Vagally-mediated Heart Rate Variability Research Articles

Meaning in life and vagally-mediated heart rate variability: Evidence of a quadratic relationship at baseline and vagal reactivity differences

Higher meaning in life (MIL) consistently predicts better health, but the physiological processes underlying this relationship are not well understood. This study examined the relationship between MIL and vagally-mediated heart rate variability (VmHRV) under resting (N = 77), stressor (n = 73), and mindfulness intervention (n = 72) conditions. Regression was used for MIL-VmHRV analyses at baseline, and longitudinal mixed models were used to examine phasic changes in VmHRV as a function of MIL. Regression revealed a quadratic MIL-VmHRV relationship, and mixed models linked higher MIL to greater stress-reactivity but not enhanced stress-attenuation. MIL and mindfulness did not interact to influence VmHRV recovery after experimental stress. Findings suggest that cardiac vagal tone and cardiac vagal reactivity are linked to MIL, shedding light on the physiology underlying MIL and its health associations.

Ethnic and sex differences in the longitudinal association between heart rate variability and blood pressure

Purpose Elevated blood pressure is a risk factor for increased cardiovascular morbidity and mortality. Decreased vagally-mediated heart rate variability has previously been prospectively linked with increased blood pressure; however, to date, no such prospective data exist regarding this relationship among Blacks. Materials and methods We examined this association in 387 normotensive young adults (mean age, 23 years, 52% female, 54% Black) who participated in two laboratory evaluations spanning approximately six years. Blood pressure was measured at both timepoints with a non-invasive oscillometric device and heart rate variability was assessed via bio-impedance. Results In the total sample, heart rate variability significantly predicted systolic (p = .022) and diastolic (p < .001) blood pressure increases six years into the future. However, this pattern varied as a function of ethnicity and sex with the effect of heart rate variability on Time 2 systolic blood pressure only significant among White males (p = .007). Heart rate variability was also predictive of Time 2 diastolic blood pressure in White males (p = .038) as well as among both White (p = .032) and Black (p = .015) females, but was not related to blood pressure among Black males. Conclusion We report for the first time significant ethnic and sex differences in the prospective relationship between heart rate variability and blood pressure change. These findings may give clues as to the underlying mechanisms that are involved in the well-known health disparities in blood pressure and hypertension-related cardiovascular diseases.

Lower values of a novel index of Vagal-Neuroimmunomodulation are associated to higher all-cause mortality in two large general population samples with 18\xa0year follow up

In recent clinical practice, a biomarker of vagal neuroimmunomodulation (NIM), namely the ratio of vagally-mediated heart rate variability (vmHRV) and CRP, was proposed to index the functionality of the cholinergic anti-inflammatory pathway. This study aims to transfer and extend the previous findings to two general population-based samples to explore the hypothesis that NIM-ratio is associated with all-cause mortality. Two large population studies (MIDUS 2: N = 1255 and Whitehall II wave 5: N = 7870) with complete data from a total of N = 3860 participants (36.1% females; average age = 56.3 years; 11.1% deaths, last exit 18.1 years post inclusion) were available. NIM indices were calculated using the vagally-mediated HRV measure RMSSD divided by measures of CRP (NIMCRP) or IL-6 (NIMIL6). The NIM-ratios were quartiled and entered into age, ethnicity and body mass index adjusted Cox proportional hazards models. For NIMIL6 the lowest quartile was 45% more likely to die during the observed period (max. 18 years follow-up) compared to the highest quartile (HR = 0.55 CI 0.41–0.73; p < .0001). NIMCRP parallel these results. Here we show that an easily computable index of IL-6 inhibition is associated with all-cause mortality in two large general population samples. These results suggest that this index might be useful for risk stratification and warrant further examination.

Effects of Dynamic Resilience on the Reactivity of Vagally Mediated Heart Rate Variability.

