The Safety and Efficacy of Transdermal Auricular Vagal Nerve Stimulation Earbud Electrodes for Modulating Autonomic Arousal, Attention, Sensory Gating, and Cortical Brain Plasticity in Humans.

Our work was motivated by the goal of developing a Targeted Neuroplasticity Training (TNT) method for enhancing foreign language learning. To this end, our primary effort was to evaluate new and optimized approaches to noninvasive vagal nerve stimulation (VNS). We considered several Human Factors Dimensions to develop methods that would be amenable to comfortable, everyday use in common training environments or contexts. Several approaches to noninvasive or external vagal nerve stimulation have been described. Transcutaneous modulation of the left cervical branch of the vagus nerve can be uncomfortable for users resulting in a distracting experience, which may not be ideal for augmenting plasticity during training. Transdermal auricular vagal nerve stimulation (taVNS) offers another approach by targeting nerve fibers innervating the external ear. Prior methods have described many different approached using electrode clips on the ear or stainless-steel ball electrodes, which can respectively result in mechanical discomfort and electrical stimulus discomfort due to high current densities. Other approaches use carbon-doped or conductive rubbers, which require wetting. This is problematic since small degrees of dehydration cause significant changes in the electrical impedance of the skin-electrode interface. Detailed human cadaveric studies have shown the external auditory meatus or ear canal is highly innervated by branches of the auricular vagus nerve. Therefore, we designed taVNS electrodes that were fabricated as a biocompatible, hydrogel earbud electrodes for unilateral or bilateral use. We then evaluated the safety and efficacy of these approaches across a range of stimulus frequencies and intensities. We further evaluated the influence of this approach on autonomic physiology by recording heart rate, heart rate variability, skin conductance, skin temperature, and respiration rate. We investigated attention using simultaneous EEG and pupillometry during auditory stimulation tasks. We further studied the effects on sensory gating and plasticity by examining EEG brain activity patterns obtained during auditory mismatch negativity tasks. Finally, we investigated the basic safety and tolerability of the methods and approaches. We found that a simple, dry (hydrogel), earbud electrode design is a safe and effective method for achieving taVNS. Given the safety, preliminary efficacy, and comfort outcomes observed, we conclude taVNS approaches using earbud electrodes warrant further development and investigation as a TNT tool, to mediate human-computer interactions, for brain-computer interfaces, and as medical devices for the treatment of pervasive health disorders.