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The Journal of Neuroscience, May 16, 2007, 27(20):5506-5514; doi:10.1523/JNEUROSCI.0601-07.2007

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Behavioral/Systems/Cognitive
Impulsive Personality Predicts Dopamine-Dependent Changes in Frontostriatal Activity during Component Processes of Working Memory

Roshan Cools,^1,2 Margaret Sheridan,¹ Emily Jacobs,¹ and Mark D'Esposito¹

¹Helen Wills Neuroscience Institute, University of California, Berkeley, Berkeley, California 94720-3190, and ²Behavioural and Clinical Neuroscience Institute, University of Cambridge, Cambridge CB2 3EB, United Kingdom

Correspondence should be addressed to Roshan Cools, Behavioural and Clinical Neuroscience Institute, Department of Experimental Psychology, University of Cambridge, Downing Street, Cambridge CB2 3EB, UK. Email: roshan.cools{at}gmail.com

Dopaminergic drugs affect a variety of cognitive processes, but the direction and extent of effects vary across individuals and tasks. Paradoxical effects are observed, by which the same drug causes cognitive enhancing as well as adverse effects. Here, we demonstrate that individual differences in impulsive personality account for the contrasting effects of dopaminergic drugs on working memory and associated frontostriatal activity. We observed that the dopamine D₂ receptor agonist bromocriptine improved the flexible updating (switching) of relevant information in working memory in high-impulsive subjects, but not in low-impulsive subjects. These behavioral effects in high-impulsive subjects accompanied dissociable effects on frontostriatal activity. Bromocriptine modulated the striatum during switching but not during distraction from relevant information in working memory. Conversely, the lateral frontal cortex was modulated by bromocriptine during distraction but not during switching. The present results provide a key link between dopamine D₂ receptor function, impulsivity, and frontostriatal activity during component processes of working memory.

Key words: dopamine; working memory; prefrontal cortex; basal ganglia; fMRI; impulsivity

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Received Feb. 11, 2007; revised April 17, 2007; accepted April 18, 2007.

Correspondence should be addressed to Roshan Cools, Behavioural and Clinical Neuroscience Institute, Department of Experimental Psychology, University of Cambridge, Downing Street, Cambridge CB2 3EB, UK. Email: roshan.cools{at}gmail.com

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