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The Journal of Neuroscience, December 8, 2004, 24(49):11017-11022; doi:10.1523/JNEUROSCI.3321-04.2004

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Behavioral/Systems/Cognitive
Executive Dysfunction in Cocaine Addiction: Evidence for Discordant Frontal, Cingulate, and Cerebellar Activity

Robert Hester¹ and Hugh Garavan^1,2

¹Department of Psychology and Institute of Neuroscience, Trinity College Dublin, Dublin 2, Ireland, and ²Department of Psychiatry and Behavioral Medicine, Medical College of Wisconsin, Milwaukee, Wisconsin 53226

Using a GO-NOGO response inhibition task in which working memory (WM) demands can be varied, we demonstrate that the compromised abilities of cocaine users to exert control over strong prepotent urges are associated with reduced activity in anterior cingulate and right prefrontal cortices, two regions thought to be critical for implementing cognitive control. Furthermore, unlike drug-naive controls, and opposite to the anterior cingulate pattern, cocaine users showed an over-reliance on the left cerebellum, a compensatory pattern previously seen in alcohol addiction. The results indicate that cocaine users find it difficult to inhibit their own actions, particularly when WM demands, which have been shown previously to increase during cue-induced craving for the drug, are increased. The results reveal a neuroanatomical basis for this dysexecutive component to addiction, supporting the suggested importance cognitive functions may play in prolonging abuse or predisposing users toward relapse.

Key words: cocaine; executive function; response inhibition; working memory; addiction; fMRI

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Received July 6, 2004; revised September 24, 2004; accepted October 3, 2004.

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