The overall aim of this proposal is to examine the neuropsychological structure of working memory (WM), its neurobiological foundations, and its relationship to other cognitive processes. These studies will address the hypothesis that WM provides a locus where information can be held temporarily and subjected to further cognitive processing, including linguistic and mathematical operations. A unique opportunity to test these hypotheses is found in certain genetic syndromes that are associated with particular strengths and weaknesses in language or math skills. Through the use of standardized and experimental neuropsychological measures, this study will attempt to describe the profiles of WM ability in Williams, Down, and Velocardiofacial syndromes. It is hypothesized that a genetically-based double dissociation will be fond between phonological and visual-spatial working memory, and the syndromic profiles of WM ability will correlate with the broader neuropsychological profiles of these populations. A comparative analysis will be made between WM measures that include an explicit requirement for simultaneous logical processing, versus those that do no, and their respective correlations with other cognitive processes. Functional neuroimaging will be utilized to help elucidate the neurobiological substrate of the cognitive processes under investigation, and to determine whether there is any overlap in the substrates for these putatively-interrelated cognitive processes. The career development plan will extend the candidate's skills in neuropsychological experimentation and neuroimaging methodologies. New skills that will be acquired include expertise in the development of experimental neuropsychological measures, the application of advanced statistical techniques for the analysis of neuropsychological data, and the design and analysis of functional neuroimaging experiments in children. The training environment includes an NICHD-sponsored Mental Retardation Research Center and the """"""""integrative neuroscience"""""""" laboratory of the sponsor, where innovative neuropsychological and neuroimaging applications are routinely developed. The candidate's long-term goal is to pursue a comprehensive understanding o language and learning disabilities, linking neurobiological mechanisms to behavioral manifestations in these common disorders. It is anticipated that such an understanding will allow theoretically-driven therapies to be found in both biological and behavioral domains.
