Work

White Matter Microstructural Alterations and Symptom Correlates in Functional Motor Disorder

Year: 2026

Type: preprint

Abstract: ABSTRACT Background Neuroimaging studies implicate network alterations in functional motor disorder (FND-motor), yet white matter remains poorly characterized. Objectives To characterize white matter microstructure in FND-motor relative to healthy (HCs) and psychiatric (PCs) controls and examine symptom associations. Methods Fifty individuals with FND-motor, 50 age- and sex-matched HCs, and 50 PCs matched on age, sex, depression, anxiety, and post-traumatic stress disorder severity underwent multi-shell diffusion MRI. Voxel-based analyses examined whole-brain white matter using diffusion tensor imaging (fractional anisotropy [FA], mean diffusivity [MD]) and neurite orientation dispersion and density imaging (NODDI) (neurite density index [NDI], orientation dispersion index, and free water fraction [FWF]) metrics. Cross-metric convergence was characterized using atlas-based tract overlap analyses and probabilistic tractography. Associations with FND symptoms and transdiagnostic physical symptoms were also evaluated. Results Compared with HCs, FND-motor showed higher FA/NDI and lower MD/FWF, predominantly in the middle cerebellar peduncle. Compared with PCs, differences were limited to lower MD/FWF, involving the corpus callosum, middle cerebellar peduncle, and left inferior longitudinal fasciculus. Greater FND symptom severity was associated with a lower FA/NDI and higher MD/FWF in the corpus callosum and right-lateralized association and projection pathways, whereas greater transdiagnostic physical symptom burden across FND-motor and PCs was associated with higher FA and lower MD/FWF in the middle cerebellar peduncle. Conclusions This study provides a comprehensive multi-metric diffusion-weighted characterization of white matter microstructure in FND-motor relative to both HCs and PCs – highlighting cortico-cerebellar connections via the middle cerebellar peduncle as distinct in FND-motor and associated transdiagnostically with physical symptom burden.

Source: medRxiv

DOI: 10.64898/2026.08.25.26361322