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到的声音的角度来研究和治疗的 听得见。然而，三个最常见、最令人衰弱的成年人听力问题反映的恰恰是相反的问题： 不是人们听不到的，而是他们听不到的。老年人或有噪音史的人 暴露经常受到无法抑制的幻觉(耳鸣)的侵袭，他们经历了 中等强度的声音听起来很响亮，令人痛苦，甚至是痛苦的(听觉过敏症)，他们努力抑制 在收听目标说话人时注意背景噪声源。尽管年龄、噪音暴露和 听力状况是这些知觉障碍的风险因素，这种联系充其量是间接的，提示了许多 对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根植于初级耳蜗肌之间的对话出错 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) 已被证明在中枢听觉通路中触发一种代偿性可塑性过程，这种可塑性过程往往过度- 射击目标，使中枢听觉神经元高度活跃，高度敏感，高度同步，并 内部“嘈杂”。发表在许多动物物种和听力损失范例上的工作的广泛共识 提示CND引起的适应不良中枢可塑性与 噪声中耳鸣、听觉过敏和选择性听力障碍的行为表现。这一假设已经 由于测量风险因素、听觉外周的挑战，很难在人类受试者中进行测试 这些听力障碍的状态、中枢可塑性特征和详细的行为表型 研究对象。在这里，通过在同一系统中进行中枢神经、自主神经和心理物理测量 在项目3中也经历了广泛的听觉外周测试的受试者，我们开发了一种 创新和详尽的方法，在人类受试者身上检验这一假说。项目4的目标1将 使用新的脑电测量来检验这样的假设，即更显著的估计CND(CNDe)水平是 与神经增益增加、对快速刺激时间特征的神经编码不良以及神经功能不良有关 抑制与任务无关的噪声源。目标2将利用声音诱发的新的自主神经测量 瞳孔扩张、皮肤电导、心率和微面部表情的变化来检验这一假设 更明显的CNDe与努力倾听时异常强烈的自主神经招募有关 以及对情感唤起的声音的反应。目标3将结合上述神经和自主措施 有详细的行为表型。使用因果调解分析，目标3将确定CNDe、Central 增益、时间编码、干扰噪声源抑制和情感声音处理具体涉及 通过对多个说话者的语音测量来识别的阈值上听力障碍的频谱 清晰度、耳鸣心理声学、耳鸣负荷、响度心理声学和听觉超敏负荷。