Vagal Stimulation Research Articles

Efficacy and safety of transcutaneous auricular vagus nerve stimulation for frequent premature ventricular complexes: rationale and design of the TASC-V trial

BackgroundPremature Ventricular Complexes (PVCs) are very common in clinical practice, with frequent PVCs (more than 30 beats per hour) or polymorphic PVCs significantly increasing the risk of mortality. Previous studies have shown that vagus nerve stimulation improves ventricular arrhythmias. Stimulation of the auricular distribution of the vagus nerve has proven to be a simple, safe, and effective method to activate the vagus nerve. Transcutaneous au ricular vagus nerve stimulation (taVNS) has shown promise in both clinical and experimental setting for PVCs; however, high-quality clinical studies are lacking, resulting in insufficient evidence of efficacy.MethodsThe study is a prospective, randomized, parallel-controlled trial with a 1:1 ratio between the two groups. Patients will be randomized to either the treatment group (taVNS) or the control group (Sham-taVNS) with a 6-week treatment and a subsequent 12-week follow-up period. The primary outcome is the proportion of patients with a ≥ 50% reduction in the number of PVCs monitored by 24-hour Holter. Secondary outcomes include the proportion of patients with a ≥ 75% reduction in PVCs, as well as the changes in premature ventricular beats, total heartbeats, and supraventricular premature beats recorded by 24-hour Holter. Additional assessments compared score changes in PVCs-related symptoms, as well as the score change of self-rating anxiety scale (SAS), self-rating depression scale (SDS), and 36-item short form health survey (SF-36).DiscussionThe TASC-V trial will help to reveal the efficacy and safety of taVNS for frequent PVCs, offering new clinical evidence for the clinical practice.Trial registrationClinicaltrials.gov: NCT04415203 (Registration Date: May 30, 2020).

Evaluating phasic transcutaneous vagus nerve stimulation (taVNS) with pupil dilation: the importance of stimulation intensity and sensory perception.

The efficacy of transcutaneous auricular vagus nerve stimulation (taVNS) as a non-invasive method to modulate physiological markers of noradrenergic activity of the Locus Coeruleus (LC), such as pupil dilation, is increasingly more discussed. However, taVNS studies show high heterogeneity of stimulation effects. Therefore, a taVNS setup was established here to test different frequencies (10 Hz and 25 Hz) and intensities (3 mA and 5 mA) during phasic stimulation (3 s) with time-synchronous recording of pupil dilation in younger adults. Specifically, phasic real taVNS and higher intensity led to increased pupil dilation, which is consistent with phasic invasive VNS studies in animals. The results also suggest that the influence of intensity on pupil dilation may be stronger than that of frequency. However, there was an attenuation of taVNS-induced pupil dilation when differences in perception of sensations were considered. Specifically, pupil dilation during phasic stimulation increased with perceived stimulation intensity. The extent to which the effect of taVNS induces pupil dilation and the involvement of sensory perception in the stimulation process are discussed here and require more extensive research. Additionally, it is crucial to strive for comparable stimulation sensations during systematic parameter testing in order to investigate possible effects of phasic taVNS on pupil dilation in more detail.

Efficacy and Safety of Vagus Nerve Stimulation in Lennox-Gastaut Syndrome: A Scoping Review.

