White matter development and language abilities during infancy in autism spectrum disorder

Abstract

White matter (WM) fiber tract differences are present in autism spectrum disorder (ASD) and could be important markers of behavior. One of the earliest phenotypic differences in ASD are language atypicalities. Although language has been linked to WM in typical development, no work has evaluated this association in early ASD. Participants came from the Infant Brain Imaging Study and included 321 infant siblings of children with ASD at high likelihood (HL) for developing ASD; 70 HL infants were later diagnosed with ASD (HL-ASD), and 251 HL infants were not diagnosed with ASD (HL-Neg). A control sample of 140 low likelihood infants not diagnosed with ASD (LL-Neg) were also included. Infants contributed expressive language, receptive language, and diffusion tensor imaging data at 6-, 12-, and 24 months. Mixed effects regression models were conducted to evaluate associations between WM and language trajectories. Trajectories of microstructural changes in the right arcuate fasciculus were associated with expressive language development. HL-ASD infants demonstrated a different developmental pattern compared to the HL-Neg and LL-Neg groups, wherein the HL-ASD group exhibited a positive association between WM fractional anisotropy and language whereas HL-Neg and LL-Neg groups showed weak or no association. No other fiber tracts demonstrated significant associations with language. In conclusion, results indicated arcuate fasciculus WM is linked to language in early toddlerhood for autistic toddlers, with the strongest associations emerging around 24 months. To our knowledge, this is the first study to evaluate associations between language and WM development during the pre-symptomatic period in ASD.

Figure 1.

White matter fiber bundles from DTI tractography for the (a) left and (b) right hemispheres. Seafoam green, anterior portion of the corpus callosum (CC-Genu); light blue, corpus callosum body (CC-Body); dark blue, splenium (CC-Splenium); orange, uncinate; red, inferior longitudinal fasciculus; yellow, arcuate fasciculus (left = arcuate fronto-temporal, right = arcuate fronto-parietal).

Figure 2.

Cross-sectional relations between white matter fractional anisotropy in the left and right arcuate segments and expressive/receptive language age equivalent by visit and likelihood group. Each data point reflects an individual’s WM arcuate fractional anisotropy and expressive (top) or receptive (bottom) language age equivalent score at each time point, colored by group status. Bold lines represent the linear relationship between WM FA and language age equivalent for each group at each visit. FT, fronto-temporal; FP, fronto-parietal. Red, HL-ASD; gray, HL-Neg; blue, LL-Neg.

Figure 3.

Model predicted mean trajectories of expressive language age equivalent scores by likelihood group paneled by right arcuate-FP fractional anisotropy (FA) percentiles for whole sample. FA percentiles were calculated by taking the participant’s difference in 24-month and 6-month visit right arcuate-FP FA values and finding its k^th percentile among the whole sample (i.e., lowest percentile represents those with the least gains in FA over this period). Lower third panel indicates percentile ≤ 33%, middle third panel indicates between percentile 33% and 66%, and upper third panel indicates percentile ≥ 66%. Differential trajectories of model-predicted language are observed for the HL-ASD group based on FA percentile group (e.g., difference in slope and predicted age-equivalent language score at 24 months in lower third vs. upper third), while similar trajectories are observed for the HL-Neg and LL-Neg samples across FA percentile groups. Breakdown by FA percentiles is for visualization purposes only; FA was treated as a continuous variable in longitudinal models.