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The Journal of Neuroscience, June 3, 2009, 29(22):7364-7378; doi:10.1523/JNEUROSCI.0810-09.2009

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Behavioral/Systems/Cognitive
L-Dopa Modulates Functional Connectivity in Striatal Cognitive and Motor Networks: A Double-Blind Placebo-Controlled Study

Clare Kelly,¹ Greig de Zubicaray,³ Adriana Di Martino,^1,5 David A. Copland,⁴ Philip T. Reiss,^2,6 Donald F. Klein,^1,6,7 F. Xavier Castellanos,^1,6 Michael P. Milham,¹ and Katie McMahon³

¹Phyllis Green and Randolph Cowen Institute for Pediatric Neuroscience, and ²Division of Biostatistics, New York University Child Study Center, New York, New York 10016, ³Centre for Magnetic Resonance and ⁴Centre for Clinical Research and School of Health and Rehabilitation Sciences, University of Queensland, Brisbane, Queensland 4072, Australia, ⁵Division of Child and Adolescent Neuropsychiatry, Department of Neuroscience, University of Cagliari, 09126 Cagliari, Italy, ⁶Nathan S. Kline Institute for Psychiatric Research, Orangeburg, New York 10962, and ⁷Department of Psychiatry, College of Physicians and Surgeons, Columbia University, New York, New York 10032

Correspondence should be addressed to either of the following: Dr. Katie McMahon, Centre for Magnetic Resonance, University of Queensland, Brisbane, QLD 4072, Australia, Email: katie.mcmahon{at}cmr.uq.edu.au; or Dr. Michael P. Milham, New York University Child Study Center, 215 Lexington Avenue, 14th Floor, New York, NY 10016, Email: michael.milham{at}nyumc.org

Functional connectivity (FC) analyses of resting-state fMRI data allow for the mapping of large-scale functional networks, and provide a novel means of examining the impact of dopaminergic challenge. Here, using a double-blind, placebo-controlled design, we examined the effect of L-dopa, a dopamine precursor, on striatal resting-state FC in 19 healthy young adults. We examined the FC of 6 striatal regions of interest (ROIs) previously shown to elicit networks known to be associated with motivational, cognitive and motor subdivisions of the caudate and putamen (Di Martino et al., 2008). In addition to replicating the previously demonstrated patterns of striatal FC, we observed robust effects of L-dopa. Specifically, L-dopa increased FC in motor pathways connecting the putamen ROIs with the cerebellum and brainstem. Although L-dopa also increased FC between the inferior ventral striatum and ventrolateral prefrontal cortex, it disrupted ventral striatal and dorsal caudate FC with the default mode network. These alterations in FC are consistent with studies that have demonstrated dopaminergic modulation of cognitive and motor striatal networks in healthy participants. Recent studies have demonstrated altered resting state FC in several conditions believed to be characterized by abnormal dopaminergic neurotransmission. Our findings suggest that the application of similar experimental pharmacological manipulations in such populations may further our understanding of the role of dopaminergic neurotransmission in those conditions.

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Received Feb. 17, 2009; revised March 30, 2009; accepted April 2, 2009.

Correspondence should be addressed to either of the following: Dr. Katie McMahon, Centre for Magnetic Resonance, University of Queensland, Brisbane, QLD 4072, Australia, Email: katie.mcmahon{at}cmr.uq.edu.au; or Dr. Michael P. Milham, New York University Child Study Center, 215 Lexington Avenue, 14th Floor, New York, NY 10016, Email: michael.milham{at}nyumc.org

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