Altered gray-white matter boundary in toddlers at risk for autism relates to later diagnosis of Autism Spectrum Disorder

Background: Recent neuroimaging studies have highlighted differences in cerebral maturation in individuals with autism spectrum disorder (ASD) in comparison to typical development. For instance, the sharpness of the gray-white matter boundary is decreased in adults with ASD. To determine how the gray-white matter boundary integrity relates to early ASD phenotypes, we used a regional structural MRI index called the gray-white matter contrast (GWC) on a sample of toddlers with a hereditary high risk for ASD. Methods: We used a surface-based approach to compute vertex-wise GWC in a longitudinal cohort of toddlers at high-risk for ASD imaged twice between 12 and 24 months (n=20). A full clinical assessment of ASD-related symptoms was performed in conjunction with imaging and again at three years of age for diagnostic outcome. Three outcome groups were defined (ASD, n=9; typical development, n=8; non-typical development, n=3).Results: ASD diagnostic outcome at age 3 was associated with widespread increases in GWC between age 12 and 24 months. Many cortical regions were affected, including regions implicated in social processing and language acquisition. In parallel, we found that early onset of ASD symptoms (i.e. prior to 18-months) was specifically associated with slower GWC rates of change during the second year of life. These alterations were found in areas mainly belonging to the central executive network.Limitations: Our study is the first to measure maturational changes in GWC in toddlers who developed autism, but the limited size of our sample characterizes its exploratory nature and warrants further replication in independent and larger samples. Conclusion: These results suggest that ASD is linked to early alterations of the gray-white matter boundary in widespread areas. Early onset of symptoms constitutes an independent clinical parameter associated with a specific corresponding neurobiological developmental trajectory. Altered neural migration and/or altered myelination processes potentially explain these findings.