Numerical Deficits Across Multiple Genetic Disorders

多种遗传疾病的数值缺陷

• 批准号: 7119240
• 负责人: TONY J SIMON
• 金额: $ 52.11万
• 依托单位: UNIVERSITY OF CALIFORNIA AT DAVIS
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-02-01 至 2008-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7119240
• 关键词: Turner' s syndrome; Williams syndrome; adolescence (12-20); age difference; behavior test; brain; brain imaging /visualization /scanning; child (0-11); children; clinical research; cognition; fragile X syndromes; functional magnetic resonance imaging; gender difference; genetic disorder; human subject; neuropsychological tests; parietal lobe /cortex

DESCRIPTION (provided by applicant): The central aim of the proposed research is to investigate whether there is a common basis for the numerical cognition deficits associated with three neurogenetic disorders: Turner, Williams, and full mutation fragile X syndromes. Despite many differences, numerical deficits have been consistently reported in individuals with Turner, Williams, full mutation fragile X, and 22q11.2 deletion (velocardiofacial/DiGeorge) syndromes, among others. The investigators hypothesize that some key aspects of visuospatial function are disturbed in each of these syndromes, and characterization of these basic processes will generate explanations of, and possibly indicate treatments for, these numerical deficits. On the other hand, the differences among these genetic syndromes will allow the investigators to control for a range of critical factors such as intelligence level, brain volume, cardiac status, and other cognitive performance domains. This project aims to study seven to fourteen year old children with Williams, Turner, and full mutation fragile X syndromes in parallel with a study of 22q11.2 deletion syndrome children already being carried out by the principal investigator. This will constitute the first parallel study of children with all of these disorders using the same methodology. Thus it has the potential to reveal critical information about a putative "common pathway" for foundational numerical cognitive competence. Little is known about why a set of neurogenetic disorders that produce such different physical and intellectual outcomes should share what appears to be a common deficit in the numerical cognition domain. The investigators' hypothesis is that the disorders all create some form of anomalous in brain development that affects the parietal lobes, as well as other brain areas, in such a way as to disturb the normal development of visual/spatial cognition. Therefore, the investigators propose a program of research in three genetic disorders: Turner, Williams, full mutation fragile X syndromes with the following aims: (1) Characterize the cognitive deficit with performance tests; (2) Specify the volumetric changes in brains of children with these disorders; (3) Determine, via diffusion tensor imaging, white matter anomalies that might contribute to cognitive dysfunction; and (4) Directly measure, via functional magnetic resonance imaging (fMRI), cortical activity as children attempt visuospatial and numerical cognition tasks. The investigators expect that the results of these studies will provide the first extensive explanation of the similarities and/or differences in foundational numerical cognitive processes that exist among these different disorders. Findings are likely to indicate critical neurocognitive factors in the development of normal and disturbed early numerical ability. It should be possible to use these results to develop interventions for children with numerical disabilities and improved teaching methods in the numerical domain for typically developing children.

描述（由申请人提供）：拟议研究的核心目的是研究与三种神经遗传疾病相关的数值认知缺陷是否存在共同基础：Turner，Williams和Full Stumation脆弱的X综合征。 尽管有很多差异，但在特纳，威廉姆斯，全突变脆弱X和22q11.2缺失（速度质体/digeorge）综合征等人等人等人等人等人等人等人等人等人等人等人等人等人等人等人等人等人等人等人等人等人综合症等人等人等人等综合症中始终如一地报道了数值不足。 研究人员假设在这些综合征中，视觉空间功能的某些关键方面受到干扰，这些基本过程的表征将产生对这些数值缺陷的解释，甚至可能表明治疗方法。 另一方面，这些遗传综合症之间的差异将使研究人员能够控制一系列关键因素，例如智力水平，大脑体积，心脏状况和其他认知性能领域。 该项目的目的是研究七至十四岁的威廉姆斯，特纳和全突变易碎X综合症的儿童，并与主要研究人员已经进行了22q11.2缺失综合征儿童的研究。 这将构成使用相同方法对所有这些疾病的儿童进行的首次平行研究。 因此，它有可能揭示有关基础数值认知能力的假定“共同途径”的关键信息。 关于为什么产生如此不同的身体和智力结果的一组神经遗传疾病的原因知之甚少，应该共享数值认知领域中常见的赤字。 研究者的假设是，这些疾病都在大脑发育中创造了某种形式的异常形式，从而影响顶叶以及其他大脑区域，以干扰视觉/空间认知的正常发展。 因此，研究人员提出了三种遗传疾病的研究计划：特纳，威廉姆斯，全突变易碎X综合征，其目的是：（1）通过绩效测试表征认知不足； （2）指定这些疾病儿童的大脑的体积变化； （3）通过扩散张量成像确定可能导致认知功能障碍的白质异常； （4）通过功能磁共振成像（fMRI）直接测量皮层活动，因为儿童尝试了视觉空间和数值认知任务。 研究人员预计，这些研究的结果将为这些不同疾病中存在的基础数值认知过程的相似性和/或差异提供第一个广泛的解释。 发现可能表明在正常和不受欢迎的早期数值能力的发展中的关键神经认知因素。 应该使用这些结果来为数值残疾儿童开发干预措施，并改善了通常发育中儿童的数值领域的教学方法。