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

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.