Dynamic resilience is a novel concept that aims to quantify how individuals are coping while operating in dynamic and complex task environments. A recently developed dynamic resilience measure, derived through autoregressive modeling, offers an avenue toward dynamic resilience classification that may yield valuable information about working personnel for industries such as defense and elite sport. However, this measure classifies dynamic resilience based upon in-task performance rather than self-regulating cognitive structures; thereby, lacking any supported self-regulating cognitive links to the dynamic resilience framework. Vagally mediated heart rate variability (vmHRV) parameters are potential physiological measures that may offer an opportunity to link self-regulating cognitive structures to dynamic resilience given their supported connection to the self-regulation of stress. This study examines if dynamic resilience classifications reveal significant differences in vagal reactivity between higher, moderate and lower dynamic resilience groups, as participants engage in a dynamic, decision-making task. An amended Three Rs paradigm was implemented that examined vagal reactivity across six concurrent vmHRV reactivity segments consisting of lower and higher task load. Overall, the results supported significant differences between higher and moderate dynamic resilience groups' vagal reactivity but rejected significant differences between the lower dynamic resilience group. Additionally, differences in vagal reactivity across vmHRV reactivity segments within an amended Three Rs paradigm were partially supported. Together, these findings offer support toward linking dynamic resilience to temporal self-regulating cognitive structures that play a role in mediating physiological adaptations during task engagement.

Inhibitory Control Moderates the Effect of Anxiety on Vagally Mediated Heart Rate Variability: Findings from a Community Sample of Young School-Aged Children

Individuals with anxiety disorders show both excessive and blunted vagally mediated heart rate variability (vmHRV) reactivity to stress. Scholars have suggested that differences in cognitive control could explain such heterogeneity, but this proposition has not been tested. The present study hence investigated the moderating effect of executive functions, particularly inhibitory control, on the relationship between anxiety symptoms and vmHRV reactivity. We evaluated anxiety symptoms (a diagnostic interview with parents) and executive functions (parent-reported questionnaire) in 262 six-year-olds from a community sample. vmHRV responses to neutral tasks and stressors were analyzed using latent growth curve modeling. Results supported a moderating effect of inhibitory control; children with more anxiety symptoms and enhanced inhibitory control showed a blunted decrease in vmHRV in response to stressors. In contrast, counterparts with impaired inhibitory control evinced an excessive decrease in vmHRV. Children with no anxiety symptoms did not differ in vmHRV reactivity, independent of the level of inhibitory control. The results could indicate that anxious children with enhanced inhibitory control successfully utilized a cognitive avoidance strategy (i.e. verbal worry) to inhibit expected autonomic arousal in response to threat. Clinical implications are discussed.

Decreased Autonomic Reactivity and Psychiatric Comorbidities in Neurological Patients with Medically Unexplained Sensory Symptoms: A Case-Control Study

Background: Up to 48% of patients with medically unexplained symptoms seen in neurological practice suffer from sensory symptoms, which could be of functional nature or secondary to mental disorders. These patients show high medical care utilization causing elevated health care costs. Despite the high prevalence, little is known about clinical characteristics and pathophysiological mechanisms. For functional disorders such as irritable bowel syndrome a reduction of heart rate variability (HRV) has been shown, suggesting a dysfunction of the autonomic nervous system (ANS). The aim of this study was to investigate psychological data and functional changes of the ANS in patients with medically unexplained sensory symptoms (MUSS). Methods: In this exploratory pilot study, 16 patients (11 females, 31·6 ± 11·9 years) with MUSS, who were recruited at a single tertiary neurological centre, underwent a structured clinical interview (SCID) to evaluate psychiatric comorbidities. Patients and age- and sex-matched healthy volunteers filled in questionnaires, and individual sensory thresholds (perception, pain) were detected by quantitative sensory testing (QST). HRV was assessed at baseline and under three different experimental conditions (tonic pain stimulus, placebo application, cold face test). All tests were repeated after 6-8 weeks. Findings: SCID interviews revealed clinical or subclinical diagnoses of psychiatric comorbidities for 12 patients. Questionnaires assessing somatization, depression, anxiety, and perceived stress significantly discriminated between patients and controls. While there was no difference in QST, reduced ANS reactivity was found in patients during experimental conditions, particularly with regard to vagally-mediated HRV. Interpretation: Our pilot study of neurological patients with MUSS reveals a high prevalence of psychiatric comorbidities and provides evidence for altered ANS function. Our data thus give insight in possible underlying mechanisms for these symptoms and may open the door for a better diagnostic and therapeutic approach for these patients in the future. Funding: No external funding was obtained for this study. Declaration of Interest: All authors declare to have no conflicts of interest. Ethical Approval: Approval for the study was obtained by the Ethics Committee of the medical faculty of Tubingen University (Project No. 765/2015BO2).

