Model based optimal multipolar stimulation without a priori knowledge of nerve structure: application to vagus nerve stimulation

Objective. Multipolar cuff electrode can selectively stimulate areas of peripheral nerves and therefore enable to control independent functions. However, the branching and fascicularization are known for a limited set of nerves and the specific organization remains subject-dependent. This paper presents general modeling and optimization methods in the context of multipolar stimulation using a cuff electrode without a priori knowledge of the nerve structure. Vagus nerve stimulation experiments based on the optimization results were then investigated. Approach. The model consisted of two independent components: a lead field matrix representing the transfer function from the applied current to the extracellular voltage present on the nodes of Ranvier along each axon, and a linear activation model. The optimization process consisted in finding the best current repartition (ratios) to reach activation of a targeted area depending on three criteria: selectivity, efficiency and robustness. Main results. The results showed that state-of-the-art configurations (tripolar transverse, tripolar longitudinal) were part of the optimized solutions but new ones could emerge depending on the trade-off between the three criteria and the targeted area. Besides, the choice of appropriate current ratios was more important than the choice of the stimulation amplitude for a stimulation without a priori knowledge of the nerve structure. We successfully assessed the solutions in vivo to selectively induce a decrease in cardiac rhythm through vagus nerve stimulation while limiting side effects. Compared to the standard whole ring configuration, a selective solution found by simulation provided on average 2.6 less adverse effects. Significance. The preliminary results showed the rightness of the simulation, using a generic nerve geometry. It suggested that this approach will have broader applications that would benefit from multicontact cuff electrodes to elicit selective responses. In the context of the vagus nerve stimulation for heart failure therapy, we show that the simulation results were confirmed and improved the therapy while decreasing the side effects.