Lack of progression of beta dynamics after long‐term subthalamic neurostimulation

Abstract

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 TM 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 Scalemotor 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.

Long-Term Subcortical Electrophysiological Recordings Link Heightened Interhemispheric Subthalamic Beta Synchrony to Progression of Bradykinesia in Parkinson’s Disease

“…In contrast to the observed increase in bilateral STN coherence over time, neither STN beta power or beta burst duration significantly changed over time, and neither were related to the observed worsening of bradykinesia. This replicates a previous finding from our lab where neither beta power or burst duration, as measured at rest, showed significant increases over three years 22 . The lack of increase in beta power within the STN implies that the observed increase in beta coherence over time is not a byproduct of changes in power, but rather evidence for a change in synchrony between the two STNs.…”

“…The advent of chronically implanted sensing neurostimulators has enabled the ability to track subcortical basal ganglia dynamics longitudinally alongside potential disease progression. Interestingly, the largest multi-year longitudinal LFP study in PD to date found that STN beta bursts and beta power measured at rest were stable over time and no worsening of overall clinical motor impairment was observed 22 . However, when examining symptom-specific changes over time, there is evidence that bradykinesia and axial symptoms may continue to worsen with chronic STN DBS 23,24 , compared to tremor, which improves over time 25,26 .…”

“…The basal ganglia, primary motor cortex (M1), and cerebellum have all been implicated in contributing to bradykinesia in PD suggesting a network-level dysfunction 1 . Recordings of local field potentials (LFPs) in the STN have revealed exaggerated neuronal oscillations and synchrony in the beta frequency band (13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27)(28)(29)(30) as a marker of pathophysiology of Parkinson's disease, including bradykinesia [2][3][4] . Similarly, reductions in beta power and burst duration with medication and/or DBS are associated with its improvement [5][6][7] .…”

Toward therapeutic electrophysiology: beta-band suppression as a biomarker in chronic local field potential recordings

“…The mean age of the participants was 60.2 ± 6.2 years (mean ± SD) with a mean disease duration of 10.6 ± 3.8 years (see Table 1 for further details). Previous studies confirmed stability of beta-band activity for at least 5 years 34 , 45 and correlation between disease duration and beta-band suppression at stimulation intensities for the best clinical effect was not significant. The mean pre-operative OFF medication UPDRS-III score was 50.9 ± 10.4.…”

“…3c , there is no consistent suppression of low-frequency activity across STNs. Overall, beta-band activity seems to be a more stable biomarker for chronic sensing enabled devices such as Percept that use a 5 Hz bin frequency band for the feedback signal 34 .…”