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Published Online: 25 March 2022
Subcortical Brain Development in Autism and Fragile X Syndrome: Evidence for Dynamic, Age- and Disorder-Specific Trajectories in Infancy
Mark D. Shen, Ph.D. [email protected], Meghan R. Swanson, Ph.D., Jason J. Wolff, Ph.D., Jed T. Elison, Ph.D., Jessica B. Girault, Ph.D., Sun Hyung Kim, Ph.D., Rachel G. Smith, B.A., … Show All … , Michael M. Graves, M.S., Leigh Anne H. Weisenfeld, M.S.W., Lisa Flake, M.S.W., Leigh MacIntyre, M.S., Julia L. Gross, B.S., Catherine A. Burrows, Ph.D., Vladimir S. Fonov, Ph.D., D. Louis Collins, Ph.D., Alan C. Evans, Ph.D., Guido Gerig, Ph.D., Robert C. McKinstry, M.D., Ph.D., Juhi Pandey, Ph.D., Tanya St. John, Ph.D., Lonnie Zwaigenbaum, M.D., Annette M. Estes, Ph.D., Stephen R. Dager, M.D., Robert T. Schultz, Ph.D., Martin A. Styner, Ph.D., Kelly N. Botteron, M.D., Heather C. Hazlett, Ph.D., and Joseph Piven, M.D. for the IBIS Network Show FewerAuthors Info & Affiliations
Publication: American Journal of Psychiatry
Abstract
Objective:
Previous research has demonstrated that the amygdala is enlarged in children with autism spectrum disorder (ASD). However, the precise onset of this enlargement during infancy, how it relates to later diagnostic behaviors, whether the timing of enlargement in infancy is specific to the amygdala, and whether it is specific to ASD (or present in other neurodevelopmental disorders, such as fragile X syndrome) are all unknown.
Methods:
Longitudinal MRIs were acquired at 6–24 months of age in 29 infants with fragile X syndrome, 58 infants at high likelihood for ASD who were later diagnosed with ASD, 212 high-likelihood infants not diagnosed with ASD, and 109 control infants (1,099 total scans).
Results:
Infants who developed ASD had typically sized amygdala volumes at 6 months, but exhibited significantly faster amygdala growth between 6 and 24 months, such that by 12 months the ASD group had significantly larger amygdala volume (Cohen’s d=0.56) compared with all other groups. Amygdala growth rate between 6 and 12 months was significantly associated with greater social deficits at 24 months when the infants were diagnosed with ASD. Infants with fragile X syndrome had a persistent and significantly enlarged caudate volume at all ages between 6 and 24 months (d=2.12), compared with all other groups, which was significantly associated with greater repetitive behaviors.
Conclusions:
This is the first MRI study comparing fragile X syndrome and ASD in infancy, demonstrating strikingly different patterns of brain and behavior development. Fragile X syndrome–related changes were present from 6 months of age, whereas ASD-related changes unfolded over the first 2 years of life, starting with no detectable group differences at 6 months. Increased amygdala growth rate between 6 and 12 months occurs prior to social deficits and well before diagnosis. This gradual onset of brain and behavior changes in ASD, but not fragile X syndrome, suggests an age- and disorder-specific pattern of cascading brain changes preceding autism diagnosis.
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History
Received: 10 September 2021
Revision received: 28 December 2021
Accepted: 24 January 2022
Published online: 25 March 2022
Published in print: August 2022
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Carolina Institute for Developmental Disabilities and Department of Psychiatry (Shen, Girault, Kim, Smith, Graves, Weisenfeld, Gross, Styner, Hazlett, Piven) and UNC Neuroscience Center (Shen), University of North Carolina at Chapel Hill School of Medicine, Chapel Hill; Department of Educational Psychology (Wolff), Institute of Child Development (Elison), and Department of Pediatrics (Elison, Burrows), University of Minnesota, Minneapolis; Mallinckrodt Institute of Radiology, Washington University School of Medicine, St. Louis (Flake, McKinstry, Botteron); Department of Radiology, University of Washington Medical Center, Seattle (Dager); Center for Autism Research, Children’s Hospital of Philadelphia, University of Pennsylvania Perelman School of Medicine, Philadelphia (Pandey, Schultz); Computer Science and Engineering, NYU Tandon School of Engineering, New York (Gerig); Montreal Neurological Institute, McGill University, Montreal (MacIntyre, Fonov, Collins, Evans); Department of Pediatrics, University of Alberta, Edmonton, Canada (Zwaigenbaum); Department of Speech and Hearing Science, University of Washington, Seattle (St. John, Estes); School of Behavioral and Brain Sciences, University of Texas at Dallas (Swanson).
Meghan R. Swanson, Ph.D.
