Mild traumatic brain injury (mild TBI) occurs frequently in combat personnel and has been linked to complaints of emotional symptoms in up to 85% of those injured, with high rates of PTSD symptoms, anxiety, depression, and mood swings. TBI may cause cerebral white matter injury and changes in white matter integrity have been correlated with behavioral changes even with very mild TBI. Patients with mild TBI also have higher rates of dishonorable discharge from the military, as well as substance abuse. Many of these behavioral changes are associated with alterations in frontal-subcortical networks, which are heavily dependent on white matter connectivity. Our primary goal in this proposed CDA-2 investigation is to begin to understand the specific neurological mechanisms that may underlie emotional dysfunction following mild TBI. White matter injury in mild TBI is not homogenous, but two white matter structures that may be of particular importance in the development of emotional disorders are the uncinate fasciculus and the anterior limb of the internal capsule (injured in between 30-40% of patients with mild TBI). Changes in these structures in other populations have been linked to fearful emotional processing and altered autonomic responses to stressors. Further, based on the literature demonstrating right-left hemispheric differences in emotional processing, there may be laterality effects of white matter injury. Thus damage to these pathways may increase a person's vulnerability to the development of abnormal emotional functioning, including symptoms associated with PTSD. A goal of this study is to compare patients with PTSD but no TBI to patients with TBI with and without emotional symptoms. It may be that the basic emotional responses of these populations are different and that these differences may help elucidate the mechanism accounting for these changes in mood and emotional behaviors. Finding a neurological and injury-specific basis for the constellation of chronic emotional symptoms observed in this population could have treatment implications such that the treatment of patients with versus those without injury induced PTSD may have different efficacies (e.g., exposure therapy may work best for the patients with non-injury related PTSD). To test these hypotheses, we will recruit 40 subjects with mild TBI from our OEF/OIF poly-trauma clinic and 40 controls (20 with PTSD but no TBI). We will test emotional behaviors using an affective neuroscience methodology with indicators chosen based on the reported symptom profiles in this population. Specifically, we will assess the relationship between white matter injury in the uncinate fasciculus and anterior limb of the internal capsule and alteration of affective response physiologically (e.g., startle response while viewing high intensity positively and negatively valenced visual scenes) and cognitively (identification of the 6 primary emotions including ratings of intensity and arousal). To determine the integrity of white matter pathways, we will use high-resolution diffusion weighted imaging (DWI) with diffusion tensor imaging (DTI) and related analysis techniques. In addition to helping better understand the basis of TBI induced emotional disorders, this project will provide the candidate with training in the technical aspects of neuroimaging methods including pre and post-processing techniques, region of interest identification, program choice and usage to accurately identify white matter, and data analyses. Further, these skills will be integrated with the candidate's psychophysiology and neuropsychology backgrounds. In addition, the candidate will gain experience with research on veterans with traumatic brain injury, while providing valuable data that will help us understand some of the disabilities and challenges faced by these patients.

Public Health Relevance

Research on potential neurological mechanisms of emotional deficits subsequent to mild traumatic brain injury (mild TBI) is important to veterans. Post traumatic stress disorder (PTSD), according to recent studies, can be seen in up to 40% of veterans with mild TBI. Understanding the pathophysiology of a disorder is often an important initial step in finding a successful treatment and in the case of emotional changes subsequent to mild TBI, it is unclear if there are contributing neurological mechanisms (as compared with psychiatric mechanisms). Linking emotional issues to anatomical white matter changes can potentially greatly further knowledge of both conditions (PTSD spectrum changes with mild TBI and PTSD spectrum behaviors without mild TBI) and potentially both refine prognosis and lead to more effective therapeutic solutions.

National Institute of Health (NIH)
Veterans Affairs (VA)
Veterans Administration (IK2)
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Veterans Health Administration
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Williamson, John B; Porges, Eric C; Lamb, Damon G et al. (2014) Maladaptive autonomic regulation in PTSD accelerates physiological aging. Front Psychol 5:1571
Williamson, John B; Heilman, Kenneth M; Porges, Eric C et al. (2013) A possible mechanism for PTSD symptoms in patients with traumatic brain injury: central autonomic network disruption. Front Neuroeng 6:13