Bradykinesia and Its Progression Are Related to Interhemispheric Beta Coherence.

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 At each visit, participants were withdrawn from medication (12/24/48 hours) and had DBS turned off (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.

Lack of progression of beta dynamics after long-term subthalamic neurostimulation.

OBJECTIVE: To investigate the progression of neural and motor features of Parkinson's disease in a longitudinal study, after washout of medication and bilateral subthalamic nucleus deep brain stimulation (STN DBS). METHODS: Participants with clinically established Parkinson's disease underwent bilateral implantation of DBS leads (18 participants, 13 male) within the STN using standard functional frameless stereotactic technique and multi-pass microelectrode recording. Both DBS leads were connected to an implanted investigative sensing neurostimulator (Activa™ PC + S, Medtronic, PLC). Resting state STN local field potentials (LFPs) were recorded and motor disability, (the Movement Disorder Society-Unified Parkinson's Disease Rating Scale - motor subscale, MDS-UPDRS III) was assessed off therapy at initial programming, and after 6 months, 1 year, and yearly out to 5 years of treatment. The primary endpoint was measured at 3 years. At each visit, medication had been held for over 12/24 h and DBS was turned off for at least 60 min, by which time LFP spectra reached a steady state. RESULTS: After 3 years of chronic DBS, there were no increases in STN beta band dynamics (p = 0.98) but there were increases in alpha band dynamics (p = 0.0027, 25 STNs). Similar results were observed in a smaller cohort out to 5 years. There was no increase in the MDS-UPDRS III score. INTERPRETATION: These findings provide evidence that the beta oscillopathy does not substantially progress following combined STN DBS plus medication in moderate to advanced Parkinson's disease.

Quantification of the Balance Error Scoring System with Mobile Technology.

PURPOSE: The aim of this project was to develop a biomechanically based quantification of the Balance Error Scoring System (BESS) using data derived from the accelerometer and gyroscope of a mobile tablet device. METHODS: Thirty-two healthy young adults completed the BESS while an iPad was positioned at the sacrum. Data from the iPad were compared to position data gathered from a three-dimensional motion capture system. Peak-to-peak (P2P), normalized path length (NPL), and root mean squared (RMS) were calculated for each system and compared. Additionally, a 95% ellipsoid volume, iBESS volume, was calculated using center of mass (CoM) movements in the anteroposterior (AP), mediolateral (ML), and trunk rotation planes of movement to provide a comprehensive, 3D metric of postural stability. RESULTS: Across all kinematic outcomes, data from the iPad were significantly correlated with the same outcomes derived from the motion capture system (rho range, 0.37-0.94; P < 0.05). The iBESS volume metric was able to detect a difference in postural stability across stance and surface, showing a significant increase in volume in increasingly difficult conditions, whereas traditional error scoring was not as sensitive to these factors. CONCLUSIONS: The kinematic data provided by the iPad are of sufficient quality relative to motion capture data to accurately quantify postural stability in healthy young adults. The iBESS volume provides a more sensitive measure of postural stability than error scoring alone, particularly in conditions 1 and 4, which often suffer from floor effects, and condition 5, which can experience ceiling effects. The iBESS metric is ideally suited for clinical and in the field applications in which characterizing postural stability is of interest.