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White Matter Microstructure and Atypical Visual Orienting in 7-Month-Olds at Risk for Autism
Jed T. Elison, Ph.D.; Sarah J. Paterson, Ph.D.; Jason J. Wolff, Ph.D.; J. Steven Reznick, Ph.D.; Noah J. Sasson, Ph.D.; Hongbin Gu, Ph.D.; Kelly N. Botteron, M.D.; Stephen R. Dager, M.D.; Annette M. Estes, Ph.D.; Alan C. Evans, Ph.D.; Guido Gerig, Ph.D.; Heather C. Hazlett, Ph.D.; Robert T. Schultz, Ph.D.; Martin Styner, Ph.D.; Lonnie Zwaigenbaum, M.D.; Joseph Piven, M.D.; for the IBIS Network
Am J Psychiatry 2013;170:899-908. doi:10.1176/appi.ajp.2012.12091150
View Disclosures and Other Information

Dr. Evans is cofounder of and holds equity in Biospective, Inc.; he has also received consulting fees from Johnson & Johnson and Pfizer. Dr. Hazlett has received travel support from Autism Speaks. All other authors report no financial relationships with commercial interests.

Supported by grants awarded to Dr. Piven from NIH/National Institute of Child Health and Development (NICHD) (Autism Center of Excellence, R01 HD055741 and HD055741-S1; Intellectual and Developmental Disabilities Research Center, P30 HD03110 and T32 HD40127), Autism Speaks, and the Simons Foundation. Dr. Elison was supported by a National Research Service Award (5-T32-HD007376) from NICHD, and aspects of this work contributed to his doctoral dissertation. Further support was provided by the National Alliance for Medical Image Computing, funded by NIH through grant U54 EB005149.

The Infant Brain Imaging Study (IBIS) Network is an NIH-funded Autism Center of Excellence project and consists of a consortium of seven universities in the United States and Canada. Clinical sites: University of North Carolina: J. Piven (IBIS Network principal investigator), H.C. Hazlett, and J.C. Chappell; University of Washington: S. Dager, A. Estes, and D. Shaw; Washington University: K. Botteron, R. McKinstry, J. Constantino, and J. Pruett; Children’s Hospital of Philadelphia: R. Schultz and S. Paterson; University of Alberta: L. Zwaigenbaum; Data Coordinating Center: Montreal Neurological Institute: A.C. Evans, D.L. Collins, G.B. Pike, P. Kostopolous, and S. Das; Image Processing Core: University of Utah: G. Gerig; University of North Carolina: M. Styner; Statistical Analysis Core: University of North Carolina: H. Gu; Genetics Analysis Core: University of North Carolina: P. Sullivan and F. Wright.

From the Carolina Institute for Developmental Disabilities and the Departments of Psychiatry, Psychology, and Computer Science, University of North Carolina at Chapel Hill; Division of Humanities and Social Sciences, California Institute of Technology, Pasadena; Center for Autism Research, Children’s Hospital of Philadelphia and University of Pennsylvania, Philadelphia; School of Behavioral and Brain Sciences, University of Texas at Dallas; Department of Psychiatry, Washington University, St. Louis; Departments of Radiology and Speech and Hearing Sciences, University of Washington, Seattle; Montreal Neurological Institute, McGill University, Montreal; Scientific Computing and Imaging Institute, University of Utah, Salt Lake City; Department of Pediatrics, University of Alberta, Edmonton.

Presented in part at the International Meeting for Autism Research, Toronto, May 17–19, 2012.

Address correspondence to Dr. Elison (jelison@caltech.edu) or Dr. Piven (jpiven@med.unc.edu).

Copyright © 2013 by the American Psychiatric Association

Abstract

Objective  The authors sought to determine whether specific patterns of oculomotor functioning and visual orienting characterize 7-month-old infants who later meet criteria for an autism spectrum disorder (ASD) and to identify the neural correlates of these behaviors.

Method  Data were collected from 97 infants, of whom 16 were high-familial-risk infants later classified as having an ASD, 40 were high-familial-risk infants who did not later meet ASD criteria (high-risk negative), and 41 were low-risk infants. All infants underwent an eye-tracking task at a mean age of 7 months and a clinical assessment at a mean age of 25 months. Diffusion-weighted imaging data were acquired for 84 of the infants at 7 months. Primary outcome measures included average saccadic reaction time in a visually guided saccade procedure and radial diffusivity (an index of white matter organization) in fiber tracts that included corticospinal pathways and the splenium and genu of the corpus callosum.

Results  Visual orienting latencies were longer in 7-month-old infants who expressed ASD symptoms at 25 months compared with both high-risk negative infants and low-risk infants. Visual orienting latencies were uniquely associated with the microstructural organization of the splenium of the corpus callosum in low-risk infants, but this association was not apparent in infants later classified as having an ASD.

Conclusions  Flexibly and efficiently orienting to salient information in the environment is critical for subsequent cognitive and social-cognitive development. Atypical visual orienting may represent an early prodromal feature of an ASD, and abnormal functional specialization of posterior cortical circuits directly informs a novel model of ASD pathogenesis.

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