Abstract

Closed-loop control strategies for deep brain stimulation (DBS) in Parkinson's disease offer the potential to provide more effective control of patient symptoms and fewer side effects than continuous stimulation, while reducing battery consumption. Most of the closed-loop methods proposed and tested to-date rely on controller parameters, such as controller gains, that remain constant over time. While the controller may operate effectively close to the operating point for which it is set, providing benefits when compared to conventional open-loop DBS, it may perform sub-optimally if the operating conditions evolve. Such changes may result from, for example, diurnal variation in symptoms, disease progression or changes in the properties of the electrode-tissue interface. In contrast, an adaptive or “self-tuning” control mechanism has the potential to accommodate slowly varying changes in system properties over a period of days, months, or years. Such an adaptive mechanism would automatically adjust the controller parameters to maintain the desired performance while limiting side effects, despite changes in the system operating point. In this paper, two neural modeling approaches are utilized to derive and test an adaptive control scheme for closed-loop DBS, whereby the gain of a feedback controller is continuously adjusted to sustain suppression of pathological beta-band oscillatory activity at a desired target level. First, the controller is derived based on a simplified firing-rate model of the reciprocally connected subthalamic nucleus (STN) and globus pallidus (GPe). Its efficacy is shown both when pathological oscillations are generated endogenously within the STN-GPe network and when they arise in response to exogenous cortical STN inputs. To account for more realistic biological features, the control scheme is then tested in a physiologically detailed model of the cortical basal ganglia network, comprised of individual conductance-based spiking neurons, and simulates the coupled DBS electric field and STN local field potential. Compared to proportional feedback methods without gain adaptation, the proposed adaptive controller was able to suppress beta-band oscillations with less power consumption, even as the properties of the controlled system evolve over time due to alterations in the target for beta suppression, beta fluctuations and variations in the electrode impedance.

Highlights

  • Deep brain stimulation (DBS) is a clinically effective treatment used in patients with advanced Parkinson’s disease (PD) to supplement or replace pharmacological treatment of symptoms

  • The firing-rate model, which we derive the self-tuning deep brain stimulation (DBS) strategy and mathematically prove its efficacy, is inspired by the subthalamic nucleus (STN)-GPe loop model originally proposed in Nevado-Holgado et al (2010) to study the emergence of pathological beta oscillations observed in the parkinsonian basal ganglia

  • Endogenous Oscillations For constant striatal and cortical inputs, beta-band oscillations emerged in the firing-rate model when the STN-GPe and GPeSTN connectivity strength was sufficiently increased (Figure 2A)

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Summary

Introduction

Deep brain stimulation (DBS) is a clinically effective treatment used in patients with advanced Parkinson’s disease (PD) to supplement or replace pharmacological treatment of symptoms. It consists of high-frequency stimulation of neurons within the basal ganglia, with the subthalamic nucleus and globus pallidus being the most common targets, using a chronically implanted electrode and a subcutaneous pulse generator. DBS is delivered clinically in an open-loop fashion where stimulation parameters remain fixed over time. This approach, may lead to overstimulation, inducing side effects and shortening battery life. Increased betaband power in the STN LFP is correlated with motor impairment symptoms in Parkinson’s disease, and its suppression, due to medication or high frequency DBS, with improved motor performance (Kühn et al, 2006, 2008; Hammond et al, 2007; Eusebio et al, 2011)

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