Examining the Boundary Sharpness Coefficient as an Index of Cortical Microstructure in Autism Spectrum Disorder

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

doi:10.1093/cercor/bhab015

Examining the Boundary Sharpness Coefficient as an Index of Cortical Microstructure in Autism Spectrum Disorder

Cereb Cortex. 2021 Jun 10;31(7):3338-3352. doi: 10.1093/cercor/bhab015.

Authors

Emily Olafson^{1

2}, Saashi A Bedford^{1

3

4}, Gabriel A Devenyi^{1

5}, Raihaan Patel^{1

6}, Stephanie Tullo^{1

3}, Min Tae M Park⁷, Olivier Parent^{1

8}, Evdokia Anagnostou^{9

10}, Simon Baron-Cohen⁴, Edward T Bullmore¹¹, Lindsay R Chura⁴, Michael C Craig^{12

13}, Christine Ecker¹⁴, Dorothea L Floris^{15

16}, Rosemary J Holt⁴, Rhoshel Lenroot¹⁷, Jason P Lerch^{18

19}, Michael V Lombardo^{4

20}, Declan G M Murphy¹², Armin Raznahan²¹, Amber N V Ruigrok⁴, Michael D Spencer⁴, John Suckling^{4

11}, Margot J Taylor^{22

23

24}; MRC AIMS Consortium; Meng-Chuan Lai^{4

25

26

27

28}, M Mallar Chakravarty^{1

3

5

6}

Affiliations

¹ Cerebral Imaging Centre, Douglas Mental Health University Institute, Montreal H4H 1R3, Canada.
² Department of Neuroscience, Weill Cornell Graduate School of Medical Sciences, New York City, NY 10021, USA.
³ Integrated Program in Neuroscience, McGill University, Montreal H3A 2B4, Canada.
⁴ Autism Research Center, Department of Psychiatry, University of Cambridge, Cambridge CB2 8AH, UK.
⁵ Department of Psychiatry, McGill University, Montreal H3A 2B4, Canada.
⁶ Department of Biological and Biomedical Engineering, McGill University, Montreal H3A 2B4, Canada.
⁷ Department of Psychiatry, Schulich School of Medicine and Dentistry, Western University, London N6A 3K7, ON, Canada.
⁸ Departement de Psychologie, Universite de Montreal, Montreal, QC, Canada.
⁹ Holland Bloorview Kids Rehabilitation Hospital, Toronto M4G 1R8, Canada.
¹⁰ Department of Pediatrics, University of Toronto, Toronto, ON, Canada.
¹¹ Brain Mapping Unit, Department of Psychiatry, University of Cambridge, Cambridge CB2 0SZ, UK.
¹² Institute of Psychiatry, Psychology and Neuroscience, King's College London, London SE5 8AF, UK.
¹³ National Autism Unit, Bethlem Royal Hospital, London BR3 3BX, UK.
¹⁴ Department of Child and Adolescent Psychiatry, Psychosomatics, and Psychotherapy, University Hospital of the Goethe University, Frankfurt am Main 60528, Germany.
¹⁵ Donders Center for Brain, Cognition and Behavior, Radboud University Nijmegen, Nijmegen 6525 HR, The Netherlands.
¹⁶ Department for Cognitive Neuroscience, Radboud University Medical Center Nijmegen, Nijmegen 02.275, The Netherlands.
¹⁷ Department of Psychiatry, University of New South Wales, Sydney, NSW 2052, Australia.
¹⁸ Department of Medical Biophysics, The University of Toronto, Toronto, ON M5G 1L7, Canada.
¹⁹ Wellcome Centre for Integrative Neuroimaging, University of Oxford, Oxford OX3 9DU, UK.
²⁰ Laboratory for Autism and Neurodevelopmental Disorders, Center for Neuroscience and Cognitive Systems, @UniTn, Istituto Italiano di Tecnologia, 38068 Rovereto, Italy.
²¹ Section on Developmental Neurogenomics, Human Genetics Branch, National Institute of Mental Health, Bethesda, MD 20892-9663, USA.
²² Diagnostic Imaging, The Hospital for Sick Children, Toronto M5G 1X8, Canada.
²³ Program in Neurosciences and Mental Health, The Hospital for Sick Children, Toronto M5G 1X8, Canada.
²⁴ Department of Medical Imaging, University of Toronto, Toronto M5G 1X8, Canada.
²⁵ The Margaret and Wallace McCain Centre for Child, Youth & Family Mental Health and Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto M6J 1H4, Canada.
²⁶ Department of Psychiatry, University of Toronto, Toronto M5T 1R8, Canada.
²⁷ Department of Psychiatry, National Taiwan University Hospital and College of Medicine, Taipei 100229, Taiwan.
²⁸ Department of Psychiatry, The Hospital for Sick Children, Toronto M5G 1X8, Canada.

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 multicenter structural magnetic resonance 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. 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. Increases were observed in different brain regions in males and females, with larger effect sizes in females. BSC correlated with ADOS-2 Calibrated Severity Score 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 with 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.

Keywords: autism spectrum disorder; cerebral cortex; microstructure; myelin; tissue contrast.

Publication types

Research Support, N.I.H., Intramural
Research Support, Non-U.S. Gov't

MeSH terms

Adolescent
Adult
Aged
Autism Spectrum Disorder / diagnostic imaging*
Brain Mapping / methods*
Cerebral Cortex / diagnostic imaging*
Child
Child, Preschool
Databases, Factual
Female
Gray Matter / diagnostic imaging*
Humans
Magnetic Resonance Imaging / methods*
Male
Middle Aged
White Matter / diagnostic imaging*
Young Adult

Abstract

Publication types

MeSH terms

Grants and funding