Auricular vagus nerve stimulator for closed-loop biofeedback-based operation

Abstract

Auricular vagus nerve stimulation (aVNS) is a novel neuromodulatory therapy used for treatment of various chronic systemic disorders. Currently, aVNS is non-individualized, disregarding the physiological state of the patient and therefore making it difficult to reach optimum therapeutic outcomes. A closed-loop aVNS system is required to avoid over-stimulation and under-stimulation of patients, leading to personalized and thus improved therapy. This can be achieved by continuous monitoring of individual physiological parameters that serve as a basis for the selection of optimal aVNS settings. In this work we developed a novel aVNS hardware for closed-loop application, which utilizes cardiorespiratory sensing using embedded sensors (and/or external sensors), processes and analyzes the acquired data in real-time, and directly governs settings of aVNS. We show in-lab that aVNS stimulation can be arbitrarily synchronized with respiratory and cardiac phases (as derived from respiration belt, electrocardiography and/or photo plethysmography) while mimicking baroreceptor-related afferent input along the vagus nerve projecting into the brain. Our designed system identified > 90% of all respiratory and cardiac cycles and activated stimulation at the target point with a precision of ± 100 ms despite the intrinsic respiratory and heart rate variability reducing the predictability. The developed system offers a solid basis for future clinical research into closed-loop aVNS in favour of personalized therapy.

Keywords: Auricular vagus nerve; Closed-loop control; Hardware; Optimization; Vagus nerve stimulation.

Conflict of interest statement

Conflict of interestThe authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

© The Author(s) 2022.

Figures

Fig. 1

a Location of the coronal sectioning plane of the head to show the relevant VN network in b. The posterior side of the sectioned head with three needle electrodes in the cymba conchae region of the external ear, which stimulate aVN endings. The stimulation is projected by the aVN branch extension from the external ear to the vagus nerve (through external auditory meatus) into the jugular ganglion and eventually to the nucleus of the solitary tract. Vessels and nerves are shown in red and black, respectively. External ear model with the associated vessels and nerves are taken from [14, 15], the head model from [16]

Fig. 2

Block diagram of the multifunctional auricular vagus nerve stimulator for experimental and standalone setup: microcontroller (blue), designed extension hardware (orange), external data acquisition module (green), the human auricle with inserted stimulation electrodes, and electrode inserted into the ear (top right). The blocks marked with “S” are used for standalone setup

Fig.3

The closed-loop aVNS with experimental and standalone setups

Fig. 4

a Experimental setup: extension board (green) is attached to the Nucleo-64 development board (white) in the form of a sandwich panel while three output channels stimulate the cymba conchae region of the external ear using miniature needle electrodes. b Standalone setup for wearable applications

Fig. 5

Designed GUI application with MATLAB

Fig. 6

aVNS synchronized with a cardiac biosignal, as a based on PPG from the finger. b The stimulation started with a delay of 100 ms with respect to the onset of the rising slope of PPG. c The applied tri-phasic stimulation pattern (applied to all three electrodes)

Fig. 7

Auricular stimulation synchronized with three different biosignals, i.e., PPG, ECG and respiration. a, b The distribution of PPG from the finger over the recording duration (interquartile range, in blue) and the density distribution of the stimulation on-sets (in red) with a zero delay and b 0.4 s delay with respect to the end of the diastolic valley (insets show stimulation bursts along PPG during calibration). The target time instant is marked with arrows. c, d The distribution of ECG and the density distribution of the stimulation on-sets with c zero delay and d 0.3 s delay with respect to Q-Peak of ECG. e, f The distribution of respiration signal and the density distribution of the stimulation on-sets with respect to e start of expiration phase and f start of inspiration phase. The results are given for the experimental setup