Transcutaneous Non-Invasive Vagus Nerve Stimulation: Changing the Paradigm for Stroke and Atrial Fibrillation Therapies?

Abstract

A new therapeutic approach, known as neuromodulation therapy-which encompasses a variety of interventional techniques meant to alter the nervous system in order to achieve therapeutic effects-has emerged in recent years as a result of advancements in neuroscience. Currently used methods for neuromodulation include direct and indirect approaches, as well as invasive and non-invasive interventions. For instance, the two primary methods of stimulating the vagus nerve (VN) are invasive VN stimulation (iVNS) and transcutaneous VN stimulation (tVNS). Since the latter is non-invasive, basic, clinical, and translational studies have focused on transcutaneous auricular VN stimulation (taVNS), the primary tVNS therapy, because of its advantages over iVNS, including ease of use, greater accessibility, and a lower side effect profile. taVNS is currently used as a novel neuromodulatory application to treat cardiovascular, mental, and autoimmune diseases. Future applications of this non-invasive neuromodulation technology to conditions like atrial fibrillation (AF) or ischemic stroke are highly likely due to its advancement.

Keywords: atrial fibrillation; cardiovascular diseases (CVD); inflammation; neuroplasticity; stroke; taVNS; vagus nerve.

Figure 1

A brief history of bioelectronic medicine. Since antiquity, a number of invasive and non-invasive electrical stimulators have been developed to treat specific diseases as a result of sequential discoveries.

Figure 2

Vagus nerve stimulation for stroke rehabilitation: neuromodulatory effects promoting neuroplasticity. Image displays application of tVNS and modulation of neurotransmitter release at synapse. Red = active left tragus stimulation by taVNS device; blue = sham control stimulation sites.

Figure 3

Inflammatory responses can be influenced by stimulation of the vagus nerve.

Figure 4

As a tool for reducing stroke infarct sizes and for beating AF, taVNS has shown promising results. (A). Autonomic nervous system (ANS) imbalance plays a significant role in the development of ischemic brain injury and stroke. taVNS has been shown to be effective in dampening underlying inflammatory processes. AF = atrial fibrillation; taVNS = transcutaneous auricular vagus nerve stimulation. (B). The cutaneous distribution of vagal fibers at the external ear (auricular branch of the vagus nerve), as described in part B, is the basis for non-invasive taVNS delivery systems. The best anatomical sites for active left tragus stimulation by the taVNS device are represented by red circles in the main image and clamps in the insert, respectively. Blue circles and clamps, on the other hand, represent sham control stimulation sites.