Bradykinesia and Its Progression Are Related to Interhemispheric Beta Coherence

Abstract

Objective: Bradykinesia is the major cardinal motor sign of Parkinson disease (PD), but its neural underpinnings are unclear. The goal of this study was to examine whether changes in bradykinesia following long-term subthalamic nucleus (STN) deep brain stimulation (DBS) are linked to local STN beta (13-30 Hz) dynamics or a wider bilateral network dysfunction.

Methods: Twenty-one individuals with PD implanted with sensing neurostimulators (Activa® PC + S, Medtronic, PLC) in the STN participated in a longitudinal 'washout' therapy study every three to 6 months for an average of 3 years. At each visit, participants were withdrawn from medication (12/24/48 hours) and had DBS turned off (>60 minutes) before completing a repetitive wrist-flexion extension task, a validated quantitative assessment of bradykinesia, while local field potentials were recorded. Local STN beta dynamics were investigated via beta power and burst duration, while interhemispheric beta synchrony was assessed with STN-STN beta coherence.

Results: Higher interhemispheric STN beta coherence, but not contralateral beta power or burst duration, was significantly associated with worse bradykinesia. Bradykinesia worsened off therapy over time. Interhemispheric STN-STN beta coherence also increased over time, whereas beta power and burst duration remained stable. The observed change in bradykinesia was related to the change in interhemispheric beta coherence, with greater increases in synchrony associated with further worsening of bradykinesia.

Interpretation: Together, these findings implicate interhemispheric beta synchrony as a neural correlate of the progression of bradykinesia following chronic STN DBS. This could imply the existence of a pathological bilateral network contributing to bradykinesia in PD. ANN NEUROL 2023;93:1029-1039.

Figure 1.

Higher Beta coherence is associated with worse bradykinesia. Scatter plot depicting beta coherence and V_rms for all participants across all visits. The gradient color depicts the participant ID. The solid line shows the average estimated slope of the relationship between beta coherence on V_rms and the dashed lines represent the 95% confidence interval for the linear mixed effects model.

Figure 2.

Bradykinesia worsens over time. (A-C) Depiction of one example of angular velocity traces during rWFE at three different timepoints. The participant shows noticeable worsening of bradykinesia at later visits. (D) Group results showing the effect of time on V_rms. The gray lines depict individual’s performance at each visit. The solid line shows the average estimated slope of the effect of time on V_rms, and the dashed lines represent the 95% confidence interval for the linear mixed effects model.

Figure 3.

Beta Coherence increases over time. (A-C) Depiction of one example of wavelet coherence during rWFE at three different timepoints. The dashed white lines denote the beta band (13–30 Hz). The color bar represents the magnitude squared coherence. The participant shows noticeable increase in coherence within the beta band as time passes. (D) Group results showing the effect of time on beta coherence. The gray lines depict individual’s coherence at each visit. The solid line shows the average estimated slope of the effect of time on beta coherence and the dashed lines represent the 95% confidence interval for the linear mixed effects model.

Figure 4.

Individual examples of bradykinesia and Beta coherence over time. Beta coherence depicted by the dashed blue line and left y-axis. V_rms shown in the solid orange line and right y-axis.

Figure 5.

Changes in Beta coherence over time are related to changes in bradykinesia. (A) Scatter plot of individuals depicting the percent change per month for beta coherence compared to the percent change per month for V_rms for each of the visits. The gradient color depicts the participant ID. (B) Scatter plot of sub-cohort of individuals depicting the percent change over two years for beta coherence compared to percent change over two years for V_rms. The solid lines show the average estimated slope of the relationship, and the dashed lines represent the 95% confidence interval.