Influence of transcutaneous vagus nerve stimulation on cardiac vagal activity: Not different from sham stimulation and no effect of stimulation intensity

Abstract

The present study investigated the effects of transcutaneous vagus nerve stimulation on cardiac vagal activity, the activity of the vagus nerve regulating cardiac functioning. We applied stimulation on the left cymba conchae and tested the effects of different stimulation intensities on a vagally-mediated heart rate variability pagerameter (i.e., the root mean square of successive differences) as well as on subjective ratings of strength of perceived stimulation intensity and unpleasantness due to the stimulation. Three experiments (within-subject designs, M = 61 healthy participants each) were carried out: In Experiment 1, to choose one fixed stimulation intensity for the subsequent studies, we compared three preset stimulation intensities (i.e., 0.5, 1.0 and 1.5 mA) with each other. In Experiment 2, we compared the set stimulation method with the free stimulation method, in which the participants were instructed to freely choose an intensity. In Experiment 3, to control for placebo effects, we compared both methods (i.e., set stimulation vs. free stimulation) with their respective sham stimulations. In the three experiments, an increase of cardiac vagal activity was found from resting to the stimulation phases. However, this increase in cardiac vagal activity was not dependent on stimulation intensity (Experiment 1), the method used to stimulate (i.e., set vs. free; Experiment 2), or whether stimulation was active or sham (Experiment 3). This pattern of results was solidly supported by Bayesian estimations. On the subjective level, higher stimulation intensities were perceived as significantly stronger and a stronger stimulation was generally also perceived as more unpleasant. The results suggest that cardiac vagal activity may be similarly influenced by afferent vagal stimuli triggered by active and sham stimulation with different stimulation intensities. Potential explanations for these findings and its implications for future research with tVNS are discussed.

Transcutaneous Vagus Nerve Stimulation May Enhance Only Specific Aspects of the Core Executive Functions. A Randomized Crossover Trial

“…Third, the lack of a difference between tVNS and sham stimulation regarding cardiac vagal activity, which is in line with previous findings (Burger et al, 2016(Burger et al, , 2019De Couck et al, 2017;Borges et al, 2019), could have contributed to the heterogeneity of the findings. Despite ample evidence on the effects of tVNS on cognition (e.g., Steenbergen et al, 2015;Sellaro et al, 2017), the evidence provided by the present study on cardiac vagal activity substantiates the arguments against the suitability of the earlobe as a sham stimulation, as discussed lately (Keute et al, 2018b;Rangon, 2018;Borges et al, 2019). At present, there is only one detailed description of the nerve distribution of the human auricle and it shows that the earlobe is free from vagal innervation (Peuker and Filler, 2002).…”

“…Each block consisted of one cognitive task and a total of three measurements: The first one was done to take only resting cardiac vagal activity into account (resting period, 4-min measuring interval), the second to measure cardiac vagal activity during the stimulation (tVNS period, 4-min period), and the third to measure cardiac vagal activity during the stimulation simultaneously with the cognitive tasks (task period, 4 min). The tVNS period was included because there is a lack of evidence on the temporal latency of the effects of tVNS (Borges et al, 2019). Thus, a build-up period of four minutes of the effects of tVNS and sham stimulation was used, as done in previous studies (e.g., Burger et al, 2019).…”

“…Accordingly, we matched the average number of participants in the studies that investigated executive functions with tVNS using a within-subject design (summarized in Table 1). Since we also measured cardiac vagal activity, we additionally considered the average sample size in Borges et al (2019), because this study systematically investigated the effect of tVNS on cardiac vagal activity in different experiments. Twenty-nine participants were calculated to be necessary to find an effect.…”

“…In the sham stimulation, the electrodes are placed on the left earlobe, which is thought to be free of vagal innervation (Peuker and Filler, 2002) and has abundantly been used as a sham stimulation in research with tVNS (van Leusden et al, 2015). The tVNS device delivers a stimulation with a pulse width of 200-300 µs at 25 Hz and an on-off cycle of 30 s. Regarding the adjustment of the stimulation intensity, cardiac vagal activity may be similarly influenced by electrical afferent stimuli that are triggered by different methods to stipulate stimulation intensity (Borges et al, 2019). Therefore, we followed procedures found in previous research with tVNS that allow participants to choose their individual intensity (Fischer et al, 2018;Ventura-Bort et al, 2018).…”

“…Using RMSSD to measure the effect of tVNS on cardiac vagal activity, different studies did not find any differences between active and sham stimulation (Burger et al, 2016(Burger et al, , 2019De Couck et al, 2017). One study showed in three experiments that tVNS consistently increased RMSSD; however, this increase was similarly observed during both active and sham stimulation, with this possibly indicating that tVNS sends non-specific signals at the brainstem level that similarly influence cardiac vagal activity in both active and sham stimulation (Borges et al, 2019). Nonetheless, this study did not take any cognitive paradigm into account, which might have contributed to understanding if this possible signal non-specificity-identified as an increase in cardiac vagal activity during both active and sham stimulationcan also be observed in cognitive functions.…”