Cardiac and Peripheral Autonomic Responses to Orthostatic Stress During Transcutaneous Vagus Nerve Stimulation in Healthy Subjects.
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ABSTRACT:
SUBMITTER: Tobaldini E
PROVIDER: S-EPMC6517949 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Working memory (WM) is one of the core components of higher cognitive functions. There exists debate regarding the extent to which current techniques can enhance human WM capacity. Here, we examined the WM modulation effects of a previously less studied technique, transcutaneous auricular vagus nerve stimulation (taVNS). In experiment 1, a within-subject study, we aimed to investigate whether and which stimulation protocols of taVNS can modulate spatial WM performance in healthy adults. Forty-eight participants performed baseline spatial n-back tasks (1, 3-back) and then received online taVNS, offline taVNS, or sham stimulation before or during (online group) the posttest of spatial n-back tasks in random order. Results showed that offline taVNS could significantly increase hits in spatial 3-back task, whereas no effect was found in online taVNS or sham group. No significant taVNS effects were found on correct rejections or reaction time of accurate trials (aRT) in both online and offline protocols. To replicate the results found in experiment 1 and further investigate the generalization effect of offline taVNS, we carried out experiment 2. Sixty participants were recruited and received offline taVNS or offline earlobe stimulation in random order between baseline and posttests of behavioral tests (spatial/digit 3-back tasks). Results replicated the findings; offline taVNS could improve hits but not correct rejections or aRT in spatial WM performance, which were found in experiment 1. However, there were no significant stimulation effects on digit 3-back task. Overall, the findings suggest that offline taVNS has potential on modulating WM performance.
| S-EPMC8733384 | biostudies-literature
Project description:BACKGROUND:Vagus nerve stimulation has been successfully used as a treatment strategy for epilepsy and affective disorders for years. Transcutaneous vagus nerve stimulation (tVNS) is a new non-invasive method to stimulate the vagus nerve, which has been shown to modulate neuronal activity in distinct brain areas. OBJECTIVES:Here we report effects of tVNS on cardiac function from a pilot study, which was conducted to evaluate the feasibility and safety of tVNS for the treatment of chronic tinnitus. METHODS:Twenty-four patients with chronic tinnitus underwent treatment with tVNS over 3-10?weeks in an open single-armed pilot study. Safety criteria and practical usability of the neurostimulating device were to investigate by clinical examination and electrocardiography at baseline and at several visits during and after tVNS treatment (week 2, 4, 8, 16, and 24). RESULTS:Two adverse cardiac events (one classified as a severe adverse event) were registered but considered very unlikely to have been caused by the tVNS device. Retrospective analyses of electrocardiographic parameters revealed a trend toward shortening of the QRS complex after tVNS. CONCLUSION:To our knowledge this is one of the first studies investigating feasibility and safety of tVNS in a clinical sample. In those subjects with no known pre-existing cardiac pathology, preliminary data do not indicate arrhythmic effects of tVNS.
| S-EPMC3413045 | biostudies-literature
Project description:ObjectivesTranscutaneous auricular vagus nerve stimulation (taVNS) modulates brain activity and heart function. The induced parasympathetic predominance leads to an increase of heart rate variability (HRV). Knowledge on the corresponding cortical activation pattern is, however, scarce. We hypothesized taVNS-induced HRV increases to be related to modulation of cortical activity that regulates the autonomic outflow to the heart.Materials and methodsIn thirteen healthy subjects, we simultaneously recorded 64-channel electroencephalography and electrocardiography during taVNS. Two taVNS stimulation targets were investigated, i.e., the cymba conchae and inner tragus, and compared to active control stimulation in the anatomical vicinity, i.e., at the crus helicis and outer tragus. We used intermitted stimulation bursts of 25 Hz applied at a periodicity of 1 Hz. HRV was estimated with different time-domain methodologies: standard deviation of RR (SDNN), the root mean squares of successive differences (RMSSD), the percentage of RR-intervals with at least 50 ms deviation from the preceding RR-interval (pNN50), and the difference of consecutive RR intervals weighted by their mean (rrHRV).ResultsThe stimulation-induced HRV increases corresponded to frequency-specific oscillatory modulation of different cortical areas. All stimulation targets induced power modulations that were proportional to the HRV elevation. The most prominent changes that corresponded to HRV increases across all parameters and stimulation locations were frontal elevations in the theta-band. In the delta-band, there were frontal increases (RMSSD, pNN50, rrHRV, SDNN) and decreases (SDNN) across stimulation sites. In higher frequencies, there was a more divers activity pattern: Outer tragus/crus helicis stimulation increased oscillatory activity with the most prominent changes for the SDNN in frontal (alpha-band, beta-band) and fronto-parietal (gamma-band) areas. During inner tragus/cymba conchae stimulation the predominant pattern was a distributed power decrease, particularly in the fronto-parietal gamma-band.ConclusionNeuro-cardiac interactions can be modulated by electrical stimulation at different auricular locations. Increased HRV during stimulation is correlated with frequency-specific increases and decreases of oscillatory activity in different brain areas. When applying specific HRV measures, cortical patterns related to parasympathetic (RMSSD, pNN50, rrHRV) and sympathetic (SDNN) modulation can be identified. Thus, cortical oscillations may be used to define stimulation locations and parameters for research and therapeutic purposes.
