Brain Structure and Function in Children at Risk for Huntington's Disease

有亨廷顿病风险的儿童的大脑结构和功能

• 批准号: 8251272
• 负责人: PEGGY C NOPOULOS
• 金额: $ 3.51万
• 依托单位: UNIVERSITY OF IOWA
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-08-15 至 2012-08-14
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8251272
• 关键词: 12 year old; Address; Adult; Age; Aggressive behavior; Attention; Behavior assessment; Behavioral; Birth; Bradykinesia; Brain; Brain Diseases; Categories; Cerebellum; Cerebral cortex; Cerebrum; Child; Cognitive; Corpus striatum structure; Development; Diagnosis; Disease; Disease Pathway; Drug or chemical Tissue Distribution; Etiology; Evaluation; Female; Gait; Gender; Genes; Growth; Head circumference; Health; Huntington Disease; Impulsivity; Intelligence; Intervention; Laboratories; Lead; Magnetic Resonance Imaging; Measures; Medial; Modeling; Motor; Neurodegenerative Disorders; Neurodevelopmental Disorder; Neurologic; Parents; Pathway interactions; Pattern; Performance; Prefrontal Cortex; Process; Protocols documentation; Research; Risk; Signs and Symptoms; Structure; Structure-Activity Relationship; Symptoms; Techniques; Testing; Thalamic structure; Triad Acrylic Resin; behavior measurement; brain morphology; brain tissue; caudate nucleus; design; disorder risk; executive function; externalizing behavior; frontal lobe; gray matter; imaging modality; male; neurodevelopment; oculomotor; prevent; putamen; white matter

DESCRIPTION (provided by applicant): 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. Several lines of evidence have suggested that in addition to the degenerative process, there may be an important developmental component to the etiology of this disease. For example, studies in our laboratory show that adult subjects who are gene positive for HD but have not yet manifested the illness (presymptomatic gene carriers or PSGCs) have significant changes in the structure of their brain, specifically, decreased intracranial volume, decreased volume of cerebral white matter, and increased volume of cerebral cortex. These changes support the possibility that these subjects may have had abnormal brain development. A growing body of research evaluating PSGCs compared to Non-Gene Carriers (NGCs) supports the notion that PSGCs not only have structural brain changes as described above, they also have subtle but significant deficits in cognitive, motor, and psychiatric symptoms. Thus, although brain changes and symptoms are present prior to diagnosis, when do they begin? Is it possible that these changes are present from birth and then progress during the course of the disease process? 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 (ages 6-12) who are at risk for developing HD. Brain structure will be evaluated using Magnetic Resonance Imaging (MRI) with quantitative measures of the entire brain, including general measures such as cerebrum and cerebellar volume as well as regional measures such as cerebral cortex, cerebral white matter, and subcortical nuclei (caudate, putamen, thalamus). Brain function will be assessed by cognitive tests, neurologic evaluation, and behavioral assessment. Subjects that are PSGCs will be compared to subjects who are NGCs. Changes in brain structure and/or function in the PSGCs would lend significant support to the notion that this disease has an important developmental component. If proven, a developmental model of HD could identify disease pathways that are dysfunctional prior to degeneration. This could lead to intervention techniques that could target and protect these pathways, preventing the disease. PUBLIC HEALTH RELEVANCE: This is a revised application for the proposal "Brain Structure and Function in Children at Risk for Huntington's Disease (1RO1 NS055903-01). The study is designed to evaluate the brain structure (using Magnetic Resonance Imaging) and brain function (using cognitive and behavioral assessment) of children (ages 6 - 12 years) at risk for Huntington's Disease. 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.

描述（由申请人提供）：亨廷顿氏病（HD）是一种常染色体显性疾病，体现在认知，精神病和运动体征和症状的三合会中。这种疾病在经典上被概念化为“纹状体的神经退行性疾病”。但是，最近的证据挑战了这一概念。几条证据表明，除了退化过程外，该疾病的病因可能还有一个重要的发展组成部分。例如，在我们的实验室中的研究表明，尚未表现出疾病的基因基因呈阳性的成年受试者（预症状基因携带者或PSGC）在大脑的结构上有重大变化，具体是颅内体积减少，体积减少，减少了体积脑白质和脑皮质体积增加。这些变化支持这些受试者可能患有异常大脑发育的可能性。与非基因携带者（NGC）相比，评估PSGC的一系列研究支持了以下观点：PSGC不仅具有如上所述的结构性大脑变化，而且在认知，运动和精神病症状上也有细微的缺陷。因此，尽管诊断之前存在大脑变化和症状，但它们何时开始？这些变化是否可能从出生开始，然后在疾病过程中进展？为了更好地了解这种脑部疾病的发育方面，当前的研究建议评估有患HD风险的儿童（6-12岁）的大脑结构和功能。将使用磁共振成像（MRI）对大脑结构进行定量测量，包括整个大脑的定量度量，包括一般措施，例如大脑和小脑体积，以及区域测量，例如脑皮质，大脑白质和亚皮层核（Caudate，Caudate，Caudate，Putamen，Putamen，Putamen，Putamen ，丘脑）。大脑功能将通过认知测试，神经系统评估和行为评估来评估。将PSGC的受试者与NGC的受试者进行比较。 PSGC中大脑结构和/或功能的变化将为这种疾病具有重要发育成分的观念提供重大支持。如果经过证实，HD的发展模型可以鉴定出退化前功能失调的疾病途径。这可能导致可以针对和保护这些途径的干预技术，从而阻止疾病。公共卫生相关性：这是提案的修订申请。使用亨廷顿氏病的风险的儿童（6至12岁）的认知和行为评估。