WILLIAMS SYNDROME--NEUROCOGNITIVE CHARACTERIZATION

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Our basic goal is to understand the biological bases of language and other cognitive functions. Williams syndrome (WMS) is a genetically-based neurodevelopmental disorder involving mental retardation that displays dissociations both within and across domains: (a) severe cognitive deficits but remarkably spared language; and (b) extreme disorders in spatial cognition but excellent facial processing. These dissociations in higher cognitive functioning make WMS an invaluable paradigm for the study of brain and behavior relationships and the mapping of brain and behavior phenotypes to the genome. Neurocognitive Characterization of WMS: Consistency and Variability. The crucial starting point of this Program Project lies in obtaining cognitive measures of each of the subjects, measured in the context of our existing profile of asymmetric cognitive functioning that distinguishes WMS. Using a Basic Neurocognitive Battery, we characterize the attributes that are relatively stable across all WMS subjects as well as the variability of these attributes; this will allow us to link patterns of co-occurrence across domains of cognitive functioning and across levels from cognition to brain and, ultimately, to the genome. Experiments on Processing Bases of Neurocognitive Dissociations. With a succession of highly focused small group studies, we investigate the basis of the unique cognitive architecture found in WMS. In the domain of language, we examine the integrity of specific aspects of grammatical and semantic processing. In the domain of visual-based functioning, we examine a bases for the extremely impaired spatial processing coupled with the remarkably good facial processing in WMS. Mapping Between Cognition and Brain Bases. Studies of neurophysiology, neuromorphology, and brain cytoarchitectonics conducted by laboratories in this Program Project suggest that neural systems subserving cognitive functions in WMS are different from normal. We will apply bi-directionally motivated analyses of brain-behavior relationships in order to elucidate the neural systems which underlie language and visual-spatial functioning. Mapping phenotype to Genotype in WMS. Our ultimate goal is to begin the search for links between the WMS phenotype, with its associated variability, and the genome. We will pursue this goal through a mapping between phenotypic attributes - - at the levels of cognitive domains, brain function, brain structure, and medical presentation -- and differential patterns of deletion on chromosome 7 manifested by our WMS population. Relationships across levels may shed valuable light on the genetic foundations of the asymmetric neurocognitive profile of WMS. In general, our studies with this genetically-based neurodevelopmental disorder will provide new opportunities to explore some of the central issues of cognitive neuroscience that tie cognitive functions to brain organization, as well as to their genetic bases.