Attention deficits are widespread and disabling after significant traumatic brain injury (TBI). Controversy remains about how to measure attention deficits in this population, as well as their appropriate treatment. Prior research suggest that prefrontal dysfunction, related to focal injury and denervation resulting from diffuse axonal injury, is central to the attention deficits seen in this population. Much of this prefrontal pathology is """"""""invisible"""""""" to studies of brain structure. The proposed research intends to use functional imaging to explore the role of prefrontal cortex in the attention deficits seen after TBI, and to examine changes in prefrontal function resulting from drug treatment, as they relate to drug-related changes in behavioral performance. Subjects with TBI will be recruited for a previously-funded study of drug treatments of attention deficits. In that study, subjects will receive methylphenidate and placebo in a cross- over design, while extensive data are collected on many different aspects of attentional functions in both drug conditions. Subsequently, 20 of the subjects with TBI and 20 control subjects will be recruited to participate in this proposed study. Subjects will receive 2 fMRI scans (one on methylphenidate and one on placebo, blinded and in counterbalanced order). In each scanning session, several measures will be taken, including: resting cerebral blood flow to prefrontal cortical regions; cerebral blood flow in these same regions during a sustained attention tasks; and BOLD activation measures within the context of a distraction paradigm. Resting blood flow measures will be used to predict severity of attention deficits. Changes in blood flow and activation (off drug) in response to the 2 probe tasks will be used to predict behavioral performance in those tasks. Finally, drug effects on blood flow and activation will be correlated with drug effects on performance to examine the mechanism of action of the drug. Collectively, these results will advance the theoretical understanding of the nature of TBI-associated attention deficits and the possible mechanism of action of therapeutically useful drugs.
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