Neural circuitry at age 6 months associated with later repetitive behavior and sensory responsiveness in autism.
Restricted and repetitive behaviors are defining features of autism spectrum disorder (ASD). Under revised diagnostic criteria for ASD, this behavioral domain now includes atypical responses to sensory stimuli. To date, little is known about the neural circuitry underlying these features of ASD early in life.



Longitudinal diffusion tensor imaging data were collected from 217 infants at high familial risk for ASD. Forty-four of these infants were diagnosed with ASD at age 2. Targeted cortical, cerebellar, and striatal white matter pathways were defined and measured at ages 6, 12, and 24 months. Dependent variables included the Repetitive Behavior Scale-Revised and the Sensory Experiences Questionnaire.



Among children diagnosed with ASD, repetitive behaviors and sensory response patterns were strongly correlated, even when accounting for developmental level or social impairment. Longitudinal analyses indicated that the genu and cerebellar pathways were significantly associated with both repetitive behaviors and sensory responsiveness but not social deficits. At age 6 months, fractional anisotropy in the genu significantly predicted repetitive behaviors and sensory responsiveness at age 2. Cerebellar pathways significantly predicted later sensory responsiveness. Exploratory analyses suggested a possible disordinal interaction based on diagnostic status for the association between fractional anisotropy and repetitive behavior.



Our findings suggest that restricted and repetitive behaviors contributing to a diagnosis of ASD at age 2 years are associated with structural properties of callosal and cerebellar white matter pathways measured during infancy and toddlerhood. We further identified that repetitive behaviors and unusual sensory response patterns co-occur and share common brain-behavior relationships. These results were strikingly specific given the absence of association between targeted pathways and social deficits.
Department of Educational Psychology, University of Minnesota, Minneapolis, MN USA.
Jason J
JJ
Wolff
Carolina Institute for Developmental Disabilities, University of North Carolina, Chapel Hill, NC USA.
Meghan R
MR
Swanson
Institute of Child Development, University of Minnesota, Minneapolis, MN USA.
Jed T
JT
Elison
Tandon School of Engineering, New York University, New York City, NY USA.
Guido
G
Gerig
Department of Psychiatry, Washington University School of Medicine, St. Louis, MO USA.
John R
JR
Pruett
Department of Psychiatry, University of North Carolina, Chapel Hill, NC USA.
Martin A
MA
Styner
Scientific Computing and Imaging Institute, University of Utah, Salt Lake City, UT USA.
Clement
C
Vachet
Department of Psychiatry, Washington University School of Medicine, St. Louis, MO USA.
Kelly N
KN
Botteron
Department of Radiology, University of Washington, Seattle, WA USA.
Stephen R
SR
Dager
Department of Speech and Hearing Sciences, University of Washington, Seattle, WA USA.
Annette M
AM
Estes
Carolina Institute for Developmental Disabilities, University of North Carolina, Chapel Hill, NC USA.|Department of Psychiatry, University of North Carolina, Chapel Hill, NC USA.
Heather C
HC
Hazlett
Center for Autism Research, Children's Hospital of Philadelphia, Philadelphia, PA USA.
Robert T
RT
Schultz
Carolina Institute for Developmental Disabilities, University of North Carolina, Chapel Hill, NC USA.
Mark D
MD
Shen
Department of Pediatrics, University of Alberta, Edmonton, AB Canada.
Lonnie
L
Zwaigenbaum
Carolina Institute for Developmental Disabilities, University of North Carolina, Chapel Hill, NC USA.|Department of Psychiatry, University of North Carolina, Chapel Hill, NC USA.
Joseph
J
Piven
D000067877:Autism Spectrum Disorder / Q000000981:diagnostic imaging / Q000523:psychology*; D001921:Brain / Q000000981:diagnostic imaging / Q000502:physiology*; D001931:Brain Mapping / Q000379:methods*; D002675:Child, Preschool; D056324:Diffusion Tensor Imaging / Q000379:methods*; D005260:Female; D006801:Humans; D007223:Infant; D008137:Longitudinal Studies; D008297:Male; D013239:Stereotyped Behavior / Q000502:physiology*
Autism; Diffusion tensor imaging; Infant; Longitudinal; Repetitive behavior; White matter