Objectives: We evaluated the development of the corpus callosum over a two year period from 3-5 years of age in a large sample of children with ASD and age-matched typically developing (TD) controls.
Methods: We acquired structural and diffusion-weighted MRIs in 218 (139 ASD, 79 TD control) children (mean age at baseline 36 months). Longitudinal imaging was carried out annually at two additional timepoints in a subset of this sample (84 with 2 scans, 26 with 3 scans). Specifically, we used (1) structural imaging to evaluate the total size of corpus callosum as well as Witelson subdivisions within the corpus callosum and (2) diffusion tensor tractography to evaluate the organization of callosal fibers based on cortical projection zones as well as the microstructural characteristics of the fibers themselves.
Separate repeated measures models were run for each corpus callosum subsection, with scan year as the repeated measure. Main effects for total cerebral volume, age, gender, and diagnostic group were tested. Interactions between age, gender, and diagnosis were also tested.
Results: Overall, we found that the corpus callosum is smaller in the ASD group than in TD controls, particularly in the rostral body and anterior midbody subsections. Evaluation of change over time revealed that the splenium increased at a faster rate in TD controls than the ASD group.
Evaluation of the organization of the corpus callosum based on cortical projection zone revealed that the region of the corpus callosum containing fibers projecting to the superior frontal cortex is smaller in ASD than in TD controls. In addition, the region containing fibers projecting to orbital frontal cortex increased at a slower rate in ASD relative to TD controls.
When examining the diffusion characteristics of callosal fibers, we found that in children with ASD, fractional anisotropy of fibers projecting to the superior frontal cortex increased at a slower rate, and mean diffusivity and radial diffusivity decreased at a slower rate relative to TD controls. The ASD group also exhibited a faster decrease in mean diffusivity over time in fibers projecting to the orbital frontal cortex than TD controls.
Conclusions: These results suggest that the corpus callosum is developing abnormally in young children with ASD. Specifically, there are abnormalities in the organization of callosal fibers projecting to superior frontal and orbital frontal regions in children with ASD and the fibers themselves are developing on a different trajectory. There are also developmental differences in the splenium that require further investigation. This pattern of results suggests that detailed examination of specific callosal pathways may provide insights into which particular parts of the white matter develop abnormally in ASD.