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Probing the Brain in Autism Using fMRI and Diffusion Tensor Imaging
Published on: September 12, 2011
Atypical age-dependent effects of autism on white matter microstructure in children of 2-7 years
Minhui Ouyang1,2,3, Hua Cheng4, Virendra Mishra2
1Department of Radiology, Children's Hospital of Philadelphia, Pennsylvania.
Insights
Autism spectrum disorder (ASD) shows atypical white matter (WM) development before age 4, with flattened maturation curves compared to typical development. These early changes in WM microstructure may impact neural development in children with ASD.
Area of Science:
- Neuroscience
- Developmental Neuroscience
- Pediatric Neurology
Background:
- Autism spectrum disorder (ASD) is associated with abnormal brain maturation.
- White matter (WM) microstructure changes with age and is crucial for brain development.
- Early manifestations of atypical WM development in ASD require systematic characterization.
Purpose of the Study:
- To systematically characterize early age-dependent changes in white matter (WM) microstructure in children with autism spectrum disorder (ASD).
- To compare WM microstructural development between children with ASD and typically developing (TD) children aged 2-7 years.
Main Methods:
- Diffusion tensor imaging (DTI) was used to measure fractional anisotropy (FA) and radial diffusivity (RD) in core WM voxels.
- A total of 31 children with ASD and 19 TD children (aged 2-7 years) were included.
- Skeletonized WM was integrated with a digital atlas to delineate WM tracts with atypical changes.
Main Results:
- Children with ASD showed unidirectional FA increases and RD decreases before age 4, with bidirectional changes between 2-7 years.
- WM maturation curves were flattened in major WM tracts (especially associational and limbic) in children with ASD compared to TD.
- Atypical age-dependent changes in FA and RD were widespread and heterogeneous across WM tracts in children with ASD, with trend lines crossing around 4 years.
Conclusions:
- Atypical age-dependent changes in white matter (WM) microstructure are evident early in autism spectrum disorder (ASD), before 4 years of age.
- These early alterations in WM integrity, characterized by flattened maturation curves, suggest abnormal neural patterning, connectivity, and pruning.
- Such early microstructural differences may contribute to the aberrant behavioral and cognitive development observed in ASD.
Abstract:
Atypical age-dependent changes of white matter (WM) microstructure play a central role in abnormal brain maturation of the children with autism spectrum disorder (ASD), but their early manifestations have not been systematically characterized. The entire brain core WM voxels were surveyed to detect differences in WM microstructural development between 31 children with ASD of 2-7 years and 19 age-matched children with typical development (TD), using measurements of fractional anisotropy (FA) and radial diffusivity (RD) from diffusion tensor imaging (DTI). The anatomical locations, distribution, and extent of the core WM voxels with atypical age-dependent changes in a specific tract or tract group were delineated and evaluated by integrating the skeletonized WM with a digital atlas. Exclusively, unidirectional FA increases and RD decreases in widespread WM tracts were revealed in children with ASD before 4 years, with bi-directional changes found for children with ASD of 2-7 years. Compared to progressive development that raised FA and lowered RD during 2-7 years in the TD group, flattened curves of WM maturation were found in multiple major WM tracts of all five tract groups, particularly associational and limbic tracts, in the ASD group with trend lines of ASD and TD crossed around 4 years. We found atypical age-dependent changes of FA and RD widely and heterogeneously distributed in WM tracts of children with ASD. The early higher WM microstructural integrity before 4 years reflects abnormal neural patterning, connectivity, and pruning that may contribute to aberrant behavioral and cognitive development in ASD. Hum Brain Mapp 37:819-832, 2016. © 2015 Wiley Periodicals, Inc.
