Exposure and neuronal excitation by wireless power transfer for auricular vagus nerve stimulation

Inductive wireless power transfer (WPT) can be used to power implanted as well as wearable medical devices, such as a percutaneous auricular vagus nerve stimulation device. This device is placed on the neck of the patient and is connected to needle electrodes in the auricle. With regard to WPT, limitations on exposure to electric and magnetic fields should not be exceeded. Furthermore, these fields should not interfere with the therapeutic goal of stimulation, i.e., with unintended peripheral nerve stimulation in the auricle. These effects are investigated by numerical simulation of induced internal fields in the head and neck and, for the first time, subsequent neuronal simulations, quantifying the potential of neuronal excitation by the fields in the auricle in particular. Internal electric field values were in the range of 1\%-5\% of the ICNIRP 2010 basic restrictions, and current densities were in the range of 30\%-45\% of the ICNIRP 1998 basic restrictions, indicating that all tested configurations are conform the guidelines. Basic restrictions on heating of tissue turned out not to be of relevance for this application. Thresholds for neuronal stimulation were two orders of magnitude higher than the induced fields, suggesting that there is almost no risk for unintended stimulation

Feasibility of pulse rate variability as feedback in closed-loop percutaneous auricular vagus nerve stimulation

Percutaneous auricular vagus nerve stimulation (pVNS) is a novel approach of treating cardiovascular and inflammatory diseases, as well as pain and neurological conditions. The treatment can be optimized by using biosignals as objective measures and feedback-control. One suitable biofeedback could be the use of pulse rate and pulse rate variability (PRV) derived from optical pulse plethysmography (PPG) instead of heart rate and heart rate variability (HRV) derived from electrocardiogram (ECG). For this purpose, a single-lead ECG on the thorax and a PPG on the earlobe were measured simultaneously on 10 healthy subjects for 420 s during three different respiratory phases. The data was analyzed and compared with scatterplots, the Pearson correlation coefficient and a Bland-Altman analysis. The outcomes show a very high correlation of heart rates from PPG and ECG (ri= 0.9663) and SDNN values (rsdnn= 0.9791). Comparison of RMSSD values showed a high positive correlation (rrmssd= 0.7963) but a mean overestimation of 10 ms in RMSSD values measured with the PPG. The results presented suggest that PRV could be and alternative biofeedback used in pVNS

Editorial: Neuromodulation in COVID-19: From basic research to clinical applications

RECEIVED 20 January 2023; ACCEPTED 08 February 2023; PUBLISHED 16 February 2023Unidad Docente de Biodiversidad, Ecología y EvoluciónFac. de Óptica y OptometríaTRUEpu

Numerical modeling of percutaneous auricular vagus nerve stimulation : a realistic 3D model to evaluate sensitivity of neural activation to electrode position

Percutaneous stimulation of the auricular branch of the vagus nerve (pVNS) by miniaturized needle electrodes in the auricle gained importance as a treatment for acute and chronic pain. The objective is to establish a realistic numerical model of pVNS and investigate the effects of stimulation waveform, electrodes' depth, and electrodes' position on nerve excitation threshold and the percentage of stimulated nerves. Simulations were performed with Sim4Life. An electrostatic solver and neural tissue models were combined for electromagnetic and neural simulation. The numerical model consisted of a realistic high-resolution model of a human ear, blood vessels, nerves, and three needle electrodes. A novel 3D ear model was established, including blood vessels and nerves. The electric field distribution was extracted and evaluated. Maximum sensitivity to needles' depth and displacement was evaluated to be 9.8 and 15.5% per 0.1 mm, respectively. Stimulation was most effective using biphasic compared to mono-phasic pulses. The established model allows easy and quantitative evaluation of various stimulation setups, enabling optimization of pVNS in experimental settings. Results suggest a high sensitivity of pVNS to the electrodes' position and depth, implying the need for precise electrode positioning. Validation of the model needs to be performed

Mental and physiological wellbeing while rowing across the North Atlantic: a single-case study of subjective versus objective data

Introduction: Unassisted rowing across the Atlantic Ocean is an extreme undertaking challenging the human body in every possible way. The reported rowing journey lasted for 42 days in a small vessel with 12 rowers, each rowing for 12 h a day, broken into 3 h shifts. This schedule disrupts the natural circadian cycle and autonomic balance, affecting subjective and objective wellbeing and sleep quality, that lack continuous empirical quantification.Methods: With a self-reported questionnaire and objective heart rate variability measurements every second day in a single female rower, we monitor evolutions of the subjective sleep quality and mental wellbeing as well as autonomic body control over the journey duration. We evaluate the hypothesis that extreme rowing impairs subjective and objective data in a similar way over time and that 3 h shifts diminish the circadian rhythm of the autonomic body control.Results: The sleep quality was mainly influenced by wake ups during sleep, while mental wellbeing was predominantly influenced by physical exhaustion. The perceived sleep quality and wellbeing dropped 2–3 days after the start with the rower not yet accommodated, in the middle of the journey with major wake ups, and again 5–6 days prior to the end with major exhaustion of the participant. Evolutions of the subjective perceptions diverge from that of the heart rate variability. The body’s autonomic recovery during short sleep periods progressively decreases over the journey duration while the vagal activity rises and the sympathovagal balance shifts towards vagal tone. The shifts of 3 h weaken the circadian rhythm of the heart rate variability.Discussion: Our results demonstrate how human body meets extreme mental and physical exhaustion on the high seas. The gained physiological and psychological insights also offer a basis for effective preparation of undertakings involving extreme physical exhaustion and sleep deprivation