Lennox-Gastaut syndrome (LGS) is a severe developmental and epileptic encephalopathy characterized by drug-resistant seizures, cognitive impairments, and abnormal electroencephalographic patterns. Vagus nerve stimulation (VNS) is a widely used neuromodulation therapy for LGS, but its effects on seizure outcomes, different seizure types, non-seizure outcomes, and adverse events in this population have not been comprehensively reviewed. To conduct a scoping review on the use of VNS in LGS, a literature search was performed in PubMed, OVID, Web of Science, and Embase from inception to 9 June 2024, using relevant keywords and without restrictions on study design. The search yielded forty eligible studies (twenty-four retrospective cohorts, fourteen prospective cohorts, and two registry analyses) comprising 1400 LGS patients treated with VNS. No randomized controlled trials were identified. Across studies, the median seizure reduction ranged from 20.6% to 65%, with 0% to 100% of patients achieving a ≥50% seizure reduction. No consistent preoperative biomarker of VNS responsiveness was identified in LGS. Although inconsistent among different studies, tonic, atonic, and tonic-clonic seizures responded best, while focal seizures responded worst. Improvements in seizure severity, alertness, and quality of life were reported in some studies, but cognitive and adaptive functioning generally remained unchanged. Adverse events were mostly mild and transient, including hoarseness, cough, and paresthesia. Device-related complications and infections were uncommon. In conclusion, further research is needed to better understand VNS's position in the evolving LGS treatment landscape and its cost effectiveness.

Characterization of idiopathic chronic diarrhea and associated intestinal inflammation and preliminary observations of effects of vagal nerve stimulation in a non-human primate.

Diarrhea is commonly associated with irritable bowel syndrome, inflammatory bowel disease, microscopic colitis, and other gastrointestinal dysfunctions. Spontaneously occurring idiopathic chronic diarrhea is frequent in rhesus macaques, but has not been used as a model for the investigation of diarrhea or its treatment. We characterized this condition and present preliminary data demonstrating that left vagal nerve stimulation provides relief. Stool consistency scores were followed for up to 12 years. Inflammation was assessed by plasma C-reactive protein, [18F]fluorodeoxyglucose (FDG) uptake, measured by positron emission tomography (PET), multiplex T cell localization, endoscopy and histology. The vagus was stimulated for 9 weeks in conscious macaques, using fully implanted electrodes, under wireless control. Macaques exhibited recurrent periods of diarrhea for up to 12 years, and signs of inflammation: elevated plasma C-reactive protein, increased bowel FDG uptake and increased mucosal T helper1 T-cells. The colon and distal ileum were endoscopically normal, and histology revealed mild colonic inflammation. Application of vagal nerve stimulation to conscious macaques (10 Hz, 30 s every 3 h; 24 h a day for 9 weeks) significantly reduced severity of diarrhea and also reduced inflammation, as measured by FDG uptake and C-reactive protein. These macaques exhibit spontaneously occurring diarrhea with intestinal inflammation that can be reduced by VNS. The data demonstrate the utility of this naturally occurring primate model to study the physiology and treatments for chronic diarrhea and the neural control circuits influencing diarrhea and inflammation that are not accessible in human subjects.

Transcutaneous cervical vagus nerve stimulation enhances second-language vocabulary acquisition while simultaneously mitigating fatigue and promoting focus

Transcutaneous vagus nerve stimulation (tVNS) is a promising technique for enhancing cognitive performance and skill acquisition. Yet, its efficacy for enhancing learning rate and long-term retention in an ecologically valid learning environment has not been demonstrated. We conducted two double-blind sham-controlled experiments examining the efficacy of auricular tVNS (taVNS: Experiment (1) and cervical tVNS (tcVNS: Experiment (2), on a 5 day second-language vocabulary acquisition protocol among highly selected career linguists at the US Department of Defense’s premier language school. tcVNS produced accelerated recall performance during training (Day 2–4), benefits of which were maintained across a 24 h retention interval with no stimulation at the final test. Consistent with prior work, tcVNS also produced fatigue-mitigating and focus-promoting effects as measured by the Air Force Research Laboratory Mood Questionnaire. Based on the current and the previous findings supporting tVNS’ efficacy on performance, training enhancement, and fatigue mitigation, we believe tcVNS to be an effective learning acceleration tool that can be utilized at language-teaching and other institutions focused on intensive training of cognitive skills.

The Effect of In-Ear and Behind-Ear Transcutaneous Auricular Vagus Nerve Stimulation on Autonomic Function: A Randomized, Single-Blind, Sham-Controlled Study.

