Neurobiological markers of future susceptibility to posttraumatic stress disorder (PTSD) may facilitate identification of vulnerable individuals in the early aftermath of trauma. Variability in resting-state networks (RSNs), patterns of intrinsic functional connectivity across the brain, has previously been linked to PTSD, and may thus be informative of PTSD susceptibility. The present data are part of an initial analysis from the AURORA study, a longitudinal, multisite study of adverse neuropsychiatric sequalae. Magnetic resonance imaging (MRI) data from 109 recently (i.e., ~2 weeks) traumatized individuals were collected and PTSD and depression symptoms were assessed at 3 months post trauma. We assessed commonly reported RSNs including the default mode network (DMN), central executive network (CEN), and salience network (SN). We also identified a proposed arousal network (AN) composed of a priori brain regions important for PTSD: the amygdala, hippocampus, mamillary bodies, midbrain, and pons. Primary analyses assessed whether variability in functional connectivity at the 2-week imaging timepoint predicted 3-month PTSD symptom severity. Left dorsolateral prefrontal cortex (DLPFC) to AN connectivity at 2 weeks post trauma was negatively related to 3-month PTSD symptoms. Further, right inferior temporal gyrus (ITG) to DMN connectivity was positively related to 3-month PTSD symptoms. Both DLPFC-AN and ITG-DMN connectivity also predicted depression symptoms at 3 months. Our results suggest that, following trauma exposure, acutely assessed variability in RSN connectivity was associated with PTSD symptom severity approximately two and a half months later. However, these patterns may reflect general susceptibility to posttraumatic dysfunction as the imaging patterns were not linked to specific disorder symptoms, at least in the subacute/early chronic phase. The present data suggest that assessment of RSNs in the early aftermath of trauma may be informative of susceptibility to posttraumatic dysfunction, with future work needed to understand neural markers of long-term (e.g., 12 months post trauma) dysfunction. Furthermore, these findings are consistent with neural models suggesting that decreased top-down cortico-limbic regulation and increased network-mediated fear generalization may contribute to ongoing dysfunction in the aftermath of trauma.
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Kessler RC, Sonnega A, Bromet E, Hughes M, Nelson CB. Posttraumatic stress disorder in the National Comorbidity Survey. Arch Gen Psychiatry. 1995;52:1048–60.
Kilpatrick DG, Resnick HS, Milanak ME, Miller MW, Keyes KM, Friedman MJ. National estimates of exposure to traumatic events and PTSD prevalence using DSM-IV and DSM-5 criteria. J Trauma Stress. 2013;26:537–47.
American Psychiatric Association. Diagnostic and statistical manual of mental disorders. 5th ed. American Psychiatric Association Press, Arlington, VA; 2013.
Galatzer-Levy IR, Ankri Y, Freedman S, Israeli-Shalev Y, Roitman P, Gilad M, et al. Early PTSD symptom trajectories: persistence, recovery, and response to treatment: results from the jerusalem trauma outreach and prevention study (J-TOPS). PLoS ONE. 2013;8:e70084.
Bonanno GA, Mancini AD. Beyond resilience and PTSD: mapping the heterogeneity of responses to potential trauma. Psychol Trauma Theory Res Pract Policy. 2012;4:74–83.
Galatzer-Levy IR, Huang SH, Bonanno GA. Trajectories of resilience and dysfunction following potential trauma: A review and statistical evaluation. Clin Psychol Rev. 2018;63:41–55.
Bryant RA, Creamer M, O’Donnell M, Silove D, McFarlane AC, Forbes D. A comparison of the capacity of DSM-IV and DSM-5 acute stress disorder definitions to predict posttraumatic stress disorder and related disorders. J Clin Psychiatry. 2015;76:391–7.
Galatzer-Levy IR, Bryant RA. 636,120 ways to have posttraumatic stress disorder. Perspect Psychol Sci. 2013;8:651–62.
van Rooij SJH, Stevens JS, Ely TD, Hinrichs R, Michopoulos V, Winters SJ, et al. The role of the hippocampus in predicting future posttraumatic stress disorder symptoms in recently traumatized civilians. Biol Psychiatry. 2018;84:106–15.
Stevens JS, Kim YJ, Galatzer-Levy IR, Reddy R, Ely TD, Nemeroff CB, et al. Amygdala reactivity and anterior cingulate habituation predict posttraumatic stress disorder symptom maintenance after acute civilian trauma. Biol Psychiatry. 2017;81:1023–9.
