Severe traumatic brain injury (TBI) is the leading cause of death and long-term disabilities in children, yet there remains a critical need for accurate markers of outcome in these patients. Identification of improved MRI markers of long-term neurocognitive outcome will improve clinical prognostication after an injury and help to direct and monitor rehabilitation strategies. Recent advances in neuroimaging have elucidated the existence of large-scale brain networks responsible for distinct cognitive and psychological functions. A network-based framework for TBI-induced cognitive dysfunction is a novel paradigm for investigating hypotheses regarding the relationship between patient-specific injury patterns and neurocognitive outcomes. Using this framework, this study will identify early imaging predictors of global and specific neuropsychological functions after severe pediatric TBI. In addition, the study will investigate the association between late MRI markers of brain network dysfunction and impairments in commonly affected cognitive domains (executive function, memory, and internalizing behavior). The project will leverage an ongoing, multi-center study of severe pediatric TBI to enable this large neuroimaging study with the following three aims:
Aim 1 : Test whether the severity and location of white and gray matter injuries identified on MRI early after injury independently predict functional and neurocognitive outcomes one year after severe pediatric TBI. Acute MRI scans will be assessed using standardized common data element (CDE) definitions, and MRI measures predictive of global and domain- specific cognitive outcomes will be determined.
Aim 2 : Test whether global or regional cerebral atrophy at one year post-injury is related to neurocognitive and behavioral impairments after TBI. Global and regional volumetrics will be determined from structural MRI scans, and correlated with neuropsychological testing measures of function in each cognitive domain.
Aim 3 : Test whether TBI-induced alterations in white matter microstructure and functional network connectivity are related to impairments in cognition and psychological functioning. Diffusion tensor imaging (DTI) and resting state functional MRI (rfMRI) will be used to investigate the relationship between damage to specific brain networks and neurocognitive function. Successful completion of this project will determine clinically useful MRI markers of neurocognitive outcome and will provide new information on the relationship between brain network dysfunction and cognitive impairments after TBI. Identifying early imaging predictors and late imaging markers of specific neuropsychological impairments would be a major advancement, providing new tools for directing rehabilitation strategies towards at-risk cognitive domains, and thereby improving long-term function and quality of life in this vulnerable population.

Public Health Relevance

Severe pediatric traumatic brain injury (TBI) is the leading cause of mortality and significant disability in children. There is a significant need for new measures of clinical and neurocognitive outcomes, which may be used to predict deficits, guide treatments and monitor the effect of therapy in these patients. This study will identify early MRI findings that predict specific neurocognitive dysfunction, and late MRI markers of TBI-induced brain network dysfunction.

National Institute of Health (NIH)
National Institute of Neurological Disorders and Stroke (NINDS)
Research Project (R01)
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Special Emphasis Panel (ZRG1)
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Bellgowan, Patrick S F
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University of Wisconsin Madison
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United States
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