Kirkby, Brenda Sue2018-07-232018-07-2319962018-07-23http://hdl.handle.net/1828/9764Structural changes in the frontal and temporal lobes and in subcortical white matter tracts often occur following closed head injury (CHI). In contrast to this well delineated structural pathology, the post-traumatic cognitively-related functional changes in these and other brain regions have not been adequately described. To characterize the long-term functional neuroanatomy of CHI, the present study compared regional cerebral blood flow (rCBF) patterns in 13 severely-injured, well-recovered, unmedicated patients to those from 13 well-matched healthy controls. rCBF was measured using oxygen-15 water intravenous bolus positron emission tomography (PET) while subjects performed the Wisconsin Card Sorting Test (WCST), an indicator of prefrontal lobe functioning that involves matching stimuli to a changing sorting principle based on external feedback, and a Cued Recall Memory Test (CRMT), which involves remembering semantically-related word pairs. The neuropsychological tasks were used to provoke specific neural systems believed to be important in task performance (the prefrontal cortex in the former, the hippocampus in the latter). Subjects also performed two specially designed sensorimotor control tasks to provide measures of baseline rCBF. Given the controversy regarding the statistical analysis of PET data, a two-pronged method was utilized: 1) Statistical Parametric Mapping, the state-of-the-art technique that examines rCBF throughout the entire brain, and 2) region of interest analysis, an anatomically-based method for examining rCBF in a limited set of brain regions. Between-group rCBF differences were tested in the four tasks separately and also in the two neuropsychological tasks after subtracting baseline rCBF (i.e., rCBF activation). To characterize the relationship between cerebral perfusion and behavior, correlations were performed between performance and rCBF activation (i.e., task-control) for each group separately, and between rCBF activation and an index of current neuropsychological functioning for the CHI patients. Analyses of each task separately revealed that, compared to controls, CHI patients showed lower rCBF in anterior cingulate cortex (ACC) and subcortical areas. Analyses of rCBF activation data revealed: 1) increases in left inferior frontal gyrus (including Broca's area) and left hippocampus of CHI patients relative to control subjects during the WCST, 2) a negative correlation between task performance and the right hippocampus during the WCST in CHI patients, and 3) correlations between the hippocampus and performance during the CRMT in the CHI patients that were in the opposite direction to those found in the control subjects. These neurofunctional changes are compatible with the structural and cognitive sequelae of CHI First, given a hypothesized role of the ACC in attentional processes, reduced rCBF in this region of CHI patients may relate to the persistent and often subtle difficulties in attention after CHI, whereas rCBF diminutions in subcortical regions may relate to diffuse damage to or deafferentation of subcortical regions in this CHI sample. Second, given similar (although slightly, but not significantly, poorer) performance on the WCST by the CHI patients, increased left prefrontal cortical activity may partially reflect behavioral compensation (e.g., subvocalization to aid memory during the task) and also physiological compensation for inefficiencies in other brain areas (e.g., subcortical regions). Finally, in light of the relatively poorer task performance of CHI patients (non-significant tendency in the WCST but highly significant in the CRMT), differences between the groups in the direction of the correlations between performance/cognition and hippocampal activation may suggest disorganization of hippocampal functioning in CHI patients. This exploratory and descriptive investigation identifies brain structures with post-traumatic changes that may be important to cognition. These results may provide evidence of both behavioral and neurophysiological compensation in patients with severe CHI.enAvailable to the World Wide WebTomography, EmissionBrain chemistryHeadWounds and injuriesThesis