Skip to main content Accessibility help
×
×
Home

Neurobiological correlates of distinct post-traumatic stress disorder symptom profiles during threat anticipation in combat veterans

  • D. W. Grupe (a1) (a2), J. Wielgosz (a1) (a2) (a3), R. J. Davidson (a1) (a2) (a3) (a4) and J. B. Nitschke (a4)
Abstract
Background

Previous research in post-traumatic stress disorder (PTSD) has identified disrupted ventromedial prefrontal cortex (vmPFC) function in those with v. without PTSD. It is unclear whether this brain region is uniformly affected in all individuals with PTSD, or whether vmPFC dysfunction is related to individual differences in discrete features of this heterogeneous disorder.

Method

In a sample of 51 male veterans of Operation Enduring Freedom/Operation Iraqi Freedom, we collected functional magnetic resonance imaging data during a novel threat anticipation task with crossed factors of threat condition and temporal unpredictability. Voxelwise regression analyses related anticipatory brain activation to individual differences in overall PTSD symptom severity, as well as individual differences in discrete symptom subscales (re-experiencing, emotional numbing/avoidance, and hyperarousal).

Results

The vmPFC showed greater anticipatory responses for safety relative to threat, driven primarily by deactivation during threat anticipation. During unpredictable threat anticipation, increased PTSD symptoms were associated with relatively greater activation for threat v. safety. However, simultaneous regression on individual symptom subscales demonstrated that this effect was driven specifically by individual differences in hyperarousal symptoms. Furthermore, this analysis revealed an additional, anatomically distinct region of the vmPFC in which re-experiencing symptoms were associated with greater activation during threat anticipation.

Conclusions

Increased anticipatory responses to unpredictable threat in distinct vmPFC subregions were uniquely associated with elevated hyperarousal and re-experiencing symptoms in combat veterans. These results underscore the disruptive impact of uncertainty for veterans, and suggest that investigating individual differences in discrete aspects of PTSD may advance our understanding of underlying neurobiological mechanisms.

