Superficial white matter (SWM) microstructural alterations in Parkinson's disease: a neurite orientation dispersion...

Superficial white matter (SWM) tracts serve not only as critical structural links connecting adjacent brain regions but also as key components of the brain's complex neural network communication system. However, research on microstructural alterations in SWM tracts associated with Parkinson's disease (PD) remains limited. This study aimed to investigate the characteristics of microstructural alterations in the SWM tracts of PD patients and their correlations with clinical measures.

A total of 35 PD patients and 36 healthy controls (HCs) were enrolled in this study. SWM tracts were reconstructed using probabilistic fiber tracking and tract-based spatial statistics (TBSS). Combining neurite orientation dispersion and density imaging (NODDI) with diffusion tensor imaging (DTI), the following metrics from the SWM were extracted: fractional anisotropy (FA), mean diffusivity (MD), neurite density index (NDI), and orientation dispersion index (ODI). Voxel-wise between-group differences in brain structure were examined with threshold-free cluster enhancement (TFCE) correction for multiple comparisons, and statistical significance was defined as P_TFCE<0.05. Correlations between brain metrics and behavioral measures were assessed using 95% bootstrap bias-corrected and accelerated (BCa) confidence intervals.

The DTI analysis of the SWM revealed significantly reduced FA in the lateral occipital cortex, superior division (LOCs), and precuneous cortex (PcC) of the PD patients, accompanied by increased MD in the LOCs and angular gyrus (AG) (all P_TFCE<0.05). Spearman's correlation analysis demonstrated that FA in the dorsal visual pathway-default mode network (DMN) was negatively correlated with Hoehn and Yahr (H-Y) stage (ρ =-0.405, P=0.022) and Unified Parkinson's Disease Rating Scale-Part III (UPDRS-III) scores (ρ =-0.366, P=0.039). Extending these DTI findings, the NODDI analysis of SWM showed significantly reduced NDI in the PD patients, not only in the DTI-identified abnormal regions (LOCs, PcC, and AG) but also in the cingulate gyrus, posterior division (CGp) (P_TFCE<0.05). Further, NDI was negatively correlated with disease duration (ρ =-0.425, P=0.015), UPDRS-III scores (ρ =-0.375, P=0.034), total Unified Parkinson's Disease Rating Scale (UPDRS) scores (ρ =-0.380, P=0.032), and H-Y stage (ρ =-0.357, P=0.045).

PD patients exhibit characteristic patterns of SWM microstructural alterations, which correlate with disease severity and may contribute to pathophysiological processes in the cortico-cortical pathways of PD. SWM imaging techniques combining DTI with the NODDI model offer novel imaging perspectives for investigating the mechanisms underlying neurodegenerative changes in PD.