Slušná Dominika, Muchart-López Jordi, Hinzen Wolfram, Canales-Rodríguez Erick J
Department of Translation and Language Sciences, Pompeu Fabra University, Barcelona, Spain.
Hospital Sant Joan de Déu, Barcelona, Spain.
Front Hum Neurosci. 2025 Aug 22;19:1551868. doi: 10.3389/fnhum.2025.1551868. eCollection 2025.
Absence 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.
This 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.
While 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.
These 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.
语言发育缺失是在多种神经发育障碍中都会遇到的一种情况，包括相当比例的自闭症谱系障碍儿童。非言语型自闭症（nvASD）的神经生物学基础仍知之甚少。
本研究采用多模态磁共振成像（MRI）来研究nvASD中白质（WM）的微观结构异常，重点关注与语言相关的通路。我们分析了扩散张量成像（DTI）指标——分数各向异性（FA）、平均扩散率（MD）和径向扩散率（RD），以及髓鞘水成像（MWI）指标，包括髓鞘水分数（MWF）和细胞内/外水T2弛豫时间（T2IE）。对10名患有nvASD的儿童和10名年龄匹配的正常发育对照儿童组成的队列，在八条主要的与语言相关的神经束以及作为运动参考的皮质脊髓束（CST）上进行了检查。
虽然DTI和MWI指标在组间未显示出显著的偏侧化差异，但MWF和T2IE仅在nvASD组中表现出明显的偏侧化。结果还揭示了nvASD中存在显著的微观结构差异。MD和RD是最敏感的DTI参数，显示出广泛增加，而FA则判别性较差。MWF相对于对照组表现出最大的百分比变化（25 - 50%），表明受影响神经束内的髓鞘含量显著减少。同时，T2IE的广泛增加表明轴突外空间的密集程度降低，这与轴突完整性改变和单位体积内细胞表面积减少一致。
这些发现与先前将髓鞘异常与自闭症联系起来的证据一致。值得注意的是，微观结构差异不仅限于与语言相关的神经束，还扩展到了CST，这表明nvASD中白质破坏更为广泛。MRI衍生指标与临床测量之间缺乏显著相关性，凸显了nvASD中神经生物学改变的复杂性。由于观察到的偏侧化模式可能部分反映了神经束定义、分割策略和纤维束成像方法中方法学变异性的影响，因此对这些结果的解释应谨慎。需要未来进行更大样本队列和纵向设计的研究，以阐明这些微观结构异常的发育轨迹、它们与语言障碍严重程度的关系以及它们作为nvASD生物标志物的潜在作用。