The Effects of Mindfulness and Meditation on Vagally Mediated Heart Rate Variability: A Meta-Analysis.

Heart rate variability (HRV) is a marker of autonomic nervous system function associated with both physical and mental health. Many studies have suggested that mindfulness and meditation-based interventions (MBIs) are associated with improvements in HRV, but findings are mixed, and to date, no comprehensive meta-analysis has synthesized results. Systematic literature searches were conducted using PsycINFO, Embase, Medline, CINAHL, ERIC, and Scopus to identify randomized controlled trials (RCTs) investigating the effects of predominantly seated MBIs on resting-state vagally mediated HRV. Risk of bias was judged using the Cochrane Risk of Bias tool. Nineteen RCTs met the criteria for inclusion in the meta-analysis. Random-effects meta-analysis found that MBIs were not efficacious in increasing vagally mediated resting-state HRV relative to control conditions (Hedges g = 0.38, 95% confidence interval [CI] = -0.014 to 0.77). When removing an outlier (g = 3.22), the effect size was reduced, CI narrowed, and findings remained nonsignificant (g = 0.19, 95% CI = -0.02 to 0.39). High heterogeneity in results (I2 = 89.12%) could not be explained by a priori-determined moderators including intervention duration, study setting, and control type. There is currently insufficient evidence to indicate that MBIs lead to improvements in vagally mediated HRV over control conditions. Future large, well-designed RCTs with low risk of methodological bias could help add to the current evidence to elucidate any role MBIs might play in impacting HRV.

Efficacy and neurophysiological predictors of treatment response of adjunct bifrontal transcranial direct current stimulation (tDCS) in treating unipolar and bipolar depression

BackgroundAlthough add-on transcranial direct current stimulation (tDCS) is a promising intervention for treating unipolar (UD) and bipolar depression (BD), its moderate antidepressant efficacy urges research into biomarkers for predicting therapeutic response and achieving highly targeted applications. MethodsThis open-label trial enrolled UD (N=58) and BD (N=22) patients who had failed 1 or more trials of adequate pharmacologic interventions (ClinicalTrials.gov ID: NCT03287037). Bifrontal tDCS (anode/cathode: F3/F4) was applied using a 2 mA current for 20 min, twice daily, for 5 consecutive weekdays. Depression was measured with Hamilton Depression Rating Scale-17 (HAMD) at baseline, after 10-session stimulation, 1- and 4-week follow-ups. Heart rate (HR) and heart rate variability (HRV) was measured at baseline, during the initial 5 min of the 1st session, after 10-session stimulation, 1- and 4-week follow-ups. Cognitive performance and other outcomes were also assessed. ResultsBifrontal tDCS rapidly and equally improved depression in both groups. The effects persisted until the end of the trial. Both groups had similar improvements in cognitive performance, anxiety, and psychosocial functioning. Compared with baseline, increased vagally-mediated HRV was observed one month after tDCS for both groups. A positive correlation was found between HR deceleration within the 1st session and treatment response after 10-session tDCS only among UD patients, explaining 20% of the variance. ConclusiontDCS as an adjunct therapy is effective for both UD and BD. Data suggest that the greater the increase in parasympathetic signaling during the 1st session, the better the clinical response after 10-session tDCS for UD patients.

Heart rate variability as an index of emotion (dys)regulation in psychosis?

The vagally-mediated heart rate variability (HRV), an indicator of the autonomic nervous system (ANS), has been proposed as a transdiagnostic marker for emotion regulation (ER). In people with psychotic disorders (PSY), HRV is profoundly reduced compared to healthy controls (HC). Similarly, questionnaire-based assessments of adaptive ER point to a deficit in PSY. To address HRV as a potential marker for ER in psychosis, we investigated a large sample including PSY (n = 40) and HC (n = 32) as well as vulnerable (n = 19 clinical high-risk) and clinical (n = 28 anxiety disorders) controls. We tested the differential effectiveness of an instructed adaptive ER strategy, whether resting-state HRV predicts adaptive ER, and whether HRV serves as a state index of ER effort. The participants repeatedly played a social exclusion ballgame while they applied either cognitive reappraisal or no regulation (“just-play”) in randomized order. PSY displayed overall higher levels of negative affect and paranoia than HC but both groups applied reappraisal successfully (i.e., more benefit: lower negative affect and paranoia after reappraisal compared to “just-play”). Resting-state HRV did not predict successful reappraisal in the total sample. However, within PSY, a higher resting-state HRV predicted more benefit from reappraisal. State HRV did not differ between the reappraisal and “just-play” condition. Contrary to our expectations, participants with psychosis applied an instructed adaptive ER strategy successfully. As expected, the ANS marker of HRV predicted that benefit; however, this was only the case in PSY. Overall, HRV was not a robust but a tentative marker of ER in the present investigation.

