Dopamine D2-receptor blockade enhances decoding of prefrontal signals in humans.
The prefrontal cortex houses representations critical for ongoing and future behavior expressed in the form of patterns of neural activity. Dopamine has long been suggested to play a key role in the integrity of such representations, with D2-receptor activation rendering them flexible but weak. However, it is currently unknown whether and how D2-receptor activation affects prefrontal representations in humans. In the current study, we use dopamine receptor-specific pharmacology and multivoxel pattern-based functional magnetic resonance imaging to test the hypothesis that blocking D2-receptor activation enhances prefrontal representations. Human subjects performed a simple reward prediction task after double-blind and placebo controlled administration of the D2-receptor antagonist amisulpride. Using a whole-brain searchlight decoding approach we show that D2-receptor blockade enhances decoding of reward signals in the medial orbitofrontal cortex. Examination of activity patterns suggests that amisulpride increases the separation of activity patterns related to reward versus no reward. Moreover, consistent with the cortical distribution of D2 receptors, post hoc analyses showed enhanced decoding of motor signals in motor cortex, but not of visual signals in visual cortex. These results suggest that D2-receptor blockade enhances content-specific representations in frontal cortex, presumably by a dopamine-mediated increase in pattern separation. These findings are in line with a dual-state model of prefrontal dopamine, and provide new insights into the potential mechanism of action of dopaminergic drugs.
Northwestern University Feinberg School of Medicine, Department of Neurology, Chicago, Illinois 60611, Laboratory for Social and Neural Systems Research, Department of Economics, University of Zurich, 8006 Zurich, Switzerland, thorsten.kahnt@northwestern.edu.
Thorsten
http://orcid.org/0000-0002-3575-2670
T
Kahnt
Laboratory for Social and Neural Systems Research, Department of Economics, University of Zurich, 8006 Zurich, Switzerland.
Susanna C
SC
Weber
Translational Neuromodeling Unit, Institute for Biomedical Engineering, University of Zurich and ETH Zurich, 8032 Zurich, Switzerland, and.
Helene
H
Haker
Department of Psychology, and Behavioural and Clinical Neuroscience Institute, University of Cambridge, Cambridge CB2 3EB, United Kingdom.
Trevor W
TW
Robbins
Laboratory for Social and Neural Systems Research, Department of Economics, University of Zurich, 8006 Zurich, Switzerland.
Philippe N
PN
Tobler
D000293:Adolescent; D000328:Adult; D000077582:Amisulpride; D001245:Association Learning / Q000187:drug effects; D018492:Dopamine Antagonists / Q000494:pharmacology*; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D017397:Prefrontal Cortex / Q000187:drug effects*; D017448:Receptors, Dopamine D2 / Q000187:drug effects*; D012201:Reward; D015398:Signal Transduction / Q000187:drug effects; D013469:Sulpiride / Q000031:analogs & derivatives / Q000494:pharmacology; D055815:Young Adult
D018492:Dopamine Antagonists; D017448:Receptors, Dopamine D2; D013469:Sulpiride; D000077582:Amisulpride
MVPA; associative learning; dopamine; fMRI; orbitofrontal cortex; reward