Dopamine D2-Receptor Blockade Enhances Decoding of Prefrontal Signals in Humans

Abstract

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.

DRD2 co-expression network and a related polygenic index predict imaging, behavioral and clinical phenotypes linked to schizophrenia

“… 31 These results are also consistent with a large body of studies demonstrating that pharmacological manipulation of dopamine D2R is associated with WM performance and with prefrontal activity measured with BOLD fMRI. 41 , 60 Critically, they are consistent with a recent study reporting that greater prefrontal D2 PET binding is positively correlated with prefrontal activity during WM. 22 Finally, these findings are consistent with several reports from our group suggesting that the T allele of rs1076560, associated with greater D2L/D2S ratio compared with the G allele, is also associated with inefficient prefrontal activity during WM.…”

Dopamine Does Double Duty in Motivating Cognitive Effort

“…Blocking D2 action, therefore, could enhance PFC representations. In a recent demonstration, DA D2 receptor blockade by amisulpride, relative to placebo, enhanced PFC representations as indexed by sharper multivariate pattern discrimination of PFC BOLD data between incentive conditions during an incentive learning task (Kahnt et al, 2015). …”

Amisulpride and l‐DOPA modulate subcortical brain nuclei connectivity in resting‐state pharmacologic magnetic resonance imaging

“…Recent studies with DA drugs in healthy individuals have shown that different areas of the DA system react different to a DA challenge (Cole, Beckmann, Oei, Both, & Van Gerven, ; Martins, Mehta, & Prata, ). In particular, amisulpride decreased the striatum's response in a cue task (Hermann et al, ) and shifted the balance of orbitofrontal connectivity from associative areas towards the frontal cortex (Kahnt, Weber, Haker, Robbins, & Tobler, ). These results point to strategic neuroanatomical hubs like the striatum or the orbitofrontal cortex but lack the description of unifying mechanisms.…”