Mapping Cortical Anatomy in Young Children with Autism Using Surface Based Morphometry

Background:  Aberrant cortical development during early childhood is thought to be an important component of autism pathophysiology. However, the challenges of measuring brain anatomy in-vivo during early childhood have limited the number of studies comparing cortical anatomy between individuals with autism and typically developing controls (TDCs) during this critical developmental window. Moreover very few studies have examined indices other than global and lobar cortical volume. 

Objectives:  To present initial structural neuroimaging findings from a new cohort of young children with autism using surface-based methods for cortical morphometry that (i) directly measure the two biologically distinct sub-components of cortical volume - cortical thickness and surface area and (ii) map cortical thickness at high spatially resolution throughout the cortical sheet. 

Methods:  This was a cross-sectional case control neuroimaging study conducted in a Federal clinical research institute. We included 75 male children with autism and 33 typically developing male controls aged 2 through 6 years. Primary outcome measures of interest were (i) Global and lobar cortical volume, thickness and surface area, and  (ii) cortical thickness at ~80,000 points.

Results:  Children with autism showed age-related global cortical volume excesses relative to TDCs, which were driven by attenuation of age-related cortical thickness reduction relative to TDCs. These thickness-driven volume excesses were apparent in all lobes, but uniquely compounded in frontal lobes by an exaggerated age-related surface area increase in children with autism relative to TDCs. Fine-mapping group differences in cortical thickness identified disruptions of cortical anatomy in autism that were already localized at an early age to regions involved in the processing of language, biological movement and social information, as well as to executive prefrontal systems involved in behavioral regulation. 

Conclusions:  Our findings  (i) parse cortical volume abnormalities in autism into more biologically tractable sub-components, and (ii) show that disease mechanisms in autism can already produce targeted disruption of cortical anatomy by early childhood.