Long term correlation of subthalamic beta band activity with motor impairment in patients with Parkinson’s disease
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.
Section snippets
Materials and methods
Fifteen patients with Parkinson’s disease who underwent bilateral implantation of DBS electrodes in the STN were included in this study. All patients participated with informed consent, which was approved by the local ethics committee. The DBS macroelectrode used was model 3389 (Medtronic). Contacts 0 and 3 were the lowermost and uppermost contacts, respectively. Intraoperative microelectrode recordings were used for target mapping in all patients. Correct placement of the DBS electrodes was
Results
Subthalamic deep brain stimulation lead to a 54.9% ± 3.4% (MEAN ± S.E.M) reduction. of UPDRS-III scores after 8 months of chronic stimulation (P < 0.001; preop UPDRS-III OFF medication: 39.4 ± 3.4; ON subthalamic stimulation, OFF dopaminergic medication at 8 months follow-up: 16.9 ± 1.2). When stimulation was turned off, medication still decreased UPDRS-III scores significantly at each timepoint (P < 0.007). Peaks in the beta frequency band were present in all patients (see Fig. 1 for an example of raw data
Discussion
We have demonstrated that beta oscillations can be consistently recorded in the subthalamic nucleus over 8 months in patients with Parkinson’s disease. Moreover, we have shown that beta peak frequency is stable across this time frame and that dopaminergic medication repeatedly suppressed beta activity at each time point. Finally, we have replicated a recent report that has shown that beta activity is directly correlated with parkinsonian motor signs as assessed by UPDRS-III. (Neumann et al., 2016a
Conclusions
We could confirm that beta oscillatory amplitudes in long term follow up recordings are correlated with symptom severity in PD patients across pooled time points and medication conditions. Future studies will have to investigate the robustness of beta activity during DBS as a measure of concurrent parkinsonian symptom severity to corroborate its role as a biomarker for long term adaptive stimulation.
Acknowledgements
WJN, FS, JS, AH and AAK were funded by the German Research Foundation (DFG, grant KFO 247). PB was funded by the Medical Research Council and National Institute for Health Research Oxford Biomedical Research Centre. Medtronic provided all pulse generators for free.
Conflict of interest
Medtronic provided all pulse generators for free.
Funding
This work was supported by the German Research Foundation (DFG, grant KFO 247).
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