Research ArticleNEUROCHEMISTRY

Dopamine D1 signaling organizes network dynamics underlying working memory

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Science Advances  03 Jun 2016:
Vol. 2, no. 6, e1501672
DOI: 10.1126/sciadv.1501672
  • 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 (Embedded Image and Embedded Image) and DN (Embedded Image and Embedded Image) (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, Embedded Image 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.

Supplementary Materials

  • Supplementary material for this article is available at http://advances.sciencemag.org/cgi/content/full/2/6/e1501672/DC1

    fig. S1. Working memory paradigm.

    fig. S2. Validation of BPnd measurements derived from cerebellar reference model against arterial input model.

    fig. S3. Working memory–related activation and connectivity changes in PET-MRI cohort.

    fig. S4. Reliability of performance measures between conventional fMRI and PET-MRI scans.

    fig. S5. Reliability of connectivity measures between conventional fMRI and PET-MRI scans.

    table S1. Working memory performance in n = 100 fMRI cohort.

    table S2. Nodes for connectivity analysis in n = 100 fMRI cohort.

    table S3. Local correlations of task-based activation with connectivity during rest and task.

    table S4. D1 density relationships among cortical networks.

    table S5. Working memory performance in n = 29 PET-MRI cohort.

    table S6. Nodes for connectivity analysis in n = 29 PET-MRI cohort.

    table S7. Correlations of PET and fMRI connectivity (FPCN and DN) markers across conditions.

    table S8. Persistence of significant (P < 0.05, FWE-corrected) cortical D1 density–connectivity correlations after partialing out effects of striatal D1 density.

    table S9. Persistence of significant (P < 0.05, FWE-corrected) striatal D1 density–connectivity correlations after partialing out effects of age and cortical D1 density.

    table S10. Correlations of PET and fMRI connectivity (FPCN and DN to visual network) markers across conditions.

  • Supplementary Materials

    This PDF file includes:

    • fig. S1. Working memory paradigm.
    • fig. S2. Validation of BPND measurements derived from cerebellar reference
      model against arterial input model.
    • fig. S3. Working memory–related activation and connectivity changes in PET-MRI
      cohort.
    • fig. S4. Reliability of performance measures between conventional fMRI and
      PET-MRI scans.
    • fig. S5. Reliability of connectivity measures between conventional fMRI and
      PET-MRI scans.
    • table S1. Working memory performance in n = 100 fMRI cohort.
    • table S2. Nodes for connectivity analysis in n = 100 fMRI cohort.
    • table S3. Local correlations of task-based activation with connectivity during rest
      and task.
    • table S4. D1 density relationships among cortical networks.
    • table S5. Working memory performance in n = 29 PET-MRI cohort.
    • table S6. Nodes for connectivity analysis in n = 29 PET-MRI cohort.
    • table S7. Correlations of PET and fMRI connectivity (FPCN and DN) markers
      across conditions.
    • table S8. Persistence of significant (P < 0.05, FWE-corrected) cortical D1 density–
      connectivity correlations after partialing out effects of striatal D1 density.
    • table S9. Persistence of significant (P < 0.05, FWE-corrected) striatal D1 density–
      connectivity correlations after partialing out effects of age and cortical D1 density.
    • table S10. Correlations of PET and fMRI connectivity (FPCN and DN to visual
      network) markers across conditions.

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