Stimulation of cranial nerves modulates central nervous system (CNS) activity via the extensive connections of their brainstem nuclei to higher-order structures. Clinical experience with vagus-nerve stimulation (VNS) demonstrates that it produces robust therapeutic effects, however, posing concerns related to its invasiveness and side-effects. Trigeminal nerve stimulation (TNS) has been recently proposed as a valid alternative to VNS. The ear presents afferent vagus and trigeminal-nerve distribution; its innervation is the theoretical basis of different reflex therapies, including auriculotherapy. An increasing number of studies have shown that several therapeutic effects induced by invasive VNS and TNS, can be reproduced by noninvasive auricular-nerve stimulation. However, the sites and neurobiologic mechanisms by which VNS and TNS produce their therapeutic effects are not clear yet. Accumulating evidence suggests that VNS and TNS share multiple levels and mechanisms of action in the CNS.

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Neuromodulation, thanks to intrinsic and extrinsic brain feedback loops, seems to be the best way to exploit brain plasticity for therapeutic purposes. In the past years, there has been tremendous advances in the field of non-pharmacological modulation of brain activity. This review of different neurostimulation techniques will focus on sites and mechanisms of both transcutaneous vagus and trigeminal nerve stimulation. These methods are scientifically validated non-invasive bottom-up brain modulation techniques, easily implemented from the outer ear. In the light of this, auricles could transpire to be the most affordable target for non-invasive manipulation of central nervous system functions.

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