Selective Impairments in White Matter Integrity of Right Inferior Longitudinal Fasciculus in ASD

Background:  One of the most widely established features of the neural phenotype of ASD is the reduced integrity of long-range white matter fiber tracts as assessed by diffusion-weighted imaging, leading to the conceptualization of ASD as a “disconnection” syndrome. Recent methodological studies, however, have shown that this same pattern of aberrant connectivity may artifactually result from excessive head motion and poorer data quality. A recent study comparing white matter integrity in children with ASD and TD controls while carefully controlling for head motion and data quality, revealed that the classical effect of reduced fractional anisotropy (FA) in multiple and widespread white matter tracts in ASD disappears (Koldewyn et al., 2014, PNAS). Instead, reduced white matter integrity was present in only one tract, the right inferior longitudinal fasciculus (ILF). This same tract has also been identified as particularly affected based on a recent quantitative meta-analysis of diffusion-weighted imaging studies in ASD (Hoppenbrouwers et al., 2014, RASD).

Objectives: We aimed to replicate these findings in an independent sample of adolescents with ASD and TD, using an identical methodological approach. Moreover, given the evidence of atypical visual processing in ASD and given the involvement of the ILF in ventral visual stream processing, we also assessed the association between ILF integrity and a series of visual processing measures.

Methods: Diffusion MRI data were obtained in 19 12-to-18-year-old boys with ASD and 19 age-matched TD boys. Anatomically constrained probabilistic diffusion tractography was carried out using TRACULA to extract integrity measures of 18 major white-matter pathways. Application of a strict head motion criterion resulted in a sample of 18 ASD and 17 TD participants, well-matched in terms of data quality. In addition to the structural connectivity data, a series of questionnaires and experiments were administered to assess ASD characteristics, attention to detail, perceptual grouping, visual processing style, motion coherence sensitivity and visual search.

Results: Comparing ASD vs. TD on each of the 18 tracts revealed similar FA values for both groups on every tract (all p>.10), with the exception of significantly reduced integrity of the right ILF in ASD (p=.022). FA values of left ILF (p=.057) and right SLFt (p=.058) were marginally significantly reduced in ASD . Apart from both questionnaires, no group differences were observed on any of the visual processing tasks. Concerning associations of white matter integrity with visual processing measures and ASD characteristics, we observed that poorer integrity of right ILF showed a (statistically insignificant) association with a more fragmented processing style (r_s=-.31,  =.07), slower perceptual grouping and detection of Gabor patterns (r_s=-.29, p=.10),slower visual search (r_s=-.32, p=.06), more attention to detail (r_s=-.33, p=.06) and more ASD characteristics (r_s=-.31, p=.06). As expected no association was observed between ILF integrity and coherent motion sensitivity (p>.28), a traditional measure of dorsal visual stream functioning.

Conclusions: Our findings support the growing evidence for a specific and selective impairment of the right ILF in ASD. Suggestive evidence for a modest association between white matter integrity of this ventral visual pathway and behavioral visual processing performance was found.