Carolina Institute for Developmental Disabilities and Department of Psychiatry (Shen, Girault, Kim, Smith, Graves, Weisenfeld, Gross, Styner, Hazlett, Piven) and UNC Neuroscience Center (Shen), University of North Carolina at Chapel Hill School of Medicine, Chapel Hill; Department of Educational Psychology (Wolff), Institute of Child Development (Elison), and Department of Pediatrics (Elison, Burrows), University of Minnesota, Minneapolis; Mallinckrodt Institute of Radiology, Washington University School of Medicine, St. Louis (Flake, McKinstry, Botteron); Department of Radiology, University of Washington Medical Center, Seattle (Dager); Center for Autism Research, Children’s Hospital of Philadelphia, University of Pennsylvania Perelman School of Medicine, Philadelphia (Pandey, Schultz); Computer Science and Engineering, NYU Tandon School of Engineering, New York (Gerig); Montreal Neurological Institute, McGill University, Montreal (MacIntyre, Fonov, Collins, Evans); Department of Pediatrics, University of Alberta, Edmonton, Canada (Zwaigenbaum); Department of Speech and Hearing Science, University of Washington, Seattle (St. John, Estes); School of Behavioral and Brain Sciences, University of Texas at Dallas (Swanson).
Jason J. Wolff, Ph.D.
Carolina Institute for Developmental Disabilities and Department of Psychiatry (Shen, Girault, Kim, Smith, Graves, Weisenfeld, Gross, Styner, Hazlett, Piven) and UNC Neuroscience Center (Shen), University of North Carolina at Chapel Hill School of Medicine, Chapel Hill; Department of Educational Psychology (Wolff), Institute of Child Development (Elison), and Department of Pediatrics (Elison, Burrows), University of Minnesota, Minneapolis; Mallinckrodt Institute of Radiology, Washington University School of Medicine, St. Louis (Flake, McKinstry, Botteron); Department of Radiology, University of Washington Medical Center, Seattle (Dager); Center for Autism Research, Children’s Hospital of Philadelphia, University of Pennsylvania Perelman School of Medicine, Philadelphia (Pandey, Schultz); Computer Science and Engineering, NYU Tandon School of Engineering, New York (Gerig); Montreal Neurological Institute, McGill University, Montreal (MacIntyre, Fonov, Collins, Evans); Department of Pediatrics, University of Alberta, Edmonton, Canada (Zwaigenbaum); Department of Speech and Hearing Science, University of Washington, Seattle (St. John, Estes); School of Behavioral and Brain Sciences, University of Texas at Dallas (Swanson).
Jed T. Elison, Ph.D.
Carolina Institute for Developmental Disabilities and Department of Psychiatry (Shen, Girault, Kim, Smith, Graves, Weisenfeld, Gross, Styner, Hazlett, Piven) and UNC Neuroscience Center (Shen), University of North Carolina at Chapel Hill School of Medicine, Chapel Hill; Department of Educational Psychology (Wolff), Institute of Child Development (Elison), and Department of Pediatrics (Elison, Burrows), University of Minnesota, Minneapolis; Mallinckrodt Institute of Radiology, Washington University School of Medicine, St. Louis (Flake, McKinstry, Botteron); Department of Radiology, University of Washington Medical Center, Seattle (Dager); Center for Autism Research, Children’s Hospital of Philadelphia, University of Pennsylvania Perelman School of Medicine, Philadelphia (Pandey, Schultz); Computer Science and Engineering, NYU Tandon School of Engineering, New York (Gerig); Montreal Neurological Institute, McGill University, Montreal (MacIntyre, Fonov, Collins, Evans); Department of Pediatrics, University of Alberta, Edmonton, Canada (Zwaigenbaum); Department of Speech and Hearing Science, University of Washington, Seattle (St. John, Estes); School of Behavioral and Brain Sciences, University of Texas at Dallas (Swanson).
Jessica B. Girault, Ph.D.
Carolina Institute for Developmental Disabilities and Department of Psychiatry (Shen, Girault, Kim, Smith, Graves, Weisenfeld, Gross, Styner, Hazlett, Piven) and UNC Neuroscience Center (Shen), University of North Carolina at Chapel Hill School of Medicine, Chapel Hill; Department of Educational Psychology (Wolff), Institute of Child Development (Elison), and Department of Pediatrics (Elison, Burrows), University of Minnesota, Minneapolis; Mallinckrodt Institute of Radiology, Washington University School of Medicine, St. Louis (Flake, McKinstry, Botteron); Department of Radiology, University of Washington Medical Center, Seattle (Dager); Center for Autism Research, Children’s Hospital of Philadelphia, University of Pennsylvania Perelman School of Medicine, Philadelphia (Pandey, Schultz); Computer Science and Engineering, NYU Tandon School of Engineering, New York (Gerig); Montreal Neurological Institute, McGill University, Montreal (MacIntyre, Fonov, Collins, Evans); Department of Pediatrics, University of Alberta, Edmonton, Canada (Zwaigenbaum); Department of Speech and Hearing Science, University of Washington, Seattle (St. John, Estes); School of Behavioral and Brain Sciences, University of Texas at Dallas (Swanson).
Sun Hyung Kim, Ph.D.
