Short-pulsed micro-magnetic stimulation of the vagus nerve

Abstract

Vagus nerve stimulation (VNS) is commonly used to treat drug-resistant epilepsy and depression. The therapeutic effect of VNS depends on stimulating the afferent vagal fibers. However, the vagus is a mixed nerve containing afferent and efferent fibers, and the stimulation of cardiac efferent fibers during VNS may produce a rare but severe risk of bradyarrhythmia. This side effect is challenging to mitigate since VNS, via electrical stimulation technology used in clinical practice, requires unique electrode design and pulse optimization for selective stimulation of only the afferent fibers. Here we describe a method of VNS using micro-magnetic stimulation (µMS), which may be an alternative technique to induce a focal stimulation, enabling a selective fiber stimulation. Micro-coils were implanted into the cervical vagus nerve in adult male Wistar rats. For comparison, the physiological responses were recorded continuously before, during, and after stimulation with arterial blood pressure (ABP), respiration rate (RR), and heart rate (HR). The electrical VNS caused a decrease in ABP, RR, and HR, whereas µM-VNS only caused a transient reduction in RR. The absence of an HR modulation indicated that µM-VNS might provide an alternative technology to VNS with fewer heart-related side effects, such as bradyarrhythmia. Numerical electromagnetic simulations helped estimate the optimal coil orientation with respect to the nerve to provide information on the electric field’s spatial distribution and strength. Furthermore, a transmission emission microscope provided very high-resolution images of the cervical vagus nerve in rats, which identified two different populations of nerve fibers categorized as large and small myelinated fibers.