Morpho-functional correlates of gait impairment in early Parkinson's disease patients: insights from a multimodal path modeling framework

Objective: To deepen the underlying pathophysiology of gait impairment in early-stage Parkinson's disease (PD) through a multimodal assessment, including MR-based brainstem morphometry and EEG functional connectivity (FC). Methods: 73 PD patients and 60 healthy controls (HC) were included. The MR Parkinsonism Index (MRPI) was calculated for each subject. FC was measured using HD-EEG in θ-α-β-low-γ-high-γ bands. Partial Least Squares Path Modeling (PLS-PM) was used to explore the causal relationships between MRPI, FC, and clinical data. Results: MRPI was higher in PD than HC (p = 0.001) and correlated with MDS-UPDRS-III gait subscore (r = 0.54,p < 0.001). α-FC was significantly lower in PD than HC (t = −5.4,p < 0.001). α-FC in PD was negatively correlated with both MRPI (r = −0.31,p = 0.007) and gait subscore (r = −0.31,p = 0.007). PLS-PM revealed MRPI's negative direct effect on α-FC (−0.59,p < 0.001) and significant positive total effect on gait performance (0.53,p < 0.001), partially mediated by α-FC (0.19, p = 0.006). Additionally, α-FC had a direct negative impact on gait performance (−0.33,p = 0.004). Conclusions: The effect of MRPI on gait performance, partially mediated by α-FC, highlights a dual pattern in which brainstem structural alterations show an association with gait impairment both directly and indirectly through their relationship with cortical functional disruptions. Significance: These findings support a multimodal framework for understanding and addressing gait disorders in PD, potentially opening avenues for personalized treatment