Carolina Institute for Developmental Disabilities and Department of Psychiatry (Shen, Girault, Kim, Smith, Graves, Weisenfeld, Gross, Styner, Hazlett, Piven) and UNC Neuroscience Center (Shen), University of North Carolina at Chapel Hill School of Medicine, Chapel Hill; Department of Educational Psychology (Wolff), Institute of Child Development (Elison), and Department of Pediatrics (Elison, Burrows), University of Minnesota, Minneapolis; Mallinckrodt Institute of Radiology, Washington University School of Medicine, St. Louis (Flake, McKinstry, Botteron); Department of Radiology, University of Washington Medical Center, Seattle (Dager); Center for Autism Research, Children’s Hospital of Philadelphia, University of Pennsylvania Perelman School of Medicine, Philadelphia (Pandey, Schultz); Computer Science and Engineering, NYU Tandon School of Engineering, New York (Gerig); Montreal Neurological Institute, McGill University, Montreal (MacIntyre, Fonov, Collins, Evans); Department of Pediatrics, University of Alberta, Edmonton, Canada (Zwaigenbaum); Department of Speech and Hearing Science, University of Washington, Seattle (St. John, Estes); School of Behavioral and Brain Sciences, University of Texas at Dallas (Swanson).
Rachel G. Smith, B.A.
Carolina Institute for Developmental Disabilities and Department of Psychiatry (Shen, Girault, Kim, Smith, Graves, Weisenfeld, Gross, Styner, Hazlett, Piven) and UNC Neuroscience Center (Shen), University of North Carolina at Chapel Hill School of Medicine, Chapel Hill; Department of Educational Psychology (Wolff), Institute of Child Development (Elison), and Department of Pediatrics (Elison, Burrows), University of Minnesota, Minneapolis; Mallinckrodt Institute of Radiology, Washington University School of Medicine, St. Louis (Flake, McKinstry, Botteron); Department of Radiology, University of Washington Medical Center, Seattle (Dager); Center for Autism Research, Children’s Hospital of Philadelphia, University of Pennsylvania Perelman School of Medicine, Philadelphia (Pandey, Schultz); Computer Science and Engineering, NYU Tandon School of Engineering, New York (Gerig); Montreal Neurological Institute, McGill University, Montreal (MacIntyre, Fonov, Collins, Evans); Department of Pediatrics, University of Alberta, Edmonton, Canada (Zwaigenbaum); Department of Speech and Hearing Science, University of Washington, Seattle (St. John, Estes); School of Behavioral and Brain Sciences, University of Texas at Dallas (Swanson).
Michael M. Graves, M.S.
Carolina Institute for Developmental Disabilities and Department of Psychiatry (Shen, Girault, Kim, Smith, Graves, Weisenfeld, Gross, Styner, Hazlett, Piven) and UNC Neuroscience Center (Shen), University of North Carolina at Chapel Hill School of Medicine, Chapel Hill; Department of Educational Psychology (Wolff), Institute of Child Development (Elison), and Department of Pediatrics (Elison, Burrows), University of Minnesota, Minneapolis; Mallinckrodt Institute of Radiology, Washington University School of Medicine, St. Louis (Flake, McKinstry, Botteron); Department of Radiology, University of Washington Medical Center, Seattle (Dager); Center for Autism Research, Children’s Hospital of Philadelphia, University of Pennsylvania Perelman School of Medicine, Philadelphia (Pandey, Schultz); Computer Science and Engineering, NYU Tandon School of Engineering, New York (Gerig); Montreal Neurological Institute, McGill University, Montreal (MacIntyre, Fonov, Collins, Evans); Department of Pediatrics, University of Alberta, Edmonton, Canada (Zwaigenbaum); Department of Speech and Hearing Science, University of Washington, Seattle (St. John, Estes); School of Behavioral and Brain Sciences, University of Texas at Dallas (Swanson).
Leigh Anne H. Weisenfeld, M.S.W.
Carolina Institute for Developmental Disabilities and Department of Psychiatry (Shen, Girault, Kim, Smith, Graves, Weisenfeld, Gross, Styner, Hazlett, Piven) and UNC Neuroscience Center (Shen), University of North Carolina at Chapel Hill School of Medicine, Chapel Hill; Department of Educational Psychology (Wolff), Institute of Child Development (Elison), and Department of Pediatrics (Elison, Burrows), University of Minnesota, Minneapolis; Mallinckrodt Institute of Radiology, Washington University School of Medicine, St. Louis (Flake, McKinstry, Botteron); Department of Radiology, University of Washington Medical Center, Seattle (Dager); Center for Autism Research, Children’s Hospital of Philadelphia, University of Pennsylvania Perelman School of Medicine, Philadelphia (Pandey, Schultz); Computer Science and Engineering, NYU Tandon School of Engineering, New York (Gerig); Montreal Neurological Institute, McGill University, Montreal (MacIntyre, Fonov, Collins, Evans); Department of Pediatrics, University of Alberta, Edmonton, Canada (Zwaigenbaum); Department of Speech and Hearing Science, University of Washington, Seattle (St. John, Estes); School of Behavioral and Brain Sciences, University of Texas at Dallas (Swanson).
Lisa Flake, M.S.W.
