Examination of Anterior-Posterior Connectivity in Children with Autism Spectrum Disorder

Background:  It has been hypothesized that the heterogeneous phenotype of Autism Spectrum Disorders (ASD) could implicate a greater likelihood of abnormalities in the connectivity between different neural networks rather than localized alterations. In particular, previous studies have provided evidence of underconnectivity in ASD, with particular respect to reduced long-range connectivity between frontal lobes and posterior brain regions (Just et al., 2004, Villalobos et al., 2005, Mostofsky et al., 2009). Structural connectivity can be effectively assessed in vivo using magnetic resonance techniques like diffusion tensor imaging (DTI). Exploring the hypothesis of an anterior-posterior underconnectivity in ASD might provide useful insight into the mechanisms of social communication, given the key role of these pathways for language, praxis, and imitation.

Objectives:  To investigate whether a well-characterized group of high-functioning children with ASD would demonstrate reduced white matter integrity, denoted by reduced FA and increased MD, in inferior fronto-occipital fasciculus (IFOF), inferior and superior longitudinal fasciculus (ILF and SLF, respectively). On the basis of established findings for impairments in language and praxis in ASD, we further hypothesized that the findings would be more prominent in the left hemisphere.

Methods:  Fifty-two children with ASD, ages 8 through 12 years, and fifty-four typically developing (TD) controls matched by sex, age, and intellectual reasoning ability participated to the study. DTI images were acquired with a single-shot, echo-planar diffusion-weighted sequence. Two runs were collected in each subject, with 32 gradient directions (b = 700 s/mm3) and one b0 in each run. Sixty 2.2-mm axial slices were acquired for each volume, with 0.8 mm in-plane reconstructed resolution. DTI data were analyzed using Automated Fiber Quantification toolbox, which employs deterministic fiber tracking for quantifying diffusion profiles along ten nodes for each reconstructed white matter tract. Diagnostic effects on fractional anisotropy (FA) and mean diffusivity (MD) were assessed using independent t-tests for each white matter tract.

Results:  Analyses revealed that TD children exhibited higher FA in nodes along the posterior portion of the left ILF, and the anterior segment of the right ILF (all p<0.05). In children with ASD, higher mean diffusivity was observed in distinct nodes along the reconstructed fiber tracts (all p<0.05), with the left SLF showing a significant group difference in 5 out of 10 nodes (see Fig. 1). Overall, most of the group differences were lateralized in the left hemisphere.

Conclusions:  The present study provides evidence for alterations in diffusion along a set of major anterior-posterior fiber tracts in children with ASD. In particular, our main finding is a consistently increased diffusivity in the left SLF in children with ASD. The SLF has been known to play a role in motor functions and other “higher” functions, including language and working memory. Accordingly, consistent with our hypothesis, our findings indicate a pattern of left-lateralized white matter abnormalities. Possible extension of the present work should investigate the relationship between localized differences in diffusion properties and core features of ASD, as well as measures of language, imitation, and motor function.