Increased Sensorimotor U-Fiber Connections in Autism: Localization and Association with Symptom Severity

Background: Autism spectrum disorder (ASD) is commonly associated with deficits with motor skills and tactile sensory processing. Multiple DTI studies have revealed abnormalities in the white matter connectivity in individuals with ASD, including in fronto-parietal regions crucial for motor and sensory control; however, U-fibers connecting primary somatosensory cortex and the primary motor cortex (“sensorimotor U-fibers”) have not been examined in detail. Mapping sensorimotor U-fibers to clusters associated with three functionally distinct regions: foot, hand, face and mouth, could help characterizing microstructure in underlying white matter tracts in children with ASD.

Objectives: To examine the sensorimotor U-fibers in order to reveal differences between children with ASD and typically developing (TD) white matter fiber integrity and symptom severity.

Methods: Diffusion weighted imaging was acquired on 20 boys with ASD and 20 typically developing (TD) boys aged 8-12 years. Groups were balanced for age and IQ. All children were right handed. MRIStudio was used to perform deterministic fiber tracking in the left sensorimotor cortex. The fibers were further segmented into face/mouth, foot, and hand regions using spherical fMRI-based seeds. Total number of streamlines (white matter connections), Fractional Anisotropy (FA) and mean diffusivity (MD), FA were calculated for the whole sensorimotor fiber map and for each region separately. ANOVA was used to examine the effect of diagnosis on number of streamlines, FA, and MD. Pearson’s correlations were used to examine associations between the number of streamlines, FA, and MD and symptom severity. Symptom severity was assessed using the Autism Diagnostic Observation Schedule (ADOS).

Results: Preliminary analysis suggests boys with ASD showed increased total number of sensorimotor U-fiber streamlines (p=0.031); this appeared to be particularly localized to the foot (p=0.032). Pearson’s correlation further revealed a positive correlation between the increased number of streamlines and increased symptom severity (ADOS total score; r=0.50, p=0.025). Interestingly, while we observed an association between increasing age and total number of streamlines for face/mouth (r=0.554, p=0.011), foot (r=0.457, p=0.043), and for all regions collapsed (r=0.443, p=0.051) in TD boys, this was not observed in boys with ASD. MD was significantly higher in ASD boys for foot (p=0.013) and hand region (p=0.042) sensorimotor U-fibers, but not for face/mouth. FA was not significantly different in any of the three regions or the overall fiber map.

Conclusions: Consistent with prior findings suggesting disorganized overgrowth of early developing white matter connections, we found children with ASD show increased volume (number of streamlines) and decreased organization of sensorimotor U-fiber connections. The findings were localized to foot and hand regions, and there was a positive association with symptom severity, such that increase volume was associated with increased symptom severity. In addition, children with ASD showed an anomalous association of sensorimotor U-fiber volume with age: whereas the number of streamlines increased with age in the TD children, this relationship was not seen in children with ASD.