The Role of Central Gain Control in Hyperacusis of Diverse Origin

中央增益控制在不同来源的听觉过敏中的作用

• 批准号: 9263685
• 负责人: Benjamin D Auerbach
• 金额: $ 6.04万
• 依托单位: STATE UNIVERSITY OF NEW YORK AT BUFFALO
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-04-01 至 2019-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9263685
• 关键词: Affect; Amygdaloid structure; Animal Model; Animals; Anxiety Disorders; Auditory; Auditory Evoked Potentials; Auditory area; Auditory system; Basic Science; Behavior; Behavioral; Behavioral Assay; Brain; Brain region; Chronic; Clinical; Clinical Sciences; Disease; Electrodes; Electrophysiology (science); Enhancers; Etiology; Exhibits; FMR1; Fragile X Syndrome; Frequencies; Functional disorder; General Population; Hearing; High Prevalence; Hyperactive behavior; Hyperacusis; Hypersensitivity; Impairment; Implant; Inferior Colliculus; Inherited; Lateral; Link; Loudness; Loudness Perception; Measurement; Measures; Mental Depression; Modeling; Neurodevelopmental Disorder; Neurons; Noise; Operant Conditioning; Pain; Peripheral; Pharmaceutical Preparations; Pharmacology; Population; Process; Rattus; Reaction Time; Risk Factors; Role; Sensorineural Hearing Loss; Sensory; Sensory Disorders; Signal Transduction; Testing; Tinnitus; Training; Vigabatrin; Williams Syndrome; Work; auditory processing; autism spectrum disorder; behavior measurement; economic impact; experimental study; hearing impairment; insight; metabotropic glutamate receptor 5; multi-electrode arrays; nervous system disorder; neural circuit; neural correlate; novel; public health relevance; relating to nervous system; response; sound; synaptic function; therapy development; treatment effect; treatment strategy

 DESCRIPTION (provided by applicant): Hyperacusis is a prevalent sensory disorder in which sounds of moderate intensity are perceived as intolerably loud or even painful. Despite the significant societal and economic impact of hyperacusis, treatments for this disorder are lacking. While hearing loss has consistently been identified as the primary risk factor for hyperacusis, many other disorders are also associated with loudness intolerance, suggesting the causes of hyperacusis can be varied. Hyperacusis is particularly prevalent in several neurodevelopmental disorders, such as Williams Syndrome, Fragile X Syndrome (FX), and autism spectrum disorders (ASD). The aim of this proposal is to directly compare the mechanisms underlying hyperacusis of distinct origin to determine if there is a shared neural disruption that manifests a auditory hypersensitivity. Specifically, the proposed work will test the hypothesis that altered central gain control is a common pathophysiological mechanism in two distinct models of hyperacusis: long-term hearing loss and an animal model of FX, the leading inherited cause of ASD. A combination of electrophysiological and behavioral measures will be used to characterize the relationship between central auditory hyperactivity and hyperacusis-like behavior in these models to: (1) determine the neural correlates of hyperacusis due to hearing loss; (2) characterize hyperacusis and the potential neural correlates in an animal model of FX; and (3) identify drugs that may ameliorate measures of hyperacusis in both hearing loss and FX models. Understanding how these distinct forms of hyperacusis are similar and/or different will provide both clinical and basic science insights relevant to understanding and treating hyperacusis.

 描述（由适用提供）：Hyper Acusis是一种普遍的感觉障碍，其中中等强度的声音被认为是响亮甚至痛苦的。尽管Hyper Acusis对社会和经济产生了重大影响，但仍缺乏对这种疾病的治疗。尽管听力损失始终被确定为HyperAcusis的主要危险因素，但许多其他疾病也与响度有关，这表明HyperAcusis的原因可能会改变。在几种神经发育障碍中，Hyper Acusis尤为普遍，例如Williams综合征，脆弱X综合征（FX）和自闭症谱系障碍（ASD）。该提案的目的是直接比较不同起源的超源物的基础机制，以确定是否存在表现出听觉性超敏反应的共同神经断开。具体而言，拟议的工作将检验以下假设：在两个不同的超源模型中，改变中央增益控制是一种常见的病理生理机制：长期听力损失和FX的动物模型，FX是ASD的主要遗传原因。在这些模型中，电生理学和行为措施的结合将用于表征中央听觉多动和类似于超值的行为之间的关系： （2）表征Hypersusis和FX动物模型中的潜在中性相关性； （3）确定可以改善听力损失和FX模型中超源量测量的药物。了解这些不同形式的超源形式是相似的和/或不同的，将提供与理解和治疗超源物相关的临床和基础科学见解。