McLaughlin KA, Busso DS, Duys A, Green JG, Alves S, Way M, et al. Amygdala response to negative stimuli predicts ptsd symptom onset following a terrorist attack. Depress Anxiety. 2014;31:834–42.
Admon R, Lubin G, Stern O, Rosenberg K, Sela L, Ben-Ami H, et al. Human vulnerability to stress depends on amygdala’s predisposition and hippocampal plasticity. Proc Natl Acad Sci USA. 2009;106:14120–5.
Harnett NG, Ference EW, Wood KH, Wheelock MD, Knight AJ, Knight DC. Trauma exposure acutely alters neural function during Pavlovian fear conditioning. Cortex. 2018;109:1–13.
Beckmann CF, DeLuca M, Devlin JT, Smith SM. Investigations into resting-state connectivity using independent component analysis. Philos Trans R Soc B Biol Sci. 2005;360:1001–13.
Damoiseaux JS, Rombouts SARB, Barkhof F, Scheltens P, Stam CJ, Smith SM, et al. Consistent resting-state networks across healthy subjects. Proc Natl Acad Sci USA. 2006;103:13848–53.
Fox MD, Greicius M. Clinical applications of resting state functional connectivity. Front Syst Neurosci. 2010;4:19.
Menon V. Large-scale brain networks and psychopathology: a unifying triple network model. Trends Cogn Sci. 2011;15:483–506.
Akiki TJ, Averill CL, Abdallah CG. A network-based neurobiological model of PTSD: evidence from structural and functional neuroimaging studies. Curr Psychiatry Rep. 2017;19:81.
Raichle ME, MacLeod AM, Snyder AZ, Powers WJ, Gusnard DA, Shulman GL. A default mode of brain function. Proc Natl Acad Sci USA. 2001;98:676–82.
Buckner RL, Andrews-Hanna JR, Schacter DL. The brain’s default network: anatomy, function, and relevance to disease. Ann NY Acad Sci. 2008;1124:1–38.
Poerio GL, Sormaz M, Wang HT, Margulies D, Jefferies E, Smallwood J. The role of the default mode network in component processes underlying the wandering mind. Soc Cogn Affect Neurosci. 2017;12:1047–62.
Dosenbach NUF, Fair DA, Miezin FM, Cohen AL, Wenger KK, Dosenbach RAT, et al. Distinct brain networks for adaptive and stable task control in humans. Proc Natl Acad Sci USA. 2007;104:11073–8.
Seeley WW, Menon V, Schatzberg AF, Keller J, Glover GH, Kenna H, et al. Dissociable intrinsic connectivity networks for salience processing and executive control. J Neurosci. 2007;27:2349–56.
Seeley WW, Menon V, Schatzberg AF, Keller J, Glover GH, Kenna H, et al. The organization of the human cerebral cortex estimated by intrinsic functional connectivity. J Neurophysiol. 2011;106:1125–65.
Abdallah CG, Averill CL, Ramage AE, Averill LA, Goktas S, Nemati S, et al. Salience network disruption in U.S. army soldiers with posttraumatic stress disorder. Chronic Stress. 2019;3:247054701985046.
Abdallah CG, Averill CL, Ramage AE, Averill LA, Alkin E, Nemati S, et al. Reduced salience and enhanced central executive connectivity following PTSD treatment. Chronic Stress. 2019;3:247054701983897.
Koch SBJ, van Zuiden M, Nawijn L, Frijling JL, Veltman DJ, Olff M. Aberrant resting-state brain activity in posttraumatic stress disorder: a meta-analysis and systematic review. Depress Anxiety. 2016;33:592–605.
Rytwinski NK, Scur MD, Feeny NC, Youngstrom EA. The co-occurrence of major depressive disorder among individuals with posttraumatic stress disorder: a meta-analysis. J Trauma Stress. 2013;26:299–309.
Mulders PC, van Eijndhoven PF, Schene AH, Beckmann CF, Tendolkar I. Resting-state functional connectivity in major depressive disorder: a review. Neurosci Biobehav Rev. 2015;56:330–44.
Cullen KR, Westlund MK, Klimes-Dougan B, Mueller BA, Houri A, Eberly LE, et al. Abnormal amygdala resting-state functional connectivity in adolescent depression. JAMA Psychiatry. 2014;71:1138–47.
