Gait-related cross-frequency coupling in the subthalamic nucleus of parkinsonian patients

Abstract

Background Analysis of coupling between the phases and amplitudes of neural oscillations has gained increasing attention as an important mechanism for large-scale brain network dynamics. In Parkinson’s disease (PD), preliminary evidence indicates abnormal beta-phase coupling to gamma-amplitude in different brain areas, including the subthalamic nucleus (STN). Objective To study gait-related, phase-amplitude coupling (PAC) of subthalamic local field potentials (LFPs) in parkinsonian patients. Methods We analyzed bilateral STN LFPs in eight subjects with PD chronically implanted with deep brain stimulation electrodes during upright quiet standing and unperturbed walking. PAC was computed using the Kullback-Liebler method, based on the Modulation Index. Neurophysiological recordings were correlated with clinical and kinematic measurements and individual molecular brain imaging studies ([123I]FP-CIT and single-photon emission computed tomography). Results We showed a dopamine-related increase in subthalamic beta-gamma PAC between standing and walking. Patients with poor PAC modulation between standing and walking and low PAC during walking spent significantly more time in the stance and double support phase of the gait cycle. Conclusion Cross-frequency coupling in the STN is a fundamental aspect of motor control for human locomotion, and could be used as an input signal for automated programming of novel stimulators.