Cortical and Subthalamic Nucleus Spectral Changes During Limb Movements in Parkinson's Disease Patients with and Without Dystonia.

BACKGROUND: Dystonia is an understudied motor feature of Parkinson's disease (PD). Although considerable efforts have focused on brain oscillations related to the cardinal symptoms of PD, whether dystonia is associated with specific electrophysiological features is unclear. OBJECTIVE: The objective of this study was to investigate subcortical and cortical field potentials at rest and during contralateral hand and foot movements in patients with PD with and without dystonia. METHODS: We examined the prevalence and distribution of dystonia in patients with PD undergoing deep brain stimulation surgery.  During surgery, we recorded intracranial electrophysiology from the motor cortex and directional electrodes in the subthalamic nucleus (STN) both at rest and during self-paced repetitive contralateral hand and foot movements. Wavelet transforms and mixed models characterized changes in spectral content in patients with and without dystonia. RESULTS: Dystonia was highly prevalent at enrollment (61%) and occurred most commonly in the foot. Regardless of dystonia status, cortical recordings display beta (13-30 Hz) desynchronization during movements versus rest, while STN signals show increased power in low frequencies (6.0 ± 3.3 and 4.2 ± 2.9 Hz peak frequencies for hand and foot movements, respectively). Patients with PD with dystonia during deep brain stimulation surgery displayed greater M1 beta power at rest and STN low-frequency power during movements versus those without dystonia. CONCLUSIONS: Spectral power in motor cortex and STN field potentials differs markedly during repetitive limb movements, with cortical beta desynchronization and subcortical low-frequency synchronization, especially in patients with PD with dystonia. Greater knowledge on field potential dynamics in human motor circuits can inform dystonia pathophysiology in PD and guide novel approaches to therapy. © 2022 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Subcortical Intermittent Theta-Burst Stimulation (iTBS) Increases Theta-Power in Dorsolateral Prefrontal Cortex (DLPFC).

INTRODUCTION: Cognitive symptoms from Parkinson's disease cause severe disability and significantly limit quality of life. Little is known about mechanisms of cognitive impairment in PD, although aberrant oscillatory activity in basal ganglia-thalamo-prefrontal cortical circuits likely plays an important role. While continuous high-frequency deep brain stimulation (DBS) improves motor symptoms, it is generally ineffective for cognitive symptoms. Although we lack robust treatment options for these symptoms, recent studies with transcranial magnetic stimulation (TMS), applying intermittent theta-burst stimulation (iTBS) to dorsolateral prefrontal cortex (DLPFC), suggest beneficial effects for certain aspects of cognition, such as memory or inhibitory control. While TMS is non-invasive, its results are transient and require repeated application. Subcortical DBS targets have strong reciprocal connections with prefrontal cortex, such that iTBS through the permanently implanted lead might represent a more durable solution. Here we demonstrate safety and feasibility for delivering iTBS from the DBS electrode and explore changes in DLPFC electrophysiology. METHODS: We enrolled seven participants with medically refractory Parkinson's disease who underwent DBS surgery targeting either the subthalamic nucleus (STN) or globus pallidus interna (GPi). We temporarily placed an electrocorticography strip over DLPFC through the DBS burr hole. After placement of the DBS electrode into either GPi (n = 3) or STN (n = 4), awake subjects rested quietly during iTBS (three 50-Hz pulses delivered at 5 Hz for 2 s, followed by 8 s of rest). We contrasted power spectra in DLPFC local field potentials during iTBS versus at rest, as well as between iTBS and conventional high-frequency stimulation (HFS). RESULTS: Dominant frequencies in DLPFC at rest varied among subjects and along the subdural strip electrode, though they were generally localized in theta (3-8 Hz) and/or beta (10-30 Hz) ranges. Both iTBS and HFS were well-tolerated and imperceptible. iTBS increased theta-frequency activity more than HFS. Further, GPi stimulation resulted in significantly greater theta-power versus STN stimulation in our sample. CONCLUSION: Acute subcortical iTBS from the DBS electrode was safe and well-tolerated. This novel stimulation pattern delivered from the GPi may increase theta-frequency power in ipsilateral DLPFC. Future studies will confirm these changes in DLPFC activity during iTBS and evaluate whether they are associated with improvements in cognitive or behavioral symptoms from PD.