Subthalamic beta-targeted neurofeedback speeds up movement initiation but increases tremor in Parkinsonian patients.

Shenghong He,Abteen Mostofi,Peter Brown,Flavie Torrecillos,Yuanqing Li,Erlick Pereira,Gerd Tinkhauser,Alek Pogosyan,Petra Fischer,Keyoumars Ashkan,Huiling Tan,Harutomo Hasegawa,Emilie Syed

doi:10.7554/elife.60979

Abstract

Previous studies have explored neurofeedback training for Parkinsonian patients to suppress beta oscillations in the subthalamic nucleus (STN). However, its impacts on movements and Parkinsonian tremor are unclear. We developed a neurofeedback paradigm targeting STN beta bursts and investigated whether neurofeedback training could improve motor initiation in Parkinson's disease compared to passive observation. Our task additionally allowed us to test which endogenous changes in oscillatory STN activities are associated with trial-to-trial motor performance. Neurofeedback training reduced beta synchrony and increased gamma activity within the STN, and reduced beta band coupling between the STN and motor cortex. These changes were accompanied by reduced reaction times in subsequently cued movements. However, in Parkinsonian patients with pre-existing symptoms of tremor, successful volitional beta suppression was associated with an amplification of tremor which correlated with theta band activity in STN local field potentials, suggesting an additional cross-frequency interaction between STN beta and theta activities.

Highlights

Enhanced synchronization of neural activity in the beta band (13–30 Hz) has been consistently observed in the subthalamic nucleus (STN) in patients with Parkinson’s disease (Kuhn et al, 2009; Neumann et al, 2016)
The position of a basketball displayed on a monitor was used as the visual feedback about the incidence of beta bursts detected in STN local field potentials (LFPs) (Figure 1A)
Considering all the individual trials across the two recording days for these hemispheres, generalized linear mixed effects (GLME) modeling using the average tremor power as dependent variable, experimental condition (T or N: ‘Training’ or ‘No Training’), experimental day (Day: 1 or 2), average beta power (b), and theta power () in the STN LFP as fixed predictors, and a random intercept for each hemisphere confirmed significant effects for all predictors (T or N: k = 4.1901 ± 0.5696, p < 0.0001; Day: k = 3.2611 ± 0.5477, p < 0.0001; b: k = À0.6253 ± 0.2073, p = 0.0027; : k = 0.7016 ± 0.0487, p < 0.0001), suggesting the reduced beta and increased theta power in the STN during neurofeedback training on Day 2 associated with the increased tremor. This is the first study to show that volitional suppression of beta bursts in the STN LFP facilitated by neurofeedback training is able to speed up movement initiation in subsequent cued movement in Parkinsonian patients

Summary

Introduction

Enhanced synchronization of neural activity in the beta band (13–30 Hz) has been consistently observed in the subthalamic nucleus (STN) in patients with Parkinson’s disease (Kuhn et al, 2009; Neumann et al, 2016) Synchrony in this frequency band takes the form of short-lived bursts of different durations and amplitudes (Tinkhauser et al, 2017a; Tinkhauser et al, 2017b). Closed-loop deep brain stimulation (DBS), which selectively truncates long duration beta bursts, can achieve clinical improvement that is at least as good as that with conventional continuous DBS in acute trials (Little et al, 2013; Little et al, 2016) These studies highlight the importance of modulating the temporal dynamics of beta activity in the STN for the treatment of Parkinson’s disease. A better understanding of the electrophysiological biomarkers underlying symptoms of bradykinesia and rigidity in Parkinson’s disease has motivated the use of neurofeedback as a therapeutic

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Results

Conclusion