Lanius RA, Bluhm RL, Coupland NJ, Hegadoren KM, Rowe B, Théberge J, et al. Default mode network connectivity as a predictor of post-traumatic stress disorder symptom severity in acutely traumatized subjects. Acta Psychiatr Scand. 2010;121:33–40.
Zhou Y, Wang Z, Qin L-d, Wan JQ, Sun Y-W, Su S-S, et al. Early altered resting-state functional connectivity predicts the severity of post-traumatic stress disorder symptoms in acutely traumatized subjects. PLoS ONE. 2012;7:e46833.
Qin L-D, Wang Z, Sun YW, Wan JQ, Su SS, Zhou Y, et al. A preliminary study of alterations in default network connectivity in post-traumatic stress disorder patients following recent trauma. Brain Res. 2012;1484:50–6.
Milad MR, Pitman RK, Ellis CB, Gold AL, Shin LM, Lasko NB, et al. Neurobiological basis of failure to recall extinction memory in posttraumatic stress disorder. Biol Psychiatry. 2009;66:1075–82.
Hayes JP, Hayes SM, Mikedis AM. Quantitative meta-analysis of neural activity in posttraumatic stress disorder. Biol Mood Anxiety Disord. 2012;2:9.
Knight DC, Smith CN, Cheng DT, Stein EA, Helmstetter FJ. Amygdala and hippocampal activity during acquisition and extinction of human fear conditioning. Cogn Affect Behav Neurosci. 2004;4:317–25.
Stevens JS, Jovanovic T, Fani N, Ely TD, Glover EM, Bradley B, et al. Disrupted amygdala-prefrontal functional connectivity in civilian women with posttraumatic stress disorder. J Psychiatr Res. 2013;47:1469–78.
Lazarov A, Zhu X, Suarez-Jimenez B, Rutherford BR, Neria Y. Resting-state functional connectivity of anterior and posterior hippocampus in posttraumatic stress disorder. J Psychiatr Res. 2017;94:15–22.
Sripada RK, King AP, Garfinkel SN, Wang X, Sripada CS, Welsh RC, et al. Altered resting-state amygdala functional connectivity in men with posttraumatic stress disorder. J Psychiatry Neurosci. 2012;37:241–9.
McLean SA, Ressler K, Koenen KC, Neylan T, Germine L, Jovanovic T, et al. The AURORA study: a longitudinal, multimodal library of brain biology and function after traumatic stress exposure. Mol Psychiatry. 2020;25:283–96.
Weathers FW, Litz BT, Keane TM, Palmieri PA, Marx BP, Schnurr PP. The PTSD checklist for DSM-5 (PCL-5). Natl Cent PTSD. 2013;5:2002.
Pilkonis PA, Choi SW, Reise SP, Stover AM, Riley WT, Cella D. Item banks for measuring emotional distress from the patient-reported outcomes measurement information system (PROMIS®): depression, anxiety, and anger. Assessment. 2011;18:263–83.
Hamilton CM, Strader LC, Pratt JG, Maiese D, Hendershot T, Kwok RK, et al. The PhenX toolkit: get the most from your measures. Am J Epidemiol. 2011;174:253–60.
Smith SM, Jenkinson M, Woolrich MW, Beckmann CF, Behrens TEJ, Johansen-Berg H, et al. Advances in functional and structural MR image analysis and implementation as FSL. Neuroimage. 2004;23:S208–19.
Nickerson LD, Smith SM, Öngür D, Beckmann CF. Using dual regression to investigate network shape and amplitude in functional connectivity analyses. Front Neurosci. 2017;11:115.
Beckmann C, Mackay C, Filippini N, Smith S. Group comparison of resting-state FMRI data using multi-subject ICA and dual regression. Neuroimage. 2009;47:S148.
Cox RW. AFNI: Software for analysis and visualization of functional magnetic resonance neuroimages. Comput Biomed Res. 1996;29:162–73.
Seligowski AV, Harnett NG, Merker JB, Ressler KJ. Nervous and endocrine system dysfunction in posttraumatic stress disorder: an overview and consideration of sex as a biological variable. Biol Psychiatry Cogn Neurosci Neuroimaging. 2020;5:381–91.
Harnett NG. Neurobiological consequences of racial disparities and environmental risks: a critical gap in understanding psychiatric disorders. Neuropsychopharmacology. 2020. https://doi.org/10.1038/s41386-020-0681-4.
