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 听力障碍通常是从想要发出听不见的声音的角度来研究和治疗的 然而，三种最常见且令人衰弱的成人听力问题恰恰反映了相反的问题： 不是人们听不到的声音，而是他们无法停止听到的声音。 暴露在外往往会受到无法抑制的幻音感知（耳鸣）的侵袭，他们会经历 中等强度的声音听起来响亮、令人痛苦，甚至痛苦（听觉过敏），并且他们努力抑制这种声音 聆听目标说话者时对背景噪声源的认识，尽管年龄、噪声暴露和 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，提示很多 动物研究表明，对干预神经过程的猜测可能更为密切。 这些疾病的根本原因可能源于人工耳蜗之间的对话出错 传入神经元和大脑声音处理中心的神经元。耳蜗神经变性（CND）。 已被证明会触发中枢听觉通路的补偿可塑性过程，该过程经常过度 击中目标，使中枢听觉神经元过度活跃、过度敏感、过度同步，并且 内部“吵闹”是许多动物物种和听力损失范例中发表的研究的广泛共识。 表明 CND 导致的适应不良中枢可塑性与 耳鸣、听力过敏和在噪声中选择性听力困难的行为表现。 由于测量风险因素、听觉外周等方面的挑战，很难在人类受试者中进行测试 这些听力障碍的状态、中心可塑性特征和详细的行为表型 在这里，通过在同一对象中进行中枢神经、自主神经和心理物理测量。 在项目 3 中也接受了广泛的听觉外围测试的受试者，我们开发了一种 项目 4 的目标 1 将采用创新且详尽的方法在人类受试者中测试这一假设。 使用新的脑电图测量方法来检验以下假设：估计 CND (CNDe) 的水平更显着 与神经增益增加、快速刺激时间特征的神经编码不良以及神经元不良相关 目标 2 将利用声音诱发的新颖自主措施来抑制与任务无关的噪声源。 瞳孔扩张、皮肤电导、心率和微面部表情的变化来检验以下假设： 更明显的 CNDe 与努力倾听时异常强烈的自主神经募集有关 目标 3 将结合上述神经和自主措施来响应情感唤起的声音。 通过详细的行为表型分析，目标 3 将确定 CNDe 如何发挥作用。 增益、时间编码、干扰噪声源抑制和情感声音处理特别相关 通过对多人讲话的测量来识别一系列阈上听力障碍 可懂度、耳鸣心理声学、耳鸣负担、响度心理声学和听觉过敏负担。