Carolina Institute for Developmental Disabilities and Department of Psychiatry (Shen, Girault, Kim, Smith, Graves, Weisenfeld, Gross, Styner, Hazlett, Piven) and UNC Neuroscience Center (Shen), University of North Carolina at Chapel Hill School of Medicine, Chapel Hill; Department of Educational Psychology (Wolff), Institute of Child Development (Elison), and Department of Pediatrics (Elison, Burrows), University of Minnesota, Minneapolis; Mallinckrodt Institute of Radiology, Washington University School of Medicine, St. Louis (Flake, McKinstry, Botteron); Department of Radiology, University of Washington Medical Center, Seattle (Dager); Center for Autism Research, Children’s Hospital of Philadelphia, University of Pennsylvania Perelman School of Medicine, Philadelphia (Pandey, Schultz); Computer Science and Engineering, NYU Tandon School of Engineering, New York (Gerig); Montreal Neurological Institute, McGill University, Montreal (MacIntyre, Fonov, Collins, Evans); Department of Pediatrics, University of Alberta, Edmonton, Canada (Zwaigenbaum); Department of Speech and Hearing Science, University of Washington, Seattle (St. John, Estes); School of Behavioral and Brain Sciences, University of Texas at Dallas (Swanson).
Leigh MacIntyre, M.S.
Carolina Institute for Developmental Disabilities and Department of Psychiatry (Shen, Girault, Kim, Smith, Graves, Weisenfeld, Gross, Styner, Hazlett, Piven) and UNC Neuroscience Center (Shen), University of North Carolina at Chapel Hill School of Medicine, Chapel Hill; Department of Educational Psychology (Wolff), Institute of Child Development (Elison), and Department of Pediatrics (Elison, Burrows), University of Minnesota, Minneapolis; Mallinckrodt Institute of Radiology, Washington University School of Medicine, St. Louis (Flake, McKinstry, Botteron); Department of Radiology, University of Washington Medical Center, Seattle (Dager); Center for Autism Research, Children’s Hospital of Philadelphia, University of Pennsylvania Perelman School of Medicine, Philadelphia (Pandey, Schultz); Computer Science and Engineering, NYU Tandon School of Engineering, New York (Gerig); Montreal Neurological Institute, McGill University, Montreal (MacIntyre, Fonov, Collins, Evans); Department of Pediatrics, University of Alberta, Edmonton, Canada (Zwaigenbaum); Department of Speech and Hearing Science, University of Washington, Seattle (St. John, Estes); School of Behavioral and Brain Sciences, University of Texas at Dallas (Swanson).
Julia L. Gross, B.S.
Carolina Institute for Developmental Disabilities and Department of Psychiatry (Shen, Girault, Kim, Smith, Graves, Weisenfeld, Gross, Styner, Hazlett, Piven) and UNC Neuroscience Center (Shen), University of North Carolina at Chapel Hill School of Medicine, Chapel Hill; Department of Educational Psychology (Wolff), Institute of Child Development (Elison), and Department of Pediatrics (Elison, Burrows), University of Minnesota, Minneapolis; Mallinckrodt Institute of Radiology, Washington University School of Medicine, St. Louis (Flake, McKinstry, Botteron); Department of Radiology, University of Washington Medical Center, Seattle (Dager); Center for Autism Research, Children’s Hospital of Philadelphia, University of Pennsylvania Perelman School of Medicine, Philadelphia (Pandey, Schultz); Computer Science and Engineering, NYU Tandon School of Engineering, New York (Gerig); Montreal Neurological Institute, McGill University, Montreal (MacIntyre, Fonov, Collins, Evans); Department of Pediatrics, University of Alberta, Edmonton, Canada (Zwaigenbaum); Department of Speech and Hearing Science, University of Washington, Seattle (St. John, Estes); School of Behavioral and Brain Sciences, University of Texas at Dallas (Swanson).
Catherine A. Burrows, Ph.D.
Carolina Institute for Developmental Disabilities and Department of Psychiatry (Shen, Girault, Kim, Smith, Graves, Weisenfeld, Gross, Styner, Hazlett, Piven) and UNC Neuroscience Center (Shen), University of North Carolina at Chapel Hill School of Medicine, Chapel Hill; Department of Educational Psychology (Wolff), Institute of Child Development (Elison), and Department of Pediatrics (Elison, Burrows), University of Minnesota, Minneapolis; Mallinckrodt Institute of Radiology, Washington University School of Medicine, St. Louis (Flake, McKinstry, Botteron); Department of Radiology, University of Washington Medical Center, Seattle (Dager); Center for Autism Research, Children’s Hospital of Philadelphia, University of Pennsylvania Perelman School of Medicine, Philadelphia (Pandey, Schultz); Computer Science and Engineering, NYU Tandon School of Engineering, New York (Gerig); Montreal Neurological Institute, McGill University, Montreal (MacIntyre, Fonov, Collins, Evans); Department of Pediatrics, University of Alberta, Edmonton, Canada (Zwaigenbaum); Department of Speech and Hearing Science, University of Washington, Seattle (St. John, Estes); School of Behavioral and Brain Sciences, University of Texas at Dallas (Swanson).
Vladimir S. Fonov, Ph.D.
