Neural Signatures of Enhanced Central Auditory Gain in Hyperacusis

项目摘要/摘要 听力亢进是一种常见的、使人衰弱的听觉障碍，描述的是中等强度的声音。 令人无法忍受的吵闹、厌恶甚至痛苦。听力过敏症通常会对听力质量产生深远的负面影响 导致失业、社会孤立和严重的精神疾病并存。尽管盛行 和自我报告的听觉和情感后遗症的异质性，其 定性在很大程度上仍然是定性的。临床医生缺乏量化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 心理声学和与痛苦相关的症状。在这个指导职业发展奖中，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记物，可以定量地 分离主诉增强的响度知觉和声音诱发的苦恼的个体 听觉过敏症，并有可能演变为一类新的临床诊断工具 听起来很不宽容。在数十年的动物模型声学损伤研究的支持下，我们假设许多 与听力亢进相关的声音不耐受症状有一个共同的根源，与适应不良有关 中枢听觉和边缘系统的过度兴奋性(即增益增加)。在目标1中，候选人将 实施一系列感知和脑电(EEG)测量来验证以下假设 听力亢进的受试者中枢听觉系统有更陡峭的电生理声级增长 与年龄匹配的神经典型对照组相比，他们对响度的感知更强。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 假设听力亢进的个体表现出更大的主观和生理声音诱发唤醒 (即，瞳孔直径、皮肤电导、心率和面部微运动的较大变化) 与年龄匹配的神经典型对照相比，中性刺激。这位候选人已经组建了一个指导团队， 世界级临床医生和听神经学家，他们在一系列相关领域拥有专业知识 建议包括人和动物中枢获得的电生理和心理物理测量 模特们。马萨诸塞州伊顿-皮博迪实验室是世界领先的 听力和耳聋的研究，为研究和专业发展提供了充足的机会。这个 K01奖将允许候选人重塑临床研究问题的覆盖范围和复杂性 这是她可以追求的，为她向独立人士发展的目标提供了至关重要的垫脚石 临床医生兼科学家。

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.