Visuospatial Cognitive Deficit in Del22q11.2 Syndrome

描述（由申请人提供）：拟议研究的中心目的是调查以下假设：与染色体22q11.2缺失（以下简称22 q）相关的特征性视觉空间和数字认知缺陷是由顶叶皮质功能障碍中表达的异常脑发育引起的。在这种遗传性疾病中，大脑的大部分区域体积减小，包括顶叶皮层，这是一个与视觉空间和数字认知相关的区域。因此，我们假设，视觉空间功能的一些关键方面受到这种异常发展的干扰，这些基本过程的变化的特征将产生的解释，并可能表明治疗，一系列的认知障碍的儿童与22q11.2综合征。虽然一些初步数据与这一假设相一致，但它需要通过假设驱动的认知、大脑结构和功能以及它们之间的动态关系的评估来进行充分的检验。虽然不是这里提出的研究设计的直接目标，这些研究也应该相当清楚的仍然知之甚少的正常视觉空间和数字能力的发展和神经基板之间的关系。22q11.2缺失综合征（包括DiGeorge，Shprintzen和Velocardiofacial Syndrome）现在已知非常普遍（1/4000至5000活产），但目前对其神经认知影响知之甚少。该综合征的特点是基于语言能力的智商（言语智商）比基于视觉空间能力的智商（表现智商）有可靠的优势，尽管智商的总分仍然在70到85的轻度弱智范围内。基于脑发育异常影响顶叶皮层从而干扰视空间认知的正常发育这一假设，我们提出了一个研究方案，其目的是：（1）通过一系列认知测验来表征视空间缺陷;（2）详细说明22 q儿童全脑和下顶叶的体积变化，包括受累组织（即灰色与白色物质）;（3）通过使用扩散张量成像确定可能导致认知功能障碍的白色物质中的任何异常;（4）通过使用功能性磁共振成像（fMRI）直接测量，22 q儿童在执行视觉空间和数字认知加工任务时的后顶叶皮层活动。

DESCRIPTION (provided by applicant): The central aim of the proposed research is to investigate the hypothesis that the characteristic visuospatial and numerical cognition deficits associated with chromosome 22q11.2 deletion (hereafter 22q) result from anomalous brain development that is expressed in parietal cortex dysfunction. In this genetic disease there is reduced volume in much of the brain, including the parietal cortex, an area linked to visuospatial and numerical cognition. Thus we hypothesize that some key aspects of visuospatial function are disturbed by this abnormal development and that a characterization of the changes to these basic processes will generate explanations of, and possibly indicate treatments for, a range of cognitive impairments in children with the 22q11.2 syndrome. Although some preliminary data are consistent with this hypothesis, it requires a full test through hypothesis-driven assessments of cognition, brain structure and function, and the dynamic relationships among them. Although not a direct goal of research designs presented here, these studies should also shed considerable light on the still poorly understood relationship between the development of normal visuospatial and numerical competence and the neural substrates involved. The 22q11.2 deletion syndrome (which encompasses DiGeorge, Shprintzen and Velocardiofacial Syndromes) is now known to be extremely prevalent (1 in 4000 to 5000 live births) and yet very little is currently known about its neurocognitive implications. The syndrome is characterized by a reliable advantage for IQ scores based on verbal abilities (Verbal IQ) over those based on visuospatial abilities (Performance IQ), though full IQ scores are still in the mildly retarded range of 70 to 85. Based on our hypothesis that anomalous brain development affects parietal cortex in such a way as to disturb the normal development of visual-spatial cognition we propose a program of research with the following aims: (1) Characterize the visual-spatial deficit by employing a set of cognitive tests; (2) Specify the volumetric changes in whole brain and inferior parietal lobes of children with 22q in terms of tissue involved (i.e. gray vs. white matter); (3) Determine, through the use of Diffusion Tensor Imaging, any anomalies in white matter that might contribute to cognitive dysfunction; (4) directly measure, through the use of functional Magnetic Resonance Imaging (fMRI), posterior parietal cortex activity in children with 22q as they carry out visuospatial and numerical cognitive processing tasks.