Persistent and reversible consequences of combat stress on the mesofrontal circuit and cognition
- aDonders Institute for Brain, Cognition, and Behaviour and
- gDepartment of Cellular Animal Physiology, Radboud University, 6500 HB, Nijmegen, The Netherlands;
- bBrain Imaging Center,
- cDepartment of Psychiatry,
- fDepartment of Radiology, and
- hDepartment of Clinical Epidemiology, Biostatistics and Bioinformatics, Academic Medical Center, University of Amsterdam, 1100 DD, Amsterdam, The Netherlands;
- dResearch Centre, Military Mental Health, Ministry of Defense, 3500 WB, Utrecht, The Netherlands;
- eDepartment of Psychiatry, Rudolf Magnus Institute of Neuroscience, Utrecht University Medical Center, 3584 CX, Utrecht, The Netherlands; and
- iDepartment for Cognitive Neuroscience, Radboud University Nijmegen Medical Centre, 6525 EZ, Nijmegen, The Netherlands
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Edited by Michael Merzenich, W. M. Keck Center for Integrative Neuroscience, San Francisco, CA, and approved July 20, 2012 (received for review April 15, 2012)

Abstract
Prolonged stress can have long-lasting effects on cognition. Animal models suggest that deficits in executive functioning could result from alterations within the mesofrontal circuit. We investigated this hypothesis in soldiers before and after deployment to Afghanistan and a control group using functional and diffusion tensor imaging. Combat stress reduced midbrain activity and integrity, which was associated to compromised sustained attention. Long-term follow-up showed that the functional and structural changes had normalized within 1.5 y. In contrast, combat stress induced a persistent reduction in functional connectivity between the midbrain and prefrontal cortex. These results demonstrate that combat stress has adverse effects on the human mesofrontal circuit and suggests that these alterations are partially reversible.
Footnotes
- ↵1To whom correspondence should be addressed. E-mail: guidovanwingen{at}gmail.com.
Author contributions: G.A.v.W., E.G., E.V., and G.F. designed research; G.A.v.W. performed research; M.W.A.C. and S.D.O. contributed new reagents/analytic tools; G.A.v.W. analyzed data; and G.A.v.W., E.G., M.W.A.C., T.K., S.D.O., D.D., E.V., and G.F. wrote the paper.
The authors declare no conflict of interest.
This article is a PNAS Direct Submission.
This article contains supporting information online at www.pnas.org/lookup/suppl/doi:10.1073/pnas.1206330109/-/DCSupplemental.