Steve Berman Tel: 310-478-3711 ext. 40696 (LA VAMC) 310-206-6657 (NPI) E-mail: sberman@ucla.edu Investigations focus on alcohol and drug abuse vulnerability studies. Starting from Dr. Noble's association of the A1 allele of the D2 dopamine receptor (DRD2) gene with a deficient dopaminergic system that predisposed to all forms of substance abuse (including obesity), I've been able to show 1) the first electrophysiological predictor of later drug use in adolescence, 2) the first electrophysiologic (P300) and neuropsychological (visuospatial ability) associates of a specific genetic polymorphism, and 3) the first gene-environment interaction in determination of behavioral markers of substance abuse vulnerability. All of our work suggests those at highest risk for substance abuse fit a self-medicating pattern of drug use long before addiction ensues. Recent work (in press) on the personality characteristic of novelty seeking discriminates between positive reinforcement sensation-seeking, and the negative reinforcement sensation-seeking more characteristic of severe substance abusers. Our newest project finds similar patterns for negative affect. We hope to soon apply these models to smoking behaviors. In another project we use brain imaging to reveal the changes during early abstinence in hospitalized methamphetamine abusers, and studies of functionally disordered gastrointestinal patients. In all of my work, I'm interested in combining the high temporal resolution of scalp-recorded electrical activity (ERPs) with the high spatial resolution of brain imaging to get a more complete picture of how our nervous system accomplishes a given task. After some success combining ERPs and positron-emission tomography (PET) to clarify hemispheric specialization of language subcomponents, we now plan to combine ERPs with fMRI to study IBS, the most common GI functional disorder. We have electrophysiological evidence that IBS patients are preattentively hyper-responsive to non-gut stimuli. Our first fMRI sessions validated our extensive PET studies of brain areas that respond to rectal pressure in these subjects, including amygdala deactivations that we believe to be antinociceptive. Combining event-related fMRI and ERPs will allow us to test pharmacologic probes in both human subjects and an in-house rodent model of IBS, and target the adrenergic and serotonergic systems that show maximal promise for intervention. Back