Traumatic brain injury (TBI) in children is postulated to disrupt development of frontally-guided, distributed neural networks mediating working memory and related cognitive control processes. To address our hypothesis that reduced working memory performance is associated with decreased prefrontal and parietal activation on functional magnetic resonance imaging (fMRI) in children following moderate to severe TBI, we will study a stratified sample of 36 TBI patients and 36 demographically-matched children with orthopedic injury (Ol) who are age 10 to 15 years and enrolled in the ongoing project. To investigate the integrity of white matter microstructure (prefrontal cortex, parietal region, temporo-occipital region, and corpus callosum), we will also perform diffusion tensor imaging (DTI) in the same session as fMRI at 3 months and 18 months post-injury. Fractional anisotropy will be measured from DTI by tracing multiple slices and secondarily by fiber tracking. We also propose to study brain activation and white matter integrity in relation to executive functioning in everyday activities and white matter integrity in relation to performance on working memory and resistance to interference tasks in the laboratory with outcome measures obtained at baseline, 3, 12, 18, and 24 months post-injury. To ensure uniform imaging and cognitive assessment in Houston and Dallas, workshops will be held in months 01 and 13, a project manual will be prepared, identical scanners will be used at both locations, and a Houston-based investigator will observe the first five fMRI acquisitions and every tenth fMRI thereafter in Dallas. Quality control procedures for the imaging and cognitive testing will be instituted. Image analysis for fMRI and DTI data will be centralized in Houston to ensure reliability. Statistic parametric mapping and region of interest analysis will be applied to the fMRI data. General linear mixed and nonlinear mixed models, and correlational techniques will address the relation between brain activation on fMRI and executive function in everyday activities and between white matter integrity and performance on cognitive tasks and executive function in daily activities. Psychiatric disorder, family history of psychiatric disorder, and medication history will be explored as control variables to mitigate confounds of the neuroimaging and cognitive variables. The supplement extends the ongoing project by relating cognitive control to brain function and white matter microstructure in addition to the analysis of brain regional volumes. ? ? ?
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