Focal brain damage protects against post-traumatic stress disorder in combat veterans

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Post-traumatic stress disorder (PTSD) is an often debilitating mental illness that is characterized by recurrent distressing memories of traumatic events. PTSD is associated with hypoactivity in the ventromedial prefrontal cortex (vmPFC), hyperactivity in the amygdala and reduced volume in the hippocampus, but it is unknown whether these neuroimaging findings reflect the underlying cause or a secondary effect of the disorder. To investigate the causal contribution of specific brain areas to PTSD symptoms, we studied a unique sample of Vietnam War veterans who suffered brain injury and emotionally traumatic events. We found a substantially reduced occurrence of PTSD among those individuals with damage to one of two regions of the brain: the vmPFC and an anterior temporal area that included the amygdala. These results suggest that the vmPFC and amygdala are critically involved in the pathogenesis of PTSD.

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Figure 1: Lesion difference analysis.
Figure 2: vmPFC group lesion overlap map.
Figure 3: Lesion overlap maps for the amygdala and temporal lobe comparison groups.


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We thank K. Reding for VHIS data management and D. Kapogiannis for helpful discussions. We thank the veterans for their participation in the VHIS. This work was supported by the US National Institute of Neurological Disorders and Stroke intramural research program and a project grant form the United Sates Army Medical Research and Material Command administered by the Henry M. Jackson Foundation (Vietnam Head Injury Study Phase III: a 30-year post-injury follow-up study, grant number DAMD17-01-1-0675).

Author information

M.K., E.D.H. and J.G. planned the study. V.R. conducted the psychiatric assessments and carried out the lesion tracing with J.G. B.C. performed additional data collection and organization. J.S. designed and implemented the lesion analysis software. M.K. and E.D.H. analyzed the psychiatric data. M.K. and J.S. analyzed the lesion data. M.K. prepared the figures and wrote the manuscript in consultation with E.D.H., E.M.W. and J.G. All authors reviewed and edited the manuscript. J.G. supervised the project.

Correspondence to Jordan Grafman.

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