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Cerebral Cortex Advance Access originally published online on March 25, 2009
Cerebral Cortex 2009 19(11):2651-2658; doi:10.1093/cercor/bhp017
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© The Author 2009. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oxfordjournals.org

Dopaminergic Neuromodulation of Semantic Processing: A 4-T fMRI Study with Levodopa

David A. Copland1,2,3, Katie L. McMahon4, Peter A. Silburn2 and Greig I. de Zubicaray4

1 Language Neuroscience Laboratory, 2 Centre for Clinical Research, 3 School of Health and Rehabilitation Sciences, 4 Centre for Magnetic Resonance, The University of Queensland, Brisbane, Queensland 4072, Australia

Address correspondence to Dr David Copland, Centre for Clinical Research, The University of Queensland, Brisbane, QLD 4072, Australia. Email: d.copland{at}uq.edu.au.

There is emerging evidence that alterations in dopaminergic transmission can influence semantic processing, yet the neural mechanisms involved are unknown. The influence of levodopa (L-DOPA) on semantic priming was investigated in healthy individuals (n = 20) using event-related functional magnetic resonance imaging with a randomized, double-blind crossover design. Critical prime–target pairs consisted of a lexical ambiguity prime and 1) a target related to the dominant meaning of the prime (e.g., bank–money), 2) a target related to the subordinate meaning (e.g., fence–sword), or 3) an unrelated target (e.g., ball–desk). Behavioral data showed that both dominant and subordinate meanings were primed on placebo. In contrast, there was preserved priming of dominant meanings and no significant priming of subordinate meanings on L-DOPA, the latter associated with decreased anterior cingulate and dorsal prefrontal cortex activity. Dominant meaning activation on L-DOPA was associated with increased activity in the left rolandic operculum and left middle temporal gyrus. These findings suggest that L-DOPA enhances frequency-based semantic focus via prefrontal and temporal modulation of automatic semantic priming and through engagement of anterior cingulate mechanisms supporting attentional/controlled priming.

Key Words: brain imaging • dopamine • fMRI • language • lexical ambiguity • semantic priming


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