Technical aspects and future approaches in transcutaneous vagus nerve stimulation (tVNS)

With the emergence of transcutaneous vagus nerve stimulation (tVNS) as a therapy option for a multitude of clinical indications, the development and improvement of the stimulators becomes an increasingly important point of focus. This paper aims to discuss electrotechnical and software-based improvements to the state-of-theart stimulators, in order to reduce the experienced side effects of the subjects as well as to increase the efficacy of the stimulation. It was found that side effects such as erythema and pain at the stimulation site are caused by electrolysis at the site of stimulation, which can be reduced by maintaining a voltage below the decomposition voltage. This can be achieved by using electroactive materials and rare-earth fractal metal coatings on the electrode, or by stimulating at the chronaxie with a biphasic rectangular waveform and an in-built short circuit to avoid an after-potential. It is furthermore discussed how the currently most promising stimulation site, the cymba conchae, can technically be stimulated in a feasible and tolerable way for the subject. Utilizing the subjects individual pain threshold is also demonstrated as a good indicator for optimal stimulation, as stimulation just below the pain threshold activates A alpha and A13-fibers, while being unable to polarize the smaller diameter AS and C-fibers responsible for pain signaling. Finally, an outlook to individualized tVNS therapy is given, by using evolution algorithms that utilize device and subject data to optimize stimulation parameters.