title: Dissociable fronto-striatal effects of dopamine D2 receptor stimulation on cognitive versus motor flexibility.
abstract: Genetic and pharmacological studies suggest an important role of the dopamine D2 receptor (DRD2) in flexible behavioral adaptation, mostly shown in reward-based learning paradigms. Recent evidence from imaging genetics indicates that also intentional cognitive flexibility, associated with lateral frontal cortex, is affected by variations in DRD2 signaling. In the present functional magnetic resonance imaging (MRI) study, we tested the effects of a direct pharmacological manipulation of DRD2 stimulation on intentional flexibility in a task-switching context, requiring switches between cognitive task rules and between response hands. In a double blind, counterbalanced design, participants received either a low dose of the DRD2 agonist bromocriptine or a placebo in two separate sessions. Bromocriptine modulated the blood-oxygen-level-dependent (BOLD) signal during rule switching: rule-switching-related activity in the left posterior lateral frontal cortex and in the striatum was increased compared to placebo, at comparable performance levels. Fronto-striatal connectivity under bromocriptine was slightly increased for rule switches compared to rule repetitions. Hand-switching-related activity, in contrast, was reduced under bromocriptine in sensorimotor regions. Our results provide converging evidence for an involvement of DRD2 signaling in fronto-striatal mechanisms underlying intentional flexibility, and indicate that the neural mechanisms underlying different types of flexibility (cognitive vs motor) are affected differently by increased dopaminergic stimulation.
authors: Department of Psychiatry and Psychotherapy, Charité Universitätsmedizin, Berlin, Germany. Electronic address: christine.stelzel@charite.de.
authors: Christine
authors: C
authors: Stelzel
authors: Christian J
authors: CJ
authors: Fiebach
authors: Roshan
authors: R
authors: Cools
authors: Sharwin
authors: S
authors: Tafazoli
authors: Mark
authors: M
authors: D'Esposito
mesh_terms: D000328:Adult; D001794:Blood Pressure / Q000187:drug effects; D001971:Bromocriptine / Q000494:pharmacology*; D003071:Cognition / Q000187:drug effects / Q000502:physiology*; D018491:Dopamine Agonists / Q000494:pharmacology*; D004311:Double-Blind Method; D005260:Female; D005625:Frontal Lobe / Q000502:physiology*; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008279:Magnetic Resonance Imaging; D008297:Male; D009068:Movement / Q000187:drug effects / Q000502:physiology*; D017072:Neostriatum / Q000502:physiology*; D010775:Photic Stimulation; D011597:Psychomotor Performance / Q000187:drug effects; D011930:Reaction Time / Q000187:drug effects / Q000502:physiology; D017448:Receptors, Dopamine D2 / Q000819:agonists / Q000502:physiology*; D055815:Young Adult
chemical_list: D018491:Dopamine Agonists; D017448:Receptors, Dopamine D2; D001971:Bromocriptine
keywords: Bromocriptine; Functional magnetic resonance imaging (fMRI); Intentional flexibility; Psychopharmacology
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