Sensitivity analysis of a numerical model for percutaneous auricular vagus nerve stimulation

Background: Less-invasive percutaneous stimulation of the auricular branch of the vagus nerve (pVNS) gained importance as a possible nonpharmacological treatment for various diseases. The objective is to perform a sensitivity analysis of a realistic numerical model of pVNS and to investigate the effects of the model parameters on the excitation threshold for single and bundled axons. Methods: Sim4Life electrostatic solver and neural tissue models were combined for electromagnetic and neural simulation. The numerical model consisted of a high-resolution model of a human ear, blood vessels, nerves, and three needle electrodes. Investigated parameters include the axon diameter and number, model temperature, ear conductivity, and electrodes' penetration depth and position. Results: The electric field distribution was evaluated. Model temperature and ear conductivity are the non-influential parameters. Axons fiber diameter and the electrodes' penetration depth are the most influential parameters with a maximum threshold voltage sensitivity of 32 mV for each 1 mu m change in the axon diameter and 38 mV for each 0.1 mm change in the electrodes' penetration depth. Conclusions: The established sensitivity analysis allows the identification of the influential and the non-influential parameters with a sensitivity quantification. Results suggest that the electrodes' penetration depth is the most influential parameter

Stimulation pattern efficiency in percutaneous auricular vagus nerve stimulation : experimental versus numerical data

Objective: 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 set-up. 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

Objective: Excitation of myelinated nerve fibers is investigated by means of numerical simulations, for the application of percutaneous auricular vagus nerve stimulation (pVNS). High sensitivity to axon diameter is of interest regarding the goal of targeting thicker fibers. Methods: Excitation and blocking thresholds for different pulse types, phase durations, axon depths, axon-electrode distances, temperatures and axon diameters are investigated. The used model consists of a 50 mm long axon and a centrally located needle electrode in a layered medium representing the auricle. Neuronal excitation is simulated using the Frankenhaeuser-Huxley equations for all combinations of parameter values. Results and conclusion: Multiple modes and locations of excitation along the axon were observed, depending on the pulse type and amplitude. When increasing the axon-electrode distance from 1 mm to 2 mm, sensitivity of thresholds to axon depth decreased with ca. 50%, while sensitivity to axon-electrode distance, axon diameter and phase duration each increased with ca. 15% to 20%, except from monophasic anodal pulses, showing a 45% decrease for axon-electrode distance. These trends for axon diameter and axon-electrode distance allow for more selective stimulation of thicker target fibers using monophasic anodal pulses at higher axon-electrode distances. Cathodal monophasic pulses did not perform well due to blocking of the thicker fibers, which was only rarely seen for other pulse types. Significance: Sensitivities of stimulation thresholds to these parameters by numerical simulation reveal how the stimulation parameters can be changed in order to increase therapeutic effect and comfort during pVNS by enabling more selective stimulation

Estimation of central blood pressure waveform from femoral blood pressure waveform by blind sources separation

BackgroundCentral blood pressure (cBP) is a better indicator of cardiovascular morbidity and mortality than peripheral BP (pBP). However, direct cBP measurement requires invasive techniques and indirect cBP measurement is based on rigid and empirical transfer functions applied to pBP. Thus, development of a personalized and well-validated method for non-invasive derivation of cBP from pBP is necessary to facilitate the clinical routine. The purpose of the present study was to develop a novel blind source separation tool to separate a single recording of pBP into their pressure waveforms composing its dynamics, to identify the compounds that lead to pressure waveform distortion at the periphery, and to estimate the cBP. The approach is patient-specific and extracts the underlying blind pressure waveforms in pBP without additional brachial cuff calibration or any a priori assumption on the arterial model.MethodsThe intra-arterial femoral BPfe and intra-aortic pressure BPao were anonymized digital recordings from previous routine cardiac catheterizations of eight patients at the German Heart Centre Berlin. The underlying pressure waveforms in BPfe were extracted by the single-channel independent component analysis (SCICA). The accuracy of the SCICA model to estimate the whole cBP waveform was evaluated by the mean absolute error (MAE), the root mean square error (RMSE), the relative RMSE (RRMSE), and the intraclass correlation coefficient (ICC). The agreement between the intra-aortic and estimated parameters including systolic (SBP), diastolic (DBP), mean arterial pressure (MAP), and pulse pressure (PP) was evaluated by the regression and Bland–Altman analyses.ResultsThe SCICA tool estimated the cBP waveform non-invasively from the intra-arterial BPfe with an MAE of 0.159 ± 1.629, an RMSE of 5.153 ± 0.957 mmHg, an RRMSE of 5.424 ± 1.304%, and an ICC of 0.94, as well as two waveforms contributing to morphological distortion at the femoral artery. The regression analysis showed a strong linear trend between the estimated and intra-aortic SBP, DBP, MAP, and PP with high coefficient of determination R2 of 0.98, 0.99, 0.99, and 0.97 respectively. The Bland–Altman plots demonstrated good agreement between estimated and intra-aortic parameters with a mean error and a standard deviation of difference of −0.54 ± 2.42 mmHg [95% confidence interval (CI): −5.28 to 4.20] for SBP, −1.97 ± 1.62 mmHg (95% CI: −5.14 to 1.20) for DBP, −1.49 ± 1.40 mmHg (95% CI: −4.25 to 1.26) for MAP, and 1.43 ± 2.79 mmHg (95% CI: −4.03 to 6.90) for PP.ConclusionsThe SCICA approach is a powerful tool that identifies sources contributing to morphological distortion at peripheral arteries and estimates cBP