Dopamine Modulates Effective Connectivity in Frontal Cortex

Journal of Cognitive Neuroscience, vol. 36, pp. 155–166

Abstract

There is increasing evidence that the left lateral frontal cortex is hierarchically organized such that higher-order regions have an asymmetric top-down influence over lower order regions. However, questions remain about the underlying neuroarchitecture of this hierarchical control organization. Within the frontal cortex, dopamine plays an important role in cognitive control functions, and we hypothesized that dopamine may preferentially influence top-down connections within the lateral frontal hierarchy. Using a randomized, double-blind, within-subject design, we analyzed resting-state fMRI data of 66 healthy young participants who were scanned once each after administration of bromocriptine (a dopamine agonist with preferential affinity for D2 receptor), tolcapone (an inhibitor of catechol-O-methyltransferase), and placebo, to determine whether dopaminergic stimulation modulated effective functional connectivity between hierarchically organized frontal regions in the left hemisphere. We found that dopaminergic drugs modulated connections from the caudal middle frontal gyrus and the inferior frontal sulcus to both rostral and caudal frontal areas. In dorsal frontal regions, effectivity connectivity strength was increased, whereas in ventral frontal regions, effective connectivity strength was decreased. These findings suggest that connections within frontal cortex are differentially modulated by dopamine, which may bias the influence that frontal regions exert over each other.

Authors 6

1. David A. Vogelsang Aachen

   Leiden University

   Affiliation as printed

   Leiden University

   University of California

2. Daniella J. Furman
   Affiliation as printed

   University of California

3. Derek Evan Nee

   Florida State University

   Affiliation as printed

   Florida State University

4. Ioannis Pappas

   University of Southern California

   Affiliation as printed

   University of California

   University of Southern California

5. Andrew S. Kayser

   VA Northern California Health Care System

   Affiliation as printed

   University of California

   VA Northern California Health Care System

6. Mark D’Esposito

   VA Northern California Health Care System

   Affiliation as printed

   University of California

   VA Northern California Health Care System