Dopamine D2-receptor blockade enhances decoding of prefrontal signals in humans.

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Weber, Susanna C 
Haker, Helene 
Robbins, Trevor W 
Tobler, Philippe N 

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.

MVPA, associative learning, dopamine, fMRI, orbitofrontal cortex, reward, Adolescent, Adult, Amisulpride, Association Learning, Dopamine Antagonists, Humans, Magnetic Resonance Imaging, Male, Prefrontal Cortex, Receptors, Dopamine D2, Reward, Signal Transduction, Sulpiride, Young Adult
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J Neurosci
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Society for Neuroscience
Medical Research Council (G0001354)
This work was supported by the Swiss National Science Foundation (grants PP00P1_128574, PP00P1_150739, and CRSII3_141965) and the Swiss National Centre of Competence in Research in Affective Sciences. The BCNI is supported by the Medical Research Council and Wellcome Trust. We acknowledge also the Neuroscience Center Zurich and thank M. Wälti and T. Baumgartner for help with data collection. T.W.R discloses consultancy with Lilly, Lundbeck, Teva, Otsuka, Shire Pharmaceuticals, ChemPartners, and Cambridge Cognition; and research grants with Lilly, Lundbeck, and GlaxoSmithKline. The remaining authors declare no competing financial interests.