In general, neuroimaging studies have revealed an emerging pattern of generalized PFC dysfunction in drug-addicted individuals that is associated with more negative outcomes — more drug use, worse PFC-related task performance and greater likelihood of relapse. In drug-addicted individuals, widespread PFC activation upon taking cocaine or other drugs and upon presentation of drug-related cues is replaced by widespread PFC hypoactivity during exposure to higher-order emotional and cognitive challenges and/or during protracted withdrawal when not stimulated. The PFC roles that are most pertinent to addiction include self-control (that is, emotion regulation and inhibitory control) to terminate actions that are not advantageous to the individual, salience attribution and maintenance of motivational arousal that is necessary to engage in goal-driven behaviours, and self-awareness. Although activity among PFC regions is highly integrated and flexible, so that any one region is involved in multiple functions, the dorsal PFC (including the dACC, DLPFC and inferior frontal gyrus) has been predominantly implicated in top-down control and meta-cognitive functions, the ventromedial PFC (including subgenual ACC and mOFC) in emotion regulation (including conditioning and assigning incentive salience to drugs
