The neuromodulatory and hormonal effects of transcutaneous vagus nerve stimulation as evidenced by salivary alpha amylase, salivary cortisol, pupil diameter, and the P3 event-related potential

Background Transcutaneous vagus nerve stimulation (tVNS) is a new, non-invasive technique being investigated as an intervention for a variety of clinical disorders, including epilepsy and depression. It is thought to exert its therapeutic effect by increasing central norepinephrine (NE) activity, but the evidence supporting this notion is limited. Objective In order to test for an impact of tVNS on psychophysiological and hormonal indices of noradrenergic function, we applied tVNS in concert with assessment of salivary alpha amylase (SAA) and cortisol, pupil size, and electroencephalograph (EEG) recordings. Methods Across three experiments, we applied real and sham tVNS to 61 healthy participants while they performed a set of simple stimulus-discrimination tasks. Before and after the task, as well as during one break, participants provided saliva samples and had their pupil size recorded. EEG was recorded throughout the task. The target for tVNS was the cymba conchae, which is heavily innervated by the auricular branch of the vagus nerve. Sham stimulation was applied to the ear lobe. Results P3 amplitude was not affected by tVNS (Experiment 1A: N=24; Experiment 1B: N=20; Bayes factor supporting null model=4.53), nor was pupil size (Experiment 2: N=16; interaction of treatment and time: p=0.79). However, tVNS increased SAA (Experiments 1A and 2: N=25) and attenuated the decline of salivary cortisol compared to sham (Experiment 2: N=17), as indicated by significant interactions involving treatment and time (p=.023 and p=.040, respectively). Conclusion These findings suggest that tVNS modulates hormonal indices but not psychophysiological indices of noradrenergic function.
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