This is a request for an NIMH Senior Scientist Award (K05). The candidate has been funded previously by two K02 Independent Scientist Awards (1994-1999 and 1999-2004) and by a Mentored Research Scientist Development Award (1988-1993). The candidate's long-term objective is to investigate clinical symptoms, cognitive impairments, and structural and functional brain abnormalities in schizophrenia and other psychiatric disorders. She is also committed to the further technical training and development needed to incorporate new advances i n n euroimaging and t he p ostprocessing of neuroimaging data into her research program. Her short-term objective is to apply for a K05 Award to support her research efforts at a crucial time in her career development. The main goal of the Research Plan is to develop further Diffusion Tensor Imaging measures and their application to schizophrenia. Here, frontal-temporal white matter connections will be evaluated, including the uncinate, arcuate, and cingulate fasciculi, where it is predicted that impairments in decision making and in episodic/verbal memory will be associated with uncinate abnormalities, that semantic priming abnormalities will be associated with arcuate abnormalities, and that error detection and self monitoring abnormalities will be associated with cingulate abnormalities. Additionally, the corpus callosum and the anterior limb of the internal capsule will be evaluated, where it is predicted that abnormalities will be associated with interhemispheric abnormalities (Dichotic Listening Fused Rhymed Task) and impairments in verbal and spatial working memory tasks, respectively. Other career enhancement plans include: (1) to develop further shape analysis tools that include more local rather than global measures of shape deformation midline structures including caudate nucleus, thalamus, amygdala-hippocampal complex, and corpus callosum -brain regions likely influenced by neurodevelopmental factors; (2) to develop further cortical thickness measures of the brain, in vivo. Here, longitudinal studies of prefrontal and temporal lobe thickness are planned in patients with first episode schizophrenia, first episode affective psychoses, chronic schizophrenia, and in controls. (3) To develop further automated segmentation methods for identifying small brain regions of interest such as the superior temporal gyms. Non-rigid registration methods that incorporate atlas information will be used, and this method will be extended to other brain regions. (4) To develop further collaborative PTSD studies with Drs. Pitman, Gilbertson, and Shalev, including an examination of nurses deployed in the Gulf War with PTSD; (5) to develop further collaborative studies with Dr. Deutsch investigating brain abnormalities and their association with facial dysmorphology; (6) to develop a new area of investigation with Dr. Gon?alves investigating narrative productions and cognitive anomalies and their association with brain abnormalities in language related areas in William's Syndrome patients. Finally, (7) to test MR and MR DTI protocols on 1.5T and 3T magnets in order to confidently move protocols to the 3T over the next 3 to 5 years.
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