Medical Department Seminar

Clinical evidence suggests that impulsivity increases after drug consumption in addicted individuals. This increase in impulsive behavior could facilitate the transition to drug abuse through increased drug exposure in vulnerable individuals. To date, however, brain mechanisms involved in the effects of drugs on impulsive behavior have not been well studied in healthy, nonaddicted subjects. Objective: The present fMRI study was designed to determine the brain regions involved in acute drug effects on impulsive behavior and emotion, as measured during a newly developed computerized measure of risk-taking behavior (Balloon Analogue Risk Task, BART) and emotional pictures from the International Affective Picture Set (IAPS). Method: Participants received d-amphetamine (20 mg oral) or placebo 90 minutes prior to fMRI scanning and performance of the BART impulsivity/risk task and IAPS picture set in a double-blind, within-subjects design. Participants were preselected based on personality traits that have been found to modulate the effects of the drug in other samples, as assessed by a standardized personality inventory with an orthogonal factor structure (Multidimensional Personality Questionnaire, Brief Form). Findings: d-amphetamine significantly altered fMRI activation in the limbic thalamus, anterior cingulate, and nucleus accumbens during high reward blocks compared to low reward blocks of the behavioral impulsivity/ risk task. D-amphetamine also decreased amygdala responses to negatively valenced blocks of the IAPS emotional picture task. These data suggest that d-amphetamine selectively shifts brain processing toward high reward, high risk stimuli and away from low reward, low risk alternatives. Individual differences in fMRI responses to amphetamine were also observed, and were found to relate primarily to the stable personality traits of reward sensitivity, harm avoidance, and stress reactivity. Potential findings with regard to SERT and DRD4 polymorphism