Background/Objectives: Transcutaneous auricular vagus nerve stimulation (TaVNS) is a non-invasive method of electrical stimulation used to autonomic neuromodulation. Position and form of the electrodes are important for the effectiveness of autonomic modulation. This study was aimed to investigate the effect of TaVNS in-ear and behind-ear on autonomic variables. Methods: A total of 76 healthy participants (male: 40, female: 36) were randomized into four groups as in-ear TaVNS, behind-ear TaVNS, in-ear sham, and behind-ear sham. The TaVNS protocol included bilateral auricular stimulation for 20 min, 25 hertz frequency, a pulse width of 250 μs, and a suprathreshold current (0.13-50 mA). Heart rate (HR), systolic and diastolic blood pressure (SBP and DBP), and heart rate variability (HRV) were measured baseline and after stimulation. The parameters RMSSD (root mean square of consecutive differences between normal heartbeats), LF power (low-frequency), and HF power (high-frequency) were assessed in the HRV analysis. Results: HR decreased in the in-ear TaVNS after intervention (p < 0.05), but did not change in behind-ear TaVNS and sham groups compared to baseline (p > 0.05). SBP and DBP decreased and RMSSD increased in the in-ear and behind-ear TaVNS groups (p < 0.05), but did not change in sham groups compared to baseline (p > 0.05). There was no significant difference in LF and HF power after TaVNS compared to baseline in all groups (p > 0.05). SBP was lower and RMSSD was higher in-ear TaVNS than behind-ear TaVNS after intervention (p < 0.05). Conclusions: In-ear TaVNS appears to be more effective than behind-ear TaVNS in modulating SBP and RMSSD, but this needs to be studied in larger populations.

Responsive neurostimulation in pediatric epilepsy: a systematic review and individual patient meta-analysis supplemented by a single institution case series in 105 aggregated patients.

To assess responsive neurostimulation (RNS) efficacy in pediatric patients with drug-resistant epilepsy, comparing response (≥ 50% reduction in seizure frequency) rates between patients with two or fewer seizure foci and those with multifocal or generalized epilepsy. This study seeks to address the gap in knowledge regarding RNS effectiveness in pediatric populations. A systematic review and meta-analysis included data from PubMed, Embase, and Web of Science through November 2023, including 17 retrospective studies and a case series of 24 patients from our practice for a total of 105 aggregated patients. The inclusion criteria of patients were age 18 and diagnosis of DRE. Exclusion criteria were nonhuman subjects and cases where RNS was not utilized to treat DRE. Study inclusion criteria were detailing the use of RNS and comparing patients with 2 foci with other focalities. Study exclusion criteria were failure to specify RNS lead placement or type of epilepsy. The risk of bias was assessed using the ROBINS-I tool for all non-randomized studies. Effect sizes and variances were aggregated to provide a comprehensive measure of RNS efficacy, and heterogeneity among the studies was assessed using I2 statistics and Cochran's Q test to evaluate the consistency of the findings. Statistical analyses were conducted using IBM SPSS. We analyzed demographics, epilepsy history, treatment outcomes, and RNS details using descriptive and inferential statistics, including Wilcoxon-Mann-Whitney, Fisher's exact, and chi-squared tests. This systematic review was not registered. Seventeen retrospective studies and a single-institution case series, encompassing 105 pediatric patients, were analyzed. Effect sizes and confidence intervals were calculated to quantify treatment effects. Analyses revealed that RNS reduces seizure frequency across a spectrum of pediatric epilepsy syndromes, irrespective of the seizures' focal, multifocal, or generalized origins. The effectiveness of RNS was not influenced by the patient's sex, age at epilepsy onset, or presence of neurological and psychiatric comorbidities. Prior vagus nerve stimulation surgery and the presence of an epileptic syndrome were factors associated with a lower likelihood of near-complete seizure remission with RNS, underscoring the complexities of treating patients with generalized epilepsies or previous interventional failures. The necessity of further research into individualized surgical strategies for patients was underscored by the mixed results of comparisons of electrode characteristics with responder rates. Limitations of our study include its reliance on retrospective studies, which introduces potential bias and limits the ability to infer causality. RNS is a safe and effective treatment in pediatric patients with DRE across demographic, comorbidity, and focality variability. FDA age and focality restrictions, along with patient and physician hesitancy, may be limiting the potential for effective treatment of pediatric DRE with RNS. Prospective randomized trials are recommended to validate these findings.

