During the present grant period, Project III has contributed significantly to this innovative interdisciplinary program project by using advanced, multifaceted imaging methods to further elucidate the """"""""Functional Neuroanatomy of Williams Syndrome"""""""". For example, prominent volume reductions in the occipital lobe, accompanied by fMRI studies showing reduced activation within areas comprising primary and secondary visual cortex constitute strong candidates for explaining the neural basis of visual-perceptual deficits in this disorder. As consistent with the long-standing history of Williams syndrome as a genetic syndrome with an identifiable social-emotional phenotype, our data also reinforce the notion of an aberrant emotion system in this disorder. In particular, data from our volumetric, voxel-based morphometric and fMRI analyses suggest that brain areas comprising or associated with the limbic system are preserved, disproportionately large, show greater gray matter density and/or are over-activated in Williams syndrome (e.g., amygdala, hippocampus, anterior cingulate, superior temporal gyrus, insular cortex). In the next project period, we plan to more specifically characterize the WS neurofunctional phenotype using high-field (3T) structural, functional and diffusion tensor magnetic resonance imaging (MRI), advanced analytical methods including new 3-D cortical and subcortical mapping and shape analyses, and recruitment of key comparison groups. These imaging analyses will directly address the brain basis of the fascinating cognitive profile associated with WS, in particular as pertaining to the neural basis of visual and emotion processing. Results from Project III will be highly relevant to the multi-level interdisciplinary research approach characterizing this program project. In particular, we propose direct linkages to the neuropsychological and behavioral data collected in Project I, electrophysiological (ERP) information derived from Project II, neuroanatomical data from Project IV, and molecular genetic analyses from Projects V. Projects V.
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