Stimulation Pattern Efficiency in Percutaneous Auricular Vagus Nerve Stimulation: Experimental versus Numerical data

Abstract

Percutaneous electrical stimulation of the auricular vagus nerve (pVNS) is an electroceutical technology. The selection of stimulation patterns is empirical, which may lead to under-stimulation or over-stimulation. The objective is to assess the efficiency of different stimulation patterns with respect to individual perception and to compare it with numerical data based on in-silico ear models. Methods: Monophasic (MS), biphasic (BS) and triphasic stimulation (TS) patterns were tested in volunteers. Different clinically-relevant perception levels were assessed. In-silico models of the human ear were created with embedded fibers and vessels to assess different excitation levels. Results: TS indicates experimental superiority over BS which is superior to MS while reaching different perception levels. TS requires about 57% and 35% of BS and MS magnitude, respectively, to reach the comfortable perception. Experimental thresholds decrease from non-bursted to bursted stimulation. Numerical results indicate a slight superiority of BS and TS over MS while reaching different excitation levels, whereas the burst length has no influence. TS yields the highest number of asynchronous action impulses per stimulation symbol for the used tripolar electrode setup. Conclusion: The comparison of experimental and numerical data favors the novel TS pattern. The analysis separates excitatory pVNS effects in the auricular periphery, as accounted by in-silico data, from the combination of peripheral and central pVNS effects in the brain, as accounted by experimental data. Significance: The proposed approach moves from an empirical selection of stimulation patterns towards efficient and optimized pVNS settings.

Sensitivity Study of Neuronal Excitation and Cathodal Blocking Thresholds of Myelinated Axons for Percutaneous Auricular Vagus Nerve Stimulation

“…Inspection and analysis of the activation of axons for these pulse types indeed showed that due to the relatively long phase duration of 0.3 ms, excitation was either induced by the anodal or the cathodal phase and was in most cases independent of the order of the two phases, yielding similar excitation thresholds. This is in accordance with [30] stating that dependency on the order of the phases is only given for short phase durations, in the order of 100 µs. Comparing biphasic pulses with anodal monophasic pulses (e.g.…”

“…The results can be validated by comparison with literature describing both experimental and numerical studies, however, a complete validation of all parameter ranges would not be practically achievable with human subjects due to the large number investigated cases. A recent experimental and numerical pVNS study [30] investigated activation of Aβfibers (8.3 µm) and Aδ-fibers (3.5 µm) for an 'individual numerical model' and a 'simple numerical model', of which the latter corresponds well to this model.…”

“…A couple of new cases with axon diameter 3.5 µm and 8.3 µm, which correspond to the axon diameters in [30], were simulated for a depth and axon-electrode distance of 1 mm.…”

International Consensus Based Review and Recommendations for Minimum Reporting Standards in Research on Transcutaneous Vagus Nerve Stimulation (Version 2020)

“…In this respect, biphasic waveforms have been lately proposed since they can lead to larger recruitment of nerve fibers compared to monophasic waveforms (Kaniusas et al, 2019a). Monophasic, biphasic and triphasic stimulation patterns for different bursts lengths were recently compared (Kaniusas et al, 2020). This aspect of being able to manipulate the waveform, therefore, may allow us to tailor the strength of our stimulation depending on the specific disease condition.…”

High-Resolution Episcopic Imaging for Visualization of Dermal Arteries and Nerves of the Auricular Cymba Conchae in Humans

“…The main challenges in the optimization of the auricular VNS are the precise targeting of aVN in the external ear and the selection of proper stimulation parameters to recruit aVN fibers close to the stimulation electrodes (Kaniusas et al, 2019c). The anatomical map of external ear innervation can address the FIGURE 6 | Inter-centroid distance and minimum distance between nerves and arteries within each slide (blue squares denote outliers).…”