Neuroimaging studies of the autism spectrum disorders (ASD) have recently yielded several replicable findings that implicate abnormalities in cortical connectivity in the pathogensis of this family of disorders. On the basis of structural MRI (sMRI) and head circumference (HC) studies, it is now well established that brain size is enlarged in autism. Most evidence also indicates that white matter volume is disproportionately enlarged compared to gray matter volume. It is not known how this enlargement affects brain function and contributes to the symptoms of autism. However, clues might be provided by new data from functional MRI (fMRI) and diffusion tensor imaging (DTI) studies of the ASDs. Several fMRI studies have shown alterations in """"""""functional connectivity"""""""" in the ASDs. While there is little published DTI work, we recently completed a study that found reduced white matter fiber coherence in several key brain areas, including a set interconnected areas that each have been implicated in the pathophysiology of autism by numerous fMRI studies - the fusiform gyrus and the superior temporal gyrus. These three neuroimaging techniques (sMRI, DTI, fMRI) have never been combined in a study of a single sample. Individually, each has interpretive limitations. Integrating the three of them in one study promises to yield a much deeper characterization and understanding of the putative connectivity deficits in the ASDs. In this project, we propose to characterize cerebral white matter abnormalities in the ASDs, both in terms of alteration in its total volume using sMRI, and through the use of DTI. We will correlate this anatomical information with fMRI functional connectivity data to look at the relationship between volume, quantitative indices of white matter fiber coherence and dynamic measurements of functional connectivity. All participants will be recruited into our genetics project as well (Project 5), which is testing for functional variants in the Contactin and Contactin Associated family of genes implicated axon pathfinding and thus there may be opportunities for evaluating specific relationships between genetic abnormalities and neuroimaging data. This project addresses a number of elements highlighted in the NIH Autism Research Matrix, including the use of a developmentally characterized cohort, testing of brain x behavioral relationships, and characterizing brain features that can be related to a specific genes.

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Yale University
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