Reduced Age-Related Trajectories of Fractional Anisotropy and Volume for the Left Arcuate Fasciculus in Autism

Background: The arcuate fasciculus is a white matter fiber bundle connecting canonical language regions in the brain. Previous diffusion tensor imaging studies comparing metrics of white matter microstructure integrity of the arcuate fasciculus between individuals with autism and typical development have been cross-sectional with regard to age and have produced inconsistent results. 

Objectives: To compare age-related trajectories of arcuate fasciculus development between individuals with autism spectrum disorder (ASD) and typically developing controls (TDC) by examining longitudinal changes in mean fractional anisotropy (FA) and total volume for both left and right arcuate fasciculi. 

Methods: Three-hundred and seventy-six diffusion-weighted imaging scans were collected from 94 males with autism (mean age of 15.1 years at first scan with age range of 3.0 – 45.4; nonverbal IQ > 60) and 43 males with typical development (mean age of 16.0 years at first scan with age range of 4.0 – 29.5). One to four scans were acquired per participant, at an average interscan interval of 2.5 years. Diffusion tensor image processing involved implementing a previously used volumetric segmentation approach to extract arcuate fasciculus white matter tracts, from which mean FA and total volume of tracts were measured. Using age mean-centered at time of first scan (15.4 years), longitudinal mixed effects models were used to identify group differences in longitudinal age-related trajectories for left arcuate mean FA, left arcuate total volume, right arcuate mean FA, and right arcuate total volume.

Results: For the left arcuate fasciculus, the ASD group showed a reduced age-related increase in mean FA compared to the TDC (group by age interaction: t(232) = 2.84, p = 0.02, Bonferroni corrected); the ASD group had significantly lower FA than the TDC (group effect: t(135) = 3.5, p = 0.002, Bonferroni corrected). Additionally, the ASD group showed a smaller age-related increase in left arcuate volume compared to the TDC (group by age interaction: t(237) = 2.68, p = .03, Bonferroni corrected), but ASD and TDC groups did not significantly differ in left arcuate volume. For the right arcuate fasciculus, no significant group or age-related group differences were found for mean FA or total volume. 

Conclusions: Our results suggest that development of the left arcuate fasciculus occurs more slowly in individuals with autism. The ASD group compared to TDC group showed a reduced age-related increase in FA, indicative of a slower increase in axonal organization and density, as well as a reduced age-related increase in volume for the left arcuate fasciculus tract. Given that language functioning is typically left lateralized, future study will examine relationships between development of language ability and white matter microstructure in the arcuate fasciculus in autism. 

Funding Source: This study was supported by NIH RO1 MH080826, NIH RO1 MH097464, and Eunice Kennedy Shriver National Institute of Child Health and Human Development T32 HD07489. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institute of Mental Health, NICHD, or the National Institutes of Health.