Importance of timing optimization for closed-loop applications of vagus nerve stimulation

Abstract

In recent decades, vagus nerve stimulation (VNS) therapy has become widely used for clinical applications including epilepsy, depression, and enhancing the effects of rehabilitation. However, several questions remain regarding optimization of this therapy to maximize clinical outcomes. Although stimulation parameters such as pulse width, amplitude, and frequency are well studied, the timing of stimulation delivery both acutely (with respect to disease events) and chronically (over the timeline of a disease's progression) has generally received less attention. Leveraging such information would provide a framework for the implementation of next generation closed-loop VNS therapies. In this mini-review, we summarize a number of VNS therapies and discuss (1) general timing considerations for these applications and (2) open questions that could lead to further therapy optimization.

Keywords: Closed-loop; Stimulus Timing; Vagus Nerve Stimulation.

Fig. 1

Overview of VNS implementation considerations. This figure illustrates factors that can affect the development of next generation closed-loop VNS therapies. The solid arrows link general VNS implementation considerations. Disease-specific signals can be fed into algorithms on computers or other processing systems to trigger VNS. There are, however, two main considerations involved in determining the optimal timing of VNS (dotted lines): 1) the timing of stimulation with respect to a disease’s progression (A, linking the patient and affected systems) and 2) timing of stimulation with respect to recorded disease-specific events (B, linking the sensor(s) and stimulation control devices). Multiple paths and design choices can be considered for constructing a VNS system (Created, in part, via Biorender.com)