Spatiotemporal neurodegeneration of the substantia nigra and its connecting cortex and subcortex in Parkinson's disease.

Abstract

Background and purpose: Neurodegeneration is uneven in Parkinson's disease (PD). This study aimed to investigate spatiotemporal neurodegeneration in functional subregions of the substantia nigra (SN) and their connected cortex and subcortex in people with PD.

Methods: A total of 120 patients with early-stage PD, 45 patients with advanced PD, and 120 healthy controls (HCs) were enrolled. The SN, cortex, and subcortex were divided into sensorimotor, associative, and limbic regions, respectively. Iron deposition in the SN was assessed by quantitative susceptibility mapping (QSM). Cortex and subcortex volumes were calculated based on T1-weighted imaging. Region of interest (ROI) analysis and voxel-based analysis (VBA) were performed to explore spatiotemporal neurodegeneration in patients with PD. p values were corrected for false discovery rate.

Results: In the ROI analysis, the QSM values for the limbic (p = 0.018) and sensorimotor SN subregions (p = 0.018) were higher in PD patients than in HCs, but were not higher in the associative SN subregion (p = 0.295). In VBA, all SN functional subregions had clusters with higher QSM values in PD patients than in HCs (p < 0.001). The limbic SN subregion was the only one in which iron deposition increased from early-stage to advanced PD (p = 0.023). The QSM values of VBA_limbic, sensorimotor, and associative SN had subregion-specific correlations with disease severity (p = 0.001 for the limbic and sensorimotor subregions, p = 0.003 for the associative subregion), motor symptoms (p = 0.057 for the limbic and sensorimotor subregion), and depression scores (p = 0.036 for the limbic subregion).

Conclusion: Iron deposition in SN functional subregions and atrophy of cortical and subcortical structures connected with the SN showed spatiotemporal selectivity. These findings reveal the potential pathogenesis of clinical heterogeneity in PD.