Structural connectivity in ventral language pathways characterizes non-verbal autism

Abstract

Language capacities in autism spectrum disorders (ASD) range from normal scores on standardized language tests to absence of functional language in a substantial minority of 30% of individuals with ASD. Due to practical difficulties of scanning at this severe end of the spectrum, insights from MRI are scarce. Here we used manual deterministic tractography to investigate, for the first time, the integrity of the core white matter tracts defining the language connectivity network in non-verbal ASD (nvASD): the three segments of the arcuate (AF), the inferior fronto-occipital (IFOF), the inferior longitudinal (ILF) and the uncinate (UF) fasciculi, and the frontal aslant tract (FAT). A multiple case series of nine individuals with nvASD were compared to matched individuals with verbal ASD (vASD) and typical development (TD). Bonferroni-corrected repeated measure ANOVAs were performed separately for each tract-Hemisphere (2:Left/Right) × Group (3:TD/vASD/nvASD). Main results revealed (i) a main effect of group consisting in a reduction in fractional anisotropy (FA) in the IFOF in nvASD relative to TD; (ii) a main effect of group revealing lower values of radial diffusivity (RD) in the long segment of the AF in nvASD compared to vASD group; and (iii) a reduced volume in the left hemisphere of the UF when compared to the right, in the vASD group only. These results do not replicate volumetric differences of the dorsal language route previously observed in nvASD, and instead point to a disruption of the ventral language pathway, in line with semantic deficits observed behaviourally in this group.

Keywords: Autism; DWI; Language; MRI; Non-verbal; Tractography.

Fig. 1

Dissections of nvASD participants. Manual deterministic tractography reconstructions from all participants of the nvASD group. Tracts reconstructed were the three segments of the arcuate fasciculus (AF) [Green = anterior, red = long, yellow = posterior segments], Frontal Aslant tract (FAT) [Cyan], Inferior Frontal Occipital Fasciculus (IFOF) [Purple], Inferior Longitudinal Fasciculus (ILF) [Dark blue] and Uncinate Fasciculus (UF) [Orange]. Abbreviations: L left. Montreal Neurological Institute space coordinates of the structural template slices are specified at the bottom of the image

Fig. 2

Regions of Interest placement examples. Regions of interest (ROI) placements for manual deterministic tractography reconstructions of the selected tracts. Tracts reconstructed were the three segments of the arcuate fasciculus (AF), Frontal Aslant tract (FAT), Uncinate Fasciculus (UF), Inferior Longitudinal Fasciculus (ILF) and Inferior Frontal Occipital Fasciculus (IFOF)

Fig. 3

Structural connectivity results: normalized volume, fractional anisotropy and radial diffusivity. Significant results of the repeated measures ANOVA performed for the structural connectivity measures (normalized volume, FA and RD) extracted from each tract, with values for both hemispheres depicted in each group (blue circles correspond to TD participants, dark pink squares show vASD participants, and teal triangles represent nvASD participants). A Left graph shows the distribution of normalized volume values in the UF, marking the significant Hemisphere × Group interaction; central graph shows the distribution of FA values in the IFOF with the Main effect of Group specified; right graph depicts the distribution of RD values in the Long segment of the AF, with the Main effect of Group specified. B All the Main effects of Hemisphere found for all tracts and measures. Top row: Normalized volume values for the long segment of the AF (left) and posterior segment (center) of the AF, and FA values of the ILF (right). Bottom row: RD measures for the long segment of the AF (left), the ILF (center) and the UF (right). All results were Bonferroni-corrected (p < .005). Abbreviations: UF Uncinate fasciculus, IFOF Inferior frontal occipital fasciculus; AF Arcuate fasciculus, ILF Inferior longitudinal fasciculus, L Left, R Right