听到。然而，最常见和令人衰弱的成人听力抱怨中的三个仅反映了相反的问题： 不是人们听不到的，而是他们无法停止听到的声音。老年人或有噪音历史的人 他们经常对幻影声音（耳鸣）的不可抑制的感知袭击，他们经历了 中等强度的声音大声，令人痛苦甚至痛苦（超声波），他们难以抑制 聆听目标扬声器时的背景噪声源的意识。虽然年龄，噪音暴露，并且 听力状态是这些感知障碍的危险因素，该连接充其量是间接的，促使 关于可能更紧密相关的中间神经过程的猜测。动物研究建议 这些疾病的根本原因可能植根于人工耳蜗主要的对话框中 在大脑的声音处理中心中传入的神经元和神经元。人工耳蜗神经元变性（CND） 已显示出在中央听觉途径中触发补偿性可塑性过程 射击标记，使中央听觉神经元过度活跃，超敏，超同步，并且 内部“嘈杂”。在许多动物物种和听力损失范式上发表的工作的广泛共识 表明由于CND而产生的不良适应性中心可塑性与 耳鸣，超声波和噪声听力有选择性难度的行为表现。这个假设有 由于衡量危险因素的挑战，听觉周围，我们很难在人类受试者中进行测试 同一听力障碍的状态，中央可塑性特征和详细的行为表型 主题。在这里，通过同一中心神经，自主和心理物理测量 在项目3中也经过了广泛的听觉外围测试的受试者，我们已经开发了一个 在人类受试者中将这一假设置于测试的创新和详尽的方法。项目4的目标1将 使用新型的脑电图测量来检验以下假设：估计的CND水平更明显 与神经增长增加，快速刺激暂时特征的神经化差和神经元差有关 抑制任务 - 无关的噪声源。 AIM 2将利用新颖的声音诱发的自主措施 学生词典，皮肤电导，心率和微面部表情的变化，以检验以下假设 在努力聆听期间，更明显的CNDE与绝对强大的自主招聘有关 并回应情感令人回味的声音。 AIM 3将结合上述神经和自主措施 具有详细的行为表型。使用因果中介分析，AIM 3将确定CNDE如何中央 增益，临时编码，干扰噪声源抑制和情感声音处理特别相关 通过测量多对话者语音来确定的一系列听力障碍范围 可理解性，耳鸣，心理声学，耳鸣伯恩，响亮的心理声学和Hyperacusis Burnen。