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: 10285833
• 负责人: Kelly Nicole Jahn
• 金额: $ 4.6万
• 依托单位: MASSACHUSETTS EYE AND EAR INFIRMARY
• 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 2021-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10285833
• 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; Diagnostic; 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; comorbidity; deafness; effective therapy; emotional distress; hearing impairment; human model; human subject; negative affect; neurophysiology; normal hearing; psychosocial; relating to nervous system; response; social; sound; tool

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.

项目总结/摘要 听觉过敏是一种常见的和衰弱的听觉障碍，其中声音的中等强度的描述 令人难以忍受的吵闹令人厌恶甚至是痛苦听觉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，严重的精神病合并症。尽管流行 和异质性的自我报告的听觉和情感后遗症继发于听觉过敏，其 定性仍然主要是定性的。临床医生缺乏定量和客观的神经生理学 这些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 心理听觉和痛苦相关的症状。在这个指导职业发展奖，候选人 提出了一个培训计划，以开发客观的，非侵入性的生理生物标志物， 分离个体的响度感知增强和声音引起的痛苦的主诉， 听觉过敏，并有可能演变成一类新的临床诊断工具，用于评估 听起来不宽容。在动物模型中数十年的声损伤研究的支持下， 与听觉过敏相关的声音不耐受症状有一个共同的根源， 过度兴奋（即，增加的增益）。在目标1中，候选人将 实施一系列感知和脑电图（EEG）测量来测试假设， 听觉过敏的受试者在中枢听觉系统中具有更陡的电生理学声级增长 以及与年龄匹配的神经型对照相比提高的响度感知。目标2：候选人 将使用补充的行为和客观措施的唤醒和情感的声音质量，以测试 假设听觉过敏的个体表现出更大的主观和生理的声音诱发的觉醒 (i.e.,瞳孔直径、皮肤电导、心率和面部微运动的较大变化）， 中性刺激比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，在一系列相关领域的专业知识， 包括人类和动物中枢增益的电生理学和心理物理学测量的建议 模型位于马萨诸塞州眼耳的伊顿-皮博迪实验室是世界领先的 学习听力和耳聋，为研究和专业发展提供充足的机会。的 K 01奖将允许候选人重塑临床研究问题的范围和复杂性 她可以追求，为她发展成为一个独立的目标提供了一个关键的垫脚石 临床科学家