Maples-Keller JL, Post LM, Price M, Goodnight JM, Burton MS, Yasinski CW, et al. Investigation of optimal dose of early intervention to prevent posttraumatic stress disorder: a multiarm randomized trial of one and three sessions of modified prolonged exposure. Depress Anxiety. 2020;37:429–37.
Ressler KJ. Alpha-adrenergic receptors in PTSD—failure or time for precision medicine? N Engl J Med. 2018;378:575–6.
Zohar J, Fostick L, Juven-Wetzler A, Kaplan Z, Shalev H, Schreiber G, et al. Secondary prevention of chronic PTSD by early and short-term administration of escitalopram: a prospective randomized, Placebo-Controlled, double-blind trial. J Clin Psychiatry. 2018;79:48–54.
Pitman RK, Sanders KM, Zusman RM, Healy AR, Cheema F, Lasko NB, et al. Pilot study of secondary prevention of posttraumatic stress disorder with propranolol. Biol Psychiatry. 2002;51:189–92.
Belleau EL, Ehret LE, Hanson JL, Brasel KJ, Larson CL, deRoon-Cassini TA. Amygdala functional connectivity in the acute aftermath of trauma prospectively predicts severity of posttraumatic stress symptoms: Functional connectivity predicts future PTSD symptoms. Neurobiol Stress. 2020;12:100217.
van Rooij SJH, Jovanovic T. Impaired inhibition as an intermediate phenotype for PTSD risk and treatment response. Prog Neuropsychopharmacol Biol Psychiatry. 2019;89:435–45.
Milad MR, Wright CI, Orr SP, Pitman RK, Quirk GJ, Rauch SL. Recall of fear extinction in humans activates the ventromedial prefrontal cortex and hippocampus in concert. Biol Psychiatry. 2007;62:446–54.
Cheng DT, Knight DC, Smith CN, Stein EA, Helmstetter FJ. Functional MRI of human amygdala activity during Pavlovian fear conditioning: stimulus processing versus response expression. Behav Neurosci. 2003;117:3–10.
Cheng DT, Disterhoft JF, Power JM, Ellis DA, Desmond JE. Neural substrates underlying human delay and trace eyeblink conditioning. Proc Natl Acad Sci USA. 2008;105:8108–13.
Comte M, Schön D, Coull JT, Reynaud E, Khalfa S, Belzeaux R, et al. Dissociating bottom-up and top-down mechanisms in the cortico-limbic system during emotion processing. Cereb Cortex. 2016;26:144–55.
Wheelock MD, Sreenivasan KR, Wood KH, Ver Hoef LW, Deshpande G, Knight DC. Threat-related learning relies on distinct dorsal prefrontal cortex network connectivity. Neuroimage. 2014;102:904–12.
Wheelock MD, Sreenivasan KR, Wood KH, Ver Hoef LW, Deshpande G, Knight DC. The neurobiology of emotion regulation in posttraumatic stress disorder: Amygdala downregulation via real-time fMRI neurofeedback. Hum Brain Mapp. 2017;38:541–60.
Berlim MT, Van Den Eynde F, Jeff Daskalakis Z. Clinically meaningful efficacy and acceptability of low-frequency repetitive transcranial magnetic stimulation (rTMS) for treating primary major depression: a meta-analysis of randomized, double-blind and sham-controlled trials. Neuropsychopharmacology. 2013;38:543–51.
Baeken C, De Raedt R, Van Schuerbeek P, Vanderhasselt MA, De Mey J, Bossuyt A, et al. Right prefrontal HF-rTMS attenuates right amygdala processing of negatively valenced emotional stimuli in healthy females. Behav Brain Res. 2010;214:450–5.
Philip NS, Barredo J, van’t Wout-Frank M, Tyrka AR, Price LH, Carpenter LL. Network mechanisms of clinical response to transcranial magnetic stimulation in posttraumatic stress disorder and major depressive disorder. Biol Psychiatry. 2018;83:263–72.
Fonzo GA, Goodkind MS, Oathes DJ, Zaiko YV, Harvey M, Peng KK, et al. PTSD psychotherapy outcome predicted by brain activation during emotional reactivity and regulation. Am J Psychiatry. 2017;174:1163–74.
