Catecholaminergic manipulation alters dynamic network topology across cognitive states

Abstract

The human brain is able to flexibly adapt its information processing capacity to meet a variety of cognitive challenges. Recent evidence suggests that this flexibility is reflected in the dynamic reorganization of the functional connectome. The ascending catecholaminergic arousal systems of the brain are a plausible candidate mechanism for driving alterations in network architecture, enabling efficient deployment of cognitive resources when the environment demands them. We tested this hypothesis by analyzing both resting-state and task-based fMRI data following the administration of atomoxetine, a noradrenaline reuptake inhibitor, compared with placebo, in two separate human fMRI studies. Our results demonstrate that the manipulation of central catecholamine levels leads to a reorganization of the functional connectome in a manner that is sensitive to ongoing cognitive demands.

Author Summary: There is emerging evidence that the flexible network structure of the brain is related to activity within the ascending arousal systems of the brain, such as the noradrenergic locus coeruleus. Here, we explored the role of catecholaminergic activity on network architecture by analyzing the graph structure of the brain measured using functional MRI following the administration of atomoxetine, a selective noradrenaline reuptake inhibitor. We estimated functional network topology in two double-blind, placebo-controlled datasets: one from the resting state and another from a parametric N-back task. Our results demonstrate that the nature of catecholaminergic network reconfiguration is differentially related to cognitive state and provide confirmatory evidence for the hypothesis that the functional network signature of the brain is sensitive to the ascending catecholaminergic arousal system.