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. 2025 Jul-Aug;35(4):e70067.
doi: 10.1111/jon.70067.

Middle Longitudinal Fascicle Maldevelopment on Free Water Corrected MR Diffusion Underlies Language Impairment in Autism

Doudou Cao  1 , Litong Ni  1 , Qi Qi  1 , Lan Zhou  2 , Wei Zhang  3 , Yi Wang  4 , Li Zhu  5 , Guolin Ma  6 , Fan Zhang  3 , Shijun Li  1
Affiliations

Middle Longitudinal Fascicle Maldevelopment on Free Water Corrected MR Diffusion Underlies Language Impairment in Autism

Doudou Cao et al. J Neuroimaging. 2025 Jul-Aug.

Abstract

Background and purpose: The middle longitudinal fascicle (MdLF), a recently characterized white matter tract within the ventral language network, remains understudied in autism spectrum disorder (ASD). We hypothesized that altered microstructural development of the MdLF contributes to language impairment in children with ASD.

Methods: Free water corrected diffusion magnetic resonance imaging (MRI) tractography was employed to reconstruct the MdLF in 57 children with ASD (5.79±0.99 years) and 37 matched typically developing (TD) controls (5.99±1.38 years), aged 4-9 years. Language impairment was assessed using the Autism Behavior Checklist language subscale. General linear models and partial correlations (covarying age) were applied to investigate age-related differences of diffusion metrics and the correlation of diffusion metrics with language impairment in ASD.

Results: Significant age-by-group interactions emerged for bilateral MdLF fractional anisotropy tissue (FAt) (TD: left/right β = 0.614/0.511, p < 0.01; ASD: p > 0.05) and axial diffusivity tissue (ADt) (ASD: left/right β = -0.458/-0.348, p < 0.05; TD: p > 0.05). In ASD, FAt (r = -0.441, p < 0.001) and ADt (r = -0.28, p = 0.037) were negatively correlated with language impairment, while radial diffusivity tissue showed a positive correlation (r = 0.355, p = 0.007) in the right MdLF. There were no significant between-group differences found in diffusion metrics.

Conclusions: The MdLF exhibits aberrant developmental trajectories in preschool children with ASD, and its microstructural integrity is linked to language impairment. These findings underscore the MdLF's role in ASD-related language deficits and highlight the importance of early neurodevelopmental assessment.

Keywords: autism spectrum disorder; language; middle longitudinal fascicle; tractography; white matter.

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