A functional MRI study of the effects of bromocriptine, a dopamine receptor agonist, on component processes of working memory.
BACKGROUND
Dopamine is abundant in the prefrontal cortex and striatum, regions implicated in working memory processes. Monkey studies suggest that subpopulations of prefrontal neurons are sensitive to component processes of working memory, and that dopaminergic actions at D1 and D2 receptors differentially affect these neurons. However, it is not known to what extent the effects of dopaminergic stimulation may differ in human subjects across the processing stages of working memory, and whether these effects are found throughout the network of task-related brain regions.


OBJECTIVE
In this study we tested the effects of the D2 dopamine agonist bromocriptine during the performance of a delayed recognition task using functional magnetic resonance imaging (fMRI).


METHODS
We measured blood oxygenation level dependent (BOLD) signals as subjects performed a spatial and object delayed recognition task. Subjects were scanned twice, once following 1.25 mg of bromocriptine and once following lactose placebo in a randomized double-blind design. Using an event-related design allowed for separate investigation of encoding, delay, and response period effects of dopaminergic stimulation.


RESULTS
A group analysis revealed that bromocriptine treatment decreased activity in the task network at encoding and increased activity at response. There was no clear pattern of change in the delay period network. Across subjects, these BOLD signal changes were accompanied by reductions in accuracy and increases in response time during delayed recognition for spatial and object information.


CONCLUSIONS
Decreased activity during encoding suggests that hyperdopaminergic stimulation may have reduced stimulus encoding processes, contributing to impaired performance.
Gibbs
Sasha E B
SE
Henry H. Wheeler Jr. Brain Imaging Center, Helen Wills Neuroscience Institute and Department of Psychology, University of California, Berkeley, 132 Barker Hall, Berkeley, CA 94720-3190, USA. sebgibbs@psych.stanford.edu
D'Esposito
Mark
M
D000328:Adult; D000704:Analysis of Variance; D001143:Arousal / Q000187:drug effects; D001921:Brain / Q000098:blood supply / Q000187:drug effects*; D001931:Brain Mapping; D001971:Bromocriptine / Q000494:pharmacology*; D003463:Cues; D018491:Dopamine Agonists / Q000494:pharmacology*; D004311:Double-Blind Method; D005260:Female; D007839:Functional Laterality; D006801:Humans; D007091:Image Processing, Computer-Assisted / Q000379:methods; D008279:Magnetic Resonance Imaging; D008297:Male; D008570:Memory, Short-Term / Q000187:drug effects*; D009483:Neuropsychological Tests / Q000706:statistics & numerical data; D010100:Oxygen / Q000097:blood; D011930:Reaction Time / Q000187:drug effects
D018491:Dopamine Agonists; D001971:Bromocriptine; D010100:Oxygen