Impaired self-control plays a fundamental role in drug-taking behaviors in addiction. Successful self-regulation functions requires top-down control from the PFC to the striatal and limbic regions involved with rewards and emotions (reviewed in Reference 57). Impaired self-control in addicted subjects is believed to reflect disrupted prefrontal regulation of striatal regions. The level of impairment is influenced by the emotional state (negative mood increases impairment) and the context (exposure to unexpected cues can also impair it). Indeed, in cocaine abusers, cognitive control of craving is associated with decreased activation of the NAc and the orbitofrontal cortex, which is dependent on proper activity of the inferior PFC (BA 44) (58) (Figure 4). Moreover, lateral PFC activity assessed in cigarette smokers performing an inhibitory task (an experimental proxy of the self-control needed against temptations or distractions) predicted their craving and smoking behavior over the subsequent three-week period (59).