Resting state heart rate variability and false memories

Recent studies have shown higher resting-state vagally-mediated heart rate variability (vmHRV) to be related to greater memory retrieval. Research has not yet linked resting vmHRV with memory encoding and retrieval, as both are thought to play an important role in correctly distinguishing between true and false memories. The current study investigated this possible link in n = 71 undergraduate students. VmHRV was assessed during a 5-minute resting baseline period. Participants then completed the Deese-Roediger-McDermott (DRM) task, where they first viewed 6 word lists (12 words per list), and were later asked to identify previously shown words (true memories) and reject non-presented words. Results showed that participants with lower resting vmHRV were less able to discriminate true from false items. These data extend previous work on resting vmHRV and memory suggesting that resting vmHRV represents a psychophysiological pathway involved in both the proper encoding and retrieval of memories.

Standardized massage interventions as protocols for the induction of psychophysiological relaxation in the laboratory: a block randomized, controlled trial

Health and disease are strongly linked to psychophysiological states. While stress research strongly benefits from standardized stressors, no established protocol focuses on the induction of psychophysiological relaxation. To maintain health, functioning regenerative systems are however likely as important as functioning stress systems. Thus, the identification of validated relaxation paradigms is needed. Here, we investigated whether standardized massages are capable of reliably inducing physiological and psychological states of relaxation. Relaxation was indicated by changes in high frequency heart rate variability (HF-HRV), a vagally-mediated heart rate variability component, and repeated ratings of subjective relaxation, and stress levels. Sixty healthy women were randomly assigned to a vagus nerve massage (n = 19), a soft shoulder massage (n = 22), or a resting control group (n = 19). During the intervention, HF-HRV and subjective relaxation increased, while subjective stress decreased significantly in all groups. Both massage interventions elicited significantly higher HF-HRV compared to the control group. Accordingly, both massage protocols increased psychophysiological relaxation, and may serve as useful tools in future research. However, future work will have to determine which of several protocols might be used as a gold standard to induce a psychophysiological state of relaxation in the laboratory.

Structural covariance of the salience network associated with heart rate variability.

The salience network (SN) anchored by the anterior insula and cingulate is crucial for the autonomic control of body homeostasis. Resting-sate fMRI studies have linked intrinsic SN connectivity with multiple autonomic measures, but little is known about the structural organization of this system relating to cardiac vagal function. To address the above issue, the current study used covariance analysis of MRI-based gray matter volume (GMV) to map structural covariance of SN with two independent datasets, and then determined whether interregional structural connections within SN related to individual differences in vagally-mediated heart rate variability (HRV). The results showed a significant positive association between structural covariance of the SN and vagal component of HRV in two independent samples. More importantly, the conjunction and pooled data analysis revealed that structural correlation from left anterior insula to dorsal anterior cingulate cortex positively interacted with vagally-mediated HRV. The current results demonstrated a crucial role of the SN in the cortical modulation of efferent vagal activity to the heart, and provided new insight into structural neural network implicated in cardiac vagal control.