| S-EPMC8005577 | biostudies-literature
Project description:Epilepsy types differ by pathophysiology and prognosis. Transcutaneous auricular vagus nerve stimulation (taVNS) is a non-invasive treatment option in epilepsy. Nevertheless, its mode of action and impact on different types of epilepsy are still unknown. We investigated whether short-term taVNS differently affects local and global characteristics of EEG-derived functional brain networks in different types of epilepsy. Thirty subjects (nine with focal epilepsy, 11 with generalized epilepsy, and 10 without epilepsy or seizures) underwent a 3-h continuous EEG-recording (1 h pre-stimulation, 1 h taVNS stimulation, 1 h post-stimulation) from which we derived evolving functional brain networks. We assessed-in a time-resolved manner-important global (topological, robustness, and stability properties) and local (centralities of vertices and edges) network characteristics. Compared to the subjects with focal epilepsies and without epilepsy, those with generalized epilepsies clearly presented with different topological properties of their functional brain network already at rest. Furthermore, subjects with focal and generalized epilepsies reacted differently to the stimulation, expressed as different taVNS-induced immediate and enduring reorganization of global network characteristics. On the local network scale, no discernible spatial pattern could be detected, which points to a rather unspecific and generalized modification of brain activity. Assessing functional brain network characteristics can provide additional information for differentiating between focal and generalized epilepsy. TaVNS-related modifications of global network characteristics clearly differ between epilepsy types. Impact of such a non-pharmaceutical intervention on clinical decision-making in the treatment of different epilepsy types needs to be assessed in future studies.
| S-EPMC9260140 | biostudies-literature
Project description:Background: Evidence suggests that vagus nerve stimulation can modulate heart rate variability (HRV). However, there is a lack of mechanistic studies in healthy subjects assessing the effects of bilateral transcutaneous auricular vagus nerve stimulation (taVNS) on HRV. Our study aims to investigate how taVNS can influence the HRV response, including the influence of demographic variables in this response. Methods: Therefore, we conducted a randomized controlled study with 44 subjects, 22 allocated to active and 22 to sham taVNS. Results: Our results showed a significant difference between groups in the high-frequency (HF) metric. Active taVNS increased the HF metric significantly as compared to sham taVNS. Also, we found that age was a significant effect modifier of the relationship between taVNS and HF-HRV, as a larger increase in HF-HRV was seen in the older subjects. Importantly, there was a decrease in HF-HRV in the sham group. Conclusions: These findings suggest that younger subjects can adapt and maintain a constant level of HF-HRV regardless of the type of stimulation, but in the older subjects, only the active taVNS recipients were able to maintain and increase their HF-HRV. These results are important because they indicate that taVNS can enhance physiological regulation processes in response to external events.
