MRI Longitudinal Study of the Cerebral Cortex through Early Childhood in Autism

Cynthia Schumann, Ph.D.1, Graham Wideman1, Cynthia Carter Barnes, Ph.D.1, Trudy Kao1, Ruth Carper, Ph.D.1, Cinnamon Bloss, Ph.D.2, Don Hagler, Ph.D.3, Catherine Lord, Ph.D.4, Nicholas Schork, Ph.D.2, and Eric Courchesne, Ph.D.1. (1) Neurosciences, University of California, San Diego, 8110 La Jolla Shores Dr. Suite 201, La Jolla, CA 92037, (2) Molecular and Experimental Medicine, Scripps Research Institute, (3) Radiology, University of California, San Diego, (4) University of Michigan Autism and Communication Disorders Center, MI

Background: A recent hypothesis has emerged that toddlers with autism undergo abnormal neuroanatomical development that includes a period of early brain overgrowth. Cross-sectional MRI and head circumference studies suggest that the overgrowth occurs before the diagnosis is typically given in the fourth year of life. MRI studies that further partition the cerebrum into lobes find that the more anterior and higher association areas exhibit the highest degree of enlargement.

Objectives: We carried out a longitudinal MRI study of the cerebral cortex in toddlers 18 months to five years of age in order to 1) identify aberrant growth patterns in specific regions of the cerebral cortex that may contribute to early enlargement and 2) correlate behavioral and clinical features with affected cortical regions in toddlers with autism.

Methods: Clinical evaluations and MRI scans (total=220) were collected at ~12 month intervals from ~18-60 months from typically-developing toddlers (n=48) and those with provisional autism spectrum disorder (n=43). Final diagnosis was given at ~4 years of age upon completion of the study with the Autism Diagnostic Observation Schedule (ADOS) and Autism Diagnostic Interview-Revised (ADI-R). For each T1-W MRI, a semi-manual segmentation program was used to delineate cerebral gray and white matter and then the program Freesurfer further parcellated the cortex into subregions.

Results: Preliminary regression analyses revealed significant enlargement in cerebral, frontal, and temporal gray matter volumes (p<.05) in toddlers with autism relative to typically-developing controls.

Conclusions: In this first longitudinal MRI study of toddlers with autism, growth trajectories of total cerebral, frontal and temporal gray were significantly different from typical toddlers. Aberrant growth patterns observed in longitudinal MRI’s at early ages provide a developmental anatomical phenotype for autism spectrum disorder.



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