Carolina Institute for Developmental Disabilities and Department of Psychiatry (Shen, Girault, Kim, Smith, Graves, Weisenfeld, Gross, Styner, Hazlett, Piven) and UNC Neuroscience Center (Shen), University of North Carolina at Chapel Hill School of Medicine, Chapel Hill; Department of Educational Psychology (Wolff), Institute of Child Development (Elison), and Department of Pediatrics (Elison, Burrows), University of Minnesota, Minneapolis; Mallinckrodt Institute of Radiology, Washington University School of Medicine, St. Louis (Flake, McKinstry, Botteron); Department of Radiology, University of Washington Medical Center, Seattle (Dager); Center for Autism Research, Children’s Hospital of Philadelphia, University of Pennsylvania Perelman School of Medicine, Philadelphia (Pandey, Schultz); Computer Science and Engineering, NYU Tandon School of Engineering, New York (Gerig); Montreal Neurological Institute, McGill University, Montreal (MacIntyre, Fonov, Collins, Evans); Department of Pediatrics, University of Alberta, Edmonton, Canada (Zwaigenbaum); Department of Speech and Hearing Science, University of Washington, Seattle (St. John, Estes); School of Behavioral and Brain Sciences, University of Texas at Dallas (Swanson).
D. Louis Collins, Ph.D.
Carolina Institute for Developmental Disabilities and Department of Psychiatry (Shen, Girault, Kim, Smith, Graves, Weisenfeld, Gross, Styner, Hazlett, Piven) and UNC Neuroscience Center (Shen), University of North Carolina at Chapel Hill School of Medicine, Chapel Hill; Department of Educational Psychology (Wolff), Institute of Child Development (Elison), and Department of Pediatrics (Elison, Burrows), University of Minnesota, Minneapolis; Mallinckrodt Institute of Radiology, Washington University School of Medicine, St. Louis (Flake, McKinstry, Botteron); Department of Radiology, University of Washington Medical Center, Seattle (Dager); Center for Autism Research, Children’s Hospital of Philadelphia, University of Pennsylvania Perelman School of Medicine, Philadelphia (Pandey, Schultz); Computer Science and Engineering, NYU Tandon School of Engineering, New York (Gerig); Montreal Neurological Institute, McGill University, Montreal (MacIntyre, Fonov, Collins, Evans); Department of Pediatrics, University of Alberta, Edmonton, Canada (Zwaigenbaum); Department of Speech and Hearing Science, University of Washington, Seattle (St. John, Estes); School of Behavioral and Brain Sciences, University of Texas at Dallas (Swanson).
Alan C. Evans, Ph.D.
Carolina Institute for Developmental Disabilities and Department of Psychiatry (Shen, Girault, Kim, Smith, Graves, Weisenfeld, Gross, Styner, Hazlett, Piven) and UNC Neuroscience Center (Shen), University of North Carolina at Chapel Hill School of Medicine, Chapel Hill; Department of Educational Psychology (Wolff), Institute of Child Development (Elison), and Department of Pediatrics (Elison, Burrows), University of Minnesota, Minneapolis; Mallinckrodt Institute of Radiology, Washington University School of Medicine, St. Louis (Flake, McKinstry, Botteron); Department of Radiology, University of Washington Medical Center, Seattle (Dager); Center for Autism Research, Children’s Hospital of Philadelphia, University of Pennsylvania Perelman School of Medicine, Philadelphia (Pandey, Schultz); Computer Science and Engineering, NYU Tandon School of Engineering, New York (Gerig); Montreal Neurological Institute, McGill University, Montreal (MacIntyre, Fonov, Collins, Evans); Department of Pediatrics, University of Alberta, Edmonton, Canada (Zwaigenbaum); Department of Speech and Hearing Science, University of Washington, Seattle (St. John, Estes); School of Behavioral and Brain Sciences, University of Texas at Dallas (Swanson).
Guido Gerig, Ph.D.
Carolina Institute for Developmental Disabilities and Department of Psychiatry (Shen, Girault, Kim, Smith, Graves, Weisenfeld, Gross, Styner, Hazlett, Piven) and UNC Neuroscience Center (Shen), University of North Carolina at Chapel Hill School of Medicine, Chapel Hill; Department of Educational Psychology (Wolff), Institute of Child Development (Elison), and Department of Pediatrics (Elison, Burrows), University of Minnesota, Minneapolis; Mallinckrodt Institute of Radiology, Washington University School of Medicine, St. Louis (Flake, McKinstry, Botteron); Department of Radiology, University of Washington Medical Center, Seattle (Dager); Center for Autism Research, Children’s Hospital of Philadelphia, University of Pennsylvania Perelman School of Medicine, Philadelphia (Pandey, Schultz); Computer Science and Engineering, NYU Tandon School of Engineering, New York (Gerig); Montreal Neurological Institute, McGill University, Montreal (MacIntyre, Fonov, Collins, Evans); Department of Pediatrics, University of Alberta, Edmonton, Canada (Zwaigenbaum); Department of Speech and Hearing Science, University of Washington, Seattle (St. John, Estes); School of Behavioral and Brain Sciences, University of Texas at Dallas (Swanson).
Robert C. McKinstry, M.D., Ph.D.
