Effects of Transcutaneous Vagus Nerve Stimulation (tVNS) on the P300 and Alpha-Amylase Level: A Pilot Study

Abstract

Recent research suggests that the P3b may be closely related to the activation of the locus coeruleus-norepinephrine (LC-NE) system. To further study the potential association, we applied a novel technique, the non-invasive transcutaneous vagus nerve stimulation (tVNS), which is speculated to increase noradrenaline levels. Using a within-subject cross-over design, 20 healthy participants received continuous tVNS and sham stimulation on two consecutive days (stimulation counterbalanced across participants) while performing a visual oddball task. During stimulation, oval non-targets (standard), normal-head (easy) and rotated-head (difficult) targets, as well as novel stimuli (scenes) were presented. As an indirect marker of noradrenergic activation we also collected salivary alpha-amylase (sAA) before and after stimulation. Results showed larger P3b amplitudes for target, relative to standard stimuli, irrespective of stimulation condition. Exploratory post hoc analyses, however, revealed that, in comparison to standard stimuli, easy (but not difficult) targets produced larger P3b (but not P3a) amplitudes during active tVNS, compared to sham stimulation. For sAA levels, although main analyses did not show differential effects of stimulation, direct testing revealed that tVNS (but not sham stimulation) increased sAA levels after stimulation. Additionally, larger differences between tVNS and sham stimulation in P3b magnitudes for easy targets were associated with larger increase in sAA levels after tVNS, but not after sham stimulation. Despite preliminary evidence for a modulatory influence of tVNS on the P3b, which may be partly mediated by activation of the noradrenergic system, additional research in this field is clearly warranted. Future studies need to clarify whether tVNS also facilitates other processes, such as learning and memory, and whether tVNS can be used as therapeutic tool.

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

“…Our results compliment work by Ventura-Bort and colleagues [17], who reported preliminary evidence that taVNS increases SAA. We demonstrate a more robust effect, using a larger sample size (25 vs. 18 participants), more post-stimulation saliva samples (2 vs. 1), and a superior method of saliva collection (whole saliva method vs. absorbent cotton sponges) [9,51].…”

“…The oddball P3 was larger in the taVNS condition (7.6 μV) than in the sham condition (6.5 μV). This difference was not significant, F (1,17)=2.32, p=.15 (Fig. 3).…”

“…SAA is a proxy marker of sympathetic-adreno-medullary activation [9,12], which is driven by central NE, leading to the assumption that SAA marks central NE activity [13][14][15][16]. One preliminary study [17] has reported suggestive evidence that taVNS increases SAA relative to sham stimulation-reason to be optimistic that a larger study with a more targeted methodology might reveal a robust effect of taVNS on SAA.…”

Exploration of the Impact of Brief Noninvasive Vagal Nerve Stimulation on EEG and Event-Related Potentials

“…However, the study of patient groups may give only partial insight into typical neuromodulatory mechanisms because key neural circuitry may already be compromised by disease or injury. Recently, Ventura-Bort and colleagues examined the impact of auricular transcutaneous VNS on P300b in neurotypical subjects, with data indicating that stimulation significantly increases P300b amplitude to easy targets (91). Importantly, this study also found VNS related increases in salivary alpha-amylase, an independent indirect marker of noradrenergic activity.…”

Promoting long-term inhibition of human fear responses by non-invasive transcutaneous vagus nerve stimulation during extinction training

“…Participants were required to rate their subjective sensation of the stimulation intensity after each adjustment of 0.1 mA on a visual 11-point scale, ranging from nothing (0), light tingling (3), strong tingling (6) to painful (10). The tVNS workup lasted until the participants reported a "tingling" sensation of 8, after which they underwent a 30 s ON and 30 s OFF stimulation protocol to experience the stimulation as it would be during the extinction training 47 . If the participant still reported a sensation of 8 after the protocol, the adjusted intensity was used during extinction training.…”