Fellowship for Benjamin Auerbach: The Role of Central Gain Control in Hyperacusis of Diverse Origin

? 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.