Abstract
High-frequency deep brain stimulation (DBS) of the subthalamic nucleus (STN) is effective in suppressing the motor symptoms of Parkinson's disease (PD). Current clinically-deployed DBS technology operates in an open-loop fashion, i.e., fixed parameter high-frequency stimulation is delivered continuously, invariant to the needs or status of the patient. This poses two major challenges: (1) depletion of the stimulator battery due to the energy demands of continuous high-frequency stimulation, (2) high-frequency stimulation-induced side-effects. Closed-loop deep brain stimulation (CL DBS) may be effective in suppressing parkinsonian symptoms with stimulation parameters that require less energy and evoke fewer side effects than open loop DBS. However, the design of CL DBS comes with several challenges including the selection of an appropriate biomarker reflecting the symptoms of PD, setting a suitable reference signal, and implementing a controller to adapt to dynamic changes in the reference signal. Dynamic changes in beta oscillatory activity occur during the course of voluntary movement, and thus there may be a performance advantage to tracking such dynamic activity. We addressed these challenges by studying the performance of a closed-loop controller using a biophysically-based network model of the basal ganglia. The model-based evaluation consisted of two parts: (1) we implemented a Proportional-Integral (PI) controller to compute optimal DBS frequencies based on the magnitude of a dynamic reference signal, the oscillatory power in the beta band (13–35 Hz) recorded from model globus pallidus internus (GPi) neurons. (2) We coupled a linear auto-regressive model based mapping function with the Routh-Hurwitz stability analysis method to compute the parameters of the PI controller to track dynamic changes in the reference signal. The simulation results demonstrated successful tracking of both constant and dynamic beta oscillatory activity by the PI controller, and the PI controller followed dynamic changes in the reference signal, something that cannot be accomplished by constant open-loop DBS.
Highlights
Parkinson’s disease (PD) is characterized by degeneration of dopaminergic neurons in the substania nigra pars compacta (SNc) resulting in motor symptoms including bradykinesia, rest tremor, postural instability, and rigidity (Davie, 2008; Jankovic, 2008)
The design of CL deep brain stimulation (DBS) controllers comes with several challenges including selection of a feedback signal reflecting PD symptoms and the capacity of the controller to adapt to dynamic changes in the reference signal (Hebb et al, 2014; Arlotti et al, 2016a; Parastarfeizabadi and Kouzani, 2017)
Grant and Lowery designed a closed-loop DBS (CL DBS) system to modulate the amplitude of DBS based on beta band oscillations of local field potentials (LFPs), where the coupling strength within the cortico-basal ganglia network was altered to illustrate the ability of CL DBS to respond to changes in network activity (Grant and Lowery, 2013)
Summary
Parkinson’s disease (PD) is characterized by degeneration of dopaminergic neurons in the substania nigra pars compacta (SNc) resulting in motor symptoms including bradykinesia, rest tremor, postural instability, and rigidity (Davie, 2008; Jankovic, 2008). The design of CL DBS controllers comes with several challenges including selection of a feedback signal reflecting PD symptoms and the capacity of the controller to adapt to dynamic changes in the reference signal (Hebb et al, 2014; Arlotti et al, 2016a; Parastarfeizabadi and Kouzani, 2017). Concurrent neuronal recordings and behavioral assessments from PD patients and animal models of PD showed a strong correlation between beta band oscillations (13–35 Hz) and PD motor symptoms, especially bradykinesia (Zaidel et al, 2010; Jenkinson and Brown, 2011; Little and Brown, 2012; Hoang et al, 2017), and beta band activity may be an appropriate feedback signal for CL DBS. A fixed beta power reference may not be appropriate for control of DBS, and it may be beneficial to include in the controller design the ability to adapt to dynamic changes in the reference signal
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