Multivariable closed-loop control of deep brain stimulation for Parkinson’s disease
Fleming JE., Senneff S., Lowery M.
Abstract Objective: Closed-loop deep brain stimulation (DBS) approaches proposed for Parkinson’s disease (PD) have considered modulation of a selected stimulation parameter to control a single biomarker. While promising performance has been demonstrated for symptoms well-correlated with the chosen biomarker, suboptimal regulation can occur for uncorrelated symptoms or when the relationship between biomarker and symptoms varies. Similarly, control of stimulation-induced side-effects is typically not considered. Approach: A multivariable control architecture is presented to selectively target suppression of either tremor or subthalamic nucleus beta band oscillations. Both DBS pulse amplitude and duration are modulated to maintain amplitude below a threshold and avoid stimulation of large diameter axons, far from the electrode, associated with stimulation-induced side effects. A supervisor selects between a bank of controllers which modulate DBS amplitude to control tremor or beta activity depending on muscle electromyographic (EMG) activity. A secondary controller modulates pulse duration to constrain pulse amplitude and target smaller diameter axons lying close to the electrode. The control architecture was investigated in a computational model of the PD motor network which simulated the cortico-basal ganglia network, motoneuron pool, force and EMG signals from the hand. Main results: Good control of both tremor and beta activity was observed with reduced power delivered when compared with conventional open loop stimulation, The supervisor avoided over- or under stimulation which occurred when-using a single controller tuned to one biomarker. When DBS amplitude was constrained, the secondary controller maintained the efficacy of stimulation by increasing pulse duration to compensate for reduced amplitude. Dual parameter control delivered effective control of the target biomarkers, with additional savings in the power delivered. Significance: Non-linear multivariable control can enable targeted suppression of motor symptoms for PD patients. Moreover, dual parameter control facilitates automatic regulation of the stimulation therapeutic dosage to prevent overstimulation, whilst providing additional power savings.