Figure. Proposed Network of Brain Circuits Involved With Addiction⁵⁷.

Circuits work together and change with experience. Each is linked to an important concept: reward (saliency), motivation (drive), memory (learning associations), inhibitory control (conflict resolution), mood (well-being),⁵⁸ and interoception (internal awareness).⁵⁹ Size of circuit ovals indicates influence in determining behavioral outcomes. Thicker line weights indicate greater influence on regulation of the circuit. A, In a nonaddicted person the decision to consume a drug (same process pertains for natural rewards) is a function of the balance between the expected pleasure (based on past experience or memory), alternative stimuli (this includes internal states such as mood and interoception but also alternative external rewards), and potential negative outcomes that oppose the motivation to take the drug (inhibitory control exerted by prefrontal cortex) and stop the drug use. B, During addiction, the enhanced value of the drug in the reward, motivation, and memory circuits overcomes the inhibitory control exerted by the prefrontal cortex, thereby favoring a positive feedback loop initiated by the consumption of the drug and perpetuated by enhanced activation of the motivation/drive and memory circuits. Decreased sensitivity to rewards also raises the hedonic threshold, disrupting mood and increasing the saliency values of drugs and behaviors temporarily associated with relief from the dysphoria. Learning and conditioning result in an enhanced interoceptive awareness of discomfort and the associated desire for the drug (craving). Absence of lines from inhibitory control circuit to reward and motivation circuits indicates loss of regulation.