The aim of this pilot project is to evaluate the neural circuitry underlying P300 deficits in alcoholism using functional magnetic resonance imaging (fMRI) and event-related potentials (ERP), and to assess its modulation by alcohol-related cue exposure and cue-induced craving. Recent findings from our laboratory using the oddball paradigm suggest that disturbances in NMDA reception function may preferentially disrupt the contribution of the frontal cortex to the processing of novelty and contribute to the disinhibition of inappropriate responses as a result. This has particular relevance to the study of neurocognitive dysfunction associated with alcoholism, as ethanol acts as an NMDA antagonist. Modulation of the prefrontal circuitry by ethanol has also significant impact on the """"""""reward"""""""" evaluation and sensitivity, as this region is a critical node in """"""""reward"""""""" pathways. The oddball paradigm employed fMRI studies grew from electrophysiological studies that have demonstrated that abstinent chronic alcohol dependent individuals and healthy individuals at increased familiar risk for alcoholism often elicit reduced P300 amplitudes and increased P300 latencies. The current proposal will use converging evidence from electrophysiological and fMRI techniques to isolate the neural underpinnings of abnormal P300 generation in alcoholic patients. Furthermore, we will examine the modulation of prefrontal neural functioning, as assessed by the oddball and novelty detection task, by exposure to alcohol cues and alcohol-cue inducing craving.
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