Structural and Functional Neuroimaging Studies of Combat Veterans
Condition: Traumatic Brain Injury; PTSD
MeSH terms: Brain Injuries; Brain Injuries, Traumatic
Study type: Observational

Summary: 
      Background:

      - Studies have shown that some people develop post-traumatic stress disorder (PTSD) after
      being exposed to the trauma of military combat. They may have repeated thoughts, images, and
      dreams of the trauma; feel detached from others; have difficulty sleeping and concentrating;
      or be easily startled. Some studies have also shown that after having a blow or blast to the
      head, some people may develop post-concussive syndrome (PCS), which may include symptoms such
      as headaches, difficulty concentrating, and feeling moody or irritable. Researchers are
      interested in using magnetic resonance imaging (MRI) to study combat veterans from Operation
      Iraqi Freedom or Operation Enduring Freedom in order to evaluate possible changes in the
      brain that may be attributed to PTSD or PCS.

      Objectives:

      - To evaluate changes in brain function in recent combat veterans that may be related to
      post-traumatic stress disorder or post-concussive syndrome.

      Eligibility:

      - Combat veterans of Operation Iraqi Freedom/Operation Enduring Freedom who are enrolled in
      Walter Reed Army Medical Center protocol 351030, have returned within the last 6 weeks from a
      deployment in Iraq or Afghanistan that lasted at least 3 months, and are able to have
      magnetic resonance imaging scans.

      Design:

        -  This study involves between 1 and 4 outpatient visits to the NIH Clinical Center over
           the course of 1 year. The second, third, and fourth visits will occur 3, 6, and 12
           months after the first visit.

        -  At the first visit, participants will have a baseline MRI scan, followed by a functional
           MRI (fMRI) scan to see what parts of the brain are used while performing simple tasks
           and responding to images. Participants will complete questionnaires after the scan to
           report on their experiences during the MRI scan.

        -  For the remaining three study visits, participants will have further MRI and fMRI scans
           and will complete additional questionnaires. Participation is complete after the
           12-month study visit, or following a diagnosis of PTSD, major depression, or PCS at any
           time during the study.

        -  No treatment will be provided as part of this protocol.
    

Detailed description: 
      Objective: Traumatic brain injury (TBI) and posttraumatic stress disorder (PTSD) are linked
      with functional impairments, poor outcomes compared to matched controls or people without
      brain dysfunction, and greater healthcare utilization. TBI can be diagnosed at the point of
      injury, but post-concussive syndrome (PCS) and PTSD are diagnosed after the initial exposure.
      Current treatments are often ineffective, and many affected military service members (SMs)
      never return to active duty. Upon return from deployment, many SMs experience an initial
      honeymoon period during which symptoms are limited in number and scope, but this may be
      followed by a sharp increase in symptoms within months. Identification of independent
      predictors of PTSD and PCS upon return from deployment could facilitate early intervention to
      prevent disability. The main purpose of this protocol is to determine whether structural and
      functional neuroimaging in SMs who are ostensibly healthy upon return can differentiate those
      who will go on to have persistent neurocognitive difficulties from those who will not.

      Study population: The study population will be returning SMs at risk for PCS or PTSD. It
      involves a prospective cohort study of 128 healthy active duty military SMs, recruited by the
      Walter Reed National Military Medical Center (WRNMMC) from National Capital Area military
      units within 8 weeks after return from Iraq or Afghanistan, with serial evaluations to
      identify both those who develop PTSD or PCS, as well as factors obtained at the time of the
      initial evaluation that prove to be most strongly associated with subsequent PTSD and PCS. A
      comprehensive baseline assessment will be performed at WRNMMC under protocol 351030 (already
      approved at both the Uniformed Services University of Health Sciences [USUHS] and WRNMMC),
      which will include demographics, neuropsychological assessment, genetic and neuroendocrine
      assays, brain imaging and synchronization, vestibular, olfactory, and psychophysiologic
      measures. Neuroimaging and fMRI activation tasks will be performed under this imaging
      protocol at NIH. The study is funded by the USUHS Center for Neuroscience and Regenerative
      Medicine (CNRM) and NIH. See the attached WRNMMC protocol 351030.

      Design: Neuroimaging including structural and functional magnetic resonance imaging (fMRI),
      and diffusion tension imaging (DTI) will be performed under this imaging protocol at NIH.
      Follow-up visits at 3, 6, and 12 months will allow repeated MRIs and fMRI activation tasks.
      Data analysis will include serial univariate and multivariate analyses to identify the
      baseline measures (including not only the results from this imaging study at NIH but also the
      results from a variety of studies to be performed at WRNMMC) that are most strongly
      associated with the subsequent development of PTSD and PCS.

      Outcome measures: The primary outcome of interest is the development of neurocognitive
      difficulties (PCS, PTSD, or depression). Multivariate analyses will assess what baseline
      measures are most strongly associated with this outcome.
    

Time perspective: Other
Keywords: Post Traumatic Stress Disorder (PTSD); MRI; TBI; Traumatic Brain Injury; Post Traumatic Stress Disorder; PTSD