Pathophysiological Mechanisms of PTSD in Soldiers Returning from Afghanistan and Iraq: Neuroimaging and Treatment

Jack B. Nitschke, Ph.D.

University of Wisconsin School of Medicine, Madison, WI, Waisman Laboratory for Brain Imaging and Behavior

Grant Program:

David Mahoney Neuroimaging Program

Funded in:

June 2009, for 3 years

Funding Amount:


Lay Summary

Characterizing PTSD Brain Alterations and Responses to Treatment Using MRI, fMRI and DTI

This study will use three types of imaging to identify specific brain alterations that occur in soldiers with post-traumatic stress disorder (PTSD) and to evaluate the effects of treatment on these changed brain structures and functions.

Studies of combat soldiers returning from Iraq and Afghanistan with PTSD suggest that the anterior cingulate cortex (ACC) and amygdala show abnormalities. The ACC integrates sensory, affective, cognitive, autonomic and motor processes. It is involved in processing emotional conflict and is implicated in severe depression. The amygdala appears to have a role in evaluating potentially dangerous situations and in maintaining alertness and readiness to act. The two areas interact in processing emotion, according to some studies. Combat veterans with PTSD have been found to decrease symptoms through use of cognitive processing therapy, in which they learn to modify the meaning of their traumatic experiences.

The researchers hypothesize, therefore, that combat soldiers with PTSD have structural and functional alterations in the ACC and amygdala and in their connections. They further hypothesize that pretreatment brain activity in these two areas and their connections predicts response to cognitive processing therapy, and that these alterations are normalized following successful treatment.

They will test these hypotheses in 40 combat veterans, 20 who have PTSD and 20 who do not. The soldiers in the former group will be scanned prior to and three months following cognitive processing therapy. Brain structures, including the ACC and amygdala, will be assessed using MRI. Brain area connections will be assessed using Diffusion Tensor Imaging (DTI). The soldiers also will undergo fMRI while undertaking two emotion-related tasks. One investigates the impact that conflicting emotional stimuli has on processing subsequent emotional stimuli. This task focuses on the ACC and amygdala. The other task measures emotional processing while anticipating and responding to emotional stimuli. Since this task involves areas in addition to the ACC and amygdala, it will help to determine if abnormalities are isolated to those two areas.

The researchers predict that soldiers with PTSD will show less ACC activity and volume, greater amygdala activity, and reduced connectivity between the two areas compared to those of soldiers without PTSD, and that these changes will be minimized or normalized following cognitive processing therapy.


Pathophysiological Mechanisms of PTSD in Soldiers Returning from Afghanistan and Iraq: Neuroimaging and Treatment

Posttraumatic stress disorder (PTSD) is a debilitating form of mental illness affecting many of our soldiers returning from Iraq and Afghanistan. The proposed study will utilize functional magnetic resonance imaging (fMRI), structural MRI, and diffusion tensor imaging (DTI) to test the hypothesis that soldiers with PTSD show alterations in the function and structure of two key brain areas, the anterior cingulate cortex (ACC) and amygdala, as well as reduced functional and structural connectivity between these areas.

This research will employ two well-validated fMRI tasks: (1) the emotional conflict task investigates temporal dynamics of emotion processing in terms of the impact of conflicting emotional stimuli on the processing of subsequent emotional stimuli (Etkin et al., 2006; Egner et al., 2008); (2) the emotional anticipation task investigates temporal dynamics of emotion processing during the anticipation of and response to emotional stimuli (Nitschke et al., 2006; Mackiewicz et al., 2006). Forty OEF/OIF veterans will be enrolled in this study, with 20 in each of two groups: combat-exposed veterans with PTSD, and veterans with combat exposure but no PTSD. Soldiers with PTSD will receive Cognitive Processing Therapy, a form of psychotherapy shown to be effective for the treatment of PTSD (Monson et al., 2006; Resick et al., 2008). All soldiers with PTSD will be scanned prior to the start of treatment and upon competion of three months of treament.

This design will allow us to examine two important issues regarding treatment: (1) whether pretreatment brain activity predicts response to treatment, as we recently found for generalized anxiety disorder (Nitschke te al. 2009; Whalen et al., 2008); and (2) whether treatment results in the normalization of neural abnormalities identified prior to the start of treatment.

Prior to treatment, we predict that PTSD soldiers will exhibit greater amygdala activity, less ACC activity, and less ACC-amygdala functional connectivity than combat-exposed soldiers without PTSD. These patterns are expected to normalize following treatment. Structural differences at the start of treatment are also hypothesized, with PTSD soldiers expected to show smaller ACC volumes and reduced white matter tracts (structural connectivity) between the ACC and amygdala. Finally, building on our recent findings for generalized anxiety disorder (Nitschke et al., 2009), pretreatment ACC activity is expected to predict better outcomes following three months of treatment.

The discovery of neural abnormalities and the degree of normalization following treatment should add to the body of work already being used in developing new clinical tools for directly targeting specific brain regions in anxiety and depression, such as neurofeedback, transcranial magnetic stimulation, epidural electrocortical stimulation, and deep brain stimulation. Psychotherapy clients may benefit from greater focus of intervention strategies on anticipatory processes or resolving emotional conflict.

The proposed study will have immediate, direct benefits for our returning soldiers suffering from PTSD by providing them with empirically supported efficacious treatment as well as potential long-term benefits by gathering data that further informs understanding of PTSD and how to best treat it.

Investigator Biographies

Jack B. Nitschke, Ph.D.

Jack B. Nitschke, Ph.D., is an assistant professor of psychiatry and psychology at the University of Wisconsin-Madison. He is an active member of the Waisman Laboratory for Brain Imaging and Behavior and the HealthEmotions Research Institute at the University of Wisconsin-Madison. He received his B.A. in psychology from the University of Pennsylvania and his M.A. and Ph.D. in clinical psychology from the University of Illinois at Urbana-Champaign.

Following graduate school he completed a postdoctoral fellowship in the NIMH Training Program in emotion research at the University of Wisconsin-Madison. In 2002, he was awarded a five-year NIMH K08 Career Research Award and a HealthEmotions Research Institute fellowship. Since then, he has received a five-year NIMH R01 grant, a five-year NIMH K02 Career Research Award, and a NARSAD Young Investigator Award.

His research examines the neuroscience of human emotion and affective disorders. Health is a general theme that courses through all his research endeavors, including such topics as anxiety, depression, the placebo effect, well-being, positive emotion, and altruism. His research studies use clinical and nonclinical samples and employ an array of methodologies including fMRI, DTI, structural MRI, EEG, peripheral psychophysiology, neuropsychological tasks, and molecular genetics.

Complementing his research program, he is a licensed psychologist in the state of Wisconsin and has clinical responsibilities that primarily involve the practice and supervision of individual and group psychotherapy with people suffering from depression, anxiety, and borderline personality disorder.