Here, we review studies that assessed the effects of stimulant and non-stimulant drugs on PFC activity (Supplementary information S2 (table)). Our model predicts drug-induced enhancements of activity in PFC areas that are involved in drug-related processes — including emotional responses, automatic behaviours and higher-order executive involvement (for example, medial OFC (mOFC) and ventromedial PFC in craving, OFC in drug expectation, ACC in attention bias and DLPFC in forming drug-related working memories). It also predicts drug-induced decreases in non-drug related activity in these same PFC regions, most notably during craving and bingeing in drug-addicted individuals, discussed below (FIG. 3). Consistent with the former prediction, intravenous cocaine administration to overnight-abstinent cocaine-addicted individuals increased self-reports of high and craving, and mainly increased fMRI blood oxygen level-dependent (BOLD) responses in various PFC subregions12,13. Interestingly, activity in the left lateral OFC, frontopolar cortex and ACC was modulated by drug expectation (that is, activity was greater after expected versus unexpected intravenous delivery of cocaine), whereas subcortical regions responded mainly to the pharmacological effects of cocaine (that is, there was no modulation by expectation); the specific direction
