Project Background: Traumatic brain injury (TBI) is estimated to have occurred in 10 to 23% of Operation Enduring Freedom/Operation Iraqi Freedom/Operation New Dawn (OEF/OIF/OND) combatants, resulting in cognitive, neurobehavioral, and emotional sequelae and disability. Diagnosis in the chronic phase is difficult because conventional brain imaging is insensitive, acute injury records may be unavailable, and symptoms of posttraumatic stress disorder (PTSD) often overlap with those of TBI. Advanced brain imaging of TBI could potentially identify disruption of white matter (WM) tracts on diffusion tensor imaging (DTI), alterations in brain activation while performing cognitive tasks during functional magnetic resonance imaging (fMRI), and changes in functional connectivity (FC) measured from resting state fMRI. Rationale: We reported that TBI indexed by DTI was related to increases in brain activation in Veterans while they performed a spatial conflict resolution (SPCR) task, a finding that we and others have attributed to increased demand upon neural resources due to WM injury. PTSD symptom severity had the opposite effect of reducing task-related brain activation. Limitations of this study included restriction to blast TBI, lack of a definitive diagnostic instrument for PTSD, and the possibility that our findings were specific to the SPCR task. We also did not evaluate resting state FC. Objectives: Study blast and non-blast mechanisms of mild TBI (mTBI), add an fMRI task of complex attention that is likely to be more sensitive to diffuse WM injury, measure FC of the default mode network (DMN), explore the effects of blast exposure in Veterans without a history of mTBI, and perform a comprehensive analysis to examine multi-modality brain imaging in relation to outcome measures. This project will determine relationships between WM tract injury (DTI), fMRI brain activation during SPCR and attention tasks, connectivity during resting state fMRI, and functional, emotional, and cognitive status in mTBI and non-TBI groups. Methods: Study SPCR and complex attention-related brain activation in 60 mTBI (e 3 months post-injury) and 60 non-TBI without blast exposure, as well as 20 Veterans and Service Members with a history of blast exposure but not TBI. DTI will measure WM integrity and resting state fMRI will provide a measure of FC. We will assess cognitive, emotional, and functional outcome to address the Aims and the Clinician Assisted PTSD Scale will be used to identify subjects with PTSD. Statistical analyses will integrate the multimodality brain imaging to evaluate the contributions of mTBI and PTSD to brain activation on the SPCR and attention tasks, as well as FC. The array of brain imaging variables will be analyzed in relation to cognitive, emotional, and functional outcome. Relevance to Veterans' Healthcare: Improved diagnosis of chronic mTBI, including effects of blast exposure without a history of TBI, would facilitate treatment planning and lead to earlier referral. Information about mechanisms may also suggest intervention approaches for TBI and PTSD and provide methods for assessing treatment response.

Public Health Relevance

The proposed project would integrate multimodality brain imaging to examine neural correlates of mild traumatic brain injury (mTBI) and posttraumatic stress disorder (PTSD) in relation to cognitive, emotional, and functional status in Veterans and Service Members. Brain activation from spatial conflict and complex attention paradigms would be analyzed in combination with measures of white matter integrity, functional connectivity, and outcome. An exploratory aim would also address the unique contributions of blast exposure in subjects without documented brain injury. This research would describe the underlying mechanisms of mTBI and PTSD and may ultimately contribute to improved diagnostic techniques, as well as suggest intervention approaches and provide new methods for monitoring response to treatment.

Agency
National Institute of Health (NIH)
Institute
Veterans Affairs (VA)
Type
Non-HHS Research Projects (I01)
Project #
5I01RX001320-02
Application #
9071861
Study Section
Brain Injury: TBI & Stroke (RRD1)
Project Start
2014-07-01
Project End
2018-09-30
Budget Start
2015-07-01
Budget End
2016-06-30
Support Year
2
Fiscal Year
2015
Total Cost
Indirect Cost
Name
Michael E Debakey VA Medical Center
Department
Type
DUNS #
078446044
City
Houston
State
TX
Country
United States
Zip Code
77030
Gordon, Evan M; Scheibel, Randall S; Zambrano-Vazquez, Laura et al. (2018) High-Fidelity Measures of Whole-Brain Functional Connectivity and White Matter Integrity Mediate Relationships between Traumatic Brain Injury and Post-Traumatic Stress Disorder Symptoms. J Neurotrauma 35:767-779
Scheibel, Randall S (2017) Functional Magnetic Resonance Imaging of Cognitive Control following Traumatic Brain Injury. Front Neurol 8:352
Troyanskaya, Maya; Pastorek, Nicholas J; Scheibel, Randall S et al. (2016) Choosing appropriate comparison group participants in studies of veterans: Characteristics of orthopedically injured and uninjured Operation Enduring Freedom/Operation Iraqi Freedom/Operation New Dawn veterans. J Clin Exp Neuropsychol 38:811-9
Newsome, Mary R; Mayer, Andrew R; Lin, Xiaodi et al. (2016) Chronic Effects of Blast-Related TBI on Subcortical Functional Connectivity in Veterans - Erratum. J Int Neuropsychol Soc 22:790-2
Newsome, Mary R; Mayer, Andrew R; Lin, Xiaodi et al. (2016) Chronic Effects of Blast-Related TBI on Subcortical Functional Connectivity in Veterans. J Int Neuropsychol Soc 22:631-42
Troyanskaya, Maya; Pastorek, Nicholas J; Scheibel, Randall S et al. (2015) Combat exposure, PTSD symptoms, and cognition following blast-related traumatic brain injury in OEF/OIF/OND service members and Veterans. Mil Med 180:285-9
Scheibel, Randall S; Pastorek, Nicholas J; Troyanskaya, Maya et al. (2015) The suppression of brain activation in post-deployment military personnel with posttraumatic stress symptoms. Brain Imaging Behav 9:513-26