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

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 (DMN), central executive (CEN), and salience networks (SN). Comorbid PTSD+mTBI is linked to worse functional outcomes, but little is known about effects on the functional connectome.

METHODS: We investigated brain phenotypes from resting-state fMRI associated with PTSD (n=326), mTBI (n=448), and comorbid PTSD+mTBI (n=289) in military veterans and civilians (n=1526) from ENIGMA-TBI and -PTSD. We examined static functional connectivity (SFC) and dynamic functional connectivity (DFC), quantified both as variability in FC (VFC) over time and as dwell time in recurring FC states identified through clustering. ANCOVA was followed by post-hoc linear regression to test main and interaction effects of diagnosis on FC metrics.

RESULTS: We found a significant (pFDR<0.05) interaction of diagnosis by age on VFC. Older comorbid subjects had greater VFC within SN, between SN-to-CEN and SN-to-DMN than older controls. Comorbid relative to control subjects had significantly greater dwell time in an externally focused state. Comorbid and mTBI groups, relative to control subjects, had greater dwell time in a moderate connectivity transition state.

CONCLUSIONS: DFC related to the SN revealed distinct brain network patterns across diagnostic groups, with comorbid PTSD+mTBI showing age- and anxiety-related effects. Older comorbid subjects 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.