Visuospatial Cognitive Deficit in Del22q11.2 Syndrome

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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.