Cortical-to-pallidal beta cascade underlies network pathophysiology in Parkinson's disease.

Parkinson's disease (PD) motor symptoms are linked to excessive beta band (13-35 Hz) oscillations and basal ganglia-cortical (BGC) synchrony, yet their dynamic inter-relation remains unclear. Based on computational modeling, we hypothesize that transient high-beta (20-35 Hz) BGC coupling induces subcortical low-beta (13-20 Hz) amplification. We recorded intraoperative neural signals from the globus pallidus internus and externus (GPi and GPe, respectively) and motor cortex (M1) in 23 PD patients during deep brain stimulation implantation. High-beta bursts in M1 and GPe were classified as either temporally synchronized or isolated. Synchronous M1-GPe high-beta bursts led by GPe were followed by GPi low-beta amplification, which were not evident with either isolated M1 high-beta bursts or M1-led synchronous bursts. Dopaminergic medication attenuated this GPi low-beta amplification and improved symptoms. These findings suggest that excessive M1 high-beta bursts following GPe high-beta activity trigger a cascade establishing low-beta propagation to GPi, which may contribute to PD motor dysfunction.