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.

Department of Clinical Psychology University of Groningen Groningen the Netherlands

Department of Physical Medicine and Rehabilitation School of Medicine Virginia Commonwealth University Richmond VA; Richmond Veterans Affairs Medical Center Central Virginia VA Health Care System Richmond VA

Department of Psychiatry Amsterdam University Medical Center Amsterdam the Netherlands; Amsterdam Neuroscience Amsterdam the Netherlands

Department of Psychiatry Amsterdam University Medical Center Amsterdam the Netherlands; ARQ National Psychotrauma Centre Diemen the Netherlands

Department of Psychiatry Amsterdam University Medical Center Amsterdam the Netherlands; Department of Clinical Psychology Utrecht University Utrecht the Netherlands

Department of Psychiatry Amsterdam University Medical Center Amsterdam the Netherlands; Department of Psychiatry Amsterdam UMC Vrije Universiteit Amsterdam the Netherlands

Department of Psychiatry Amsterdam University Medical Center Amsterdam the Netherlands; Department of Psychology Marquette University Milwaukee WI

Department of Psychiatry Amsterdam University Medical Center Amsterdam the Netherlands; Donders Institute for Brain Cognition and Behavior Centre for Cognitive Neuroimaging Radboud University Nijmegen the Netherlands

Department of Psychiatry Texas A and M University Bryan TX

Department of Psychiatry University of Michigan Ann Arbor MI

Department of Psychology Vanderbilt University Nashville TN

Duke UNC Brain Imaging and Analysis Center Duke University Durham NC

Duke UNC Brain Imaging and Analysis Center Duke University Durham NC; Department of Molecular Biomedical Sciences North Carolina State College of Veterinary Medicine Raleigh NC

Duke UNC Brain Imaging and Analysis Center Duke University Durham NC; Department of Psychiatry and Behavioral Sciences Duke University Durham NC; Mental Illness Research Education and Clinical Center for Post Deployment Mental Health Durham VA Medical Center Durham NC

George E Wahlen Veterans Affairs Medical Center Salt Lake City UT; Department of Neurology University of Utah Salt Lake City UT

George E Wahlen Veterans Affairs Medical Center Salt Lake City UT; Department of Neurology University of Utah Salt Lake City UT; H Ben Taub Department of PM and R Baylor College of Medicine Houston TX

Imaging Genetics Center Stevens Institute for Neuroimaging and Informatics Keck USC School of Medicine Los Angeles CA

Meninger Department of Psychiatry and Behavioral Sciences Baylor College of Medicine Houston TX; Core for Advanced Magnetic Resonance Imaging Baylor College of Medicine Houston TX

Multimodal and Functional Neuroimaging Research Group CEITEC Central European Institute of Technology Masaryk University Brno Czech Republic

Munroe Meyer Institute University of Nebraska Medical Center Omaha NE; Department of Psychiatry and Behavioral Sciences Vanderbilt University Medical Center Nashville TN

University Medical Center Charité Berlin Germany

References provided by Crossref.org