Visuospatial Cognitive Deficit in Del22q11.2 Syndrome

描述(由申请人提供)：拟议研究的中心目标是调查与染色体22q11.2缺失相关的特征性视觉空间和数字认知缺陷(以下简称22q)是由于大脑发育异常导致顶叶皮质功能障碍的假说。在这种遗传病中，大脑的大部分区域，包括与视觉空间和数字认知有关的顶叶皮质，体积都缩小了。因此，我们假设视觉空间功能的某些关键方面受到这种异常发育的干扰，对这些基本过程的变化的特征将对22q11.2综合征儿童的一系列认知障碍产生解释，并可能指示治疗。尽管一些初步数据与这一假说一致，但它需要通过假说驱动的认知、大脑结构和功能以及它们之间的动态关系的评估进行全面测试。尽管这些研究不是这里提出的研究设计的直接目标，但这些研究也应该对正常视觉空间和数字能力的发展与所涉及的神经底物之间的关系提供相当大的帮助。22q11.2缺失综合征(包括DiGeorge综合征、Shprint tzen综合征和VelHearofacial综合征)现在非常普遍(每4000到5000名活产儿中就有一例)，但目前对其神经认知影响知之甚少。这种综合症的特点是，基于言语能力(言语智商)的智商分数比基于视觉空间能力(操作智商)的智商分数有可靠的优势，尽管完整的智商分数仍在70至85的轻度迟缓范围内。根据我们的假设，大脑发育异常会影响顶叶皮质，从而干扰视觉空间认知的正常发展，我们提出了一项研究计划，目的如下：(1)通过一系列认知测试来表征视觉空间缺陷；(2)根据受累组织(即灰质与白质)来确定22q儿童全脑和顶下叶的体积变化；(3)通过扩散张量成像来确定白质中任何可能导致认知功能障碍的异常；(4)在进行视觉空间和数字认知加工任务时，通过功能磁共振成像(FMRI)直接测量22q儿童的顶叶后皮质活动。

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.