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Original Investigation |

Pervasive Rightward Asymmetry Shifts of Functional Networks in Autism Spectrum Disorder

Ryan C. Cardinale, BA1,2; Patricia Shih, MA1,3; Inna Fishman, PhD1; Leanne M. Ford, BA1; Ralph-Axel Müller, PhD1
[+] Author Affiliations
1Brain Development Imaging Laboratory, Department of Psychology, San Diego State University, San Diego, California
2Department of Psychology, University of Michigan, Ann Arbor
3Department of Neuroscience, Brown University, Providence, Rhode Island
JAMA Psychiatry. 2013;70(9):975-982. doi:10.1001/jamapsychiatry.2013.382.
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Importance  Autism spectrum disorder (ASD) is a brain-based pervasive developmental disorder, which—by growing consensus—is associated with abnormal organization of functional networks. Several previous studies of ASD have indicated atypical hemispheric asymmetries for language.

Objective  To examine the asymmetry of functional networks using a data-driven approach for a comprehensive investigation of hemispheric asymmetry in ASD.

Design, Setting, and Participants  This cross-sectional study involved 24 children with ASD and 26 matched typically developing children at San Diego State University and the University of California, San Diego. Data from 10 children had to be excluded for excessive motion, resulting in final samples of 20 participants per group.

Main Outcomes and Measures  Asymmetry indices of functional networks identified from independent component analysis of resting-state functional magnetic resonance imaging data.

Results  Temporal concatenation independent component analysis, performed separately in each group, showed significant group differences in asymmetry indices for 10 out of 17 functional networks. Without exception, these networks (visual, auditory, motor, executive, language, and attentional) showed atypical rightward asymmetry shifts in the ASD group.

Conclusions and Relevance  Atypical rightward asymmetry may be a pervasive feature of functional brain organization in ASD, affecting sensorimotor, as well as higher cognitive, domains.

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Components From Auto-dimensionality Analysis

In each panel, the typically developing component is shown at the top and the matched autism spectrum disorder (ASD) component at the bottom (with spatial correlation coefficient shown on the left). Next to the group labels are the group asymmetry indices. P values are derived from between-group permutation tests of asymmetry indices controlling for age. The matching of components to those from previous studies is abbreviated as: mtL, matched to Laird et al,22,23 and mtS, matched to Smith et al.22 A, Component involving visuospatial processing and reasoning (mtL); B, lateral visual area component (mtS); C, right frontoparietal component (mtL and mtS); D, auditory component (mtS); E and F, sensorimotor components (mtL and mtS); G, executive component (mtS); H, left frontoparietal component (mtL and mtS); I, lateral visual area component (mts); J, unmatched component (neither mtL nor mtS); and K, right frontoparietal component (mtL and mtS). Note that a single ASD component was matched to 2 separate TD components, shown in panels C and K. All images shown in neurological convention (left side is left hemisphere). Asymmetry index (AI) labels defined as follows: B indicates bilateral (AI: −0.1 to 0.1); L, left lateralized (AI < −0.3); (L), weakly left lateralized (AI: −0.3 to −0.1); R, right lateralized (AI > 0.3); and (R), weakly right lateralized (AI: 0.1 to 0.3).

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