Hostname: page-component-cd9895bd7-8ctnn Total loading time: 0 Render date: 2024-12-29T03:47:51.509Z Has data issue: false hasContentIssue false
  • English
  • Français

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

Published online by Cambridge University Press:  16 March 2016

D. W. Grupe ,
J. Wielgosz ,
R. J. Davidson  and
J. B. Nitschke
D. W. Grupe*
Affiliation:
Waisman Laboratory for Brain Imaging and Behavior, University of Wisconsin-Madison, Madison, WI, USA The Center for Healthy Minds, University of Wisconsin-Madison, Madison, WI, USA
J. Wielgosz
Affiliation:
Waisman Laboratory for Brain Imaging and Behavior, University of Wisconsin-Madison, Madison, WI, USA The Center for Healthy Minds, University of Wisconsin-Madison, Madison, WI, USA Department of Psychology, University of Wisconsin-Madison, Madison, WI, USA
R. J. Davidson
Affiliation:
Waisman Laboratory for Brain Imaging and Behavior, University of Wisconsin-Madison, Madison, WI, USA The Center for Healthy Minds, University of Wisconsin-Madison, Madison, WI, USA Department of Psychology, University of Wisconsin-Madison, Madison, WI, USA Department of Psychiatry, University of Wisconsin-Madison, Madison, WI, USA
J. B. Nitschke
Affiliation:
Department of Psychiatry, University of Wisconsin-Madison, Madison, WI, USA
*
*Address for correspondence: D. Grupe, Ph.D., Waisman Laboratory for Brain Imaging and Behavior, 1500 Highland Avenue, Madison, WI 53705, USA. (Email: [email protected])
Get access Rights & Permissions [Opens in a new window]

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.

Keywords

Functional magnetic resonance imaginghyperarousalpost-traumatic stress disorderventromedial prefrontal cortexveterans
Type
Original Articles
Information
Psychological Medicine , Volume 46 , Issue 9 , July 2016 , pp. 1885 - 1895
Copyright
Copyright © Cambridge University Press 2016 

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

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, 337–347.CrossRefGoogle ScholarPubMed
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, 187–188.Google Scholar
Buckner, RL, Carroll, DC (2007). Self-projection and the brain. Trends in Cognitive Sciences 11, 49–57.CrossRefGoogle ScholarPubMed
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, 258–266.CrossRefGoogle ScholarPubMed
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, 968–980.CrossRefGoogle ScholarPubMed
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, 1476–1488.CrossRefGoogle ScholarPubMed
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.Google Scholar
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, 13435–13443.CrossRefGoogle ScholarPubMed
Gianaros, PJ, Wager, TD (2015). Brain–body pathways linking psychological stress and physical health. Current Directions in Psychological Science 24, 313–321.CrossRefGoogle ScholarPubMed
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, 47–53.CrossRefGoogle ScholarPubMed
Grupe, DW, Nitschke, JB (2013). Uncertainty and anticipation in anxiety: an integrated neurobiological and psychological perspective. Nature Reviews Neuroscience 14, 488–501.CrossRefGoogle ScholarPubMed
Grupe, DW, Oathes, DJ, Nitschke, JB (2013). Dissecting the anticipation of aversion reveals dissociable neural networks. Cerebral Cortex 23, 1874–1883.CrossRefGoogle ScholarPubMed
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.CrossRefGoogle ScholarPubMed
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, 713–725.CrossRefGoogle ScholarPubMed
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, 748–751.CrossRefGoogle Scholar
Kimble, MO, Fleming, K, Bennion, KA (2013). Contributors to hypervigilance in a military and civilian sample. Journal of Interpersonal Violence 28, 1672–1692.CrossRefGoogle Scholar
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, 265–270.CrossRefGoogle ScholarPubMed
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, 1233–1239.CrossRefGoogle ScholarPubMed
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, 11261–11273.CrossRefGoogle ScholarPubMed
Mechias, M-L, Etkin, A, Kalisch, R (2010). A meta-analysis of instructed fear studies: implications for conscious appraisal of threat. NeuroImage 49, 1760–1768.CrossRefGoogle ScholarPubMed
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, 1075–1082.CrossRefGoogle ScholarPubMed
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.CrossRefGoogle ScholarPubMed
Motzkin, JC, Newman, JP, Kiehl, KA, Koenigs, M (2011). Reduced prefrontal connectivity in psychopathy. Journal of Neuroscience 31, 17348–17357.CrossRefGoogle ScholarPubMed
Peirce, JW (2007). PsychoPy – Psychophysics software in Python. Journal of Neuroscience Methods 162, 8–13.CrossRefGoogle ScholarPubMed
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, 2014–2016.CrossRefGoogle ScholarPubMed
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, 676–682.CrossRefGoogle ScholarPubMed
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, 227–236.CrossRefGoogle ScholarPubMed
Roy, M, Shohamy, D, Wager, TD (2012). Ventromedial prefrontal–subcortical systems and the generation of affective meaning. Trends in Cognitive Sciences 16, 147–156.CrossRefGoogle ScholarPubMed
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, 748–755.CrossRefGoogle ScholarPubMed
Satpute, AB, Mumford, JA, Naliboff, BD, Poldrack, RA (2012). Human anterior and posterior hippocampus respond distinctly to state and trait anxiety. Emotion 12, 58–68.CrossRefGoogle ScholarPubMed
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. 87–115. Rand Corporation: Santa Monica, CA.Google Scholar
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, 11517–11525.CrossRefGoogle ScholarPubMed
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, 154–167.CrossRefGoogle ScholarPubMed
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, 1942–1947.CrossRefGoogle ScholarPubMed
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, 1981–1996.CrossRefGoogle ScholarPubMed
Spielberg, JM, McGlinchey, RE, Milberg, WP, Salat, DH (2015). Brain network disturbance related to posttraumatic stress & traumatic brain injury in veterans. Biological Psychiatry 78, 210–216.CrossRefGoogle ScholarPubMed
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, 904–911.CrossRefGoogle ScholarPubMed
Svoboda, E, McKinnon, MC, Levine, B (2006). The functional neuroanatomy of autobiographical memory: a meta-analysis. Neuropsychologia 44, 2189–2208.CrossRefGoogle ScholarPubMed
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, 747–756.CrossRefGoogle ScholarPubMed
Tulving, E (2002). Episodic memory: from mind to brain. Annual Review of Psychology 53, 1–25.CrossRefGoogle Scholar
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. 3–27. Guilford Press: New York.Google Scholar
Woolrich, MW, Ripley, BD, Brady, M, Smith, SM (2001). Temporal autocorrelation in univariate linear modeling of fMRI data. NeuroImage 14, 1370–1386.CrossRefGoogle ScholarPubMed
Supplementary material: File

Grupe Supplementary Material

Grupe Supplementary Material

Download Grupe Supplementary Material(File)
File 2.6 MB