The Cortical Contributions to Turning Performance Through Muscle Synergies in Parkinson's Disease: A Mediation Study

Turning impairment is a major contributor to falls in Parkinson's disease (PD), yet the mechanisms linking cortical dysfunction to altered motor behavior remain unclear. In particular, it is unknown whether disrupted cortical communication impairs turning by altering muscle coordination. This study investigates a novel mechanistic pathway: whether muscle synergy complexity mediates the relationship between cortical network connectivity and turning performance in PD. Specifically, electroencephalography (EEG) and electromyography (EMG) were recorded from 12 individuals with PD and 12 age-matched healthy controls during a 180° turning task. Directed cortical connectivity, muscle synergy complexity, and spatiotemporal turning performance were quantified. Mediation analysis was used to determine whether cortical influences on behavior operate indirectly through neuromuscular coordination. Compared to controls, individuals with PD performed slower turns with shorter stride lengths and reduced synergy complexity (p < 0.05), alongside altered frontal cortical connectivity (p < 0.05). Across participants, higher synergy complexity was associated with faster, longer strides (p < 0.04). Cortical connectivity strength strongly predicted synergy complexity (R² = 0.66, p < 0.001) and exerted a significant indirect effect on turning performance (β = 0.312; 95% CI [0.072, 0.605]; p = 0.008). In PD, reliance on this indirect pathway increased with disease severity and poorer turning ability (r > 0.57, p < 0.03). This work establishes how muscle synergy complexity significantly mediates the relationship between cortical connectivity and turning performance in PD. Our findings provide evidence of a cortical-neuromuscular-behavioral pathway underlying turning deficits, highlighting coordination as a key target for neurorehabilitation.