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.

Micromagnetic stimulation (µMS) dose-response of the rat sciatic nerve

“…The fact that we were able to observe this frequency-dependent phenomenon experimentally validates the hypothesis that we were activating the sciatic nerve using µMS rather than through electrical stimulation contributed by current leakage from the µcoils; in electrical stimulation, one would expect to observe strong leg movements at higher duration-higher amplitude combinations and weak leg movements at lower duration-higher amplitude combinations. Furthermore, this dose-response relationship further confirms that the frequency-dependent activation of the sciatic nerve cannot be the result of the Joule heating effect from the µcoils [38] (see supplementary information S7). To prevent activation of the sciatic nerve through current leakage at the µcoil connections of the MagPen, a water-tight and biocompatible coating was used to insulate the MagPen.…”

“…ous study by Minusa et al [27] reported a temperature increase of ∼1-1.5 • C in aCSF when the µcoils were driven by the alternating current necessary for neural activation. Recently, Jeong et al [38] used an optical probe to measure the temperature increase in the neural tissue during micromagnetic activation and reported a similar observation. Park et al [41] used FEA techniques to optimize the geometrical parameters of a planar µcoil such that the temperature rise in neural tissues is below 1 • C. We have performed an independent study involving experimental and numerical calculations of the heat energy released from the µcoil.…”

“…Finite element analysis (FEA) has been previously used to study the thermal effects of Utah microelectrode arrays on grey matter tissues [36]. An experimental method to determine the temperature increase caused by Utah Arrays using infrared cameras in in vitro salt baths has also been previously reported [37,38]. We have used FEA and numerical techniques to corroborate those in vitro salt bath temperature measurements to affirm that the nature of stimulation imposed by the MagPen is indeed micromagnetic.…”

Improving focality and consistency in micromagnetic stimulation

“…When compared to monophasic stimulation, biphasic stimulation causes less tissue damage due to the neutralization properties of electrochemical reactions ( Tai et al, 2005 ). The intrinsic biphasic nature of the induced electric field suggests that micro-coil stimulation can lead to a null charge integrated over time, and provide biocompatible stimulation ( Jeong et al, 2022 ).…”

Impact of anesthesia on micromagnetic stimulation (μMS) of the vagus nerve

“…Jeong et al [41] has recently reported micromagnetic vagus nerve stimulation (μVNS) where the animals were anesthetized using isoflurane as the anesthesia. However, isoflurane has a depressive effect on the peripheral nervous system (PNS), particularly on the baroreflex [22,31].…”