Copyright
Corresponding author
*Address for correspondence: D. Grupe, Ph.D., Waisman Laboratory for Brain Imaging and Behavior, 1500 Highland Avenue, Madison, WI 53705, USA. (Email: grupe@wisc.edu)
References
Hide All
Admon, R, Milad, MR, Hendler, T (2013). A causal model of post-traumatic stress disorder: disentangling predisposed from acquired neural abnormalities. Trends in Cognitive Sciences 17, 337347.
Blake, D, Weathers, R, Namy, L, Kaloupek, D, Klauminzer, G, Charnet, D, Keane, T (1990). A clinician rating scale for assessing current and lifetime PTSD: the CAPS-1. Behavior Therapist 13, 187188.
Buckner, RL, Carroll, DC (2007). Self-projection and the brain. Trends in Cognitive Sciences 11, 4957.
Daniels, JK, Mcfarlane, AC, Bluhm, RL, Moores, KA, Clark, CR, Shaw, ME, Williamson, PC, Densmore, M, Lanius, RA (2010). Switching between executive and default mode networks in posttraumatic stress disorder: alterations in functional connectivity. Journal of Psychiatry and Neuroscience 35, 258266.
Desikan, RS, Ségonne, F, Fischl, B, Quinn, BT, Dickerson, BC, Blacker, D, Buckner, RL, Dale, AM, Maguire, RP, Hyman, BT, Albert, MS, Killiany, RJ (2006). An automated labeling system for subdividing the human cerebral cortex on MRI scans into gyral based regions of interest. NeuroImage 31, 968980.
Etkin, A, Wager, TD (2007). Functional neuroimaging of anxiety: a meta-analysis of emotional processing in PTSD, social anxiety disorder, and specific phobia. American Journal of Psychiatry 164, 14761488.
First, MB, Spitzer, RL, Gibbon, M, Williams, JB (2002). Structured Clinical Interview for DSM-IV-TR Axis I Disorders, Research Version, Patient Edition (SCID-I/P) . Biometrics Research, New York State Psychiatric Institute: New York.
Garfinkel, SN, Abelson, JL, King, AP, Sripada, RK, Wang, X, Gaines, LM, Liberzon, I (2014). Impaired contextual modulation of memories in PTSD: an fMRI and psychophysiological study of extinction retention and fear renewal. Journal of Neuroscience 34, 1343513443.
Gianaros, PJ, Wager, TD (2015). Brain–body pathways linking psychological stress and physical health. Current Directions in Psychological Science 24, 313321.
Grillon, C, Pine, DS, Lissek, S, Rabin, S, Bonne, O, Vythilingam, M (2009). Increased anxiety during anticipation of unpredictable aversive stimuli in posttraumatic stress disorder but not in generalized anxiety disorder. Biological Psychiatry 66, 4753.
Grupe, DW, Nitschke, JB (2013). Uncertainty and anticipation in anxiety: an integrated neurobiological and psychological perspective. Nature Reviews Neuroscience 14, 488501.
Grupe, DW, Oathes, DJ, Nitschke, JB (2013). Dissecting the anticipation of aversion reveals dissociable neural networks. Cerebral Cortex 23, 18741883.
Hayes, JP, Hayes, SM, Mikedis, AM (2012). Quantitative meta-analysis of neural activity in posttraumatic stress disorder. Biology of Mood and Anxiety Disorders 2, 9.
Hopper, JW, Frewen, PA, van der Kolk, BA, Lanius, RA (2007). Neural correlates of reexperiencing, avoidance, and dissociation in PTSD: symptom dimensions and emotion dysregulation in responses to script-driven trauma imagery. Journal of Traumatic Stress 20, 713725.
Insel, T, Cuthbert, B, Garvey, M, Heinssen, R, Pine, DS, Quinn, K, Sanislow, C, Wang, P (2010). Research domain criteria (RDoC): toward a new classification framework for research on mental disorders. American Journal of Psychiatry 167, 748751.
Kimble, MO, Fleming, K, Bennion, KA (2013). Contributors to hypervigilance in a military and civilian sample. Journal of Interpersonal Violence 28, 16721692.
Lissek, S, Pine, DS, Grillon, C (2006). The strong situation: a potential impediment to studying the psychobiology and pharmacology of anxiety disorders. Biological Psychology 72, 265270.
Maldjian, JA, Laurienti, PJ, Kraft, RA, Burdette, JH (2003). An automated method for neuroanatomic and cytoarchitectonic atlas-based interrogation of fMRI data sets. NeuroImage 19, 12331239.
McMenamin, BW, Langeslag, SJE, Sirbu, M, Padmala, S, Pessoa, L (2014). Network organization unfolds over time during periods of anxious anticipation. Journal of Neuroscience 34, 1126111273.
Mechias, M-L, Etkin, A, Kalisch, R (2010). A meta-analysis of instructed fear studies: implications for conscious appraisal of threat. NeuroImage 49, 17601768.
Milad, MR, Pitman, RK, Ellis, CB, Gold, AL, Shin, LM, Lasko, NB, Zeidan, MA, Handwerger, K, Orr, SP, Rauch, SL (2009). Neurobiological basis of failure to recall extinction memory in posttraumatic stress disorder. Biological Psychiatry 66, 10751082.
Morey, RA, Dunsmoor, JE, Haswell, CC, Brown, VM, Vora, A, Weiner, J, Stjepanovic, D, Wagner, HR, Brancu, M, Marx, CE, Naylor, JC, Van Voorhees, E, Taber, KH, Beckham, JC, Calhoun, PS, Fairbank, JA, Szabo, ST, LaBar, KS (2015). Fear learning circuitry is biased toward generalization of fear associations in posttraumatic stress disorder. Translational Psychiatry 5, e700.
