Electrical stimulation of the auricular vagus nerve (aVNS) is an emerging technology in the field of bioelectronic medicine with applications in therapy. Modulation of the afferent vagus nerve affects a large number of physiological processes and bodily states associated with information transfer between the brain and body. These include disease mitigating effects and sustainable therapeutic applications ranging from chronic pain diseases, neurodegenerative and metabolic ailments to inflammatory and cardiovascular diseases. Given the current evidence from experimental research in animal and clinical studies we discuss basic aVNS mechanisms and their potential clinical effects. Collectively, we provide a focused review on the physiological role of the vagus nerve and formulate a biology-driven rationale for aVNS. For the first time, two international workshops on aVNS have been held in Warsaw and Vienna in 2017 within the framework of EU COST Action "European network for innovative uses of EMFs in biomedical applications (BM1309)." Both workshops focused critically on the driving physiological mechanisms of aVNS, its experimental and clinical studies in animals and humans, in silico aVNS studies, technological advancements, and regulatory barriers. The results of the workshops are covered in two reviews, covering physiological and engineering aspects. The present review summarizes on physiological aspects - a discussion of engineering aspects is provided by our accompanying article (Kaniusas et al., 2019). Both reviews build a reasonable bridge from the rationale of aVNS as a therapeutic tool to current research lines, all of them being highly relevant for the promising aVNS technology to reach the patient.

Electrical stimulation of the auricular vagus nerve (aVNS) is an emerging electroceutical technology in the field of bioelectronic medicine with applications in therapy. Artificial modulation of the afferent vagus nerve – a powerful entrance to the brain – affects a large number of physiological processes implicating interactions between the brain and body. Engineering aspects of aVNS determine its efficiency in application. The relevant safety and regulatory issues need to be appropriately addressed. In particular, in silico modeling acts as a tool for aVNS optimization. The evolution of personalized electroceuticals using novel architectures of the closed-loop aVNS paradigms with biofeedback can be expected to optimally meet therapy needs. For the first time, two international workshops on aVNS have been held in Warsaw and Vienna in 2017 within the scope of EU COST Action “European network for innovative uses of EMFs in biomedical applications (BM1309).” Both workshops focused critically on the driving physiological mechanisms of aVNS, its experimental and clinical studies in animals and humans, in silico aVNS studies, technological advancements, and regulatory barriers. The results of the workshops are covered in two reviews, covering physiological and engineering aspects. The present review summarizes on engineering aspects – a discussion of physiological aspects is provided by our accompanying article (Kaniusas et al., 2019). Both reviews build a reasonable bridge from the rationale of aVNS as a therapeutic tool to current research lines, all of them being highly relevant for the promising aVNS technology to reach the patient.

The study aim was to validate that dielectric permittivity measurement using the open-ended coaxial probe can be reliably modeled using electromagnetic modeling and simulations, followed by the postprocessing calculations based on the simple capacitive-load model. Saline solutions with various NaCl concentrations were used as materials under test (MUTs) to investigate how ionic conductivity affects the model validity. Two different solvers and simulation methods were used: FEKO for the frequency domain and CST for the time domain. Furthermore, we performed physical experiments with the same probe and MUTs, again implementing the capacitive-load model on the measurement data to observe the model validity. Relative error of the capacitive-load model with respect to the reference permittivity values, both in measurements and simulations, was within 10% for all cases except for the measured ${\epsilon }_r^{\prime }$ of 1M solution at the lowest frequencies. The model yielded average relative errors well below 1% for the physiological saline, which is relevant for biological materials. The error increased for higher concentrations and for the lowest simulated frequencies but was within the declared measurement accuracy of the probe itself. This makes the simple capacitive-load model valid for all analyzed concentrations in the microwave frequency range from 0.5 to 18 GHz.

We provide the results of human body absorption cross-section (ACS) measurements. The setup was based on the reverberation chamber as a well-known measurement environment capable of performing ACS measurements. The approach was supported by reference measurements on canonically shaped objects which were convenient for analytical (Mie scattering theory) ACS calculations. Measured ACS of canonical objects was in excellent agreement with calculated values. The ACS measurements of a human model were performed: 1) on an actual human body in an upright posture and 2) on a cylindrical water model made of vertically stacked water-filled jugs. The cylindrical model had the same water content as an average human body. Comparison between these two models showed a small difference in measured ACS within the measurement uncertainty of our setup. Thus, the cylindrical water model proved to be a useful artifact, especially for time-consuming broadband ACS measurements.

Accurate knowledge about the dielectric properties of biological tissues in the microwave frequency range may lead to advancement of biomedical applications based on microwave technology. However, the published data are very scarce, especially for human brain tissues. The aim of this work was to measure and report the complex permittivity of brain white matter, grey matter and cerebellum. Complex permittivity was measured on human, bovine and porcine brain tissues in the microwave frequency range from 0.5 to 18 GHz using an open-ended coaxial probe. The results present a valuable addition to the available data on the brain tissue complex permittivity. Some noticeable variations between the results lead to several conclusions. Complex permittivity variation within the same tissue type of the individual species was comparable to interspecies variation. The difference was prominent between human brains obtained from autopsies, while bovine brains obtained from healthy animals showed very similar complex permittivity. We hypothesize that the difference might have been caused by the basic pathologies of the patients, where the associated therapies could have affected the brain water content. We also examined the effect of excised tissue degradation on its complex permittivity over the course of three days, and the results suggest the gradual dehydration of the samples.