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™ 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.

Figure 1

Lead location and shared volumes of tissue modulated (VTAs). (A) Lead location for all 18 participants within the subthalamic nucleus (blue). (B) Depiction of the VTAs (yellow) at the 3‐year timepoint that are shared across all participants.

Figure 2

Off therapy grand average STN LFP power spectral density analysis before (IP) and at six different timepoints after activation of DBS: IP, 6 months, 1 year (A, 33 STNs), including 2 years (B, 25 STNs), including 3 years (C, 25 STNs), including 4 years (D, 16 STNs), and including 5 years (E, 6 STNs). (F) Quantification of alpha (8–12 Hz) and beta (13–30 Hz) spectral bands at IP and after 3 years of DBS (*p = 0.0027).

Figure 3

Off therapy burst duration (A) and burst peak power (B) at initial programing and after 3 years of DBS. Burst durations and peak power were calculated for the alpha band (8–12 Hz), for the participant specific 6‐Hz beta band centered at the peak beta power (beta peak) and for the total beta band (13–30 Hz, beta total), *p = 0.009.

Figure 4

STN beta band power, burst duration, and lateralized MDS‐UPDRS III scores over time in a single patient. Dashed lines represent the period when the less affected STN was not receiving DBS therapy. (A) Normalized STN beta band power, (B) STN beta band burst durations, and (C) modified lateralized off therapy MDS‐UPDRS III scores (tremor, bradykinesia, and rigidity) over time for the more (closed circles) and less affected (open squares) STNs.