Neural Signatures of Enhanced Central Auditory Gain in Hyperacusis

听觉过敏中枢听觉增益增强的神经特征

• 批准号: 10456238
• 负责人: Kelly Nicole Jahn
• 金额: $ 13.82万
• 依托单位: UNIVERSITY OF TEXAS DALLAS
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-08-01 至 2024-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10456238
• 关键词: Acoustic Nerve; Acoustics; Address; Adverse reactions; Affective; Age; Animal Model; Area; Arousal; Auditory; Auditory Threshold; Auditory system; Behavioral; Biological Assay; Biological Markers; Caliber; Clinical; Clinical Research; Code; Development; Diagnosis; Disease; Distress; Ear; Electroencephalography; Electrophysiology (science); Emotional; Employment; Exhibits; Eye; Face; Fright; Functional disorder; Galvanic Skin Response; General Population; Goals; Growth; Hearing; Hearing problem; Heart Rate; Heterogeneity; Hyperactivity; Hyperacusis; Hypersensitivity; Individual; Injury; Intervention; Investigation; K-Series Research Career Programs; Laboratories; Lead; Libraries; Limbic System; Link; Loudness; Loudness Perception; Maps; Massachusetts; Measures; Mentored Research Scientist Development Award; Mentors; Mentorship; Methods; Monitor; Movement; Mus; Negative Valence; Neuraxis; Output; Pain; Patient Self-Report; Patients; Perception; Peripheral; Physiological; Plant Roots; Prevalence; Psychoacoustics; Psychophysics; Pupil; Quality of life; Questionnaires; Reflex action; Reporting; Research; Scientist; Secondary to; Social isolation; Stimulus; Symptoms; Testing; Training; accurate diagnosis; associated symptom; auditory pathway; avoidance behavior; behavior measurement; clinical diagnostics; deafness; diagnostic tool; effective therapy; emotional distress; hearing impairment; human model; human subject; negative affect; neurophysiology; normal hearing; psychiatric comorbidity; psychosocial; relating to nervous system; response; social; sound

PROJECT SUMMARY/ABSTRACT Hyperacusis is a common and debilitating auditory disorder wherein sounds of moderate intensity are described as unbearably loud, aversive, or even painful. Hyperacusis often has a profoundly negative impact on quality of life, leading to loss of employment, social isolation, and severe psychiatric co-morbidities. Despite the prevalence and heterogeneity of self-reported auditory and emotional sequelae secondary to hyperacusis, its characterization remains largely qualitative. Clinicians lack quantitative and objective neurophysiological markers that would illuminate the neural basis for hyperacusis and allow accurate diagnosis and surveillance of psychoacoustic and distress-related symptoms. In this mentored career development award, the Candidate proposes a training plan to develop objective, non-invasive physiological biomarkers that can quantitatively dissociate complaints of enhanced loudness perception and sound-evoked distress in individuals with hyperacusis, and which have the potential to evolve into a new class of clinical diagnostic tools for evaluating sound intolerance. Supported by decades of research on acoustic injury in animal models, we posit that many of the sound intolerance symptoms associated with hyperacusis share a common root related to maladaptive hyperexcitability (i.e., increased gain) in the central auditory and limbic systems. In Aim 1, the Candidate will implement a battery of perceptual and electroencephalography (EEG) measures to test the hypothesis that subjects with hyperacusis have steeper electrophysiological sound-level growth in the central auditory system and heightened loudness perception as compared to age-matched neurotypical controls. In Aim 2, the Candidate will use complementary behavioral and objective measures of arousal and affective sound quality to test the hypothesis that individuals with hyperacusis exhibit greater subjective and physiological sound-evoked arousal (i.e., larger changes in pupil diameter, skin conductance, heart rate, and facial micro-movements) for emotionally neutral stimuli than age-matched neurotypical controls. The Candidate has assembled a mentorship team of world-class clinicians and auditory neuroscientists that have expertise in a range of relevant areas for the proposal including electrophysiological and psychophysical measures of central gain in humans and animal models. The Eaton-Peabody Laboratories at Massachusetts Eye and Ear is the world’s leading center for the study of hearing and deafness, allowing ample opportunities for research and professional development. The K01 award will allow the Candidate to reshape the reach and sophistication of the clinical research questions that she can pursue, providing a crucial stepping-stone toward her goal of developing into an independent clinician-scientist.

项目概要/摘要 听觉过敏是一种常见且令人衰弱的听觉障碍，其中描述了中等强度的声音 声音难以忍受、令人厌恶，甚至令人痛苦。听力过敏通常会对听力质量产生深远的负面影响 生活，导致失业、社会孤立和严重的精神并发症。尽管流行 以及继发于听觉过敏的自我报告的听觉和情感后遗症的异质性，其 特征描述在很大程度上仍然是定性的。临床医生缺乏定量和客观的神经生理学 标记物将阐明听觉过敏的神经基础，并允许准确诊断和监测 心理声学和痛苦相关症状。在这个指导性职业发展奖中，候选人 提出了一项培训计划，以开发客观的、非侵入性的生理生物标志物，可以定量 将患有以下疾病的个体对响度感知增强和声音诱发的痛苦的抱怨分开 听觉过敏，有可能发展成为一类新的临床诊断工具，用于评估 声音不宽容。在动物模型声损伤数十年研究的支持下，我们认为许多 与听觉过敏相关的声音不耐受症状有一个与适应不良相关的共同根源 中枢听觉和边缘系统过度兴奋（即增益增加）。在目标 1 中，候选人将 实施一系列感知和脑电图 (EEG) 测量来检验以下假设： 患有听觉过敏的受试者中枢听觉系统的电生理声级增长更陡峭 与年龄匹配的神经典型对照相比，响度感知增强。在目标 2 中，候选人 将使用唤醒和情感声音质量的补充行为和客观测量来测试 假设患有听觉过敏的个体表现出更大的主观和生理声音诱发的唤醒 （即瞳孔直径、皮肤电导、心率和面部微动作的较大变化） 中性刺激高于年龄匹配的神经典型对照。候选人组建了一个导师团队 世界一流的临床医生和听觉神经科学家，在一系列相关领域拥有专业知识 提案包括对人类和动物的中心增益进行电生理学和心理物理学测量 模型。马萨诸塞州眼耳科伊顿-皮博迪实验室是世界领先的眼耳科研究中心 听力和耳聋的研究，为研究和专业发展提供充足的机会。这 K01 奖将使候选人能够重塑临床研究问题的范围和复杂性 她可以追求的目标，为她发展为独立的目标提供了重要的垫脚石 临床医生科学家。