Claire J McKinnon1, Adam T Eggebrecht2, Alexandre Todorov3, Jason J Wolff4, Jed T Elison5, Chloe M Adams3, Abraham Z Snyder2, Annette M Estes6, Lonnie Zwaigenbaum7, Kelly N Botteron8, Robert C McKinstry2, Natasha Marrus3, Alan Evans9, Heather C Hazlett10, Stephen R Dager11, Sarah J Paterson12, Juhi Pandey13, Robert T Schultz13, Martin A Styner10, Guido Gerig14, Bradley L Schlaggar15, Steven E Petersen16, Joseph Piven10, John R Pruett3. 1. Department of Psychiatry, Washington University School of Medicine, St. Louis, Missouri; Biological Sciences Division, University of Chicago, Chicago, Illinois. Electronic address: cmckinnon@uchicago.edu. 2. Mallinckrodt Institute of Radiology, Washington University School of Medicine, St. Louis, Missouri. 3. Department of Psychiatry, Washington University School of Medicine, St. Louis, Missouri. 4. Department of Educational Psychology, University of Minnesota, Minneapolis, Minnesota. 5. Institute of Child Development, University of Minnesota, Minneapolis, Minnesota. 6. Department of Speech and Hearing Sciences, University of Washington, Seattle, Washington. 7. Department of Pediatrics, University of Alberta, Edmonton, Alberta. 8. Department of Psychiatry, Washington University School of Medicine, St. Louis, Missouri; Mallinckrodt Institute of Radiology, Washington University School of Medicine, St. Louis, Missouri. 9. McConnell Brain Imaging Center, Montreal Neurological Institute, McGill University, Montreal, Quebec, Canada. 10. The Carolina Institute for Developmental Disabilities, University of North Carolina at Chapel Hill, Carborro, North Carolina. 11. Department of Radiology and Bioengineering, University of Washington, Seattle, Washington. 12. Department of Psychology, Temple University, Philadelphia, Pennsylvania. 13. Center for Autism Research, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania; Department of Psychiatry, University of Pennsylvania, Philadelphia, Pennsylvania. 14. Tandon School of Engineering, New York University, Brooklyn, New York. 15. Department of Psychiatry, Washington University School of Medicine, St. Louis, Missouri; Department of Neurology, Washington University School of Medicine, St. Louis, Missouri; Mallinckrodt Institute of Radiology, Washington University School of Medicine, St. Louis, Missouri. 16. Department of Neurology, Washington University School of Medicine, St. Louis, Missouri; Mallinckrodt Institute of Radiology, Washington University School of Medicine, St. Louis, Missouri; Department of Psychological and Brain Sciences, Washington University in St. Louis, St. Louis, Missouri; Department of Biomedical Engineering, Washington University in St. Louis, St. Louis, Missouri.
Abstract
BACKGROUND: Restricted and repetitive behaviors (RRBs), detectable by 12 months in many infants in whom autism spectrum disorder (ASD) is later diagnosed, may represent some of the earliest behavioral markers of ASD. However, brain function underlying the emergence of these key behaviors remains unknown. METHODS: Behavioral and resting-state functional connectivity (fc) magnetic resonance imaging data were collected from 167 children at high and low familial risk for ASD at 12 and 24 months (n = 38 at both time points). Twenty infants met criteria for ASD at 24 months. We divided RRBs into four subcategories (restricted, stereotyped, ritualistic/sameness, self-injurious) and used a data-driven approach to identify functional brain networks associated with the development of each RRB subcategory. RESULTS: Higher scores for ritualistic/sameness behavior were associated with less positive fc between visual and control networks at 12 and 24 months. Ritualistic/sameness and stereotyped behaviors were associated with less positive fc between visual and default mode networks at 12 months. At 24 months, stereotyped and restricted behaviors were associated with more positive fc between default mode and control networks. Additionally, at 24 months, stereotyped behavior was associated with more positive fc between dorsal attention and subcortical networks, whereas restricted behavior was associated with more positive fc between default mode and dorsal attention networks. No significant network-level associations were observed for self-injurious behavior. CONCLUSIONS: These observations mark the earliest known description of functional brain systems underlying RRBs, reinforce the construct validity of RRB subcategories in infants, and implicate specific neural substrates for future interventions targeting RRBs.
BACKGROUND: Restricted and repetitive behaviors (RRBs), detectable by 12 months in many infants in whom autism spectrum disorder (ASD) is later diagnosed, may represent some of the earliest behavioral markers of ASD. However, brain function underlying the emergence of these key behaviors remains unknown. METHODS: Behavioral and resting-state functional connectivity (fc) magnetic resonance imaging data were collected from 167 children at high and low familial risk for ASD at 12 and 24 months (n = 38 at both time points). Twenty infants met criteria for ASD at 24 months. We divided RRBs into four subcategories (restricted, stereotyped, ritualistic/sameness, self-injurious) and used a data-driven approach to identify functional brain networks associated with the development of each RRB subcategory. RESULTS: Higher scores for ritualistic/sameness behavior were associated with less positive fc between visual and control networks at 12 and 24 months. Ritualistic/sameness and stereotyped behaviors were associated with less positive fc between visual and default mode networks at 12 months. At 24 months, stereotyped and restricted behaviors were associated with more positive fc between default mode and control networks. Additionally, at 24 months, stereotyped behavior was associated with more positive fc between dorsal attention and subcortical networks, whereas restricted behavior was associated with more positive fc between default mode and dorsal attention networks. No significant network-level associations were observed for self-injurious behavior. CONCLUSIONS: These observations mark the earliest known description of functional brain systems underlying RRBs, reinforce the construct validity of RRB subcategories in infants, and implicate specific neural substrates for future interventions targeting RRBs.
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