Mahsa Malekmohammadi1, Nicholas AuYong2, Joni Ricks-Oddie3, Yvette Bordelon4, Nader Pouratian5. 1. Department of Neurosurgery, University of California, Los Angeles, CA, USA. Electronic address: mmalekmohammadi@mednet.ucla.edu. 2. Department of Neurosurgery, University of California, Los Angeles, CA, USA. 3. Institute for Digital Research and Education (IDRE), University of California, Los Angeles, CA, USA. 4. Department of Neurology, University of California, Los Angeles, CA, USA. 5. Department of Neurosurgery, University of California, Los Angeles, CA, USA; Department of Bioengineering, University of California, Los Angeles, CA, USA; Neuroscience Interdepartmental Program, University of California, Los Angeles, CA, USA; Brain Research Institute, University of California, Los Angeles, CA, USA.
Abstract
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 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. METHODS: Right 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. RESULTS: Movement 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). CONCLUSIONS: Similar 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.
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 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. METHODS: Right sensorimotor electrocorticographic signals were recorded in 10 PDpatients 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. RESULTS: Movement 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). CONCLUSIONS: Similar 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.
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