The effects of transcutaneous auricular vagus nerve stimulation (taVNS) on cholinergic neural networks in humans: A neurophysiological study.

• The activity of cholinergic circuits is critical for the induction of vagus nerve stimulation (VNS)-mediated plasticity. • Transcutaneous auricular VNS (taVNS) stimulation does not influence short-latency afferent inhibition. • Cholinergic circuits explored by SAI are different from cholinergic circuits engaged by taVNS. The mechanisms of actions of transcutaneous auricular vagus nerve stimulation (taVNS) are still unclear, however the activity of the cholinergic system seems to be critical for the induction of VNS-mediated plasticity. Transcranial Magnetic Stimulation (TMS) is a well-suited, non-invasive tool to investigate cortical microcircuits involving different neurotransmitters. Herein, we evaluated the effect of taVNS on short-latency afferent inhibition (SAI), a TMS paradigm specifically measuring cholinergic neurotransmission. Fifteen healthy subjects participated in this randomized placebo-controlled double-blind study. Each subject underwent two different sessions of 1-hour exposure to taVNS (real and sham) separated by a minimum of 48 h. Real taVNS was administered at left external acoustic meatus, while sham stimulation was performed at left ear lobe. We evaluated SAI bilaterally over the motor cortex before and after exposure to taVNS. No side effects were reported by any of the participants. Statistical analysis did not show any significant effect of taVNS on SAI. Our study demonstrated that cholinergic circuits explored by SAI are different from circuits engaged by taVNS. Since the influence of VNS on cholinergic neurotransmission has been exhaustively demonstrated in animal models, further studies are mandatory to understand the actual impact of VNS on cholinergic circuits in humans. [ABSTRACT FROM AUTHOR]