A literature review on the neurophysiological underpinnings and cognitive effects of transcutaneous vagus nerve stimulation: challenges and future directions

Brain stimulation approaches are important to gain causal mechanistic insights into the relevance of functional brain regions and/or neurophysiological systems for human cognitive functions. In recent years, transcutaneous vagus nerve stimulation (tVNS) has attracted considerable popularity. It is a noninvasive brain stimulation technique based on the stimulation of the vagus nerve. The stimulation of this nerve activates subcortical nuclei, such as the locus coeruleus and the nucleus of the solitary tract, and from there, the activation propagates to the cortex. Since tVNS is a novel stimulation technique, this literature review outlines a brief historical background of tVNS, before detailing underlying neurophysiological mechanisms of action, stimulation parameters, cognitive effects of tVNS on healthy humans, and, lastly, current challenges and future directions of tVNS research in cognitive functions. Although more research is needed, we conclude that tVNS, by increasing norepineprine (NE) and gamma-aminobutyric acid (GABA) levels, affects NE- and GABA-related cognitive performance. The review provides detailed background information how to use tVNS as a neuromodulatory tool in cognitive neuroscience and outlines important future leads of research on tVNS.