Girls and Boys with Autism Spectrum Disorder Relative to Same-Sex Typically Developing Peers Exhibit Distinct Cortical Folding Abnormalities during Late Childhood and Adolescence

Thursday, May 11, 2017: 1:57 PM
Yerba Buena 7 (Marriott Marquis Hotel)
D. Yang1,2, S. M. Abdullahi3, A. Jack1, P. E. Ventola3, E. H. Aylward4, M. Dapretto5, D. H. Geschwind5, J. Duncan6,7, S. J. Webb8, S. Y. Bookheimer5, L. Kenworthy2, J. D. Van Horn9 and K. A. Pelphrey1,2, (1)Autism and Neurodevelopmental Disorders Institute, The George Washington University, Washington, DC, (2)Children's National Health System, Washington, DC, (3)Yale Child Study Center, New Haven, CT, (4)Seattle Children's Research Institute, Seattle, WA, (5)University of California, Los Angeles, Los Angeles, CA, (6)Department of Radiology & Biomedical Imaging, Yale University School of Medicine, New Haven, CT, (7)Department of Biomedical Engineering, Yale University, New Haven, CT, (8)Psychiatry and Behavioral Sciences, University of Washington, Seattle, WA, (9)Laboratory of NeuroImaging, University of Southern California, Los Angeles, CA
Background: Anatomical imaging studies have revealed pronounced and widespread reductions in gyrification during adolescence in healthy subjects, reflecting a late period of brain maturation. It is not known whether males and females with Autism Spectrum Disorder (ASD) relative to same-sex peers without ASD exhibit cortical folding abnormalities during this developmental period, and how much the abnormalities may overlap.

Objectives: To examine and compare cortical folding abnormalities as measured by an index of local gyrification in girls and boys with ASD during late childhood and adolescence.

Methods: The sample included 219 children and teens (age: M = 13.01y, SD = 2.91y, range = 8.03 – 17.99y; IQ: M = 107.50, SD = 17.87, range = 75 - 167) recruited from five research sites (Yale, Harvard, UCLA, Seattle-1, Seattle-2). There were 54 ASD females, 52 TD females, 59 ASD males and 54 TD males. The four groups were well-matched on age and IQ. Females and males with ASD were well-matched on ASD symptom severity, language ability and adaptive behaviors. F-ASD and F-TD were well-matched on intracranial volume, so were M-ASD and M-TD. All participants underwent a T1-weighted structural scan. Cortical folding was estimated using FreeSurfer v5.3.0 with an additional flag of local gyrification index. Quality of the sMRI images were independently blind-rated by two authors (DY and SA); 30 subjects (6 F-ASD, 5 F-TD, 17 M-ASD, 2 M-TD) exhibiting obvious head motion were discarded. Age was centered before entered into analysis. Results were thresholded at Z>1.96 (vertex-level) and p<.05 (cluster-level) (two-sided).

Results: While across all participants, there were widespread age-related reductions in cortical folding, ASD males relative to TD males exhibited lower mean levels of cortical folding in the right insula and right postcentral gyrus, combined with abnormally accelerated age-related reductions in cortical folding in the right pars triangularis and the left lateral orbital frontal gyrus. In contrast, ASD females relative to TD females exhibited lower mean levels of cortical folding in the left superior parietal gyrus, and abnormally accelerated age-related reductions in cortical folding in the left rostral middle frontal gyrus.

Conclusions: Our results reveal that females and males with autism relative to their same-sex healthy control counterparts exhibit cortical folding abnormalities during late childhood and adolescence, suggesting abnormally accelerated brain maturation during this period in autism. The specific brain regions exhibiting abnormalities vary by sex, revealing different neurodevelopmental signatures of autism in girls vs. boys.