Abstract
Advances in the field of closed-loop neuromodulation call for analysis and modeling approaches capable of confronting challenges related to the complex neuronal response to stimulation and the presence of strong internal and measurement noise in neural recordings. Here we elaborate on the algorithmic aspects of a noise-resistant closed-loop subthalamic nucleus deep brain stimulation system for advanced Parkinson’s disease and treatment-refractory obsessive-compulsive disorder, ensuring remarkable performance in terms of both efficiency and selectivity of stimulation, as well as in terms of computational speed. First, we propose an efficient method drawn from dynamical systems theory, for the reliable assessment of significant nonlinear coupling between beta and high-frequency subthalamic neuronal activity, as a biomarker for feedback control. Further, we present a model-based strategy through which optimal parameters of stimulation for minimum energy desynchronizing control of neuronal activity are being identified. The strategy integrates stochastic modeling and derivative-free optimization of neural dynamics based on quadratic modeling. On the basis of numerical simulations, we demonstrate the potential of the presented modeling approach to identify, at a relatively low computational cost, stimulation settings potentially associated with a significantly higher degree of efficiency and selectivity compared with stimulation settings determined post-operatively. Our data reinforce the hypothesis that model-based control strategies are crucial for the design of novel stimulation protocols at the backstage of clinical applications.
Highlights
The use of electrical deep brain stimulation (DBS), during approximately the last 30 years, has been proven to provide striking benefits for patients with advanced Parkinson’s disease (PD), essential tremor and dystonia [1,2,3,4] who have failed conventional therapies
A total of 31 acceptable microelectrode recordings (MERs) trajectories acquired during subthalamic nucleus (STN)-DBS for PD and 12 acceptable MER trajectories acquired during STN-DBS for obsessive-compulsive disorder (OCD) were selected for offline analysis
OCD, we evaluated s2 pst simulating the application of regular 130 Hz stimulation and based upon the model parameters estimated for two subsets of recordings: a total of 39 MERs of subthalamic neuronal activity acquired during DBS for OCD and characterized by a high mean discharge rate (39.7 ± 14.71 Hz), a high intraburst frequency and a short interburst interval vs. a total of 39 MERs of subthalamic neuronal activity characterized by a low mean discharge rate
Summary
The use of electrical deep brain stimulation (DBS), during approximately the last 30 years, has been proven to provide striking benefits for patients with advanced Parkinson’s disease (PD), essential tremor and dystonia [1,2,3,4] who have failed conventional therapies. Apart from being considerably time consuming, this trialand-error procedure may not necessarily yield the optimal trade-off between maximal therapeutic benefit and minimal stimulation-induced side-effects [12]. It fails to keep pace with the fact that movement and neuropsychiatric disorder symptoms may fluctuate over significantly shorter time-scales of seconds to days. The open-loop nature and monomorph pattern of conventional high-frequency stimulation appears to favor tolerance/ habituation phenomena, while being associated with a significant rate of power consumption [13]
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