This is a revised application for a Mentored Clinical Scientist Development Award (K08). The candidate proposes a combination of didactics, individual meetings with mentors and consultants, and the implementation of a research study to develop an expertise in neurodevelopmental models of functional and effective connectivity. The purpose of this training grant is to obtain the skills and experience necessary to become competent in statistical models to study connectivity in fMRI and diffusion tensor imaging (DTI) and to develop the skills to integrate these imaging modalities. The models will include the initial use of exploratory multivariate techniques, followed by structural equation modeling. These models will be used to study typical neurodevelopment from late childhood through adolescence and schizophrenia in children and adolescents. The candidate has a background in electrical engineering and clinical training in the phenomenology of schizophrenia and structural brain imaging. However, her focus in engineering was in the design of analog electronic circuits for bioengineering applications and she requires retooling in digital signal processing and statistical paradigms to measure functional and effective connectivity. She is also proposing additional training in neuroanatomy and cognitive developmental neuroscience related to the prefrontal cortex and its connections with other brain regions. This training will be integrated into a neurodevelopmental study of the functional connectivity and microstructure of nodes involved in a spatial working memory circuit. The study will involve imaging (fMRI and DTI) first in two groups (n=15) of typically developing children (10- 12 y.o.) and young adults (18-19 y.o.), then in patients with schizophrenia (n=36) compared to a matched sample who are between the ages of 10 and 19. The candidate has an organized program of training that includes coursework in imaging, digital signal processing, statistics, neuroanatomy, cognitive developmental neuroscience, and the bioethics of research. She will meet regularly with her sponsor and consultants, who have a track record of excellence in research and will assist with her training and career development. She has also set forth a timeline for the completion of the projects. Her long term goals are to use the inherent plasticity of the brain to study intervention strategies that bring about a protective 'rewiring' in children at risk. ? ?
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