Dynamic and Static Resting-State Functional Connectivity of Canonical Networks in Military and Civilian Populations with Posttraumatic Stress Disorder and/or Mild Traumatic Brain Injury

Abstract

Background: Posttraumatic stress disorder (PTSD) and mild traumatic brain injury (mTBI) are associated with alterations in the functional connectome, specifically in canonical resting-state networks including the default mode network (DMN), central executive network (CEN), and salience network (SN). Comorbid PTSD+TBI is linked to worse functional outcomes, but little is known about effects on the functional connectome. Methods: We investigated brain phenotypes from resting-state functional magnetic resonance imaging associated with PTSD (n = 326), mTBI (n = 448), and comorbid PTSD+mTBI (n = 289) in military veterans and civilians (N = 1526) from the ENIGMA (Enhancing Neuro Imaging Genetics through Meta Analysis)-TBI and ENIGMA-PTSD studies. We examined static functional connectivity (FC) and dynamic functional connectivity (DFC), which we quantified both as variability in FC (VFC) over time and as dwell time in recurring FC states identified through clustering. Analysis of covariance was followed by post hoc linear regression analysis to test main and interaction effects of diagnosis on FC metrics. Results: We found a significant (false discovery rate–corrected p < .05) interaction of diagnosis × age on VFC. Older participants with comorbid PTSD+mTBI had greater VFC within the SN, between the SN and CEN, and between the SN and DMN than older control participants. Compared with control participants, comorbid participants had significantly greater dwell time in an externally focused state. Participants in the comorbid and mTBI groups had greater dwell time in a moderate-connectivity transition state than control participants. Conclusions: DFC related to the SN revealed distinct brain network patterns across diagnostic groups, with participants with comorbid PTSD+mTBI showing age- and anxiety-related effects. Older comorbid participants had heightened hypervigilance and reduced network segregation. PTSD and anxiety may synergistically worsen network instability, while mTBI reflects more rigid, disconnected states, highlighting DFC as a sensitive marker of neuropsychiatric comorbidity.