Intense noise exposure and ototoxic drugs cause hearing loss and reduce the neural output of the cochlea. Paradoxically, cochlear damage often enhances neural activity in the central auditory pathway at suprathreshold intensities. This compensatory increase in the central auditory pathway is referred to as Enhanced Central Gain. Enhanced Central Gain is believed to be responsible for hyperacusis (loudness intolerance) and tinnitus, two debilitating conditions that afflict millions of Americans. The goal of this project s to experimentally test the Central Gain model to determine if it can account for hyperacusis and tinnitus induced by ototoxic drugs or intense noise exposure. To accomplish this, we will determine if the temporal and spectral properties of noise-induced or drug-induced hyperacusis match time course and spectral features of the electrophysiological metric of increased central gain in auditory cortex (AC), medial geniculate body (MGB), lateral amygdala and inferior colliculus (IC). We will also determine if the time course of noise-induced or drug- induced tinnitus is correlated with the time course and spectral features of hyperacusis and increased central gain in the AC, MGB, LA or IC. Since hyperexcitability disorders can be controlled by drugs that regulate potassium channel permeability, we will test the hypothesis that potassium channel modulators can suppress noise- or drug-induced hyperacusis and enhanced central gain. The proposed studies are designed to increase our understanding of the neural mechanisms of hyperacusis and tinnitus and test the efficacy of novel pharmacological agents to treat these two debilitating disorders.

Public Health Relevance

Individuals with hearing loss suffer from hyperacusis (loudness intolerance) and tinnitus, conditions thought to arise from increased neural gain in the central auditory pathway. Experiments are planned to determine if the time course and spectral features of increased central gain matches the time course and spectral properties of tinnitus and hyperacusis. Potassium channel modulators, used to treat hyperexcitability disorders, will be evaluated to determine if they can suppress hyperacusis and decrease central gain.

National Institute of Health (NIH)
National Institute on Deafness and Other Communication Disorders (NIDCD)
Research Project (R01)
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Special Emphasis Panel (ZRG1)
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Miller, Roger
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State University of New York at Buffalo
Other Health Professions
Schools of Arts and Sciences
United States
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