Cortical thinning and altered directed connectivity in Parkinson’s disease: a cortical thickness–guided voxel-wise granger causality study

Background Parkinson’s disease (PD) involves both regional cortical degeneration and large-scale network dysfunction. This study examined whether cortical regions showing structural abnormalities in PD also exhibit altered directed connectivity. Methods Sixty-two patients with PD and 46 healthy controls underwent structural magnetic resonance imaging (MRI) and resting-state functional magnetic resonance imaging (fMRI). Whole-brain cortical thickness was analyzed using FreeSurfer. Regions showing significant cortical thinning were used as seeds for voxel-wise Granger causality analysis (GCA). Associations between imaging measures and Montreal Cognitive Assessment (MoCA) scores were examined using partial correlation analyses. Results Patients with PD showed significantly reduced cortical thickness in the right medial superior frontal gyrus (SFGmed.R) and right precentral gyrus (PreCG.R), with no regions showing significantly greater cortical thickness than healthy controls. Compared with controls, patients with PD exhibited increased GCA from SFGmed.R to the left inferior temporal gyrus and from PreCG.R to the calcarine/medial visual cortex, whereas decreased GCA was observed from PreCG.R to the left supramarginal gyrus and from the right superior temporal gyrus and left olfactory-related region to PreCG.R. SFGmed.R cortical thickness was positively associated with MoCA scores after adjustment for age, sex, and education level, and this association remained significant after Bonferroni correction for seven exploratory correlation analyses (partial Spearman’s ρ = 0.847, p < 0.001). No other imaging–MoCA associations reached the corrected significance threshold. Conclusion Cortical thinning in frontal-executive and motor regions of patients with PD is accompanied by altered directed interactions with distributed sensory and associative regions. Medial superior frontal cortical thickness may also be related to global cognitive performance.