Numerical Deficits Across Multiple Genetic Disorders

描述(由申请人提供)：拟议研究的中心目标是调查与三种神经遗传障碍相关的数字认知缺陷是否有共同的基础：特纳、威廉姆斯和全突变脆性X综合征。尽管有许多不同之处，但在Turner、Williams、全突变脆性X和22q11.2缺失(瓣膜面部/DiGeorge)综合征等患者中，数字缺陷的报告一直存在。研究人员假设，在这些综合征中，视觉空间功能的一些关键方面受到了干扰，这些基本过程的特征将产生对这些数字缺陷的解释，并可能指示对其进行治疗。另一方面，这些遗传综合征之间的差异将使研究人员能够控制一系列关键因素，如智力水平、脑容量、心脏状态和其他认知表现领域。 该项目旨在研究患有Williams、Turner和全突变脆性X综合征的7至14岁儿童，同时首席研究员已经对22q11.2缺失综合征儿童进行了研究。这将是使用相同方法对所有这些障碍的儿童进行的第一项平行研究。因此，它有可能揭示关于基础数字认知能力的假定的“共同途径”的关键信息。很少有人知道，为什么一组神经遗传疾病会产生如此不同的身体和智力结果，但它们在数字认知领域似乎存在共同的缺陷。研究人员的假设是，这些障碍都会在大脑发育中造成某种形式的异常，影响顶叶以及其他大脑区域，从而扰乱视觉/空间认知的正常发展。因此，研究人员提出了一项针对三种遗传性疾病的研究计划：特纳、威廉姆斯、全突变脆性X综合征，其目标如下：(1)通过操作测试确定认知缺陷的特征；(2)确定患有这些疾病的儿童大脑的体积变化；(3)通过扩散张量成像确定可能导致认知功能障碍的脑白质异常；以及(4)通过功能磁共振成像(FMRI)直接测量儿童在尝试视觉空间和数字认知任务时的皮质活动。研究人员预计，这些研究的结果将为这些不同障碍之间在基础数字认知过程中存在的相似和/或差异提供第一个广泛的解释。研究结果可能表明，关键的神经认知因素在正常和紊乱的早期数字能力的发展中起作用。应该可以利用这些结果为数字残疾儿童制定干预措施，并为典型发育儿童改进数字领域的教学方法。

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.