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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])
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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 

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