Background: Vagus nerve stimulation (VNS) has been demonstrated to reduce stress-induced cortisol release. Several non-invasive techniques for VNS are currently available, including transcutaneous auricular and cervical VNS. Cervical VNS potentially activates efferent and afferent vagal nerve fibers, while auricular VNS activates the auricular branch of the vagus nerve, which is a purely afferent nerve. We hypothesized that VNS causes a state of mental tranquility, thereby reducing arterial blood pressure. Methods: The study was approved by the Burrell College Institutional Review Board and included 16 healthy young participants (5 ♂) who provided written informed consent. Exclusion criteria included pregnancy, acute or chronic illnesses, and use of prescription medications, except contraceptives. Participants were randomly assigned to: time control (CTR, no intervention), transcutaneous cervical VNS (cVNS), transcutaneous auricular VNS applied to either the tragus (atVNS) or the cymba conchae (acVNS). A 30-minute baseline recording was followed by VNS or no intervention. VNS was applied three times for 5 min. Each 5-minute VNS was followed by 1 minute without stimulation. cVNS was delivered bilaterally using the Pulsetto device (25 Hz, 100 μs, < 40 mA). atVNS and acVNS (10 Hz, 300 μs, 2-3 mA). Heart rate (ECG), blood pressure (finger plethysmography), and a single-channel EEG (FP1 location) were recorded continuously. Statistics included one-way ANOVA for repeated measures with post-hoc t-tests for each experimental group. P < 0.05 was considered significant, 0.05 < P < 0.10 was considered a trend. Results: Systolic blood pressure only decreased during cVNS (133.6±5.0 mmHg at baseline vs. 124.2±4.8 mmHg, n=7, P<0.05) but not in the time control or both auricular VNS groups. No significant changes in heart rate were observed in any group. The amplitude of alpha waves in the EEG increased only in the cVNS group (0.654±0.070 arb. units at baseline vs. 0.827±0.076 arb. units, n=7, P=0.06) but not in the time control or both auricular VNS groups. No significant changes were observed for any other EEG waves. Conclusion: Non-invasive transcutaneous VNS reduced systolic blood pressure and increased alpha waves in the EEG of the frontal lobe when the cervical vagus nerve was targeted bilaterally, but not when the auricular branch of the vagus nerve was stimulated unilaterally. Increased alpha waves are consistent with a more relaxed mental state, which may have caused the reduction in systolic blood pressure with cVNS, potentially through decreased stress hormone release.

NOTE: All listed authors contributed equally.