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

Abstract

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.

Keywords: Biomarker; Dystonia; Motor Cortex; Parkinson; Spectral Analysis; Subthalamic Nucleus.

© 2022 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Figures

FIG 1

Cortical and subcortical signal recording. (A) Primary motor cortex (M1) and primary somatosensory cortex (S1) regions are overlaid on segmented brain from a preoperative magnetic resonance imaging scan. The (ECoG) strip with six contacts is placed over the hand knob area of the primary sensorimotor cortex (contacts are outlined in red). It is inserted through the burr hole (blue) during a surgical deep brain stimulation (DBS) procedure. (B) Directional DBS electrode organization with two rings and two rows of three contacts each (1‐3‐3‐1). It is placed along the dorsolateral border of subthalamic nucleus (STN) as part of routine care. (C) Resting state wavelet scalogram example from S1 (top) and DBS contact 2 (bottom) for a single participant. The mean spectral power estimated on the right is computed by averaging each row of the scalogram over time.

FIG 2

Cortical and subcortical field potentials at rest in participants with Parkinson's disease. Spectral power from all electrode contacts over the ipsilateral cortex (first row) and the subthalamic nucleus (STN) region (second and third rows) are categorized by anatomical location obtained from imaging, regardless of dystonia status. For each location, there is one plot per participant color‐coded by participant number. Means are represented by darker black lines. Beta frequency power is present and relatively large in essentially all electrocorticography (ECoG) contacts, whereas lower beta power is present in most, but not all, deep brain stimulation (DBS) contacts, along with greater relative power at lower frequencies. dPMC, dorsal premotor cortex; M1, primary motor cortex; S1, primary somatosensory cortex; SMA, supplementary motor area.

FIG 3

Cortical and subcortical spectral perturbations in participants with Parkinson's disease (PD) during continuous, repetitive hand and foot movements minus rest. (A) Spectral power for all participants (n = 25) and recording sites are summarized in row 1 for sensorimotor cortex and rows 2 and 3 for dorsal and ventral deep brain stimulation (DBS) contacts (mean across participants ± standard error). Red and yellow traces correspond to hand and foot signals, respectively. (B, C) Frequencies that displayed the strongest deviations during movement versus rest in cortex and subthalamic nucleus (STN; ie, either desynchronization or synchronization). If the spectral perturbations are identical, observations will appear on or near the unity line (diagonal line). (B) Frequencies corresponding to power minima in dorsal premotor cortex/supplementary motor area, primary motor cortex (M1), primary somatosensory cortex (S1), and S2/S3 contacts during foot versus hand movements. (C) Frequencies corresponding to power maxima from all DBS contacts during foot versus hand movements. ECoG, electrocorticography.

FIG 4

Prevalence and anatomic distribution of dystonia in participants with Parkinson's disease (PD) evaluated for deep brain stimulation (DBS) surgery during baseline visit and clinical outcomes. (A) Venn diagram of anatomic distribution of dystonia clustered into four groups (arms, legs, bulbar, neck/trunk). The number in each circle intersection denotes the number of participants who had the corresponding parts affected by the dystonia (self‐reported or discovered by Burke‐Fahn‐Marsden [BFM] dystonia rating scale). Fifteen of 38 participants had no dystonia at baseline. (B) Three‐dimensional histogram of Unified Parkinson's Disease Rating Scale (UPDRS) dystonia item 4.6 (painful dystonia scale) versus BFM total score. Orange bars denote participants with dystonia, and the blue bar denotes participants with no dystonia. (C) Dystonia motor outcomes after DBS. Error bars indicate standard error. Both 2 and 4 months are significant from baseline (P = 0.002; P < 0.001).

FIG 5

Cortical and subcortical spectral perturbations during rest and hand and foot movements in participants with Parkinson's disease (PD) with versus without dystonia during deep brain stimulation (DBS) surgery. Spectral power from electrocorticography (ECoG) contacts in ipsilateral cortical (first row) and DBS contacts in subthalamic nucleus (STN) region (second row) are categorized by the presence or absence of dystonia during DBS surgery (mean ± standard error). Dashed and solid lines represent average spectral power in patients with PD with and without dystonia, respectively. Yellow, blue, and red colors correspond to rest, hand, and foot movements. Shaded standard errors are for visual purposes only and do not necessarily reflect the statistical confidence intervals of nonnormal variance. Horizontal colored bars above the plots correspond to frequency intervals with statistically significant differences. dPMC, dorsal premotor cortex; M1, primary motor cortex; S1, primary somatosensory cortex; SMA, supplementary motor area.