Increased beta-HFO phase-amplitude coupling in the subthalamic nucleus during movement in Parkinson's disease

In Parkinson's disease (PD), increased amplitude of high-frequency oscillations (HFO) has been confirmed to be coupled with the beta oscillations phase, resulting in increased phase-amplitude coupling (PAC) in the subthalamic nucleus (STN). This pathological coupling correlates with the severity of motor symptoms and is known to be modulated by therapeutic interventions. For example, dopaminergic medications and deep brain stimulation (DBS) were previously shown to reduce PAC, which changes in magnitude between states of rest and movement. However, PAC alterations during kinetic and static movements in the presence and absence of medications remain to be determined. Furthermore, there is little evidence on the relationship between PAC and clinical symptoms of PD. In this study, we investigated these two issues. We analyzed a publicly available dataset, which contained STN local field potential registrations (n = 20) and concurrent limb electromyography during resting, static, and kinetic movements with and without levodopa intake. We calculated the PAC within the STN during different conditions, and the PAC between the limb tremor and the ipsilateral LFP oscillations. Beta-HFO STN PAC was increased during the medication off period, especially during kinetic movement and was highly correlated with bradykinesia and negatively correlated with tremor. We observed no interaction between tremor frequency oscillation phase on electromyography and beta or HFO oscillation amplitude within the STN in either of the conditions. These results point out that beta-HFO PAC provides complementary information to beta power for electrophysiological localization during DBS implantation and during adaptive DBS.