Archival Report| Volume 78, ISSUE 3, P210-216, August 01, 2015

Brain Network Disturbance Related to Posttraumatic Stress and Traumatic Brain Injury in Veterans

Published:February 19, 2015DOI:



      Understanding the neural causes and consequences of posttraumatic stress disorder (PTSD) and mild traumatic brain injury (mTBI) is a high research priority, given the high rates of associated disability and suicide. Despite remarkable progress in elucidating the brain mechanisms of PTSD and mTBI, a comprehensive understanding of these conditions at the level of brain networks has yet to be achieved. The present study sought to identify functional brain networks and topological properties (measures of network organization and function) related to current PTSD severity and mTBI.


      Graph theoretic tools were used to analyze resting-state functional magnetic resonance imaging data from 208 veterans of Operation Enduring Freedom, Operation Iraqi Freedom, and Operation New Dawn, all of whom had experienced a traumatic event qualifying for PTSD criterion A. Analyses identified brain networks and topological network properties linked to current PTSD symptom severity, mTBI, and the interaction between PTSD and mTBI.


      Two brain networks were identified in which weaker connectivity was linked to higher PTSD re-experiencing symptoms, one of which was present only in veterans with comorbid mTBI. Re-experiencing was also linked to worse functional segregation (necessary for specialized processing) and diminished influence of key regions on the network, including the hippocampus.


      Findings of this study demonstrate that PTSD re-experiencing symptoms are linked to weakened connectivity in a network involved in providing contextual information. A similar relationship was found in a separate network typically engaged in the gating of working memory, but only in veterans with mTBI.


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        • Gates M.A.
        • Holowka D.W.
        • Vasterling J.J.
        • Keane T.M.
        • Marx B.P.
        • Rosen R.C.
        Posttraumatic stress disorder in veterans and military personnel: Epidemiology, screening, and case recognition.
        Psychol Serv. 2012; 9: 361-382
        • MacGregor A.J.
        • Shaffer R.A.
        • Dougherty A.L.
        • Galarneau M.R.
        • Raman R.
        • Baker D.G.
        • et al.
        Prevalence and psychological correlates of traumatic brain injury in Operation Iraqi Freedom.
        J Head Trauma Rehabil. 2010; 25: 1-8
      1. Obama B (2012): Improving access to mental health services for veterans, service members, and military families. Executive Order issued August 31, 2012 by President Barack Obama. Available at: Accessed April 11, 2014.

