fMRI study of developing medial prefrontal cortical function in pediatric OCD

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DESCRIPTION (provided by applicant): Obsessive compulsive disorder (OCD) is a common and disabling psychiatric illness that is often refractory to available treatments. The onset of OCD during childhood and adolescence suggests that atypical brain maturation may underlie the disorder, and mandates the study of pediatric patients to define a "developmental window" at which therapeutic interventions may be directed to abort progression to chronic illness. To probe the mechanisms of neurobehavioral development relevant to pediatric OCD, the Candidate has begun work in functional magnetic resonance imaging (fMRI) and child psychiatry. Addressing the need for additional skill acquisition, a 5-year career development plan will provide an essential grounding in 1) pediatric neuroimaging, 2) developmental neuroscience, and 3) clinical research skills. Career development will be shaped by a research project designed to extend preliminary findings of cortico-striatal-pallidalthalamic (CSPT) involvement in pediatric OCD by testing for hypothesized maturational abnormalities of CSPT function and structure in young patients. Hyperactive response of CSPT elements - the rostral anterior cingulate cortex, posterior medial frontal cortex, and dorsolateral prefrontal cortex - occurs in adult OCD when patients commit errors on simple cognitive tasks. In addition, excessive white matter connectivity within CSPT circuitry has been demonstrated in adult OCD, and could be driven by hyperactivity of CSPT functions, such as the response to errors. In the proposed study, error-processing function and white matter coherence of CSPT circuitry will be studied across prepubertal, pubertal and adolescent stages of development to begin to elucidate how CSPT abnormalities emerge and progress during the early course of OCD. Outstanding departmental support; collective expertise in fMRI, pediatric OCD, cognitive-emotional development, and clinical research; and, opportunities for future translational research make the University of Michigan an ideal environment for this award. PUBLIC HEALTH RELEVANCE: OCD affects millions of American children, and understanding the abnormalities of brain maturation associated with early onset illness will help to foster improved understanding, treatment, and eventually, prevention of this disabling condition.