Pallidal deep brain stimulation modulates excessive cortical high β phase amplitude coupling in Parkinson disease

Objective: Deep brain stimulation (DBS) of the subthalamic nucleus (STN) and globus pallidus internus (GPi) are equally efficacious in the management of Parkinson disease (PD). Studies of STN-DBS have revealed a therapeutic reduction in excessive cortical beta-gamma phase-amplitude coupling (PAC). It is unclear whether this is specific to STN-DBS and potentially mediated by modulation of the hyperdirect pathway or if it is a generalizable mechanism seen with DBS of other targets. Moreover, it remains unclear how cortical signals are differentially modulated by movement versus therapy. To clarify, the effects of GPiDBS and movement on cortical beta power and beta-gamma PAC were examined. Methods: Right sensorimotor electrocorticographic signals were recorded in 10 PD patients undergoing GPi-DBS implantation surgery. We evaluated cortical beta power and beta-gamma PAC during blocks of rest and contralateral hand movement (finger tapping) with GPi-DBS off and on. Results: Movement suppressed cortical low b power (P = 0.008) and high beta-gamma PAC (P = 0.028). Linear mixed effect modeling (LMEM) showed that power in low and high b bands are differentially modulated by movement (P = 0.022). GPi-DBS also results in a significant suppression of high beta-gamma PAC but without power modulation in either b sub-band (P = 0.008). Cortical high beta-gamma PAC is significantly correlated with severity of bradykinesia (Rho = 0.59, P = 0.045) and changes proportionally with therapeutic improvement (Rho = 0.61, P = 0.04). Conclusions: Similar to STN-DBS, GPi-DBS reduces motor cortical beta-gamma PAC, like that also reported with dopaminergic mediations, suggesting it is a generalizable symptom biomarker in PD, independent of therapeutic target or proximity to the hyperdirect pathway. (C) 2018 Elsevier Inc. All rights reserved.