        • Friedman M.J.
        • Schnurr P.P.
        • McDonagh-Coyle A.
        Post-traumatic stress disorder in the military veteran.
        Psychiatr Clin North Am. 1994; 17: 265-277
        • Panagioti M.
        • Gooding P.A.
        • Tarrier N.
        A meta-analysis of the association between posttraumatic stress disorder and suicidality: The role of comorbid depression.
        Compr Psychiatry. 2012; 53: 915-930
        • Wisco B.E.
        • Marx B.P.
        • Holowka D.W.
        • Vasterling J.J.
        • Han S.C.
        • Chen M.S.
        • et al.
        Traumatic brain injury, PTSD, and current suicidal ideation among Iraq and Afghanistan U.S. veterans.
        J Trauma Stress. 2014; 27: 244-248
        • Insel T.R.
        Faulty circuits.
        Sci Am. 2010; 302: 44-51
        • Morris S.E.
        • Cuthbert B.N.
        Research Domain Criteria: Cognitive systems, neural circuits, and dimensions of behavior.
        Dialogues Clin Neurosci. 2012; 14: 29-37
        • Garfinkel S.N.
        • Liberzon I.
        A review of neuroimaging findings.
        Psychiatr Ann. 2009; 39: 370-381
        • Shin L.M.
        • Rauch S.L.
        • Pitman R.K.
        Amygdala, medial prefrontal cortex, and hippocampal function in PTSD.
        Ann N Y Acad Sci. 2006; 1071: 67-79
        • Liberzon I.
        • Sripada C.S.
        The functional neuroanatomy of PTSD: A critical review.
        Prog Brain Res. 2008; 167: 151-169
        • Suvak M.K.
        • Barrett L.F.
        Considering PTSD from the perspective of brain processes: A psychological construction approach.
        J Trauma Stress. 2011; 24: 3-24
        • Etkin A.
        • Wager T.
        Functional neuroimaging of anxiety: A meta-analysis of emotional processing in PTSD, social anxiety disorder, and specific phobia.
        Am J Psychiatry. 2007; 164: 1476-1488
        • Vasterling J.J.
        • Verfaellie M.
        • Sullivan K.D.
        Mild traumatic brain injury and posttraumatic stress disorder in returning veterans: Perspectives from cognitive neuroscience.
        Clin Psychol Rev. 2009; 29: 674-684
        • Brown V.M.
        • LaBar K.S.
        • Haswell C.C.
        • Gold A.L.
        • McCarthy G.
        • Morey R.A.
        Altered resting-state functional connectivity of basolateral and centromedial amygdala complexes in posttraumatic stress disorder.
        Neuropsychopharmacology. 2014; 39: 351-359
        • Sadeh N.
        • Spielberg J.M.
        • Warren S.L.
        • Miller G.A.
        • Heller W.
        Aberrant neural connectivity during emotional processing associated with posttraumatic stress.
        Clin Psychol Sci. 2014; 2: 748-755
        • Rubinov M.
        • Bullmore E.
        Fledgling pathoconnectomics of psychiatric disorders.
        Trends Cogn Sci. 2013; 17: 641-647
        • Turk-Browne N.B.
        Functional interactions as big data in the human brain.
        Science. 2013; 342: 580-584
        • Rubinov M.
        • Sporns O.
        Complex network measures of brain connectivity: Uses and interpretations.
        Neuroimage. 2010; 52: 1059-1069
        • Bonnelle V.
        • Leech R.
        • Kinnunen K.M.
        • Ham T.E.
        • Beckmann C.F.
        • De Boissezon X.
        • et al.
        Default mode network connectivity predicts sustained attention deficits after traumatic brain injury.
        J Neurosci. 2011; 31: 13442-13451
        • Zalesky A.
        • Fornito A.
        • Bullmore E.T.
        Network-based statistic: Identifying differences in brain networks.
        Neuroimage. 2010; 53: 1197-1207
        • Hyvärinen A.
        • Smith S.M.
        Pairwise likelihood ratios for estimation of non-Gaussian structural equation models.
        J Mach Learn Res. 2013; 14: 111-152
        • Ramsey J.D.
        • Sanchez-Romero R.
        • Glymour C.
        Non-Gaussian methods and high-pass filters in the estimation of effective connections.
        Neuroimage. 2014; 84: 986-1006
        • Banich M.T.
        Executive function the search for an integrated account.
        Current Directions in Psychological Science. 2009; 18: 89-94
        • Konkel A.
        • Cohen N.J.
        Relational memory and the hippocampus: Representations and methods.
        Front Neurosci. 2009; 3: 166-174
        • Brown A.D.
        • Root J.C.
        • Romano T.A.
        • Chang L.J.
        • Bryant R.A.
        • Hirst W.
        Overgeneralized autobiographical memory and future thinking in combat veterans with posttraumatic stress disorder.
        J Behav Ther Exp Psychiatry. 2013; 44: 129-134
        • van den Heuvel M.P.
        • Sporns O.
        Network hubs in the human brain.
        Trends Cogn Sci. 2013; 17: 683-696
        • Badre D.
        • Frank M.J.
        Mechanisms of hierarchical reinforcement learning in cortico-striatal circuits 2: Evidence from fMRI.
        Cereb Cortex. 2012; 22: 527-536
        • Seeley W.W.
        • Menon V.
        • Schatzberg A.F.
        • Keller J.
        • Glover G.H.
        • Kenna H.
        • et al.
        Dissociable intrinsic connectivity networks for salience processing and executive control.
        J Neurosci. 2007; 27: 2349-2356
        • Duman R.S.
        • Monteggia L.M.
        A neurotrophic model for stress-related mood disorders.
        Biol Psychiatry. 2006; 59: 1116-1127
        • Castellanos F.X.
        • Di Martino A.
        • Craddock R.C.
        • Mehta A.D.
        • Milham M.P.
        Clinical applications of the functional connectome.
        Neuroimage. 2013; 80: 527-540
        • Klöppel S.
        • Abdulkadir A.
        • Jack Jr, C.R.
        • Koutsouleris N.
        • Mourão-miranda J.
        • Vemuri P.
        Diagnostic neuroimaing across diseases.
        Neuroimage. 2012; 61: 457-463

      Linked Article

      • Trauma Re-experiencing Symptoms Modulate Topology of Intrinsic Functional Networks
        Biological PsychiatryVol. 78Issue 3
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          The article by Spielberg et al. (1) in this issue of Biological Psychiatry explores the large-scale topology of intrinsic functional networks in military veterans with posttraumatic stress disorder (PTSD) and mild traumatic brain injury (mTBI). The emerging approach, already applied to other neuropsychiatric disorders, begins to account for the reality that neural representations of symptoms are distributed across widespread, dynamically interacting brain regions and subnetworks, which are further modulated by affective and cognitive states.
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