Altered white matter connectivity of ventral language networks in autism spectrum disorder: An automated fiber quantification analysis with multi-site datasets

Comprehension and pragmatic deficits are prevalent in autism spectrum disorder (ASD) and are potentially linked to altered connectivity in the ventral language networks. However, previous magnetic resonance imaging studies have not sufficiently explored the microstructural abnormalities in the ventral fiber tracts underlying comprehension dysfunction in ASD. Additionally, the precise locations of white matter (WM) changes in the long tracts of patients with ASD remain poorly understood. In the current study, we applied the automated fiber-tract quantification (AFQ) method to investigate the fine-grained WM properties of the ventral language pathway and their relationships with comprehension and symptom manifestation in ASD. The analysis included diffusion/T1 weighted imaging data of 83 individuals with ASD and 83 age-matched typically developing (TD) controls. Case-control comparisons were performed on the diffusion metrics of the ventral tracts at both the global and point-wise levels. We also explored correlations between diffusion metrics, comprehension performance, and ASD traits, and conducted subgroup analyses based on age range to examine developmental moderating effects. Individuals with ASD exhibited remarkable hypoconnectivity in the ventral tracts, particularly in the temporal portions of the left inferior longitudinal fasciculus (ILF) and the inferior fronto-occipital fasciculus (IFOF). These WM abnormalities were associated with poor comprehension and more severe ASD symptoms. Furthermore, WM alterations in the ventral tract and their correlation with comprehension dysfunction were more prominent in younger children with ASD than in adolescents. These findings indicate that WM disruptions in the temporal portions of the left ILF/IFOF are most notable in ASD, potentially constituting the core neurological underpinnings of comprehension and communication deficits in autism. Moreover, impaired WM connectivity and comprehension ability in patients with ASD appear to improve with age.