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

Abstract

ObjectiveDeep 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 β-γ 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 GPi-DBS and movement on cortical β power and β-γ PAC were examined. MethodsRight sensorimotor electrocorticographic signals were recorded in 10 PD patients undergoing GPi-DBS implantation surgery. We evaluated cortical β power and β-γ PAC during blocks of rest and contralateral hand movement (finger tapping) with GPi-DBS off and on. ResultsMovement suppressed cortical low β power (P = 0.008) and high β-γ PAC (P = 0.028). Linear mixed effect modeling (LMEM) showed that power in low and high β bands are differentially modulated by movement (P = 0.022). GPi-DBS also results in a significant suppression of high β-γ PAC but without power modulation in either β sub-band (P = 0.008). Cortical high β-γ 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). ConclusionsSimilar to STN-DBS, GPi-DBS reduces motor cortical β-γ 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.