| S-EPMC11278058 | biostudies-literature
Project description:IntroductionAuricular low-level transcutaneous vagus nerve stimulation (aLL-tVNS) has emerged as a promising technology for cardiac arrhythmia management but is still experimental. In this physiological study, we hypothesized that aLL-tVNS modulated the autonomic nervous balance through a reduction of sympathetic tone and an increase in heart rate variability (HRV). We investigated the muscle sympathetic nerve activity (MSNA) recorded by microneurography during vagally mediated aLL-tVNS and active control on healthy volunteers.MethodsIn this crossover, double-blind controlled study, healthy men (N = 28; 27 ± 4 years old) were assigned to aLL-tVNS applied to cymba and lobe (active control) of the right ear. Each participant was randomly allocated to the three sequences (5 Hz, 20 Hz, and active control-5 Hz) during one session. MSNA signal was recorded at rest, during voluntarily apnea and aLL-tVNS. Sympathetic activity was expressed as: 1) number of bursts per minute (burst frequency, BF) and 2) MSNA activity calculated as BF x mean burst amplitude and expressed as changes from baseline (%). RR intervals, HRV parameters and sympathetic activity were analyzed during 5 min-baseline, 10 min-stimulation, and 10 min-recovery periods. Mixed regression models were performed to evaluate cymba-(5-20 Hz) effects on the parameters with stimulation.ResultsDuring apnea and compared to baseline, BF and MSNA activity increased (p = 0.002, p = 0.001, respectively). No stimulation effect on RR intervals and HRV parameters were showed excepted a slightly increase of the LF/HF ratio with stimulation in the cymba-5Hz sequence (coef. ± SE: 0.76 ± 0.32%; p = 0.02). During stimulation, reductions from baseline in BF (Coef. ± SE: -4.8 ± 1.1, p < 0.001) was observed but was not statistically different from that one in the active control. Reduction of MSNA activity was not significantly different between sequences.ConclusionAcute right cymba aLL-tVNS did not induce any overall effects neither on heart rate, HRV nor MSNA variables on healthy subjects when compared to active control. Interestingly, these findings questioned the role of active controls in medical device clinical trials that implied subjective endpoints.
| S-EPMC7744823 | biostudies-literature
Project description:Accurate senses depend on high-fidelity encoding by sensory receptors and error-free processing in the brain. Progress has been made towards restoring damaged sensory receptors. However, methods for on-demand treatment of impaired central sensory processing are scarce. Prior invasive studies demonstrated that continuous vagus nerve stimulation (VNS) in rodents can activate the locus coeruleus-norepinephrine system to rapidly improve central sensory processing. Here, we investigated whether transcutaneous VNS improves sensory performance in humans. We conducted three sham-controlled experiments, each with 12 neurotypical adults, that measured the effects of transcutaneous VNS on metrics of auditory and visual performance, and heart rate variability (HRV). Continuous stimulation was delivered to cervical (tcVNS) or auricular (taVNS) branches of the vagus nerve while participants performed psychophysics tasks or passively viewed a display. Relative to sham stimulation, tcVNS improved auditory performance by 37% (p=0.00052) and visual performance by 23% (p=0.038). Participants with lower performance during sham conditions experienced larger tcVNS-evoked improvements (p=0.0040). Lastly, tcVNS increased HRV during passive viewing, corroborating vagal engagement. No evidence for an effect of taVNS was observed. These findings validate the effectiveness of tcVNS in humans and position it as a method for on-demand interventions of impairments associated with central sensory processing dysfunction.
| S-EPMC10441305 | biostudies-literature
Project description:Vagus nerve stimulation (VNS) facilitates weight loss in animals and patients treated with VNS for depression or epilepsy. Likewise, chronic transcutaneous auricular VNS (taVNS) reduces weight gain and improves glucose tolerance in Zucker diabetic fatty rats. If these metabolic effects of taVNS observed in rats translate to humans is unknown. Therefore, the hypothesis of this study was that acute application of taVNS affects glucotropic and orexigenic hormones which could potentially facilitate weight loss and improve glucose tolerance if taVNS were applied chronically. In two single-blinded randomized cross-over protocols, blood glucose levels, plasma concentrations of insulin, C-peptide, glucagon, leptin, and ghrelin, together with heart rate variability and baroreceptor-heart rate reflex sensitivity were determined before and after taVNS (left ear, 10 Hz, 300 µs, 2.0-2.5 mA, 30 min) or sham-taVNS (electrode attached to ear with the stimulator turned off). In a first protocol, subjects (n = 16) were fasted throughout the protocol and in a second protocol, subjects (n = 10) received a high-calorie beverage (220 kCal) after the first blood sample, just before initiation of taVNS or sham-taVNS. No significant effects of taVNS on heart rate variability and baroreceptor-heart rate reflex sensitivity and only minor effects on glucotropic hormones were observed. However, in the second protocol taVNS significantly lowered postprandial plasma ghrelin levels (taVNS: -115.5 ± 28.3 pg/ml vs. sham-taVNS: -51.2 ± 30.6 pg/ml, p < 0.05). This finding provides a rationale for follow-up studies testing the hypothesis that chronic application of taVNS may reduce food intake through inhibition of ghrelin and, therefore, may indirectly improve glucose tolerance through weight loss.
