Dopamine D1 signaling organizes network dynamics underlying working memory

Abstract

Local prefrontal dopamine signaling supports working memory by tuning pyramidal neurons to task-relevant stimuli. Enabled by simultaneous positron emission tomography-magnetic resonance imaging (PET-MRI), we determined whether neuromodulatory effects of dopamine scale to the level of cortical networks and coordinate their interplay during working memory. Among network territories, mean cortical D1 receptor densities differed substantially but were strongly interrelated, suggesting cross-network regulation. Indeed, mean cortical D1 density predicted working memory-emergent decoupling of the frontoparietal and default networks, which respectively manage task-related and internal stimuli. In contrast, striatal D1 predicted opposing effects within these two networks but no between-network effects. These findings specifically link cortical dopamine signaling to network crosstalk that redirects cognitive resources to working memory, echoing neuromodulatory effects of D1 signaling on the level of cortical microcircuits.

Keywords: Neuroscience; dopamine; working memory.

Fig. 1. Working memory reflects changes in cortical network dynamics.

(A) Working memory performance robustly activates “task-positive” regions, including dlPFC (peaks at points A and C) and iPS (points B and D), and deactivates “task-negative” regions, including mPFC (points E and G) and pCing (points F and H). Maps are thresholded at the false discovery rate (FDR) (q = 0.05). (B) Activated regions correspond closely with FPCN, as previously defined (20) using resting-state data from 1000 healthy individuals (orange network), whereas deactivated regions fall largely within DN (red network). (C) Correlations of blood oxygen level–dependent (BOLD) signal time courses between seed pairs (for example, A→B represents left dlPFC to left iPS) indicates robust decoupling of FPCN and DN as subjects shift from rest to task condition (main effect of condition: F = 55.7, P = 3.7 × 10⁻¹¹; main effect of within-/between-network: F = 876, P = 2.3 × 10⁻⁵⁰; condition × within-/between-network interaction: F = 56.3, P = 3.0 × 10⁻¹¹). (D) A similar pattern is seen using average BOLD signal time courses within FPCN ($\overline{\text{AB}}$ and $\overline{\text{CD}}$) and DN ($\overline{\text{EF}}$ and $\overline{\text{GH}}$) (main effect of condition: F = 57.7, P = 1.9 × 10⁻¹¹; main effect of within-/between-network: F = 928, P = 1.8 × 10⁻⁵¹; condition × within-/between-network interaction: F = 58.8, P = 1.4 × 10⁻¹¹). Bars indicate SE.

Fig. 2. D₁ receptor density in cortical networks and striatum.

(A) Group average surface maps indicate mean density of D₁ receptors across the cortical mantle. (B) D₁ receptor density within seven cortical networks (circles are individual subjects, and bars are mean values), indicating a fourfold difference among individuals. Density within DN was higher than every other network (P < 0.001). (C) D₁ receptor density in DN correlated strongly with every other cortical network. (D) Coronal and horizontal views of group average volume map indicate striatal D₁ density. (E) Mean striatal D₁ density correlated weakly with mean cortical D₁ density (R = 0.36, P = 0.064).

Fig. 3. Contributions of cortical and striatal D₁ density to within- and between-network connectivity underlying working memory.

(A) Correlation matrices indicate the relationship between seed-to-seed (for example, A→B represents left dlPFC to left iPS) or network-to-network (for example, $\overline{\text{AB}}\to \overline{\text{CD}}$ represents left FPCN to right FPCN) FC and cortical D₁ density. Between-network correlations are located inside the black lines, and within-network measurements are outside the black lines. (B) Lower cortical D₁ density predicted a greater decline in right FPCN to right DN connectivity between resting and task states. (C) Correlations of FC and striatal D₁ density, as in (A). (D) At rest, reduced striatal D₁ density predicted enhanced connectivity within DN (left mPFC to right mPFC). (E) During task, higher striatal D₁ density predicted stronger connectivity within FPCN (right dlPFC to right iPS). All analyses were adjusted for mean global signal and head motion. *P < .05, FDR-corrected; **P < .05, familywise error (FWE)–corrected.