The online version of this article (doi:10.1186/s13229-017-0126-z) contains supplementary material, which is available to authorized users.
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.
Additional file 1: Table A1. Longitudinal model results for axial and radial diffusivities with repetitive behavior and sensory responsiveness, HR-ASD. Table A2 Axial and radial diffusivities at age 6 months predicting repetitive behavior and sensory responsiveness measured at age 2 years, HR-ASD. Table A3 Nonparametric correlations for subscales derived from the RBS-R and SEQ among HR-Neg. Table A4 Longitudinal model results for fractional anisotropy of bilateral pathways with repetitive behavior and sensory responsiveness, HR-ASD. Table A5 Fractional anisotropy of bilateral pathways at age 6 months predicting repetitive behavior and sensory responsiveness measured at age 2 years, HR-ASD. Table A6 Interaction of diagnostic status and fractional anisotropy on behavior. (DOCX 27 kb)13229_2017_126_MOESM1_ESM.docx
Additional file 2: Figure S1. Scatterplots of FA in select white matter pathways at age 6 months with RBS-R and SEQ scores. Scatterplots show relationship of FA in two pathways measured at age 6 months (genu, cortico-spinal tract) with total Repetitive Behavior Scale-Revised (RBS-R) and Sensory Experiences Questionnaire (SEQ) scores at age 24 months. Panels a and c were selected to provide visualization of a significant relationship between brain-and behavior in children with ASD (HR-ASD, in red). Panels b and d provide examples of a non-significant relationship (RBS-R and SEQ, respectively). High-risk children without ASD (HR-Neg) are shown in blue. Note that linear trend lines are for visualization purposes only and were not the basis of statistical modeling. (TIF 191 kb)13229_2017_126_MOESM2_ESM.tif
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- 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
John R. Pruett Jr.
Martin A. Styner
Kelly N. Botteron
Stephen R. Dager
Annette M. Estes
Heather C. Hazlett
Robert T. Schultz
Mark D. Shen
The IBIS Network
- BioMed Central