Associations Between Behavioral and Neural Correlates of Inhibitory Control and Amphetamine Reward Sensitivity

Poor inhibitory control and sensitivity to drug reward are two significant risk factors for drug abuse. Although the two have been largely viewed as separate and independent risk factors, there is new evidence to suggest that they may be related at both the behavioral and neural level. This study examined associations between behavioral and neural correlates of inhibitory control and sensitivity to the subjective rewarding effects of amphetamine in humans. Healthy volunteers (n=63) first completed the stop signal task, a behavioral measure of inhibitory control. Then they participated in four sessions in which they received amphetamine (20 mg) and placebo in alternating order, providing self-report measures of euphoria and arousal at regular intervals. Finally, a subset of participants (n=38) underwent an fMRI scan to assess neural correlates of inhibitory control. In the first phase of the study, participants with longer stop signal reaction time (SSRT) reported greater amphetamine-induced euphoria and stimulation than those with shorter SSRT. In the second phase, fMRI of response inhibition showed the expected activation in right prefrontal regions. Further, individuals who exhibited less activation in the right middle frontal gyrus during the inhibition task reported more euphoria during the amphetamine sessions. This study is the first to show associations between poor inhibitory control and amphetamine reward sensitivity at both behavioral and neural levels in humans. These findings extend our understanding of risk for drug abuse in individuals with poor inhibitory control and suggest novel targets for prevention efforts.