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.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Specialized Center (P50)
Project #
5P50MH081756-05
Application #
8376560
Study Section
Special Emphasis Panel (ZHD1-MRG-C)
Project Start
Project End
2014-03-31
Budget Start
2012-04-27
Budget End
2013-03-31
Support Year
5
Fiscal Year
2012
Total Cost
$315,268
Indirect Cost
$76,369
Name
Yale University
Department
Type
DUNS #
043207562
City
New Haven
State
CT
Country
United States
Zip Code
06520
Chawarska, Katarzyna; Ye, Saier; Shic, Frederick et al. (2016) Multilevel Differences in Spontaneous Social Attention in Toddlers With Autism Spectrum Disorder. Child Dev 87:543-57
Shic, Frederick (2016) Eye Tracking as a Behavioral Biomarker for Psychiatric Conditions: The Road Ahead. J Am Acad Child Adolesc Psychiatry 55:267-8
Szatmari, Peter; Chawarska, Katarzyna; Dawson, Geraldine et al. (2016) Prospective Longitudinal Studies of Infant Siblings of Children With Autism: Lessons Learned and Future Directions. J Am Acad Child Adolesc Psychiatry 55:179-87
Kim, So Hyun; Macari, Suzanne; Koller, Judah et al. (2015) Examining the phenotypic heterogeneity of early Autism Spectrum Disorder: subtypes and short-term outcomes. J Child Psychol Psychiatry :
Klintwall, Lars; Macari, Suzanne; Eikeseth, Svein et al. (2015) Interest level in 2-year-olds with autism spectrum disorder predicts rate of verbal, nonverbal, and adaptive skill acquisition. Autism 19:925-33
Chawarska, Katarzyna; Chang, Joseph; Campbell, Daniel (2015) In Reply. J Am Acad Child Adolesc Psychiatry 54:958-9
Chawarska, Katarzyna; Shic, Frederick; Macari, Suzanne et al. (2014) 18-month predictors of later outcomes in younger siblings of children with autism spectrum disorder: a baby siblings research consortium study. J Am Acad Child Adolesc Psychiatry 53:1317-1327.e1
Paul, Rhea; Loomis, Rebecca; Chawarska, Katarzyna (2014) Adaptive behavior in toddlers under two with autism spectrum disorders. J Autism Dev Disord 44:264-70
Shic, Frederick; Macari, Suzanne; Chawarska, Katarzyna (2014) Speech disturbs face scanning in 6-month-old infants who develop autism spectrum disorder. Biol Psychiatry 75:231-7
Ventola, Pamela; Saulnier, Celine A; Steinberg, Elizabeth et al. (2014) Early-emerging social adaptive skills in toddlers with autism spectrum disorders: an item analysis. J Autism Dev Disord 44:283-93

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