Amphetamine use disorder is associated with striatum hypoactivation during anticipation of loss and reward

Background: Dysregulated ventral striatum function has been proposed as one important process occurring in individuals with substance use disorder. This study investigates the role of altered reward and loss processing, which is an important component of impaired decision-making, impulsivity, and vulnerability to relapse in individuals with amphetamine use disorder (AMP). Aims: To determine whether AMP is associated with blunted striatum, prefrontal cortex, and insula signals during win and loss anticipation. Methods: Participants with and without AMP (AMP+ n = 46, AMP- n = 90) from the Tulsa 1000 study completed a monetary incentive delay (MID) task during functional magnetic resonance imaging. Results: Group main effects indicated that: (1) AMP+ exhibited lower bilateral caudate/putamen and left nucleus accumbens signal than AMP- across anticipation of wins and losses; and (2) AMP+ showed slower reaction times than AMP- during loss anticipation. Group*condition interactions demonstrated that AMP+ exhibited greater right amygdala signal than AMP- while anticipating large wins, a pattern that reversed when anticipating small losses. Left caudate/putamen attenuations in AMP+ during small loss anticipation were also evident. Groups did not differ in prefrontal or insula signals. Conclusions: AMP+ individuals have altered neural processing and response patterns during reward and loss anticipation, potentially reflecting impairments in dopamine function, which may influence their decision-making and reactions to different win/loss scenarios. These findings help to explain why AMP+ have difficulty with decision-making and exhibit a heightened focus on immediate rewards or punishments.