This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. It is not known why some tinnitus patients are not markedly impaired whereas others report attentional and cognitive difficulties, depression, and even suicidal tendencies. Our results suggest that patients with severe' tinnitus manifest dysregulation of pre-attentional processes related to arousal. We hypothesize that tinnitus is characterized by dysregulation of ascending reticular activating system input through the intralaminar thalamus, which is involved in the modulation of cortical desynchronization, i.e. arousal. We believe that assessment of pre-attentional, attentional, and cortical processes will allow us to quantitatively differentiate between different subpopulations of patients with tinnitus. We will measure pre-attentional/arousal processes using the sleep state-dependent P50 midlatency auditory evoked potential, whose amplitude is a measure of arousal level, and whose habituation to repetitive stimuli is a measure of sensory gating, the process behind distractibility. We will assess attention using the Psychomotor Vigilance Task (PVT), a measure of simple reaction time, and evaluate the ability to sustain attention and respond in a timely manner to salient signals. We will measure relative frontal lobe blood flow using Near Infrared Spectroscopy (NIRS) before and during PVT performance to assess changes in blood flow to cortical regions involved in critical judgment, which are impaired in depression and other psychiatric disorders. This design will allow us to determine at which level of the neuraxis (brainstem-thalamus, thalamo-cortical, and/or cortical) different subpopulations of tinnitus patients manifest quantitative physiological deficits. By localizing the level of the neuraxis affected in different subpopulations of patients with tinnitus, we can develop more informed therapies to selectively alleviate pre-attentional, attentional, and/or cognitive deficits, even if the underlying tinnitus is not cured, thus providing relief for this debilitating condition. Quantitative physiological investigation of these potential neurological substrates for tinnitus represents a novel, comprehensive program of research with great promise for developing innovative therapies for this devastating condition.
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