Transcutaneous Auricular Vagus Nerve Stimulation.

Invasive vagus nerve stimulation (VNS) is an approved treatment for drug-resistant epilepsy. Besides recognized clinical efficacy in about 60% of patients, there are major drawbacks such as invasiveness and common side effects including hoarseness, sore throat, shortness of breath, and coughing. Invasive VNS applies electrical stimulation to the left cervical branch of the vagus nerve and excites thick-myelinated afferent nerve fibers. Peripheral vagus nerve afferent volley initiates brainstem activity in the nucleus of the solitary tract and provokes typical brainstem and cerebral activation patterns that mediate the anticonvulsive mode of action. Whereas invasive VNS is an established neuromodulatory treatment in drug-resistant epilepsy, transcutaneous VNS (tVNS) of the auricular branch of the vagus nerve is suggested to be an alternative access path to the same neuronal network without invasiveness. Preclinical and clinical studies indicate that especially the cymba conchae of the auricle is selectively supplied by the auricular branch of the vagus nerve. Recent anatomical data demonstrate existence and quantity of thick-myelinated afferent nerve fibers of the left auricular branch of the vagus nerve that carries 21% of thick-myelinated afferent nerve fibers counted in the left thoracic vagus nerve in humans. Projection of auricular branch of the vagus nerve afferents from the auricle to the nucleus of the solitary tract is known from histochemical and electrophysiological experiments in rodents and confirmed in humans by functional imaging. Cerebral activation patterns triggered by invasive and tVNS resemble each other in appearance. Clinical trials in patients address safety and performance of tVNS and provide evidence for application in drug-resistant epilepsy.