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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
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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