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 higherorder 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.Addiction is a complex disease process of the brain that results from recurring drug intoxication and is modulated by genetic, developmental, experiential, and environmental factors. The neurobiological changes that accompany drug addiction are not well understood. While until recently it was believed that addiction predominantly involved reward processes mediated by limbic circuits (see, for example, the reward deficiency syndrome [1]), results from recent neuroimaging studies have implicated additional brain areas, especially the frontal cortex. Here we summarize the findings from these neuroimaging studies and incorporate them with pertinent results from preclinical studies in suggesting a basis for an integrated model of drug addiction.Most imaging studies have concentrated on the involvement of dopamine in the process of drug addiction because the ability of drugs of abuse to increase brain dopamine concentration in limbic brain regions is considered crucial for their reinforcing effects (2,3). However, the Address reprint requests to Dr. Goldstein, Brookhaven National Laboratory, Medical Research, Bldg. 490, 30 Bell Ave, Upton, NY 11973; rgoldstein@bnl.gov (e-mail NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author Manuscript increase in dopamine per se is insufficient to account for the process of addiction, since drugs of abuse increase dopamine in n...

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