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The Journal of Neuroscience, April 2, 2008, 28(14):3697-3706; doi:10.1523/JNEUROSCI.3921-07.2008

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Behavioral/Systems/Cognitive
Dopamine Depletion Impairs Frontostriatal Functional Connectivity during a Set-Shifting Task

Atsuko Nagano-Saito,¹ Marco Leyton,² Oury Monchi,³ Yael K. Goldberg,¹ Yong He,¹ and Alain Dagher¹

¹Montreal Neurological Institute and ²Department of Psychiatry, Faculty of Medicine, McGill University, Montréal, Quebec, Canada H3A 2B4, and ³Centre de Recherche, Institut Universitaire de Gériatrie de Montréal, Université de Montréal, Montréal, Quebec, Canada H3W 1W5

Correspondence should be addressed to Dr. Alain Dagher, Montreal Neurological Institute, 3801 University Street, Montreal, Quebec, Canada H3A 2B4. Email: alain.dagher{at}mcgill.ca

We investigated the effect of transient dopamine depletion on functional connectivity during performance of the Wisconsin Card Sorting Task. Functional magnetic resonance imaging data were analyzed as a psychophysiological interaction, a statistical method used to identify functional connectivity during experimental manipulations. Nineteen healthy subjects were scanned, double blind, on 2 separate days: once after drinking an amino acid mixture deficient in the dopamine precursors tyrosine and phenylalanine, and once after drinking a nutritionally balanced mixture. In the balanced drink session, statistically significant connectivity between the frontal lobes and striatum was observed during set shifting, and the greater the prefrontostriatal connectivity, the faster the response time after a shift. Neither of these associations were observed after dopamine depletion. Moreover, dopamine depletion also reduced the degree of deactivation in areas normally suppressed during attention-demanding tasks, including the medial prefrontal cortex, posterior cingulate cortex, and hippocampus. Together, these results suggest that functional connectivity between the frontal lobes and basal ganglia during set shifting contributes to more efficient performance and that dopamine modulates this corticostriatal connectivity.

Key words: dopamine; tyrosine depletion; striatum; prefrontal cortex; fMRI; connectivity; set shifting

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Received Aug. 28, 2007; revised Feb. 5, 2008; accepted Feb. 18, 2008.

Correspondence should be addressed to Dr. Alain Dagher, Montreal Neurological Institute, 3801 University Street, Montreal, Quebec, Canada H3A 2B4. Email: alain.dagher{at}mcgill.ca

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