Shalev AY, Gevonden M, Ratanatharathorn A, Laska E, van der Mei WF, Qi W, et al. Estimating the risk of PTSD in recent trauma survivors: results of the International Consortium to Predict PTSD (ICPP). World Psychiatry. 2019;18:77–87.
Raichle ME. The brain’s default mode network. Annu Rev Neurosci. 2015. https://doi.org/10.1146/annurev-neuro-071013-014030.
Harrison BJ, Pujol J, López-Solà M, Hernández-Ribas R, Deus J, Ortiz H, et al. Consistency and functional specialization in the default mode brain network. Proc Natl Acad Sci USA. 2008. https://doi.org/10.1073/pnas.0711791105.
Goodman AM, Harnett NG, Knight DC. Pavlovian conditioned diminution of the neurobehavioral response to threat. Neurosci Biobehav Rev. 2018;84:218–24.
Pan J, Zhan L, Hu CL, Yang J, Wang C, Gu L, et al. Emotion regulation and complex brain networks: Association between expressive suppression and efficiency in the fronto-parietal network and default-mode network. Front Hum Neurosci. 2018;12:70.
Satpute AB, Lindquist KA. The default mode network’s role in discrete emotion. Trends Cogn Sci. 2019;23:851–64.
Kravitz DJ, Saleem KS, Baker CI, Ungerleider LG, Mishkin M. The ventral visual pathway: an expanded neural framework for the processing of object quality. Trends Cogn Sci. 2013;17:26–49.
D’Argembeau A, Xue G, Lu ZL, Van der Linden M, Bechara A. Neural correlates of envisioning emotional events in the near and far future. Neuroimage. 2008. https://doi.org/10.1016/j.neuroimage.2007.11.025.
Pitman RK, Delahanty DL. Conceptually driven pharmacologic approaches to acute trauma. CNS Spectr. 2005;10:99–106.
Jovanovic T, Ressler KJ. How the neurocircuitry and genetics of fear inhibition may inform our understanding of PTSD. Am J Psychiatry. 2010;167:648–62.
Morey RA, Haswell CC, Stjepanović D, Brancu M, Beckham JC, Calhoun PS, et al. Neural correlates of conceptual-level fear generalization in posttraumatic stress disorder. Neuropsychopharmacology. 2020. https://doi.org/10.1038/s41386-020-0661-8.
Berg H, Ma Y, Rueter A, Kaczkurkin A, Burton PC, DeYoung CG, et al. Salience and central executive networks track overgeneralization of conditioned-fear in post-traumatic stress disorder. Psychol Med. 2020;1–10.
Norman KA, Polyn SM, Detre GJ, Haxby JV. Beyond mind-reading: multi-voxel pattern analysis of fMRI data. Trends Cogn Sci. 2006;10:424–30.
Morey RA, Dunsmoor JE, Haswell CC, Brown VM, Vora A, Weiner J, et al. Fear learning circuitry is biased toward generalization of fear associations in posttraumatic stress disorder. Transl Psychiatry. 2015;5:e700.
Tomasi DG, Shokri-Kojori E, Volkow ND. Temporal evolution of brain functional connectivity metrics: Could 7 min of rest be enough? Cereb Cortex. 2017;27:4153–65.
Shehzad Z, Kelly AMC, Reiss PT, Gee DG, Gotimer K, Uddin LQ, et al. The resting brain: unconstrained yet reliable. Cereb Cortex. 2009;19:2209–29.
Noble S, Spann MN, Tokoglu F, Shen X, Constable RT, Scheinost D. Influences on the test-retest reliability of functional connectivity MRI and its relationship with behavioral utility. Cereb Cortex 2017;27:5415–29.
The authors would like to thank Rebecca Price, Adam Hively, Saswati Data, Suraj Oomman, and the other members of the UNC Institute for Trauma Recovery for their efforts and aide in this research. We would also like to thank research staff at McLean Hospital, Emory University, Temple University, and Wayne State University for their efforts and aide. We further express our gratitude to the participants and their families for their willingness to participate in this research.
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Harnett, N.G., van Rooij, S.J.H., Ely, T.D. et al. Prognostic neuroimaging biomarkers of trauma-related psychopathology: resting-state fMRI shortly after trauma predicts future PTSD and depression symptoms in the AURORA study. Neuropsychopharmacol. 46, 1263–1271 (2021). https://doi.org/10.1038/s41386-020-00946-8