A novel controller based on state-transition models for closed-loop vagus nerve stimulation: Application to heart rate regulation.

Vagus nerve stimulation (VNS) is an established adjunctive therapy for pharmacologically refractory epilepsy and depression and is currently in active clinical research for other applications. In current clinical studies, VNS is delivered in an open-loop approach, where VNS parameters are defined during a manual titration phase. However, the physiological response to a given VNS configuration shows significant inter and intra-patient variability and may significantly evolve through time.

Closed-Loop Vagus Nerve Stimulation Based on State Transition Models.

Objective: Vagus nerve stimulation (VNS) is a potential therapeutic approach in a number of clinical applications. Although VNS is commonly delivered in an open-loop approach, it is now recognized that closed-loop stimulation may be necessary to optimize the therapy. In this paper, we propose an original generic closed-loop control system that can be readily integrated into an implantable device and allows for the adaptive modulation of multiple VNS parameters.

An original piecewise model for computing energy expenditure from accelerometer and heart rate signals.

Objective: Activity energy expenditure (EE) plays an important role in healthcare, therefore, accurate EE measures are required. Currently available reference EE acquisition methods, such as doubly labeled water and indirect calorimetry, are complex, expensive, uncomfortable, and/or difficult to apply on real time. To overcome these drawbacks, the goal of this paper is to propose a model for computing EE in real time (minute-by-minute) from heart rate and accelerometer signals.

Sensitivity Analysis of Vagus Nerve Stimulation Parameters on Acute Cardiac Autonomic Responses: Chronotropic, Inotropic and Dromotropic Effects.

Although the therapeutic effects of Vagus Nerve Stimulation (VNS) have been recognized in pre-clinical and pilot clinical studies, the effect of different stimulation configurations on the cardiovascular response is still an open question, especially in the case of VNS delivered synchronously with cardiac activity. In this paper, we propose a formal mathematical methodology to analyze the acute cardiac response to different VNS configurations, jointly considering the chronotropic, dromotropic and inotropic cardiac effects. A latin hypercube sampling method was chosen to design a uniform experimental plan, composed of 75 different VNS configurations, with different values for the main parameters (current amplitude, number of delivered pulses, pulse width, interpulse period and the delay between the detected cardiac event and VNS onset).

Model-Based Design and Experimental Validation of Control Modules for Neuromodulation Devices.

Goal: The goal of this paper is to propose a model-based control design framework, adapted to the development of control modules for medical devices. A particular example is presented in which instantaneous heart rate is regulated in real-time, by modulating, in an adaptive manner, the current delivered to the vagus nerve by a neuromodulator.

Methods: The proposed framework couples a control module, based on a classical PI controller, a mathematical model of the medical device, and a physiological model representing the cardiovascular responses to vagus nerve stimulation (VNS).