Numerical Deficits Across Multiple Genetic Disorders

描述（由申请人提供）：拟议研究的中心目的是调查与三种神经遗传性疾病（特纳、威廉姆斯和全突变脆性X综合征）相关的数字认知缺陷是否存在共同基础。 尽管存在许多差异，但在Turner、威廉姆斯、脆性X染色体完全突变和22 q11.2缺失（velocardiofacial/DiGeorge）综合征患者中，一直有数字缺陷的报道。 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，并可能指示这些数字缺陷的治疗。 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7至14岁的儿童与威廉姆斯，特纳，和完全突变脆性X综合征的研究平行的22 q11.2缺失综合征的儿童已经进行的主要研究者。 这将构成第一个使用相同方法对所有这些疾病儿童进行的平行研究。 因此，它有可能揭示一个假定的“共同途径”的基础数字认知能力的关键信息。 对于为什么一组产生如此不同的身体和智力结果的神经遗传性疾病应该共享似乎是数字认知领域的共同缺陷，人们知之甚少。 研究人员的假设是，这些疾病都会在大脑发育中产生某种形式的异常，影响顶叶以及其他大脑区域，从而干扰视觉/空间认知的正常发育。 因此，研究人员提出了一个研究计划，在三个遗传疾病：特纳，威廉姆斯，全突变脆性X综合征与以下目标：（1）表征认知缺陷与性能测试;（2）指定的体积变化，在儿童的大脑与这些疾病;（3）确定，通过扩散张量成像，白色物质异常，可能有助于认知功能障碍;（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层活动。 研究人员预计，这些研究的结果将首次广泛解释这些不同疾病之间存在的基础数字认知过程的相似性和/或差异。 研究结果可能表明，在正常和干扰的早期数字能力的发展中，关键的神经认知因素。 应该可以利用这些结果来制定干预措施，为数字残疾儿童和改善教学方法，在数字领域的典型发展中国家的儿童。

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.