White matter microstructure of language pathways in non-verbal autism: insights from diffusion tensor imaging and myelin water imaging

IntroductionAbsence of language development is a condition encountered across a large range of neurodevelopmental disorders, including a significant proportion of children with autism spectrum disorder. The neurobiological underpinnings of non-verbal ASD (nvASD) remain poorly understood.MethodsThis...

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Main Authors: Dominika Slušná, Jordi Muchart-López, Wolfram Hinzen, Erick J. Canales-Rodríguez
Format: Article
Language:English
Published: Frontiers Media S.A. 2025-08-01
Series:Frontiers in Human Neuroscience
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Online Access:https://www.frontiersin.org/articles/10.3389/fnhum.2025.1551868/full
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author Dominika Slušná
Jordi Muchart-López
Wolfram Hinzen
Wolfram Hinzen
Erick J. Canales-Rodríguez
author_facet Dominika Slušná
Jordi Muchart-López
Wolfram Hinzen
Wolfram Hinzen
Erick J. Canales-Rodríguez
author_sort Dominika Slušná
collection DOAJ
description IntroductionAbsence of language development is a condition encountered across a large range of neurodevelopmental disorders, including a significant proportion of children with autism spectrum disorder. The neurobiological underpinnings of non-verbal ASD (nvASD) remain poorly understood.MethodsThis study employed multimodal MRI to investigate white matter (WM) microstructural abnormalities in nvASD, focusing on language-related pathways. We analyzed diffusion tensor imaging (DTI) metrics–fractional anisotropy (FA), mean diffusivity (MD), and radial diffusivity (RD)–alongside myelin water imaging (MWI) metrics, including myelin water fraction (MWF) and intra/extracellular water T2 relaxation time (T2IE). A cohort of 10 children with nvASD and 10 age-matched typically developing controls was examined across eight major language-related tracts and the corticospinal tract (CST) as a motor reference.ResultsWhile DTI and MWI metrics showed no significant inter-group lateralization differences, MWF and T2IE exhibited pronounced lateralization exclusively in the nvASD group. Results also revealed significant microstructural differences in nvASD. MD and RD were the most sensitive DTI parameters, demonstrating widespread increases, whereas FA was less discriminatory. MWF exhibited the largest percentage change relative to controls (25–50%), suggesting a marked reduction in myelin content within affected tracts. Concurrently, widespread increases in T2IE indicate a less densely packed extra-axonal space, consistent with altered axonal integrity and reduced cellular surface area per unit volume.DiscussionThese findings align with prior evidence linking myelin abnormalities to ASD. Notably, microstructural differences were not restricted to language-related tracts but also extended to the CST, suggesting a more extensive WM disruption in nvASD. The absence of significant correlations between MRI-derived metrics and clinical measures highlights the complexity of the neurobiological alterations in nvASD. As the observed lateralization patterns may reflect, in part, the influence of methodological variability in tract definition, segmentation strategy, and tractography method, these results should be interpreted with caution. Future studies with larger cohorts and longitudinal designs are required to clarify the developmental trajectory of these microstructural abnormalities, their relationship with language impairment severity, and their potential role as biomarkers for nvASD.
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spelling doaj-art-0e50e69c4cce4c48a8f48e445e5470262025-08-22T05:26:44ZengFrontiers Media S.A.Frontiers in Human Neuroscience1662-51612025-08-011910.3389/fnhum.2025.15518681551868White matter microstructure of language pathways in non-verbal autism: insights from diffusion tensor imaging and myelin water imagingDominika Slušná0Jordi Muchart-López1Wolfram Hinzen2Wolfram Hinzen3Erick J. Canales-Rodríguez4Department of Translation and Language Sciences, Pompeu Fabra University, Barcelona, SpainHospital Sant Joan de Déu, Barcelona, SpainDepartment of Translation and Language Sciences, Pompeu Fabra University, Barcelona, SpainInstitució Catalana de Recerca I Estudis Avancats (ICREA), Barcelona, SpainSignal Processing Laboratory (LTS5), École Polytechnique Féderale de Lausanne (EPFL), Lausanne, SwitzerlandIntroductionAbsence of language development is a condition encountered across a large range of neurodevelopmental disorders, including a significant proportion of children with autism spectrum disorder. The neurobiological underpinnings of non-verbal ASD (nvASD) remain poorly understood.MethodsThis study employed multimodal MRI to investigate white matter (WM) microstructural abnormalities in nvASD, focusing on language-related pathways. We analyzed diffusion tensor imaging (DTI) metrics–fractional anisotropy (FA), mean diffusivity (MD), and radial diffusivity (RD)–alongside myelin water imaging (MWI) metrics, including myelin water fraction (MWF) and intra/extracellular water T2 relaxation time (T2IE). A cohort of 10 children with nvASD and 10 age-matched typically developing controls was examined across eight major language-related tracts and the corticospinal tract (CST) as a motor reference.ResultsWhile DTI and MWI metrics showed no significant inter-group lateralization differences, MWF and T2IE exhibited pronounced lateralization exclusively in the nvASD group. Results also revealed significant microstructural differences in nvASD. MD and RD were the most sensitive DTI parameters, demonstrating widespread increases, whereas FA was less discriminatory. MWF exhibited the largest percentage change relative to controls (25–50%), suggesting a marked reduction in myelin content within affected tracts. Concurrently, widespread increases in T2IE indicate a less densely packed extra-axonal space, consistent with altered axonal integrity and reduced cellular surface area per unit volume.DiscussionThese findings align with prior evidence linking myelin abnormalities to ASD. Notably, microstructural differences were not restricted to language-related tracts but also extended to the CST, suggesting a more extensive WM disruption in nvASD. The absence of significant correlations between MRI-derived metrics and clinical measures highlights the complexity of the neurobiological alterations in nvASD. As the observed lateralization patterns may reflect, in part, the influence of methodological variability in tract definition, segmentation strategy, and tractography method, these results should be interpreted with caution. Future studies with larger cohorts and longitudinal designs are required to clarify the developmental trajectory of these microstructural abnormalities, their relationship with language impairment severity, and their potential role as biomarkers for nvASD.https://www.frontiersin.org/articles/10.3389/fnhum.2025.1551868/fullnon-verbal autismabsent speechwhite matter tractsmicrostructuremyelin water imagingdiffusion tensor imaging
spellingShingle Dominika Slušná
Jordi Muchart-López
Wolfram Hinzen
Wolfram Hinzen
Erick J. Canales-Rodríguez
White matter microstructure of language pathways in non-verbal autism: insights from diffusion tensor imaging and myelin water imaging
Frontiers in Human Neuroscience
non-verbal autism
absent speech
white matter tracts
microstructure
myelin water imaging
diffusion tensor imaging
title White matter microstructure of language pathways in non-verbal autism: insights from diffusion tensor imaging and myelin water imaging
title_full White matter microstructure of language pathways in non-verbal autism: insights from diffusion tensor imaging and myelin water imaging
title_fullStr White matter microstructure of language pathways in non-verbal autism: insights from diffusion tensor imaging and myelin water imaging
title_full_unstemmed White matter microstructure of language pathways in non-verbal autism: insights from diffusion tensor imaging and myelin water imaging
title_short White matter microstructure of language pathways in non-verbal autism: insights from diffusion tensor imaging and myelin water imaging
title_sort white matter microstructure of language pathways in non verbal autism insights from diffusion tensor imaging and myelin water imaging
topic non-verbal autism
absent speech
white matter tracts
microstructure
myelin water imaging
diffusion tensor imaging
url https://www.frontiersin.org/articles/10.3389/fnhum.2025.1551868/full
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