Carolina Institute for Developmental Disabilities and Department of Psychiatry (Shen, Girault, Kim, Smith, Graves, Weisenfeld, Gross, Styner, Hazlett, Piven) and UNC Neuroscience Center (Shen), University of North Carolina at Chapel Hill School of Medicine, Chapel Hill; Department of Educational Psychology (Wolff), Institute of Child Development (Elison), and Department of Pediatrics (Elison, Burrows), University of Minnesota, Minneapolis; Mallinckrodt Institute of Radiology, Washington University School of Medicine, St. Louis (Flake, McKinstry, Botteron); Department of Radiology, University of Washington Medical Center, Seattle (Dager); Center for Autism Research, Children’s Hospital of Philadelphia, University of Pennsylvania Perelman School of Medicine, Philadelphia (Pandey, Schultz); Computer Science and Engineering, NYU Tandon School of Engineering, New York (Gerig); Montreal Neurological Institute, McGill University, Montreal (MacIntyre, Fonov, Collins, Evans); Department of Pediatrics, University of Alberta, Edmonton, Canada (Zwaigenbaum); Department of Speech and Hearing Science, University of Washington, Seattle (St. John, Estes); School of Behavioral and Brain Sciences, University of Texas at Dallas (Swanson).
Juhi Pandey, Ph.D.
Carolina Institute for Developmental Disabilities and Department of Psychiatry (Shen, Girault, Kim, Smith, Graves, Weisenfeld, Gross, Styner, Hazlett, Piven) and UNC Neuroscience Center (Shen), University of North Carolina at Chapel Hill School of Medicine, Chapel Hill; Department of Educational Psychology (Wolff), Institute of Child Development (Elison), and Department of Pediatrics (Elison, Burrows), University of Minnesota, Minneapolis; Mallinckrodt Institute of Radiology, Washington University School of Medicine, St. Louis (Flake, McKinstry, Botteron); Department of Radiology, University of Washington Medical Center, Seattle (Dager); Center for Autism Research, Children’s Hospital of Philadelphia, University of Pennsylvania Perelman School of Medicine, Philadelphia (Pandey, Schultz); Computer Science and Engineering, NYU Tandon School of Engineering, New York (Gerig); Montreal Neurological Institute, McGill University, Montreal (MacIntyre, Fonov, Collins, Evans); Department of Pediatrics, University of Alberta, Edmonton, Canada (Zwaigenbaum); Department of Speech and Hearing Science, University of Washington, Seattle (St. John, Estes); School of Behavioral and Brain Sciences, University of Texas at Dallas (Swanson).
Tanya St. John, Ph.D.
Carolina Institute for Developmental Disabilities and Department of Psychiatry (Shen, Girault, Kim, Smith, Graves, Weisenfeld, Gross, Styner, Hazlett, Piven) and UNC Neuroscience Center (Shen), University of North Carolina at Chapel Hill School of Medicine, Chapel Hill; Department of Educational Psychology (Wolff), Institute of Child Development (Elison), and Department of Pediatrics (Elison, Burrows), University of Minnesota, Minneapolis; Mallinckrodt Institute of Radiology, Washington University School of Medicine, St. Louis (Flake, McKinstry, Botteron); Department of Radiology, University of Washington Medical Center, Seattle (Dager); Center for Autism Research, Children’s Hospital of Philadelphia, University of Pennsylvania Perelman School of Medicine, Philadelphia (Pandey, Schultz); Computer Science and Engineering, NYU Tandon School of Engineering, New York (Gerig); Montreal Neurological Institute, McGill University, Montreal (MacIntyre, Fonov, Collins, Evans); Department of Pediatrics, University of Alberta, Edmonton, Canada (Zwaigenbaum); Department of Speech and Hearing Science, University of Washington, Seattle (St. John, Estes); School of Behavioral and Brain Sciences, University of Texas at Dallas (Swanson).
Lonnie Zwaigenbaum, M.D.
Carolina Institute for Developmental Disabilities and Department of Psychiatry (Shen, Girault, Kim, Smith, Graves, Weisenfeld, Gross, Styner, Hazlett, Piven) and UNC Neuroscience Center (Shen), University of North Carolina at Chapel Hill School of Medicine, Chapel Hill; Department of Educational Psychology (Wolff), Institute of Child Development (Elison), and Department of Pediatrics (Elison, Burrows), University of Minnesota, Minneapolis; Mallinckrodt Institute of Radiology, Washington University School of Medicine, St. Louis (Flake, McKinstry, Botteron); Department of Radiology, University of Washington Medical Center, Seattle (Dager); Center for Autism Research, Children’s Hospital of Philadelphia, University of Pennsylvania Perelman School of Medicine, Philadelphia (Pandey, Schultz); Computer Science and Engineering, NYU Tandon School of Engineering, New York (Gerig); Montreal Neurological Institute, McGill University, Montreal (MacIntyre, Fonov, Collins, Evans); Department of Pediatrics, University of Alberta, Edmonton, Canada (Zwaigenbaum); Department of Speech and Hearing Science, University of Washington, Seattle (St. John, Estes); School of Behavioral and Brain Sciences, University of Texas at Dallas (Swanson).
Annette M. Estes, Ph.D.
