Posttraumatic stress disorder (PTSD) is a major public and VA health concern and exerts substantial burden on as many as 20% of soldiers returning from deployment in Afghanistan and Iraq. Evidence of cognitive and affective neuroscience approaches suggest that the medial frontal cortex (MFC) dysfunction during fear processing and emotion regulation is central in the pathophysiology of PTSD. However, much of this evidence comes from studies of older veterans from combat theaters from decades ago, and from brain imaging techniques that are relatively expensive with limited translation to clinical settings. Little is known about the neura mechanism involved in recovery from the disorder. The overarching goal of the present application is to advance an alternative approach to the study of brain function through the use of electroencephalography (EEG) measures of event-related potentials (ERP), a portable technique that can be deployed in the 'real world'office setting and provides time-locked stimulus neural response metrics that are reliable. Much of our recent work focuses on MFC ERPs reflecting neural reactivity to social signals of threat/danger and neural engagement during cognitive, volitional regulation of negative affect through reappraisal strategies - processes tightly related to avoidance of threat/danger and dysregulated affect, hallmark symptoms of PTSD. The proposed prospective, naturalistic longitudinal study will assess and follow the clinical status, trajectory and brain function during two validated ERP tasks involving threat processing and emotion regulation in veterans with PTSD (n=120) related to their combat trauma during deployment and in veterans (n=60) with similar levels of combat exposure who did not develop PTSD (CEC). Moreover, comprehensive clinical assessments, including close tracking of treatment, will be conducted at study entry, 6 months later and 12 months later to ascertain persistence of or recovery from PTSD. ERP imaging will also occur at entry, 6 months and one year later in order to address 4 Aims: 1) Characterize neurophysiological function during threat perception and emotion regulation in PTSD patients compared to CECs at study entry;2) Compare neurophysiological function of patients with persistent PTSD and patients who recover and combat-exposed controls (CEC), one year later;3) Relate change in neurophysiological function to change in PTSD symptomatology;and 4) Examine clinical and psychosocial moderators and mediators of the hypothesized relationship between neurophysiological function and PTSD symptomatology. The findings of this study will shed new light on the brain mechanisms underlying disturbances in appraising social signals of threat and emotion regulation in PTSD and the clinical relevance of this brain dysfunction to the maintenance of and recovery from PTSD. Such knowledge is critically important to identifying the appropriate brain targets to guide current interventions and innovating new interventions, aimed at primary and secondary prevention of PTSD in our returning soldiers.

Public Health Relevance

Veterans with post-traumatic stress disorder (PTSD) exhibit brain dysfunction that could explain disturbances in how they perceive others around them and how they manage negative emotions and stress. Little is known if these patterns of brain dysfunction exist in soldiers returning from deployment in Afghanistan and Iraq who subsequently develop PTSD, or if and how the brain changes in those veterans whose PTSD persists and in those who recover from PTSD. The purpose of the proposed study is to use a brain imaging technique that is non-invasive, inexpensive, easy-to-conduct, and portable to the outpatient clinical setting. The imaging will be used to study the brain processes involved in the processing of fear and in the regulation of negative emotions to evaluate how these brain processes change over the course of one year in relation to PTSD in OEF/OIF/OND veterans. This knowledge should improve our understanding and treatment of PTSD.

National Institute of Health (NIH)
Veterans Affairs (VA)
Non-HHS Research Projects (I01)
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Mental Health and Behavioral Science A (MHBA)
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Jesse Brown VA Medical Center
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Fitzgerald, Jacklynn M; DiGangi, Julia A; Phan, K Luan (2018) Functional Neuroanatomy of Emotion and Its Regulation in PTSD. Harv Rev Psychiatry 26:116-128
Crane, Natania A; Gorka, Stephanie M; Burkhouse, Katie L et al. (2018) Neural response to errors is associated with problematic alcohol use over time in combat-exposed returning veterans: An event-related potential study. Drug Alcohol Depend 183:155-161
Fitzgerald, Jacklynn M; MacNamara, Annmarie; Kennedy, Amy E et al. (2017) Individual differences in cognitive reappraisal use and emotion regulatory brain function in combat-exposed veterans with and without PTSD. Depress Anxiety 34:79-88
Fitzgerald, Jacklynn M; MacNamara, Annmarie; DiGangi, Julia A et al. (2016) An electrocortical investigation of voluntary emotion regulation in combat-related posttraumatic stress disorder. Psychiatry Res Neuroimaging 249:113-21