Given its non-invasive nature, there is increasing interest in the use of transcutaneous vagus nerve stimulation (tVNS) across basic, translational and clinical research. Contemporaneously, tVNS can be achieved by stimulating either the auricular branch or the cervical bundle of the vagus nerve, referred to as transcutaneous auricular vagus nerve stimulation(VNS) and transcutaneous cervical VNS, respectively. In order to advance the field in a systematic manner, studies using these technologies need to adequately report sufficient methodological detail to enable comparison of results between studies, replication of studies, as well as enhancing study participant safety. We systematically reviewed the existing tVNS literature to evaluate current reporting practices. Based on this review, and consensus among participating authors, we propose a set of minimal reporting items to guide future tVNS studies. The suggested items address specific technical aspects of the device and stimulation parameters. We also cover general recommendations including inclusion and exclusion criteria for participants, outcome parameters and the detailed reporting of side effects. Furthermore, we review strategies used to identify the optimal stimulation parameters for a given research setting and summarize ongoing developments in animal research with potential implications for the application of tVNS in humans. Finally, we discuss the potential of tVNS in future research as well as the associated challenges across several disciplines in research and clinical practice.

Transcutaneous vagus nerve stimulation or tVNS is a non-invasive neurostimulation technique that is currently being tested as a potential treatment for a myriad of neurological and psychiatric disorders.However, the working mechanisms underlying tVNS are poorly understood, and it remains unclear whether stimulation activates the vagus nerve for every participant. Finding a biological marker of tVNS is imperative, as it can help guide research on clinical applications, and can inform researchers on optimal stimulation sites and parameters to further optimize treatment efficacy. In this narrative review, we discuss five potential biomarkers for tVNS, and review currently available evidence for these markers for both invasive and transcutaneous VNS. While some of these biomarkers hold promise from a theoretical perspective, none of the potential biomarkers provide clear and definitive indications that tVNS increases vagal activity or augments activity in the locus coeruleus-noradrenaline network. We conclude the review by providing several recommendations for how to tackle the challenges and opportunities when researching potential biomarkers for the effects of tVNS.

Exposure therapy, i.e., repeated exposure to fear-provoking stimuli, is an effective cognitive behavioral therapy strategy for the treatment of anxiety and trauma-related disorders (Hofmann & Smits, 2008). Extinction learning is considered a major mechanism for the reduction of fear during exposure, as it involves learning that the stimulus previously appraised as threatening no longer leads to the feared outcome (Lonsdorf et al., 2017). The predominant view is that extinction hereby results in a new memory (i.e., extinction memory) that competes with the fear memory and can inhibit anticipatory fear reactions (Bouton, 1988). Although exposure therapy has been shown to be effective in the treatment of anxiety disorders when compared to placebo treatments (Hofmann and Smits,

No abstract

Although transcutaneous auricular vagus nerve stimulation (taVNS) is thought to increase central noradrenergic activity, findings supporting such mechanism are scarce and inconsistent. This study aimed to investigate whether taVNS modulates indirect markers of phasic and tonic noradrenergic activity. Sixty-six healthy participants performed a novelty auditory oddball task twice on separate days: once while receiving taVNS (left cymba concha), once during sham (left earlobe) stimulation.To maximize potential effects, the stimulation was delivered continuously (frequency: 25 Hz; width: 250 μs) at an intensity individually calibrated to the maximal level below pain threshold. The stimulation was administered 10 min before the oddball task and maintained throughout the session. Event-related pupil dilation (ERPD) to target stimuli and pre-stimulus baseline pupil size were assessed during the oddball task as markers of phasic and tonic noradrenergic activity, respectively.Prior to and at the end of stimulation, tonic pupil size at rest, cortisol, and salivary alpha-amylase were assessed as markers of tonic noradrenergic activity. Finally, we explored the effect of taVNS on cardiac vagal activity, respiratory rate, and salivary flow rate. Results showed a greater ERPD to both target and novelty compared to standard stimuli in the oddball task. In contrast to our hypotheses, taVNS did not impact any of the tested markers. Our findings strongly suggest that continuous stimulation of the cymba concha with the tested stimulation parameters is ineffective to increase noradrenergic activity via a vagal pathway.