No clear benefit of transcutaneous auricular vagus nerve stimulation for non-native speech sound learning

IntroductionLearning to understand and speak a new language can be challenging and discouraging for adults. One potential tool for improving learning is transcutaneous auricular vagus nerve stimulation (taVNS), which modulates perception, memory, and attention systems. It has recently been reported that taVNS can improve English speakers' ability to perceive unfamiliar Mandarin tones. The current project explored the potential benefits of taVNS for language learning beyond tone perception.MethodsWe studied adults' ability to perceive and produce unfamiliar speech sounds as well as any potential change in language learning motivation from pre- to post-training. Forty-five native English speakers were divided into three groups and were trained to perceive German sounds: one group received stimulation during easier-to-learn sounds (vowels), one group received stimulation during harder-to-learn sounds (fricatives), and a control group received no stimulation.Results and discussionWe did not find evidence that taVNS improved perception or production of the German sounds, but there was evidence that it did improve some aspects of motivation. Specifically, the group that received taVNS during easier sounds showed a significant decrease in feelings of tension/pressure about language learning, while the other groups did not. Overall, the present study does not find that taVNS holds benefits for the acquisition of new speech sounds; however, the field is nascent, and so the potential applications of taVNS for language learning remain to be clarified.

Vagus Nerve and Gut-Brain Communication.

The vagus nerve, as an important component of the gut-brain axis, plays a crucial role in the communication between the gut and brain. It influences food intake, fat metabolism, and emotion by regulating the gut-brain axis, which is closely associated with the development of gastrointestinal, psychiatric, and metabolism-related disorders. In recent years, significant progress has been made in understanding the vagus-mediated regulatory pathway, highlighting its profound implications in the development of many diseases. Here, we summarize the latest advancements in vagus-mediated gut-brain pathways and the novel interventions targeting the vagus nerve. This will provide valuable insights for future research on treatment of obesity and gastrointestinal and depressive disorders based on vagus nerve stimulation.

Influence of a 2-week transcutaneous auricular vagus nerve stimulation on memory: findings from a randomized placebo controlled trial in non-clinical adults.

Memory plays an essential role in daily life and is one of the first functions to deteriorate in cognitive impairment and dementia. Transcutaneous vagus nerve stimulation (tVNS) is a promising therapeutic method; however, its ability to enhance memory is underexplored, especially considering long-term stimulation. We aimed to investigate the effect of a 2-week course of auricular tVNS (taVNS) on memory in a non-clinical population. This single-blind randomized placebo-wait-list controlled trial recruited 76 participants (30 men; mean age 48.32years) and randomized them into four groups: early active/sham taVNS and late active/sham taVNS. Participation in the study lasted 4weeks; early groups underwent 2weeks intervention immediately following the first study site visit (days0-13) and late groups 2weeks after the first study site visit (days14-27). Active and sham taVNS included 2weeks of daily 4-h neurostimulation at the tragus or earlobe, respectively. To assess memory, we used the Rey Auditory Verbal Learning Test. Two weeks of active taVNS, but not sham taVNS, improved immediate recall and short-term memory score both in early and late groups. Furthermore, the improvements persisted over subsequent follow-up in early active taVNS. Importantly, the effect of active taVNS was superior to sham for immediate recall in both early and late groups. There were no statistical differences in delayed recall. Our findings suggest that taVNS has potential to improve memory, particularly immediate recall, and may be an effective method in preventing memory loss and mitigating cognitive aging.

Age as an Effect Modifier of the Effects of Transcutaneous Auricular Vagus Nerve Stimulation (taVNS) on Heart Rate Variability in Healthy Subjects.