Carolina Institute for Developmental Disabilities and Department of Psychiatry (Shen, Girault, Kim, Smith, Graves, Weisenfeld, Gross, Styner, Hazlett, Piven) and UNC Neuroscience Center (Shen), University of North Carolina at Chapel Hill School of Medicine, Chapel Hill; Department of Educational Psychology (Wolff), Institute of Child Development (Elison), and Department of Pediatrics (Elison, Burrows), University of Minnesota, Minneapolis; Mallinckrodt Institute of Radiology, Washington University School of Medicine, St. Louis (Flake, McKinstry, Botteron); Department of Radiology, University of Washington Medical Center, Seattle (Dager); Center for Autism Research, Children’s Hospital of Philadelphia, University of Pennsylvania Perelman School of Medicine, Philadelphia (Pandey, Schultz); Computer Science and Engineering, NYU Tandon School of Engineering, New York (Gerig); Montreal Neurological Institute, McGill University, Montreal (MacIntyre, Fonov, Collins, Evans); Department of Pediatrics, University of Alberta, Edmonton, Canada (Zwaigenbaum); Department of Speech and Hearing Science, University of Washington, Seattle (St. John, Estes); School of Behavioral and Brain Sciences, University of Texas at Dallas (Swanson).
Stephen R. Dager, M.D.
Carolina Institute for Developmental Disabilities and Department of Psychiatry (Shen, Girault, Kim, Smith, Graves, Weisenfeld, Gross, Styner, Hazlett, Piven) and UNC Neuroscience Center (Shen), University of North Carolina at Chapel Hill School of Medicine, Chapel Hill; Department of Educational Psychology (Wolff), Institute of Child Development (Elison), and Department of Pediatrics (Elison, Burrows), University of Minnesota, Minneapolis; Mallinckrodt Institute of Radiology, Washington University School of Medicine, St. Louis (Flake, McKinstry, Botteron); Department of Radiology, University of Washington Medical Center, Seattle (Dager); Center for Autism Research, Children’s Hospital of Philadelphia, University of Pennsylvania Perelman School of Medicine, Philadelphia (Pandey, Schultz); Computer Science and Engineering, NYU Tandon School of Engineering, New York (Gerig); Montreal Neurological Institute, McGill University, Montreal (MacIntyre, Fonov, Collins, Evans); Department of Pediatrics, University of Alberta, Edmonton, Canada (Zwaigenbaum); Department of Speech and Hearing Science, University of Washington, Seattle (St. John, Estes); School of Behavioral and Brain Sciences, University of Texas at Dallas (Swanson).
Robert T. Schultz, Ph.D.
Carolina Institute for Developmental Disabilities and Department of Psychiatry (Shen, Girault, Kim, Smith, Graves, Weisenfeld, Gross, Styner, Hazlett, Piven) and UNC Neuroscience Center (Shen), University of North Carolina at Chapel Hill School of Medicine, Chapel Hill; Department of Educational Psychology (Wolff), Institute of Child Development (Elison), and Department of Pediatrics (Elison, Burrows), University of Minnesota, Minneapolis; Mallinckrodt Institute of Radiology, Washington University School of Medicine, St. Louis (Flake, McKinstry, Botteron); Department of Radiology, University of Washington Medical Center, Seattle (Dager); Center for Autism Research, Children’s Hospital of Philadelphia, University of Pennsylvania Perelman School of Medicine, Philadelphia (Pandey, Schultz); Computer Science and Engineering, NYU Tandon School of Engineering, New York (Gerig); Montreal Neurological Institute, McGill University, Montreal (MacIntyre, Fonov, Collins, Evans); Department of Pediatrics, University of Alberta, Edmonton, Canada (Zwaigenbaum); Department of Speech and Hearing Science, University of Washington, Seattle (St. John, Estes); School of Behavioral and Brain Sciences, University of Texas at Dallas (Swanson).
Martin A. Styner, Ph.D.
Carolina Institute for Developmental Disabilities and Department of Psychiatry (Shen, Girault, Kim, Smith, Graves, Weisenfeld, Gross, Styner, Hazlett, Piven) and UNC Neuroscience Center (Shen), University of North Carolina at Chapel Hill School of Medicine, Chapel Hill; Department of Educational Psychology (Wolff), Institute of Child Development (Elison), and Department of Pediatrics (Elison, Burrows), University of Minnesota, Minneapolis; Mallinckrodt Institute of Radiology, Washington University School of Medicine, St. Louis (Flake, McKinstry, Botteron); Department of Radiology, University of Washington Medical Center, Seattle (Dager); Center for Autism Research, Children’s Hospital of Philadelphia, University of Pennsylvania Perelman School of Medicine, Philadelphia (Pandey, Schultz); Computer Science and Engineering, NYU Tandon School of Engineering, New York (Gerig); Montreal Neurological Institute, McGill University, Montreal (MacIntyre, Fonov, Collins, Evans); Department of Pediatrics, University of Alberta, Edmonton, Canada (Zwaigenbaum); Department of Speech and Hearing Science, University of Washington, Seattle (St. John, Estes); School of Behavioral and Brain Sciences, University of Texas at Dallas (Swanson).
Kelly N. Botteron, M.D.
