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

Abstract

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.

Graded recruitment of pupil-linked neuromodulation by parametric stimulation of the vagus nerve

“…Transcutaneous VNS is a recent development that holds promise for non-invasive and low-risk stimulation of the vagus nerve, by electrically stimulating its cervical or auricular branches, which are situated close to the surface of the skin of the neck and outer ear, respectively. However, it was recently reported that t-VNS though its auricular branch did not affect pupil size (Keute et al, 2019;Warren et al, 2019). The discrepancy between these findings and ours implies that the transcutaneous protocol likely insufficiently stimulated the vagus nerve, perhaps due to the site of stimulation (auricular vs cervical branches) or due to the chosen stimulation parameters (pulse amplitude, width, rate).…”

Baseline-dependent effect of dopamine’s precursor L-tyrosine on working memory gating but not updating

“…Although the present findings are remarkably consistent with studies that related gate switching in the reference-back task to a dopaminergic marker (Rac-Lubashevsky, Slagter, & Kessler, 2017) and activity in BG (Nir-Cohen et al, 2019), an explanation of the present results in terms of noradrenaline cannot be definitively ruled out. Future research therefore should include and control for measures of noradrenaline activity, for example pupil dilation (Joshi, Li, Kalwani, & Gold, 2016;Murphy, O'Connell, O'Sullivan, Robertson, & Balsters, 2014;Reimer et al, 2016) or salivary alpha amylase levels (Warren et al, 2019;Warren, van den Brink, Nieuwenhuis, & Bosch, 2017).…”

The Safety and Efficacy of Transdermal Auricular Vagal Nerve Stimulation Earbud Electrodes for Modulating Autonomic Arousal, Attention, Sensory Gating, and Cortical Brain Plasticity in Humans

“…Further some of these clip electrodes are made from a high impedance rubber or carbon that is not ideal for noninvasive, transcutaneous electrical nerve modulation. Other fairly coarse approaches have implemented small (1-2 mm) stainlesssteel ball electrodes positioned at two or more locations in the concha and external ear [39], which can result in discomfort due to high current densities at the electrode-skin interface.…”

“…We analyzed the continuous EEG spectral data collected globally from channels F3, Fz, F4, C3, Cz, C4, P3, Pz, and P4 during passive auditory tasks before and following taVNS treatment. For each of the treatment conditions evaluated, we investigated changes in the absolute and relative power of the following EEG spectral bands: delta (1 -4 Hz), theta (4 -8 Hz), alpha (8 -12 Hz), beta 1 (12 -15 Hz), beta 2 (15)(16)(17)(18)(19)(20), beta 3 (20 -30 Hz) and gamma (30)(31)(32)(33)(34)(35)(36)(37)(38)(39)(40). Data from these investigations are summarized in Tables 6 and 7 and illustrated in Figures 27-32.…”

“…Further some of these clip electrodes are made from a high impedance rubber or carbon that is not ideal for noninvasive, transcutaneous electrical nerve modulation. Other fairly coarse approaches have implemented small (1-2 mm) stainlesssteel ball electrodes positioned at two or more locations in the concha and external ear [37], which can result in discomfort due to high current densities at the electrode-skin interface. In our investigations, we aimed to ensure wear comfort and comfort during electrical stimulation treatments were optimized as not to distract users or induce pain that may cause significant confounds when trying to enhance brain plasticity or optimize human performance.…”