| S-EPMC9020171 | biostudies-literature
Project description:BackgroundTranscutaneous auricular vagus nerve stimulation (taVNS) stimulating the auricular branch of the vagus nerve along a well-defined neuroanatomical pathway, has promising therapeutic efficacy. Potentially, taVNS can modulate autonomic responses. Specifically, taVNS can induce more consistent parasympathetic activation and may lead to increased heart rate variability (HRV). However, the effects of taVNS on HRV remain inconclusive. Here, we investigated changes in HRV due to brief alteration periods of parasympathetic-vagal cardiac activity produced by taVNS on the cymba as opposed to control administration via the helix.Materials and methodsWe compared the effect of 10 min of active stimulation (i.e., cymba conchae) to sham stimulation (i.e., helix) on peripheral cardiovascular response, in 28 healthy young adults. HRV was estimated in the time domain and frequency domain during the overall stimulation.ResultsAlthough active-taVNS and sham-taVNS stimulation did not differ in subjective intensity ratings, the active stimulation of the cymba led to vagally mediated HRV increases in both the time and frequency domains. Differences were significant between active-taVNS and both sham-taVNS and resting conditions in the absence of stimulation for various HRV parameters, but not for the low-frequency index of HRV, where no differences were found between active-taVNS and sham-taVNS conditions.ConclusionThis work supports the hypothesis that taVNS reliably induces a rapid increase in HRV parameters when auricular stimulation is used to recruit fibers in the cymba compared to stimulation at another site. The results suggest that HRV can be used as a physiological indicator of autonomic tone in taVNS for research and potential therapeutic applications, in line with the established effects of invasive VNS. Knowledge of the physiological effect of taVNS short sessions in modulating cardiovagal processing is essential for enhancing its clinical use.
| S-EPMC9686410 | biostudies-literature
Project description:IntroductionAlthough heart failure (HF) outcomes have improved dramatically with the use of guideline directed medical therapy and implantable devices, the overall prognosis of patients with HF and reduced ejection fraction (HFrEF) remains poor. Autonomic Regulation Therapy (ART) using chronic vagus nerve stimulation (VNS) has been evaluated in the ANTHEM-HF study, using changes in heart rate (HR) dynamics as a biomarker of autonomic nervous system engagement and cardiac control to guide VNS titration. ART was associated with sustained improvement in cardiac function and HF symptoms in patients with HFrEF and persistent HF symptoms despite guideline-directed medical therapy (GDMT). We sought to determine whether the responsiveness of the autonomic nervous system to ART, as reflected in HR response to vagus stimulation during the VNS duty cycle, is maintained after long-term chronic VNS administration.MethodsFifteen patients with HFrEF and implanted with a VNS systems in the ANTHEM-HF study were evaluated after 4.7 ± 0.3 years (range: 4.0-5.0 years) of chronic ART. ECG electrodes were placed on each patient's wrists, and ECG rhythm strips were recorded. Instantaneous HR time series was computed at each patient's chronically programmed VNS intensity and during progressively increasing VNS intensity. HR during active stimulation (on-time) was compared to HR just prior to initiation of each stimulation cycle (off-time).ResultsPersistent autonomic engagement was observed in a majority of patients (11 of 15, 73%) after chronic ART for four or more years. The average magnitude of HR reduction during ART on-time in all patients was 2.4 ± 3.2 bpm at the chronically programmed VNS pulse parameter settings.ConclusionAutonomic responsiveness to VNS persists in patients with HFrEF who received chronic ART for up to 5 years as a supplement to GDMT. This suggests that the effects of ART on autonomic engagement and cardiac control remain durable over time.Clinical trial registration[ClinicalTrials.gov], identifier [#NCT01823887, CTRI registration #CTRI/2012/05/002681].
| S-EPMC8963780 | biostudies-literature