Cortical Electrical Suppression of Noise-Induced Tinnitus

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DESCRIPTION (provided by applicant): Tinnitus is a phantom sound that occurs in the absence of external stimulation. It can have debilitating effects on millions of patients, creating a significant economic impact on our society. Among numerous management strategies being sought, auditory cortex electrical stimulation (ACES) has recently been used clinically to suppress tinnitus. This treatment has yielded promising results and has the potential of becoming an important approach in managing tinnitus. However, large variability in the efficacy of ACES-induced tinnitus suppression across individuals has hindered its development into a reliable therapy. The goal of this project is to develop an ACES rat model of tinnitus suppression. In Aim 1, we will test the hypothesis that ACES suppresses noised-induced tinnitus in rats. To test this hypothesis, we will implant chronic electrode arrays in the rat auditory cortex (AC). Following recovery from surgery, baseline behavioral data before noise exposure will be evaluated for tinnitus using a gap detection startle reflex paradigm. To induce tinnitus, each animal will be exposed to a 16 kHz octave band noise delivered at 124-130 dB SPL for 15 minutes or 2 hours. Upon confirming the presence of tinnitus, electrical stimulation of the AC will be performed. Behavioral testing for tinnitus will again be performed after ACES to determine its suppressive effects on the behavioral evidence of tinnitus. Before and after tinnitus induction with noise exposure, hearing thresholds will be measured by the pre-pulse inhibition startle reflex and the acoustically evoked auditory brainstem responses. The data will be used to separate tinnitus positive animals without hearing loss from those with hearing loss. In Aim 2, we will optimize stimulation strategies of ACES to suppress noise-induced tinnitus. We will conduct comparative studies to determine where and how to stimulate in order to obtain maximum suppression of tinnitus. The comparisons will be made between stimulation of the ipsilateral and contralateral AC to a manipulated ear, auditory core and belt regions, and epidural and intra-parenchymal (intracortical) tissues. In addition, we will examine the suppressive effects using different stimulation parameters such as single and train pulses, intensity, pulse rate, and duration. Developing this animal model is a crucial step for identifying optimal stimulation strategies - directly impacting clinically relevant issues. Establishing this model will also allow an in-depth investigation of the mechanisms that underlie ACES-induced tinnitus suppression. A clear understanding of these mechanisms will in turn facilitate the development of ACES as a reliable therapy. Finally, research in this direction will help gain more insights into the mechanisms of tinnitus. Tinnitus is a prevalent public health problem that affects millions of people and imposes a significant economic burden to society. Among numerous management strategies being sought, auditory cortex electrical stimulation (ACES) has become an important and promising approach in managing tinnitus. The goal of this project is to establish an animal model of ACES to suppress tinnitus. Developing this animal model will allow in-depth investigation of the mechanisms underlying ACES-induced tinnitus suppression, stimulate advanced clinical trials and facilitate development of ACES as a reliable therapy.