Long term correlation of subthalamic beta band activity with motor impairment in patients with Parkinson’s disease

Highlights

• Subthalamic beta activity was recorded with an implantable DBS pulse generator over 8 months in 12 patients with Parkinson's disease.

• Dopaminergic medication suppresses subthalamic beta activity at operation, 3 and 8 months after DBS.

• Beta activity correlates with parkinsonian symptom severity over time.

Abstract

Objectives

To investigate the long term association of subthalamic beta activity with parkinsonian motor signs.

Methods

We recruited 15 patients with Parkinson’s disease undergoing subthalamic DBS for local field potential recordings after electrode implantation, and at 3 and 8 months post-operatively using the implantable sensing enabled Activa PC + S (Medtronic). Three patients dropped out leaving 12 patients. Recordings were conducted ON and OFF levodopa at rest. Beta (13–35 Hz) peak amplitudes were extracted, compared across time points and correlated with UPDRS-III hemibody scores.

Results

Peaks in the beta frequency band (13–35 Hz) in the OFF medication state were found in all hemispheres. Mean beta activity was significantly suppressed by levodopa at all recorded time points (P < 0.007) and individual beta power amplitude correlated with parkinsonian motor impairment across time points and dopaminergic states (pooled data; ρ = 0.25, P < 0.001).

Conclusions

Our results indicate that beta-activity is correlated with parkinsonian motor signs over a time period of 8 months.

Significance

Beta-activity may be a chronically detectable biomarker of symptom severity in PD that should be further evaluated under ongoing DBS.

Introduction

Oscillatory activity in the human motor network is synchronized in the beta frequency band (13–35 Hz) at rest (Pfurtscheller and Lopes da Silva, 1999). Features like movement related desynchronization and post movement rebound synchronisation have led to the suggestion that beta activity serves to promote maintenance of the status quo and is, in these terms, antikinetic (Engel and Fries, 2010). Patients with Parkinson’s disease (PD) exhibit exaggerated beta oscillations in the basal ganglia, which have been related to bradykinesia and rigidity in line with the above hypothesis (Brittain and Brown, 2014). Beta activity recorded from implanted deep brain stimulation (DBS) electrodes in the subthalamic nucleus (STN) of PD patients correlates with signs of parkinsonian symptom severity (as assessed by UPDRS-III) in the hypodopaminergic state (Neumann et al., 2016a). Both, dopaminergic medication and DBS significantly decrease beta activity in parallel with the clinically apparent symptom alleviation (Brown et al., 2001, Neumann et al., 2016b), and the degree of beta suppression correlates with the change in UPDRS-III scores for either therapeutic procedure (Kühn et al., 2006, Kuhn et al., 2009, Oswal et al., 2016). Thus, beta amplitude may serve as a biomarker for instantaneous monitoring of concurrent therapeutic demand (Little and Brown, 2012). This has led to the trial of adaptive deep brain stimulation algorithms, utilizing a closed loop system that can trigger stimulation according to the level of beta activity in the STN. (Little et al., 2013, Little et al., 2016a, Little et al., 2016b, Rosa et al., 2015) Although initial results have been promising, most of the relevant studies have been performed a few days after electrode implantation with DBS leads externalized. Therefore, little is known about the evolution of beta activity after chronic DBS and more importantly its relation to motor impairment over the long term. In the present study we aim to investigate the relation of subthalamic beta activity with parkinsonian motor signs directly after DBS surgery, after three months and eight months of chronic continuous DBS with an implantable sensing enabled pulse generator.