In recovered cocaine users, activation patterns during easy choices were similar to those in HCs, but recovered users still revealed impairments during difficult choices (Meade et al. 2011). Only three studies are available employing functional neuroimaging during DDTs in stimulant dependence, two of which were performed in methamphetamine abusers (see Table 3). Although one study was conducted in active users (Monterosso et al. 2007) and the other in abstinent abusers

(Hoffman et al. 2008), similar brain areas were found to be less active in SAs compared with HCs for difficult Crizotinib cost versus easy choices. Similar results were obtained in active cocaine using HIV Inhibitors,research,lifescience,medical patients (Meade et al. 2011). These findings, therefore, indicate that, even after sustained abstinence, brain functions remain altered in methamphetamine and cocaine abusers, resulting in sustained periods with a high probability of relapse into drug use. In the methamphetamine studies, these group-by-task load effects were probably due to Inhibitors,research,lifescience,medical increased regional brain activity in methamphetamine users during “easy” choices, presumably reflecting lower efficiency of cognitive control circuitry. In

contrast to Monterosso et al. (2007), Hoffman et al. (2008) observed significant correlations between discounting rates and activity in the DLPFC, amygdala, posterior cingulate cortex, and posterior parietal cortex. Inhibitors,research,lifescience,medical These latter findings are consistent with the hypothesis that both ventral/limbic and dorsal systems are involved in impulsive decisions: the ventral system (amygdala, ventral striatum, VLPFC, insula)

Inhibitors,research,lifescience,medical for decisions involving salient and immediate rewards and the dorsal system (DLPFC, dorsal ACC, and posterior Inhibitors,research,lifescience,medical parietal cortex) when decision making requires elaborate comparison and choice making (McClure et al. 2004). Hoffman et al. (2008) suggested that their findings were consistent with a model wherein dorsal cognitive systems modulate the neural response of ventral regions. This switch from ventral to more dorsal striatal control is consistent with the hypothesis of a switch from salience-based behavior toward more habitual behavior and is linked with decreased sensitivity to outcome values (Habitual Behavioral Model). Indeed, methamphetamine-dependent patients, who strongly preferred smaller immediate over larger delayed rewards, appeared to activate the dorsal cognitive the control system to overcome their preference for small immediate rewards. Moreover, activation of the amygdala during choice of delayed rewards was associated with a greater degree of discounting, suggesting that heavily discounting methamphetamine abusers may be more responsive to the negative salience of delayed rewards than controls. In contrast, in the Meade et al. (2011) study, differences in discounting rates, although in the expected direction, failed to reach statistical significance.