Linking psychophysiological adaptation, emotion regulation, and subjective stress to the occurrence of paranoia in daily life

As stress is relevant to the formation of paranoia, maladaptive behavioral and physiological stress regulation is discussed as a crucial indicator of vulnerability. This is supported by research linking psychosis to the tendency to make less use of functional and more use of dysfunctional emotion regulation strategies (ER) and with a lower vagally-mediated heart rate variability (HRV). However, it remains unclear whether ER serves as a mediator between resting-state HRV on the one hand and subjective stress levels and paranoia on the other and whether this is specific to paranoia as compared to depression. We used an experience sampling method during seven days to repeatedly assess the experience of stress, usage of ER strategies, paranoia und depression (9/day) in a sample with subclinical positive symptoms (N = 32). Resting-state HRV was measured during a 5min interval in the laboratory. Data was analyzed by multi-level models. Higher resting-state HRV was predictive of lower stress-levels and of using more functional ER strategies (reappraisal, acceptance) in daily life, but did not predict the use of dysfunctional strategies (rumination, suppression) or paranoia. The association between resting-state HRV and stress was mediated by the usage of functional ER. Less functional and more dysfunctional ER were linked to higher levels of stress, paranoia and depression. Our study highlights that deficits in ER represent a link between psychophysiological and phenomenological aspects of paranoia but also of depression. This encourages to further investigate transdiagnostic prevention and therapy programs aiming to improve ER and to increase HRV.

Inertia of emotions and inertia of the heart: Physiological processes underlying inertia of negative emotions at work

Emotional inertia is a key feature of emotional dynamics and it refers to the degree to which a current emotional state can be predicted by a previous emotional state. In this study, using the experience sampling method, we examined the relationship between inertia of negative emotions at work and parasympathetic activity, measured by vagally-mediated heart rate variability (HRV). In line with current literature on HRV, we propose that temporal dependency of negative emotions at work may be associated to lower HRV, an important marker of the ability to flexibly adjust to a changing environment. Participants (n = 120) were prompted six times during a regular workday, while wearing a heart rate monitor. In accordance with the polyvagal theory and the model of neurovisceral integration, findings supported our hypothesis and indicated that workers with lower HRV tend to show high time persistence of negative emotions at work. Practical implications and directions for future research are discussed.

Entropy in Heart Rate Dynamics Reflects How HRV-Biofeedback Training Improves Neurovisceral Complexity during Stress-Cognition Interactions.

Despite considerable appeal, the growing appreciation of biosignals complexity reflects that system complexity needs additional support. A dynamically coordinated network of neurovisceral integration has been described that links prefrontal-subcortical inhibitory circuits to vagally-mediated heart rate variability. Chronic stress is known to alter network interactions by impairing amygdala functional connectivity. HRV-biofeedback training can counteract stress defects. We hypothesized the great value of an entropy-based approach of beat-to-beat biosignals to illustrate how HRVB training restores neurovisceral complexity, which should be reflected in signal complexity. In thirteen moderately-stressed participants, we obtained vagal tone markers and psychological indexes (state anxiety, cognitive workload, and Perceived Stress Scale) before and after five-weeks of daily HRVB training, at rest and during stressful cognitive tasking. Refined Composite Multiscale Entropy (RCMSE) was computed over short time scales as a marker of signal complexity. Heightened vagal tone at rest and during stressful tasking illustrates training benefits in the brain-to-heart circuitry. The entropy index reached the highest significance levels in both variance and ROC curves analyses. Restored vagal activity at rest correlated with gain in entropy. We conclude that HRVB training is efficient in restoring healthy neurovisceral complexity and stress defense, which is reflected in HRV signal complexity. The very mechanisms that are involved in system complexity remain to be elucidated, despite abundant literature existing on the role played by amygdala in brain interconnections.

Menstrual Cycle Changes in Vagally-Mediated Heart Rate Variability are Associated with Progesterone: Evidence from Two Within-Person Studies.

A recent meta-analysis revealed that cardiac vagal activity (mostly indicated by vagally-mediated heart rate variability; HRV) decreases significantly from the follicular to luteal menstrual cycle phase in naturally-cycling participants. However, the question remains as to whether cyclical changes in estradiol (E2), progesterone (P4), or both are responsible for HRV fluctuations. We present the first studies to use repeated measures of E2, P4, and HRV across the cycle to model both the unique and interactive effects of person-centered E2 and P4 on HRV in multilevel models. In study one, 40 naturally-cycling participants were assessed weekly across four weeks, and were blind to the cycle focus of the study. In study two, 50 naturally-cycling participants were examined in three precisely defined cycle phases via ovulation testing. Both studies revealed that only P4 was correlated with HRV, such that higher-than-usual P4 significantly predicted lower-than-usual HRV within a given participant. In line with this, cycle phase comparisons revealed lower HRV in the mid-luteal phase (characterized by elevated P4) than in other phases. No significant main or interactive effects of E2 on HRV were found. Future female health studies should investigate individual differences in these effects and potential consequences of cyclical HRV changes on daily functioning.