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.

Parameter optimization of non-invasive vagus nerve stimulation for second language learning in typically developing young adults

Although the ability to acquire a second language (L2) and attain fluency in that language is beneficial for a growing number of people, it is significantly more difficult to acquire such skills in adulthood. While traditional in-person and computer training programs can aid in this process, learning is often slow and retention is quite poor. A method for driving long-lasting neural plasticity during language learning would be valuable for those who need or want to achieve fluency in a second language later in life. However, little is known about the effect of neuromodulation methods on language learning. In the current study, we investigated the effect of non-invasive transcutaneous auricular vagus nerve stimulation (taVNS) on vocabulary word-learning in healthy young adults. Importantly, we approached this research question by investigating two key parameters of taVNS, stimulation frequency (Experiment 1) and current intensity (Experiment 2). Typically developing young adults completed a 1-h training session in which they learned 30 concrete, Palauan nouns while receiving real or sham stimulation to the left posterior tragus (Experiment 1) or stimulation at various intensities (Experiment 2). Participants completed a Palau-to-English translation test immediately after training and seven days later to quantify learning and retention. The results largely revealed that high frequency stimulation above sensory threshold improved retention of learned words. These results suggest that taVNS may improve retention of vocabulary words in a second language and that stimulation frequency may impact efficacy.

ТЕРАПЕВТИЧЕСКАЯ СИЛА ВОКАЛЬНОГО ЗВУКА, ИЛИ КАКИМ ОБРАЗОМ ВОКАЛЬНЫЙ ЗВУК МОЖЕТ ПОЛОЖИТЕЛЬНО ВЛИЯТЬ НА КЛЕТКИ ВАШЕГО ТЕЛА И КЛЕТКИ ТЕХ, КТО НАХОДИТСЯ РЯДОМ С ВАМИ

The therapeutic power of the human voice is well known, but the mechanisms by which vocal sound can promote healing have received little attention in the scientific and medical communities. In this article, UK acoustic-physics scientist, John Stuart Reid, begins by describing the sound bubble model of sound, as distinct from sound wave model, and discusses the significance of the little known physics fact that "sound gives birth to light”. Due to the inelastic atomic collisions that are a fundamental aspect of sound production, this phenomenon leads to the intriguing hypothesis that our songs will, in the fullness of time, reach the stars in the form of modulated infrared energy. The article proceeds to distill, in accessible language, deep insights into the biological therapeutic mechanisms that underpin vocalizations, including vocal sound's ability to mediate chronic inflammation by vagus nerve stimulation. The article ends with a reference to the work of Professor Sergey Petoukhov, and the thought that we are actually singing form of genetic music, music that brings healing to all life.

Evaluating the Efficacy of Vagus Nerve Stimulation across 'Minor' and 'Major' Seizure Types: A Retrospective Analysis of Clinical Outcomes in Pharmacoresistant Epilepsy.

Background: Evaluating the differential impact of vagus nerve stimulation (VNS) therapy across various seizure types, our study explores its efficacy specifically in patients with categorized minor and major seizures. Methods: We conducted a retrospective cohort study involving 76 patients with pharmacoresistant epilepsy treated at the University Emergency Hospital of Bucharest between 2021 and 2024. Seizures were classified as 'minor' (including focal-aware and non-motor/absence seizures) and 'major' (including focal to bilateral tonic-clonic and generalized motor seizures), based on modified International League Against Epilepsy (ILAE) criteria. This classification allowed us to assess the response to VNS therapy, defined by a 50% or greater reduction in seizure frequency at the 12-month follow-up. Results: Our findings reveal that major seizures respond more favorably to VNS therapy, significantly reducing both frequency and intensity. In contrast, minor seizures showed a less pronounced response in frequency reduction but noted improvements in neurocognitive functions, suggesting a nuanced benefit of VNS in these cases. Conclusion: The study underscores the importance of seizure type in determining the efficacy of VNS therapy, advocating for personalized treatment approaches based on seizure classification. This approach could potentially enhance clinical outcomes by tailoring VNS settings to specific seizure types, improving overall management strategies in pharmacoresistant epilepsy.

