Drug Addiction and Its Underlying Neurobiological Basis: Neuroimaging Evidence for the Involvement of the Frontal Cortex

• Published in: The American journal of psychiatry Vol. 159; no. 10; pp. 1642 - 1652
• Main Authors: Goldstein, Rita Z., Volkow, Nora D.
• Format: Journal Article
• Language: English
• Published: Washington, DC American Psychiatric Publishing 01.10.2002; American Psychiatric Association
• Subjects: Addictive behaviors; Adult and adolescent clinical studies; Alcoholism; Behavior, Addictive - physiopathology; Biological and medical sciences; Brain; Cerebral Cortex - metabolism; Cerebral Cortex - physiopathology; Cocaine-Related Disorders - metabolism; Cocaine-Related Disorders - physiopathology; Compulsive Behavior - physiopathology; Dopamine - physiology; Drug addiction; Fluorodeoxyglucose F18; Frontal Lobe - diagnostic imaging; Frontal Lobe - metabolism; Frontal Lobe - physiopathology; Humans; Limbic System - physiopathology; Medical sciences; Models, Theoretical; Neurobiology; Neuroimaging; Neurology; Psychology. Psychoanalysis. Psychiatry; Psychopathology. Psychiatry; Reinforcement (Psychology); Substance Withdrawal Syndrome - physiopathology; Substance-Related Disorders - diagnostic imaging; Substance-Related Disorders - physiopathology; Substance-Related Disorders - psychology; Syndrome; Terminology as Topic; Tomography, Emission-Computed; Human; Drug addiction; Orbitofrontal cortex; Abuse; Illicit drug; Craving; Biological model; Central nervous system; Cognition; Emotion emotionality; Limbic system; Review; Frontal cortex; Metabolism; Addiction; Cingulate cortex; Dependence; Anterior nucleus; Withdrawal syndrome; Neuropsychologia; Comparative study; Brain (vertebrata)
• ISSN: 0002-953X; 1535-7228
• DOI: 10.1176/appi.ajp.159.10.1642

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.