Pallidal Spectral and Phase-Amplitude Coupling Differences in Parkinson’s Disease Locomotor States

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Abstract Background Deep brain stimulation of the subthalamic nucleus or Globus Pallidus internus is an established therapy for Parkinson’s Disease that is sub-optimally managed with medication. While post-operative motor studies have defined neurophysiological signatures of the subthalamic nucleic local field potentials, comparable studies in the Globus pallidus internus are needed. Recent work shows that bandpower and phase-amplitude coupling in the subthalamic nucleus reliably distinguish locomotor states, motivating parallel investigation in the Globus pallidus internus. Objectives To characterize pallidal bandpower and phase-amplitude coupling across locomotor states (sitting, standing, and overground walking) in Parkinson’s, and relate to clinical motor scores. Methods Bandpower and phase-amplitude coupling from pallidal signals of six adults with Parkinson’s were compared across locomotor states; inter-state differences were correlated with clinical scores. Results High beta and gamma power differentiated sitting from walking, while delta power distinguished standing from walking. Phase-amplitude coupling between lower phases and gamma amplitude decreased during walking. Standing-to-walking delta-power modulation strongly correlated with Unified Parkinson’s Disease Rating Scale scores (R 2 = 0.82, q < 0.05). Standing-to-walking beta-gamma phase-amplitude coupling modulation highly correlated with freezing-of-gait scores (R 2 = 0.96, p < 0.05). Conclusions This study provides the first detailed characterization of Globus pallidus internus activity in these locomotor states in Parkinson’s. The coupling between lower frequencies and gamma was lower during walking compared to sitting and standing, revealing an inverse relationship to what has been reported in the subthalamic nucleus. These findings suggest that movement coordination in the Globus pallidus internus may rely on a balance of single- and cross-frequency mechanisms.

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