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The Journal of Neuroscience, October 15, 2008, 28(42):10687-10695; doi:10.1523/JNEUROSCI.2933-08.2008

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Neurobiology of Disease
Dopaminergic Suppression of Brain Deactivation Responses during Sequence Learning

Miklos Argyelan,1 Maren Carbon,1,2 Maria-Felice Ghilardi,3 Andrew Feigin,1,2 Paul Mattis,1,2 Chengke Tang,1,2 Vijay Dhawan,1,2 and David Eidelberg1,2

1Center for Neurosciences, The Feinstein Institute for Medical Research and 2Departments of Neurology and Medicine, North Shore University Hospital, Manhasset, New York 11030, and 3Department of Pharmacology and Physiology, City University of New York Medical School, New York, New York 10031

Correspondence should be addressed to Dr. David Eidelberg, Center for Neurosciences, The Feinstein Institute for Medical Research, 350 Community Drive, Manhasset, NY 11030. Email: david1{at}nshs.edu

Cognitive processing is associated with deactivation of the default mode network. The presence of dopaminoceptive neurons in proximity to the medial prefrontal node of this network suggests that this neurotransmitter may modulate deactivation in this region. We therefore used positron emission tomography to measure cerebral blood flow in 15 Parkinson's disease (PD) patients while they performed a motor sequence learning task and a simple movement task. Scanning was conducted before and during intravenous levodopa infusion; the pace and extent of movement was controlled across tasks and treatment conditions. In normal and unmedicated PD patients, learning-related deactivation was present in the ventromedial prefrontal cortex (p < 0.001). This response was absent in the treated condition. Treatment-mediated changes in deactivation correlated with baseline performance (p < 0.002) and with the val158met catechol-O-methyltransferase genotype. Our findings suggest that dopamine can influence prefrontal deactivation during learning, and that these changes are linked to baseline performance and genotype.

Key words: levodopa; Parkinson's disease; sequence learning; deactivation; default mode network; COMT genotype

Received June 24, 2008; revised Aug. 8, 2008; accepted Aug. 19, 2008.

Correspondence should be addressed to Dr. David Eidelberg, Center for Neurosciences, The Feinstein Institute for Medical Research, 350 Community Drive, Manhasset, NY 11030. Email: david1{at}nshs.edu






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