First‐in‐human microelectrode recordings from the vagus nerve during clinical vagus nerve stimulation

INTRODUCTION: Vagus nerve stimulation (VNS) is an effective treatment for people with drug-resistant epilepsy. However, its mechanisms of action are poorly understood, including which nerve fibers are activated in humans during VNS in typical clinical settings and which are required for clinical efficacy. In particular, there have been no intraneural recordings of vagus nerve fiber activation in awake humans undergoing chronic VNS. In this study, for the first time, we report recordings from the vagus nerve in this setting. METHODS: The recordings were performed using a sterile tungsten microelectrode inserted percutaneously into the cervical vagus nerve under ultrasound guidance. The clinical VNS systems were used to deliver stimulation while activity in the vagus nerve was recorded. RESULTS: In addition to activating myelinated axons at low currents, we provide evidence that VNS can also activate unmyelinated C fibers in the vagus nerve at currents <1 mA. CONCLUSIONS: These results add to our understanding of how VNS exerts its beneficial effects in drug-resistant epilepsy. PLAIN LANGUAGE STATEMENT: Here we describe for the first time, electrical recordings from the vagus nerve in awake drug-resistant epilepsy patients with an implanted vagus nerve stimulation (VNS) device. We found that the VNS device was able to activate both myelinated and unmyelinated fibers within the vagus nerve, which contributes to our understanding of how VNS works in the context of drug-resistant epilepsy.