Theta-burst stimulation and frontotemporal regulation of cardiovascular autonomic outputs: The role of state anxiety

Dysregulation of autonomic cardiovascular homeostasis is an important cardiological and neurological risk factor. Cortical regions including the prefrontal and insular cortices exert tonic control over cardiovascular autonomic functions. Transcranial Magnetic Stimulation (TMS) may be a suitable approach for studying top-down control of visceromotor processes. However, there is inconsistent evidence as to whether TMS can modify cardiovascular autonomic states. One reason for the inconsistency may arise from the lack of studies accounting for the acute affective states of participants with respect to the stimulation procedures. To gain more insights into these processes, we evaluated the effects of intermittent and continuous theta-burst stimulation (TBS) to the right frontotemporal cortex on state anxiety and cardiovascular responses in a preliminary study. State anxiety significantly increased for both intermittent and continuous TBS relative to sham. Intermittent TBS also significantly increased heart-rate variability (HRV) at natural and slow-paced breathing rates. The effect of intermittent TBS on vagally-mediated HRV was attenuated after accounting for stimulation-induced anxiety, suggesting that increased HRV after stimulation may reflect a response to a transient stressor (i.e., the stimulation itself), rather than TBS effects on visceromotor networks. In contrast, continuous TBS increased pulse transit time latency across breathing rates, an effect that was enhanced after accounting for state anxiety. TMS is a promising approach to study cortical involvement in cardiovascular autonomic regulation. The findings show that TBS induces effects on visceromotor networks, and that analysis of state covariates such as anxiety can be important for increasing the precision of these estimates. Future non-invasive brain stimulation studies of top-down neurocardiac regulation should account for the potential influence of non-specific arousal or anxiety responses to stimulation.

First Evaluation of an Index of Low Vagally-Mediated Heart Rate Variability as a Marker of Health Risks in Human Adults: Proof of Concept.

Multiple studies have demonstrated low vagally-mediated heart rate variability (HRV) being associated with a range of risk factors for heart disease and stroke, including inflammation, hyperglycemia, hyperlipidemia, and hypertension. Yet, no cut point exists that indicates elevated risk. In the present study we sought to identify a cut point-value for HRV that is associated with elevated risk across a range of known risk factors. Methods: A total of 9550 working adults from 19 study sites took part in a health assessment that included measures of inflammation, hyperglycemia, hyperlipidemia, and hypertension and vagally-mediated HRV (Root mean square of successive differences between normal heartbeats (RMSSD)). Multiple age and sex adjusted logistic regressions were calculated per risk factor (normal versus clinical range), with RMSSD being entered in binary at different cut points ranging from 15–39 msec with a 2 msec increment. Results: For daytime RMSSD, values below 25 ± 4 indicated elevated risk (odds ratios (OR) 1.5–3.5 across risk factors). For nighttime RMSSD, values below 29 ± 4 indicated elevated risk (OR 1.2–2.0). Conclusion: These results provide the first evidence that a single value of RMSSD may be associated with elevated risk across a range of established cardiovascular risk factors and may present an easy to assess novel marker of cardiovascular risk.

Heart rate variability in response to the recall of attachment memories

ABSTRACT Internal Working Models of the attachment system modulate emotional responses and the Disorganized attachment pattern is characterized by the breakdown of such regulation. Vagally-mediated heart rate variability (vmHRV) is an index of flexible emotional responding. This study investigated vmHRV in non-clinical adults with an Organized or Disorganized attachment pattern before, during, and after the recall of attachment memories via the Adult Attachment Interview (AAI). Whereas the Organized group exhibited a typical decrease in vmHRV during the AAI and asubsequent return to a baseline-like pattern, the Disorganized group unexpectedly showed a sustained increase in vmHRV during the AAI which also persisted during the recovery phase. Results suggest that while Organized face the recollection of attachment memories by showing the adaptive stress response characterized by parasympathetic withdrawal and immediate recovery, individuals with Disorganized attachment need to keep regulating their emotions effortfully both during and after the recall of potential traumatic events.

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

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.