Rates of mild traumatic brain injury (mTBI) are high among combat veterans, with reports suggesting 10-20% of Iraq and Afghanistan Veterans meet diagnostic criteria for mTBI, the vast majority of which being related to explosive blasts. There is on-going debate as to whether blast-related mTBI may result in long-term neuropsychological impairment, given the paucity of positive findings, despite on-going complaints of cognitive difficulties within this cohort. One possible explanation for this discrepancy is that traditional neuropsychological test procedures may lack sensitivity in capturing subtle deficits in everyday functioning in blast-related mTBI. Prospective memory (PM) is the ability to remember to execute an action at a certain point in the future, or is the fulfillment of delayed intentions. PM may be more sensitive to the functional difficulties described by some Veterans with mTBI (e.g., forgetting appointments) than those domains typically assessed (e.g., executive functions, attention and retrospective memory). Results of functional neuroimaging studies suggest that PM is dependent on a frontally-guided cortical network comprised of the anterior prefrontal cortex, dorsolateral prefrontal cortex, the anterior cingulate and parietal cortex. Neurostructural damage to the white matter pathways that integrate this network presents a possible underlying mechanism for PM disruption in mTBI. To date, few studies have investigated the effect of mTBI on PM, and no published studies have investigated the neurocircuitry of PM in OEF/OIF Veterans with a history of blast-related mTBI. The proposed study aims to utilize neuropsychological assessment and an integrated multi-modal neuroimaging analysis to study prospective memory (PM) functioning in Veterans with histories of blast-related mTBI. Eighty participants will be recruited from within an existing VA-funded TBI research study and will include Veterans with a history of blast-related mTBI (n = 40) or deployed Veterans without a history of mTBI (n = 40). Participants will complete a broad neurocognitive assessment which includes PM questionnaires and objective measures of PM. Veterans will also undergo an MRI scan which includes diffusion tensor imaging (DTI) and completion of a PM fMRI task. The study aims are to investigate PM performance in Veterans with histories of blast-related mTBI, investigate the neural network associated with PM functions via integration of fMRI and DTI modalities and determine whether this network is disrupted for Veterans with mTBI. The candidate is a current VA postdoctoral fellow studying mTBI and neuroimaging research, has trained in the neuropsychological assessment of mTBI, has demonstrated a capacity to learn neuroimaging research methods across multiple imaging modalities and has collaborated with the proposed mentorship team on several prior grant applications and manuscripts related to neuroimaging and cognitive functions following TBI. Successful completion of this VA Career Development Award-2 with advance the candidate further toward a long-term research career goal of being an independent clinical researcher in the VA focusing on the integration of neuroimaging and neuropsychological assessment in the study of TBI. The CDA-2 will lead to independence not only through the experience of conducting the proposed research and training plan, but also by providing critical pilot data for a VA Merit Award. The specific immediate training objectives of this CDA-2 are to: (1) develop expertise in integrating neuroimaging modalities including fMRI and DTI, (2) develop expertise in the study of prospective memory, (3) achieve proficiency in advanced biostatistics and (4) continue my professional development aimed toward transitioning from a postdoctoral fellow into an independent VA clinical scientist. These goals will be achieved via collaboration with the identified mentorship team that will provide further specialized training in neuropsychological assessment, TBI research and neuroimaging techniques.

Public Health Relevance

The proposed multidisciplinary project utilizes neuropsychological assessment and an integrated multi-modal neuroimaging analysis to investigate prospective memory (PM) functioning in Veterans with histories of blast- related mild traumatic brain injury (mTBI). It investigates the neural network associated with PM functions via integration of functional MRI (fMRI) and diffusion tensor imaging (DTI) modalities and examines whether this network is disrupted for Veterans with mTBI. This line of research will provide important information regarding (1) cognitive outcomes following mTBI, specifically PM, and (2) the underlying mechanisms for PM dysfunction in mild TBI. This project will serve to advance the care of VA patients with blast-related mTBI by informing neuropsychological assessment approaches and helping elucidate the neural signature of PM, which may also provide biomarker information to evaluate cognitive rehabilitation treatment response in future trials.

National Institute of Health (NIH)
Veterans Affairs (VA)
Veterans Administration (IK2)
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Neurobiology C (NURC)
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VA San Diego Healthcare System
San Diego
United States
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Clark, Alexandra L; Sorg, Scott F; Holiday, Kelsey et al. (2018) Fatigue Is Associated With Global and Regional Thalamic Morphometry in Veterans With a History of Mild Traumatic Brain Injury. J Head Trauma Rehabil 33:382-392
Clark, Alexandra L; Merritt, Victoria C; Bigler, Erin D et al. (2018) Blast-Exposed Veterans With Mild Traumatic Brain Injury Show Greater Frontal Cortical Thinning and Poorer Executive Functioning. Front Neurol 9:873