BRAIN STRUCTURE, FUNCTION IN CHILDREN, ADOLESCENTS, YOUNG ADULTS AT RISK FOR HD

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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Huntington's disease (HD) is an autosomal dominant disease manifested in a triad of cognitive, psychiatric, and motor signs and symptoms. This disease has classically been conceptualized as a "neurodegenerative disease of the striatum". However, recent evidence challenges this concept. First, several lines of evidence have suggested that there may be an important developmental component to the etiology of this disease. For example, studies show that subjects who are gene positive for HD but have not yet manifested the illness (pre-HD subjects) have significant changes in the structure of their brain, specifically decreased volume of cerebral white matter and increased volume of cerebral cortex. These changes support the notion that the brain of these subjects did not develop properly, although an alternative explanation is that degeneration begins decades before manifest onset of the disease. Second, the changes that are seen in the brain of pre-HD subjects are most prominent in extra-triatal regions of the brain - the cerebral white matter and the cerebral gray matter. In an effort to better understand the developmental aspects of this brain disease, the current study proposes to evaluate brain structure and function in children, adolescents, and young adults (ages 6-25) who are at risk for developing HD. Brain structure will be evaluated using magnetic resonance imaging (MRI) with quantitative measures of the entire brain, cerebral cortex, as well as white matter integrity via Diffusion Tensor Imaging. Brain function will be assessed by cognitive tests, neurological evaluation, and behavioral assessment. Subjects that are gene positive will be compared to subjects who are gene negative and to matched healthy controls. Changes in brain structure and/or function in the gene positive group would lend significant support to the notion that this disease has an important developmental component.