Examining the boundary sharpness coefficient as an index of cortical microstructure and its relationship to age and sex in autism spectrum disorder

Emily R. Olafson; Saashi A. Bedford; Gabriel A. Devenyi; Raihaan Patel; Stéphanie Tullo; Min Tae M Park; Olivier Parent; Evdokia A. Anagnostou; Simon Baron‐Cohen; Edward Thomas Bullmore; Lindsay Rachel Chura; Michael Craig; Christine Ecker; Dorothea L. Floris; Rosemary Holt; Rhoshel Lenroot; Jason P. Lerch; Michael Vincent Lombardo; Declan Murphy; Armin Raznahan; Amber N. V. Ruigrok; Michael D. Spencer; John Suckling A; Margot J. Taylor; Meng‐Chuan Lai; M. Mallar Chakravarty

doi:10.1101/2020.07.09.196212

NeurosciencebioRxivJul 9, 2020

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Examining the boundary sharpness coefficient as an index of cortical microstructure and its relationship to age and sex in autism spectrum disorder

Emily R. Olafson iD, Saashi A. Bedford iD, Gabriel A. Devenyi iD, Raihaan Patel iD, Stéphanie Tullo iD, Min Tae M Park iD, Olivier Parent iD, Evdokia A. Anagnostou iD, Simon Baron‐Cohen iD, Edward Thomas Bullmore iD, Lindsay Rachel Chura, Michael Craig iD, Christine Ecker iD, Dorothea L. Floris iD, Rosemary Holt iD, Rhoshel Lenroot iD, Jason P. Lerch iD, Michael Vincent Lombardo iD, Declan Murphy iD, Armin Raznahan iD, Amber N. V. Ruigrok iD, Michael D. Spencer iD, John Suckling A iD, Margot J. Taylor iD, Meng‐Chuan Lai iD, M. Mallar Chakravarty iD

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Abstract

Autism spectrum disorder (ASD) is associated with atypical brain development. However, the phenotype of regionally specific increased cortical thickness observed in ASD may be driven by several independent biological processes that influence the gray/white matter boundary, such as synaptic pruning, myelination, or atypical migration. Here, we propose to use the boundary sharpness coefficient (BSC), a proxy for alterations in microstructure at the cortical gray/white matter boundary, to investigate brain differences in individuals with ASD, including factors that may influence ASD-related heterogeneity (age, sex, and intelligence quotient). Using a vertex-based meta-analysis and a large multi-center magnetic resonance structural imaging (MRI) dataset, with a total of 1136 individuals, 415 with ASD (112 female; 303 male) and 721 controls (283 female; 438 male), we observed that individuals with ASD had significantly greater BSC in the bilateral superior temporal gyrus and left inferior frontal gyrus indicating an abrupt transition (high contrast) between white matter and cortical intensities. Increases were observed in different brain regions in males and females, with larger effect sizes in females. Individuals with ASD under 18 had significantly greater BSC in the bilateral superior temporal gyrus and right postcentral gyrus; individuals with ASD over 18 had significantly increased BSC in the bilateral precuneus and superior temporal gyrus. BSC correlated with ADOS-2 CSS in individuals with ASD in the right medial temporal pole. Importantly, there was a significant spatial overlap between maps of the effect of diagnosis on BSC when compared to cortical thickness. These results invite studies to use BSC as a possible new measure of cortical development in ASD and to further examine the microstructural underpinnings of BSC-related differences and their impact on measures of cortical morphology.