Restricted and Repetitive Behavior and Brain Functional Connectivity in Infants at Risk for Developing Autism Spectrum Disorder

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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.

Original languageEnglish (US)
Pages (from-to)50-61
Number of pages12
JournalBiological Psychiatry: Cognitive Neuroscience and Neuroimaging
Volume4
Issue number1
DOIs
StatePublished - Jan 2019

Bibliographical note

Funding Information:
This work was supported by the National Institutes of Health (Grant No. K01 MH103594 [to ATE], Grant No. R01 MH093510 [to JRP], Grant No. K01 MH101653 [to JJW], and Grant No. P30 NS098577 [to AZS]), National Institutes of Health Autism Centers of Excellence Network (Grant No. R01 HD055741 [to JPi]), Autism Speaks (Grant No. 6020 [to JPi]), Simons Foundation (Grant No. 140209 [to JPi]), U54 Intellectual and Developmental Disabilities Research Centers (Grant No. HD079124 to University of North Carolina [to JPi], Grant No. HD087011 to Washington University [to J. Constantino and BLS], Grant No. HD086984 to Children's Hospital of Philadelphia [to RTS], and Grant No. HD083091 to University of Washington [to AME]), and the McDonnell Center for Systems Neuroscience. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

Funding Information:
This work was supported by the National Institutes of Health (Grant No. K01 MH103594 [to ATE], Grant No. R01 MH093510 [to JRP], Grant No. K01 MH101653 [to JJW], and Grant No. P30 NS098577 [to AZS]), National Institutes of Health Autism Centers of Excellence Network (Grant No. R01 HD055741 [to JPi]), Autism Speaks (Grant No. 6020 [to JPi]), Simons Foundation (Grant No. 140209 [to JPi]), U54 Intellectual and Developmental Disabilities Research Centers (Grant No. HD079124 to University of North Carolina [to JPi], Grant No. HD087011 to Washington University [to J. Constantino and BLS], Grant No. HD086984 to Children's Hospital of Philadelphia [to RTS], and Grant No. HD083091 to University of Washington [to AME]), and the McDonnell Center for Systems Neuroscience. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

Publisher Copyright:
© 2018 Society of Biological Psychiatry

Keywords

  • Autism spectrum disorder
  • Brain development
  • Functional connectivity
  • Functional magnetic resonance imaging
  • Infant
  • Restricted and repetitive behavior

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