Neural circuitry at age 6 months associated with later repetitive behavior and sensory responsiveness in autism

Jason J. Wolff, Meghan R. Swanson, Jed T. Elison, Guido Gerig, John R. Pruett, Martin A. Styner, Clement Vachet, Kelly N. Botteron, Stephen R. Dager, Annette M. Estes, Heather C. Hazlett, Robert T. Schultz, Mark D. Shen, Lonnie Zwaigenbaum, Joseph Piven, J. Piven, H. C. Hazlett, S. Dager, A. Estes, D. ShawK. Botteron, R. McKinstry, J. Constantino, J. Pruett, R. Schultz, S. Paterson, L. Zwaigenbaum, J. Elison, A. C. Evans, D. L. Collins, G. B. Pike, V. Fonov, P. Kostopoulos, S. Das, G. Gerig, M. Styner, H. Gu

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81 Scopus citations


Background: 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. Methods: 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. Results: 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. Conclusions: 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.

Original languageEnglish
Article number8
JournalMolecular Autism
Issue number1
StatePublished - Mar 4 2017


  • Autism
  • Diffusion tensor imaging
  • Infant
  • Longitudinal
  • Repetitive behavior
  • White matter


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