Carolina Institute for Developmental Disabilities and Department of Psychiatry (Shen, Girault, Kim, Smith, Graves, Weisenfeld, Gross, Styner, Hazlett, Piven) and UNC Neuroscience Center (Shen), University of North Carolina at Chapel Hill School of Medicine, Chapel Hill; Department of Educational Psychology (Wolff), Institute of Child Development (Elison), and Department of Pediatrics (Elison, Burrows), University of Minnesota, Minneapolis; Mallinckrodt Institute of Radiology, Washington University School of Medicine, St. Louis (Flake, McKinstry, Botteron); Department of Radiology, University of Washington Medical Center, Seattle (Dager); Center for Autism Research, Children’s Hospital of Philadelphia, University of Pennsylvania Perelman School of Medicine, Philadelphia (Pandey, Schultz); Computer Science and Engineering, NYU Tandon School of Engineering, New York (Gerig); Montreal Neurological Institute, McGill University, Montreal (MacIntyre, Fonov, Collins, Evans); Department of Pediatrics, University of Alberta, Edmonton, Canada (Zwaigenbaum); Department of Speech and Hearing Science, University of Washington, Seattle (St. John, Estes); School of Behavioral and Brain Sciences, University of Texas at Dallas (Swanson).
Heather C. Hazlett, Ph.D.
Carolina Institute for Developmental Disabilities and Department of Psychiatry (Shen, Girault, Kim, Smith, Graves, Weisenfeld, Gross, Styner, Hazlett, Piven) and UNC Neuroscience Center (Shen), University of North Carolina at Chapel Hill School of Medicine, Chapel Hill; Department of Educational Psychology (Wolff), Institute of Child Development (Elison), and Department of Pediatrics (Elison, Burrows), University of Minnesota, Minneapolis; Mallinckrodt Institute of Radiology, Washington University School of Medicine, St. Louis (Flake, McKinstry, Botteron); Department of Radiology, University of Washington Medical Center, Seattle (Dager); Center for Autism Research, Children’s Hospital of Philadelphia, University of Pennsylvania Perelman School of Medicine, Philadelphia (Pandey, Schultz); Computer Science and Engineering, NYU Tandon School of Engineering, New York (Gerig); Montreal Neurological Institute, McGill University, Montreal (MacIntyre, Fonov, Collins, Evans); Department of Pediatrics, University of Alberta, Edmonton, Canada (Zwaigenbaum); Department of Speech and Hearing Science, University of Washington, Seattle (St. John, Estes); School of Behavioral and Brain Sciences, University of Texas at Dallas (Swanson).
Joseph Piven, M.D.
Carolina Institute for Developmental Disabilities and Department of Psychiatry (Shen, Girault, Kim, Smith, Graves, Weisenfeld, Gross, Styner, Hazlett, Piven) and UNC Neuroscience Center (Shen), University of North Carolina at Chapel Hill School of Medicine, Chapel Hill; Department of Educational Psychology (Wolff), Institute of Child Development (Elison), and Department of Pediatrics (Elison, Burrows), University of Minnesota, Minneapolis; Mallinckrodt Institute of Radiology, Washington University School of Medicine, St. Louis (Flake, McKinstry, Botteron); Department of Radiology, University of Washington Medical Center, Seattle (Dager); Center for Autism Research, Children’s Hospital of Philadelphia, University of Pennsylvania Perelman School of Medicine, Philadelphia (Pandey, Schultz); Computer Science and Engineering, NYU Tandon School of Engineering, New York (Gerig); Montreal Neurological Institute, McGill University, Montreal (MacIntyre, Fonov, Collins, Evans); Department of Pediatrics, University of Alberta, Edmonton, Canada (Zwaigenbaum); Department of Speech and Hearing Science, University of Washington, Seattle (St. John, Estes); School of Behavioral and Brain Sciences, University of Texas at Dallas (Swanson).
for the IBIS Network
Carolina Institute for Developmental Disabilities and Department of Psychiatry (Shen, Girault, Kim, Smith, Graves, Weisenfeld, Gross, Styner, Hazlett, Piven) and UNC Neuroscience Center (Shen), University of North Carolina at Chapel Hill School of Medicine, Chapel Hill; Department of Educational Psychology (Wolff), Institute of Child Development (Elison), and Department of Pediatrics (Elison, Burrows), University of Minnesota, Minneapolis; Mallinckrodt Institute of Radiology, Washington University School of Medicine, St. Louis (Flake, McKinstry, Botteron); Department of Radiology, University of Washington Medical Center, Seattle (Dager); Center for Autism Research, Children’s Hospital of Philadelphia, University of Pennsylvania Perelman School of Medicine, Philadelphia (Pandey, Schultz); Computer Science and Engineering, NYU Tandon School of Engineering, New York (Gerig); Montreal Neurological Institute, McGill University, Montreal (MacIntyre, Fonov, Collins, Evans); Department of Pediatrics, University of Alberta, Edmonton, Canada (Zwaigenbaum); Department of Speech and Hearing Science, University of Washington, Seattle (St. John, Estes); School of Behavioral and Brain Sciences, University of Texas at Dallas (Swanson).
Notes
Send correspondence to Dr. Shen ([email protected]).
Competing Interests
Dr. McKinstry has served on a medical advisory board for Nous Imaging and has equity in the company, and he has received travel support from Siemens Healthineers and Philips Healthcare. The other authors report no financial relationships with commercial interests.
Funding Information
Supported by NIH grants R01-HD055741, R01-HD059854, R01-MH118362-01, R01-MH118362-02S1, T32-HD040127, U54-HD079124, P50-HD103573 (project ID 8084), R01-EB021391, and U54-HD086984; by Autism Speaks; and by the Simons Foundation (grant 140209). Dr. Shen was supported by an NIH career development award (K12-HD001441).
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