Network Functional Architecture and Aberrant Functional Connectivity in Post-Traumatic Stress Disorder: A Clinical Application of Network Convergence.

Abstract

Posttraumatic stress disorder (PTSD) is associated with disrupted functional connectivity in multiple neural networks. Multinetwork models of PTSD hypothesize that aberrant regional connectivity emerges from broad network-level disruptions. However, few studies have tested how characteristics of network-level organization influence regional functional connectivity in PTSD. This gap in knowledge impacts both our understanding of the pathophysiology of the disorder and the development of network-targeted PTSD treatments. We acquired resting-state imaging from a naturalistic sample of patients with PTSD (n = 42) and healthy controls (n = 42). Group differences in functional connectivity were identified using region of interest analyses and estimations of within- and between neural network activity; PTSD patients demonstrated reduced amygdala-orbitofrontal connectivity and increased default mode network (DMN) connectivity compared with controls. We then used convergence-a novel measure representing the capacity for functional integration-to test whether differences in functional architecture underlie connectivity signatures of PTSD. This approach found that reduced frontoparietal network (FPN) convergence was associated with reduced amygdala-orbitofrontal connectivity. Furthermore, in controls only, increased DMN convergence was associated with reduced DMN-to-salience network connectivity, and increased FPN convergence was associated with reduced FPN-to-ventral attention network connectivity. These results suggest that FPN functional architecture may underlie insufficiencies in top-down control in PTSD, with results broadly supporting the notion that networks' functional architecture influences the breakdown of normative functional relationships in PTSD. This work also indicates the potential of convergence to be applied to clinical populations in future research studies.