This is a revised application for an NIAAA-sponsored Research Project Grant (R01) entitled """"""""Spatiotemporal Brain Imaging of Alcohol Effects on Inhibitory Control"""""""" Problem drinkers often exhibit deficits in self-control and sustained goal-oriented behavior. This observation is consistent with the evidence suggesting that acute intoxication interferes with the ability to evaluate conflicting task demands, inhibit impulsive responses and execute cognitive control. These impairments may result in a decreased ability to exert self restraint, contributing to increased drinking and alcohol dependence. The overall goal of the proposed research is to use multimodal brain imaging to identify the temporal (""""""""when"""""""") and spatial (""""""""where"""""""") characteristics of the neural circuits subserving inhibitory control and to determine their sensitivity to the acute effects of alcohol. Functional magnetic resonance imaging (fMRI) will be used in order to determine where the alcohol-induced induced changes are occurring. Excellent temporal resolution of magneto- (MEG) and electroencephalography (EEG) will elucidate the timing of these abnormalities. Effects of alcohol on both """"""""input"""""""" (stimulus evaluation) and """"""""output"""""""" (response preparation, inhibition and execution) will be studied concurrently and with the multimodal neuroimaging approach. It is hypothesized that alcohol intoxication primarily disrupts integrated prefrontal circuitry that exerts inhibitory top-down control on behavior. Since the strategic control is exerted via a complex system involving multiple stages of these integrated """"""""input"""""""" and """"""""output"""""""" streams in addition to error monitoring and regulatory feedback loops, multimodal imaging approach may reveal the real-time stages of the underlying neural areas and their sensitivity to alcohol intoxication. Healthy subjects will serve as their own controls as they participate in alcohol and placebo conditions in three tasks probing inhibitory control and selective attention. In addition, dispositional traits obtained in the same individuals will be considered together with the neurophysiological indices and may reveal the idiosyncratic aspects of alcohol effects on the brain and the multidimensional nature of inhibitory control. This research has ramifications for traffic- or work-related hazards and may elucidate the alcohol-induced impairment of self-regulatory functions contributing to alcohol abuse and dependence
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