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

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 亨廷顿病(HD)是一种常染色体显性遗传病，表现为认知、精神和运动三重体征和症状。这种疾病被经典地定义为“纹状体神经退行性疾病”。然而，最近的证据对这一概念提出了挑战。首先，有几条证据表明，这种疾病的病因可能有一个重要的发育因素。例如，研究表明，HD基因阳性但尚未表现出疾病的受试者(HD前受试者)的大脑结构有显著变化，特别是大脑白质体积减少和大脑皮层体积增加。这些变化支持这样一种观点，即这些受试者的大脑没有正常发育，尽管另一种解释是，变性在疾病明显发作前几十年就开始了。其次，HD前受试者的大脑中所见的变化在大脑的产外区域--大脑白质和大脑灰质--最为突出。 为了更好地了解这种大脑疾病的发育方面，目前的研究建议评估有患HD风险的儿童、青少年和年轻人(6-25岁)的大脑结构和功能。大脑结构将使用磁共振成像(MRI)进行评估，通过扩散张量成像对整个大脑、大脑皮层和脑白质完整性进行定量测量。大脑功能将通过认知测试、神经评估和行为评估进行评估。基因阳性的受试者将与基因阴性的受试者进行比较，并与匹配的健康对照组进行比较。基因阳性组的大脑结构和/或功能的变化将极大地支持这种疾病具有重要发育成分的观点。

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.