Reward processing in problem substance users has been studied using a monetary incentive delay (MID) task during functional magnetic resonance imaging (fMRI) finding increased ventral striatal and mesial frontal cortex activation (Bjork et al., 2008b) yet reduced activation in the cerebellum and orbital frontal cortex compared to control subjects (Goldstein et al., 2007). Lack of orbitofrontal activation has been associated with decision-making and regulation deficits in substance-dependent subjects (Paulus et al., 2002). Comparing heroin users to control subjects, stronger resting state connectivity was found between the NAcc reward center and both the medial orbital frontal cortex and the ventral/rostral anterior cingulate, a region associated with craving and emotion regulation (Ma et al., 2010). In heavy drinkers, cue-elicited craving produced strong correlations between the striatum, ventral tegmental/substantia nigra and medial prefrontal cortex, involved in complex cognition (Filbey et al., 2008; Koechlin and Hyafil, 2007). Together, these studies of problem users suggest increased saliency responses, likely associated with craving, perhaps due to compromised regulatory/inhibitory control. However, it is unclear from these studies whether abnormalities are a consequence of substance use, learned addiction-related behaviors, or are related to pre-existing risk.