Atrial fibrillation radiofrequency ablation in a patient with vagus nerve stimulation

Vagus nerve stimulation (VNS) is an effective neuromodulatory treatment for patients with drug resistant epilepsy who cannot undergo curative surgical resection. Safety information states that the use of radiofrequency ablation devices may damage the VNS generator and leads. However, documented cases are scarce. This 62-year-old patient with bitemporal lobe epilepsy treated with VNS underwent radiofrequency ablation of an atrial fibrillation without any perioperative or postoperative complications.

Effects of Transcutaneous Auricular Vagus Nerve Stimulation on the P300: Do Stimulation Duration and Stimulation Type Matter?

Non-invasive transcutaneous auricular vagus nerve stimulation (taVNS) has attracted increasing interest as a neurostimulation tool with potential applications in modulating cognitive processes such as attention and memory, possibly through the modulation of the locus-coeruleus noradrenaline system. Studies examining the P300 brain-related component as a correlate of noradrenergic activity, however, have yielded inconsistent findings, possibly due to differences in stimulation parameters, thus necessitating further investigation. In this event-related potential study involving 61 participants, therefore, we examined how changes in taVNS parameters, specifically stimulation type (interval vs. continuous stimulation) and duration, influence P300 amplitudes during a visual novelty oddball task. Although no effects of stimulation were found over the whole cluster and time window of the P300, cluster-based permutation tests revealed a distinct impact of taVNS on the P300 response for a small electrode cluster, characterized by larger amplitudes observed for easy targets (i.e., stimuli that are easily discernible from standards) following taVNS compared to sham stimulation. Notably, our findings suggested that the type of stimulation significantly modulated taVNS effects on the P300, with continuous stimulation showing larger P300 differences (taVNS vs. sham) for hard targets and standards compared to interval stimulation. We observed no interaction effects of stimulation duration on the target-related P300. While our findings align with previous research, further investigation is warranted to fully elucidate the influence of taVNS on the P300 component and its potential utility as a reliable marker for neuromodulation in this field.

Transcutaneous auricular vagus nerve stimulation modulates masseter muscle activity, pain perception, and anxiety levels in university students: a double-blind, randomized, controlled clinical trial.

Chronic anxiety is a statemarked by sustained activation of the masseter muscle, manifesting in both mental and physical strain. This prolonged tension can significantly impact mental wellbeing and cognitive abilities, posing a risk for a range of health complications. This double-blind, randomized, controlled clinical trial investigated the impact of transcutaneous auricular vagus nerve stimulation (TAVNS) on masseter muscle activity, pressure pain threshold (PPT), and anxiety levels in university students with elevated anxiety. Forty-two participants meeting inclusion criteria were randomly assigned to either active TAVNS or sham TAVNS groups. Various parameters, including masseter muscle electromyographic (EMG) signals, PPT, and Beck Anxiety Inventory (BAI) scores, were assessed before pretreatment, immediately after the intervention week, and 2 weeks follow-up. Active TAVNS significantly reduced both left and right masseter activation during resting mandibular position, persisting for 2 weeks post-intervention. Additionally, TAVNS induced a lasting decrease in both left and right masseter PPT, indicative of altered pain perception. Notably, BAI scores showed a substantial reduction, emphasizing TAVNS as a potential intervention for anxiety, with effects maintained at the 2-week follow-up. This study provides comprehensive insights into the multifaceted effects of TAVNS on physiological and psychological aspects associated with anxiety in university students. The promising results underscore TAVNS as a potential neuromodulatory intervention for anxiety-related conditions, warranting further research and clinical exploration. https://ensaiosclinicos.gov.br/rg/RBR-4s4kt2r.

Closed-Loop Multimodal Neuromodulation of Vagus Nerve for Control of Heart Rate.

