L-dopa modulates functional connectivity in striatal cognitive and motor networks: a double-blind placebo-controlled study.
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.
Kelly
Clare
C
Phyllis Green and Randolph Cowen Institute for Pediatric Neuroscience, New York University Child Study Center, New York, New York 10016, USA.
de Zubicaray
Greig
G
Di Martino
Adriana
A
Copland
David A
DA
Reiss
Philip T
PT
Klein
Donald F
DF
Castellanos
F Xavier
FX
Milham
Michael P
MP
McMahon
Katie
K
D000328:Adult; D001545:Benserazide / Q000494:pharmacology*; D001931:Brain Mapping; D003071:Cognition / Q000187:drug effects*; D003342:Corpus Striatum / Q000098:blood supply / Q000187:drug effects* / Q000502:physiology; D015259:Dopamine Agents / Q000494:pharmacology*; D004311:Double-Blind Method; D004338:Drug Combinations; D005260:Female; D007839:Functional Laterality / Q000187:drug effects; D006801:Humans; D007091:Image Processing, Computer-Assisted / Q000379:methods; D007980:Levodopa / Q000494:pharmacology*; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D009068:Movement / Q000187:drug effects*; D009434:Neural Pathways / Q000098:blood supply / Q000187:drug effects / Q000502:physiology; D009483:Neuropsychological Tests; D010100:Oxygen / Q000097:blood; D011336:Probability
D015259:Dopamine Agents; D004338:Drug Combinations; C005177:benserazide, levodopa drug combination; D007980:Levodopa; D001545:Benserazide; D010100:Oxygen