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.