Drug addiction and its underlying neurobiological basis: neuroimaging evidence for the involvement of the frontal cortex

Abstract

Objective: Studies of the neurobiological processes underlying drug addiction primarily have focused on limbic subcortical structures. Here the authors evaluated the role of frontal cortical structures in drug addiction.

Method: An integrated model of drug addiction that encompasses intoxication, bingeing, withdrawal, and craving is proposed. This model and findings from neuroimaging studies on the behavioral, cognitive, and emotional processes that are at the core of drug addiction were used to analyze the involvement of frontal structures in drug addiction.

Results: The orbitofrontal cortex and the anterior cingulate gyrus, which are regions neuroanatomically connected with limbic structures, are the frontal cortical areas most frequently implicated in drug addiction. They are activated in addicted subjects during intoxication, craving, and bingeing, and they are deactivated during withdrawal. These regions are also involved in higher-order cognitive and motivational functions, such as the ability to track, update, and modulate the salience of a reinforcer as a function of context and expectation and the ability to control and inhibit prepotent responses.

Conclusions: These results imply that addiction connotes cortically regulated cognitive and emotional processes, which result in the overvaluing of drug reinforcers, the undervaluing of alternative reinforcers, and deficits in inhibitory control for drug responses. These changes in addiction, which the authors call I-RISA (impaired response inhibition and salience attribution), expand the traditional concepts of drug dependence that emphasize limbic-regulated responses to pleasure and reward.

FIGURE 1

Behavioral Manifestations of the I-RISA (Impaired Response Inhibition and Salience Attribution) Syndrome of Drug Addiction

FIGURE 2

Orbitofrontal Cortical Activation in Active Cocaine Abusers During a Cocaine Theme Interview and a Neutral Theme Interview, as Measured by FDG PET

FIGURE 3

Lower Relative Glucose Metabolism in the Prefrontal Cortex and Anterior Cingulate Gyrus of a Cocaine Abuser Than in a Normal Comparison Subject

FIGURE 4

Lower Striatal Dopamine D2 Receptor Binding in Drug Users During Withdrawal From Cocaine, Meth-amphetamine, and Alcohol Than in Normal Comparison Subjects

FIGURE 5

Relation of Striatal Dopamine D2 Receptor Availability and Orbitofrontal Cortical Metabolism in Cocaine Users a, b. ^a Adapted from an earlier article (59). Reprinted from Synapse, ©1993 Wiley-Liss, Inc., with permission. ^b r=0.7, p<0.0001.

FIGURE 6

Interactions of the Mesocortical and Mesolimbic Circuits in Drug Addiction

FIGURE 7

Integrative Model of Brain and Behavior: the I-RISA (Impaired Response Inhibition and Salience Attribution) Syndrome of Drug Addiction