Abnormalities in white matter microstructure and connectivity have been reported in autism, but no studies have included a large sample in early childhood. It is also unclear how measures of microstructure, connectivity, and cortical shape interact and are associated with autism symptomatology.
To evaluate multiple aspects of white matter integrity in a large sample of young children with autism. Analyses include an examination of the microstructure of white matter tracts, the connectivity between tracts and cortical regions, and patterns of cortical folding and sulcal organization. This study was conducted as part of a larger multidisciplinary study at the M.I.N.D. Institute, the Autism Phenome Project.
Diffusion-weighted images were acquired on 100 children (64 ASD, 36 TD; mean age ASD 3.2 years, TD 3.4 years). The total sample included 75 boys and 25 girls; the subset of girls will be analyzed separately. Tract-based spatial statistics (TBSS) were applied to determine whether specific white matter tracts show between-group differences in measures of white matter integrity. Tractography analyses were performed to examine the connectivity between white matter tracts, particularly fibers that project through the corpus callosum. Manual segmentation of callosal fibers allowed for the identification of fibers that projected to each cortical area (e.g. occipital, parietal, temporal, and frontal fibers). Diffusion-weighted variables such as fractional anisotropy (FA), mean diffusivity (MD), and radial diffusivity (RD) were analyzed as measures of white matter integrity.
Preliminary results of the tract-based analysis show reductions in FA for the autism group, in several regions including: the corpus callosum, left medial parietal lobe adjacent to the splenium of the corpus callosum, left superior temporal lobe, and right middle frontal gyrus. Tractography results suggest that children with autism have compromised white matter integrity in corpus callosum fibers that project to the frontal lobe, particularly oribitofrontal cortex. Moreover, greater white matter irregularity in these fibers correlated with more severe autism symptoms.
These findings provide evidence in early autism for white matter abnormalities in specific tracts and in fibers that project between cortical areas, including the frontal lobe. This is a reflection of impaired anatomical connectivity that may underlie cortical networks important for social cognition, which may relate to autism symptoms. Surface-based analyses of structural MRIs will be conducted to examine whether cortical folding abnormalities are related to regions of abnormal white matter microstructure and connectivity. Finally, this multimodal MRI analysis will be correlated with other behavioral, diagnostic, genetic, and immunological measures to further understand how possible subtypes of autism are associated with differential development of white matter.