Altered Myelination of the Corpus Callosum In Autism

Background: Existing literature indicates that autism may be associated with atypical functional connectivity. It has been suggested that abnormalities in white matter myelination may contribute to this connectivity dysfunction; yet there is lack of data specifically examining myelination of the corpus callosum (the major interhemispheric white matter tract) in autism. Magnetic transfer imaging (MTI) is an MRI technique that detects the exchange of magnetization between protons bound to large, poorly mobile macromolecules (such as myelin) and mobile protons in free water. The most common MTI measure is the magnetization transfer ratio (MTR), which provides quantitative information about the presence of myelin in the brain.

Objectives: In this study, MTI was used to investigate corpus callosum myelination in children with autism compared to typically developing children. Children with autism with and without a history of regression were analyzed separately to determine whether differences in myelination may support these as distinct subtypes. While MTI has been successfully applied in disorders affecting myelin such as multiple sclerosis, no studies are currently available using this technique in autism.

Methods: Subjects included 23 children with regressive autism (17 males, 6 females; mean age=4.1, sd=1.2), 23 children with non-regressive autism (17 males, 6 females; mean age=4.1, sd=1.4), and 23 typically developing children (17 males, 6 females; mean age=4.0, sd=1.6). Gender and age did not differ between groups. Experienced clinicians confirmed the diagnoses using the ADI-R and ADOS. Autistic subjects were sedated for scanning; controls were scanned without sedation. All subjects were scanned using a 1.5 Tesla scanner. The corpus callosum was manually traced on each subject's anatomical MRI by an experienced rater. The magnetization transfer images were then co-registered with the anatomical images. Within the corpus callosum, MTR values were calculated and plotted as a histogram. Each subject’s histogram was analyzed in terms of the MTR peak location (most frequent value) and MTR peak height (the number of voxels having the most frequent value, a measure of uniformity). Group comparisons of MTR parameters were performed using analysis of variance (ANOVA) and post-hoc tests.

Results: Peak height was significantly different between groups (regressive autism: mean=.097, sd=.011; non-regressive autism: mean=.097, sd=.008; controls: mean=.087, sd=.012; p=.004). LSD post hoc comparisons revealed that peak height was significantly higher in the children with regressive (p=.003) and non-regressive (p=.005) autism relative to the typically developing children; peak height did not differ between regressive and non-regressive groups. Peak location was not significantly different between groups (regressive autism: mean=26.04, sd=2.36; non-regressive autism: mean=25.87, sd=2.01; controls: mean=24.83, sd=1.8; p=.11).

Conclusions: This is the first study investigating the myelination of the corpus callosum in autism using MTI. Compared to typically developing children, autistic children showed increased MTR peak height, providing evidence of altered myelination in the corpus callosum. The lack of significant differences between children with regressive and non-regressive autism does not support these as distinct subtypes of autism. Our findings of atypical white matter development are consistent with the theory of abnormal connectivity in autism and may provide additional clues to the neuropathology of autism.