This revised application for an academic career development award for clinical research (K23) outlines a program for training and research focusing on the evaluation and treatment of neuropsychiatric disorders secondary to traumatic brain injury (TBI). The particular focus of the research is on prefrontal dysfunction, as the frontal lobes are the most common site of lesion in TBI. This can result in impaired executive cognitive function, mood disorders such as depression, and behavioral changes such as apathy, impulsivity and aggression. Over 2,000,000 cases of TBI occur per year in the US, resulting in significant long term disability. These patients often present to psychiatry, but there are no clear guidelines on treatment of these neurobehavioral disorders. Frontal dysfunction has been shown to play a role in other psychiatric illnesses as well, such that research into effective treatments to improve frontal function could be broadly beneficial. There is a significant need to train psychiatric clinical researchers in this area. Current technologies in MRI, including functional MRI and techniques to assess white matter such as DTI (diffusion tensor imaging) have the potential to further understanding of this brain disorder. There are two primary aims of the proposed career development plan. First, the PI will learn to utilize state of the art structural and functional imaging methods of MRI, along with neurophysiological (oculomotor studies) and neuropsychological procedures, for assessing effects of frontal lobe injury. This will allow for a thorough delineation of the anatomic and neurobehavioral sequelae of TBI. Second, the PI will develop expertise in pharmacologic clinical trials in this special population. The lack of effective treatments to improve quality of life underscores the need to train psychiatric researchers with the necessary skills to fill this void. Further, the need for neuropsychiatric investigators trained to evaluate the cognition-enhancing properties of new pharmacotherapies will be very great in coming years. During the proposed career development program, the PI will utilize MRI and neurobehavioral assessments in a controlled clinical trial with amantadine in patients with frontal lobe dysfunction following TBI. The PI will learn to integrate imaging findings into clinical trials, developing guidelines for selection of therapeutic interventions. This application is designed to enable the candidate to transition into an independent clinical investigator with the necessary research skills needed to study neuropathology, outcomes, and interventions.
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