Dopamine Modulates the Functional Organization of the Orbitofrontal Cortex

Abstract

Neuromodulators such as dopamine can alter the intrinsic firing properties of neurons and may thereby change the configuration of larger functional circuits. The primate orbitofrontal cortex (OFC) receives dopaminergic input from midbrain nuclei, but the role of dopamine in the OFC is still unclear. Here we tested the idea that dopaminergic activity changes the pattern of connectivity between the OFC and the rest of the brain and thereby reconfigures functional networks in the OFC. To this end, we combined double-blind, placebocontrolled pharmacology [D 2 receptor (D2R) antagonist amisulpride] in humans with resting-state functional magnetic resonance imaging and clustering methods. In the placebo group, we replicated previously observed parcellations of the OFC into two and six subregions based on connectivity patterns with the rest of the brain. Most importantly, while the twofold clustering did not differ significantly between groups, blocking D2Rs significantly changed the composition of the sixfold parcellation, suggesting a dopaminedependent reconfiguration of functional OFC subregions. Moreover, multivariate decoding analyses revealed that amisulpride changed the whole-brain connectivity patterns of individual OFC subregions. In particular, D2R blockade shifted the balance of OFC connectivity from associative areas in the temporal and parietal lobe toward functional connectivity with the frontal cortex. In summary, our results suggest that dopamine alters the composition of functional OFC circuits, possibly indicating a broader role for neuromodulators in the dynamic reconfiguration of functional brain networks.

Dopamine is a double-edged sword: Enhancing memory retrieval performance at the expense of metacognition

“…In addition to acute haloperidol-induced enhancement of dopamine release, it is possible that postsynaptic effects are present to some degree even at low doses of D2 antagonists. As such, increased dopamine release combined with postsynaptic D2 receptor blockade might decrease the ratio of D2 to D1 receptor activation (Kahnt and Tobler, 2017;Shi et al, 1997). Such an activation shift from D2 to D1 receptors might have additionally contributed to the retrieval performance and metamemory effects reported here, rather than increased dopamine release alone.…”

Interactions between human orbitofrontal cortex and hippocampus support model-based inference

“…The HPC was further segmented into anterior and posterior portions based on the uncal apex landmark [34]. Masks for the medial and lateral OFC were taken from a previous study, which used unsupervised clustering of resting-state connectivity to parcellate the OFC [80]. For MVPA analysis, ROIs were inverse-normalized into native space.…”

Effective learning is accompanied by high-dimensional and efficient representations of neural activity

“…To test this hypothesis, we examine blood oxygen level dependent (BOLD) magnitudes at the regional and voxel levels, in a cohort of 20 healthy adult human subjects as they learn the values of twelve novel objects over the course of 4 consecutive days for a total of 80 experimental imaging sessions. Motivated by a desire to study parsimonious representations and also by recent work decoding object identity [23][24][25], stimulus response [26,27], and markers of emotional and affective processing [28,29] from coarse-scale measurements across the brain, we spatially average these indirect measurements of neural activity in 83 regions of interest (ROIs) defined by a whole-brain anatomical parcellation. Next, we use a general linear 2 model to deconvolve the hemodynamic response function to obtain approximate neural responses to each stimulus at the time point at which it was presented.…”