Motzkin, JC, Newman, JP, Kiehl, KA, Koenigs, M (2011). Reduced prefrontal connectivity in psychopathy. Journal of Neuroscience 31, 1734817357.
Peirce, JW (2007). PsychoPy – Psychophysics software in Python. Journal of Neuroscience Methods 162, 813.
Pietrzak, RH, Averill, LA, Abdallah, CG, Neumeister, A, Krystal, JH, Levy, I, Harpaz-Rotem, I (2015). Amygdala-hippocampal volume and the phenotypic heterogeneity of posttraumatic stress disorder: a cross-sectional study. JAMA Psychiatry 72, 20142016.
Raichle, ME, MacLeod, AM, Snyder, AZ, Powers, WJ, Gusnard, DA, Shulman, GL (2001). A default mode of brain function. Proceedings of the National Academy of Sciences 98, 676682.
Rougemont-Bücking, A, Linnman, C, Zeffiro, TA, Zeidan, MA, Lebron-Milad, K, Rodriguez-Romaguera, J, Rauch, SL, Pitman, RK, Milad, MR (2011). Altered processing of contextual information during fear extinction in PTSD: an fMRI study. CNS Neuroscience and Therapeutics 17, 227236.
Roy, M, Shohamy, D, Wager, TD (2012). Ventromedial prefrontal–subcortical systems and the generation of affective meaning. Trends in Cognitive Sciences 16, 147156.
Sadeh, N, Spielberg, JM, Warren, SL, Miller, GA, Heller, W (2014). Aberrant neural connectivity during emotional processing associated with posttraumatic stress. Clinical Psychological Science 2, 748755.
Satpute, AB, Mumford, JA, Naliboff, BD, Poldrack, RA (2012). Human anterior and posterior hippocampus respond distinctly to state and trait anxiety. Emotion 12, 5868.
Schell, TL, Marshall, GN (2008). Survey of individuals previously deployed for OEF/OIF. In Invisible Wounds of War: Psychological and Cognitive Injuries, their Consequences, and Services to Assist Recovery (ed. Tanielian, T. and Jaycox, L. H.), pp. 87115. Rand Corporation: Santa Monica, CA.
Schiller, D, Levy, I, LeDoux, JE, Niv, Y, Phelps, EA (2008). From fear to safety and back: reversal of fear in the human brain. Journal of Neuroscience 28, 1151711525.
Shackman, AJ, Salomons, TV, Slagter, HA, Fox, AS, Winter, JJ, Davidson, RJ (2011). The integration of negative affect, pain and cognitive control in the cingulate cortex. Nature Reviews Neuroscience 12, 154167.
Sheline, YI, Barch, DM, Price, JL, Rundle, MM, Vaishnavi, SN, Snyder, AZ, Mintun, MA, Wang, S, Coalson, RS, Raichle, ME (2009). The default mode network and self-referential processes in depression. Proceedings of the National Academy of Sciences of the United States of America 106, 19421947.
Siegel, JS, Power, JD, Dubis, JW, Vogel, AC, Church, JA, Schlaggar, BL, Petersen, SE (2014). Statistical improvements in functional magnetic resonance imaging analyses produced by censoring high-motion data points. Human Brain Mapping 35, 19811996.
Spielberg, JM, McGlinchey, RE, Milberg, WP, Salat, DH (2015). Brain network disturbance related to posttraumatic stress & traumatic brain injury in veterans. Biological Psychiatry 78, 210216.
Sripada, RK, King, AP, Welsh, RC, Garfinkel, SN, Wang, X, Sripada, CS, Liberzon, I (2012). Neural dysregulation in posttraumatic stress disorder: evidence for disrupted equilibrium between salience and default mode brain networks. Psychosomatic Medicine 74, 904911.
Svoboda, E, McKinnon, MC, Levine, B (2006). The functional neuroanatomy of autobiographical memory: a meta-analysis. Neuropsychologia 44, 21892208.
Thayer, JF, Ahs, F, Fredrikson, M, Sollers, JJ, Wager, TD (2012). A meta-analysis of heart rate variability and neuroimaging studies: implications for heart rate variability as a marker of stress and health. Neuroscience and Biobehavioral Reviews 36, 747756.
Tulving, E (2002). Episodic memory: from mind to brain. Annual Review of Psychology 53, 125.
Wilson, JP, Friedman, MJ, Lindy, JD (2001). Treatment goals for PTSD. In Treating Psychological Trauma & PTSD (ed. Wilson, J. P., Friedman, M. J. and Lindy, J. D.), pp. 327. Guilford Press: New York.
Woolrich, MW, Ripley, BD, Brady, M, Smith, SM (2001). Temporal autocorrelation in univariate linear modeling of fMRI data. NeuroImage 14, 13701386.
Recommend this journal

Email your librarian or administrator to recommend adding this journal to your organisation's collection.

Psychological Medicine
  • ISSN: 0033-2917
  • EISSN: 1469-8978
  • URL: /core/journals/psychological-medicine
Please enter your name
Please enter a valid email address
Who would you like to send this to? *
×

Keywords

Type Description Title
WORD
Supplementary materials

Grupe Supplementary Material
Grupe Supplementary Material

 Word (2.6 MB)
2.6 MB

Metrics

Altmetric attention score

Full text views

Total number of HTML views: 0
Total number of PDF views: 0 *
Loading metrics...

Abstract views

Total abstract views: 0 *
Loading metrics...

* Views captured on Cambridge Core between <date>. This data will be updated every 24 hours.

Usage data cannot currently be displayed