Beta-coupled high-frequency activity and beta-locked neuronal spiking in the subthalamic nucleus of Parkinson's disease

Beta frequency (13-30 Hz) oscillatory activity in the subthalamic nucleus (STN) of Parkinson's disease (PD) has been shown to influence the temporal dynamics of high-frequency oscillations (HFOs; 200-500 Hz) and single neurons, potentially compromising the functional flexibility of the motor circuit. We examined these interactions by simultaneously recording both local field potential and single-unit activity from the basal ganglia of 15 patients with PD during deep brain stimulation (DBS) surgery of the bilateral STN. Phase-amplitude coupling (PAC) in the STN was specific to beta phase and HFO amplitude, and this coupling was strongest at the dorsal STN border. We found higher beta-HFO PAC near DBS lead contacts that were clinically effective compared with the remaining non-effective contacts, indicating that PAC may be predictive of response to STN DBS. Neuronal spiking was locked to the phase of 8-30 Hz oscillations, and the spatial topography of spike-phase locking (SPL) was similar to that of PAC. Comparisons of PAC and SPL showed a lack of spatiotemporal correlations. Beta-coupled HFOs and field-locked neurons had different preferred phase angles and did not co-occur within the same cycle of the modulating oscillation. Our findings provide additional support that beta-HFO PAC may be central to the pathophysiology of PD and suggest that field-locked neurons alone are not sufficient for the emergence of beta-coupled HFOs.