Enlarged Corpus Callosum in Down Syndrome Compared to Autism and Neurotypical Children

Background The corpus callosum is the brain’s largest white matter tract and plays a key role in communication between the two hemispheres. Differences in its size and development have been observed in several neurodevelopmental conditions, including Autism Spectrum Disorder (ASD) and Down syndrome (DS). However, findings have been mixed, especially when it comes to accounting for overall brain size. This study looks at the midsagittal area of the corpus callosum and its subregions in school-aged children with ASD and DS compared to neurotypical (NT) peers, with a focus on differences relative to total brain volume.   Methods MRI data were collected from 293 children between the ages of 9 and 10 as part of ongoing neurodevelopmental studies at UNC-Chapel Hill. Participants were grouped as follows: neurotypical (NT), low-likelihood ASD-positive (LL+), high-likelihood ASD-negative (HL−), high-likelihood ASD-positive (HL+), and children with Down syndrome (DS). T1- and T2-weighted scans were used to segment the midsagittal corpus callosum, which was then reviewed and corrected manually. The total corpus callosum area and areas of four subregions (anterior frontal, posterior frontal, parietal, and occipital + temporal) were measured and normalized to each participant’s total cerebral volume (TCV). Group comparisons were made using ANCOVA, controlling for age and sex.   Results There were no significant group differences in the raw midsagittal corpus callosum area. However, once measurements were normalized to brain size, clear group differences emerged. The DS group had significantly larger corpus callosum-to-brain volume ratios compared to the NT, HL−, and HL+ groups across all four subregions. These findings were strongest in the anterior and posterior frontal regions. The DS group also had significantly smaller total brain volumes. In contrast, no significant differences in corpus callosum ratios were observed between the ASD groups and the NT group. There were several group-by-age interactions, suggesting that developmental patterns differ across groups.   Discussion Children with Down syndrome had relatively larger corpus callosum areas despite having smaller brains overall, which may reflect differences in white matter development or compensatory mechanisms. These results support earlier findings of atypical callosal development in DS, especially in regions involved in executive function. The ASD groups did not show significant callosal differences compared to neurotypical controls, possibly due to sample size limitations or the broad variability within ASD. The significant group-by-age interactions point to different developmental trajectories across groups. More work is needed to explore how these structural differences relate to cognitive and behavioral outcomes. Longitudinal studies and additional imaging methods like diffusion tensor imaging could help clarify the role of the corpus callosum in these conditions.