The use of electrical current to modulate neurons for autonomic regulation requires the ability to both up-regulate and down-regulate the nervous system. An implanted system employing this electrical neuromodulation would also need to adapt to changes in autonomic state in real-time. Stimulation of autonomic nerves at frequencies in the range 1-30 Hz has been a well-established technique for increasing neural activity. Vagus nerve stimulation (VNS) has been shown to be sensitive to frequency adjustments, which can be used to more precisely control the effect as compared to amplitude modulation. Kilohertz frequency alternating current (KHFAC) is a proven technique for blocking action potential conduction to reduce neural activity. Additionally, KHFAC can be reliably modulated by simple amplitude modulation. Although there are many types of commonly used closed-loop controllers, many conventional methods do not respond well to long system delays or discontinuities. Fuzzy logic control (FLC) is a state-based controller that can describe the discontinuities of the system linguistically and then translate the state transition to a continuous output signal. In our preparation, a single bipolar electrode was placed on the vagus nerve and controlled by a fuzzy logic controller to deliver both stimulation and KHFAC to control heart rate. The FLC was able to both change the heart rate to selected values and maintain the heart rate at a constant value in response to a physiological perturbation.

Analysis of taVNS effects on autonomic and central nervous systems in healthy young adults based on HRV, EEG parameters

Objective. Transcutaneous auricular vagus nerve stimulation (taVNS), a non-invasive method of stimulating the vagus nerve, simultaneously affects the autonomic nervous system (ANS) and central nervous system (CNS) through efferent and afferent pathways. The purpose of this study is to analyze the effect of taVNS on the ANS and CNS through heart rate variability (HRV) and electroencephalography (EEG) parameters of identified responders. Approach. Two sets of data were collected from each of 10 healthy adult male subjects in their 20 s, and five HRV parameters from the time domain (RMSSD, pNN50, pNN30, pNN20, ppNNx) and two EEG parameters (power of alpha band, power of delta band) were extracted. Main results. Based on pNN50, responders to taVNS were identified; among them, pNN50 (p = 0.0041) and ppNNx (p = 0.0037) showed significant differences before and after taVNS. At the same time, for alpha power and delta power of EEG, significant difference (p < 0.05) was observed in most channels after taVNS compared to before stimulation. Significance. This study demonstrated the validity of identifying responders using pNN50 and the influence of taVNS on both the ANS and CNS. We conclude that taVNS can be used to treat a variety of diseases and as a tool to help control the ANS and CNS.

Vagus nerve stimulation for the therapy of Dravet syndrome: a systematic review and meta-analysis.

Dravet syndrome (DS) is a refractory developmental and epileptic encephalopathy characterized by seizures, developmental delay and cognitive impairment with a variety of comorbidities, including autism-like behavior, speech dysfunction, and ataxia. Vagus nerve stimulation (VNS) is one of the common therapies for DS. Here, we aim to perform a meta-analysis and systematic review of the efficacy of VNS in DS patients. We systematically searched four databases (PubMed, Embase, Cochrane and CNKI) to identify potentially eligible studies from their inception to January 2024. These studies provided the effective rate of VNS in treating patients with DS. The proportions of DS patients achieving ≥50% reduction of seizure frequency were extracted from these studies. Meta-analyses were performed to respectively evaluate the efficacy of VNS for DS after 3, 6, 12, 18, 24 and 36 months. Sixteen trials with a total of 173 patients were included. Meta-analyses showed that the pooled efficiency was 0.54 (95% CI 0.43-0.65) in the DS patients treated with VNS (p < 0.05). Meanwhile, the pooled efficiency respectively was 0.42 (95% CI 0.25-0.61), 0.54 (95% CI 0.39-0.69), 0.51 (95% CI 0.39-0.66), and 0.49 (95% CI 0.36-0.63) in the DS patients treated with VNS after 3, 6, 12 and 24 months (p < 0.05). This study suggests that VNS is effective in the treatment of DS. However, few studies have focused on VNS for DS, and there is a lack of high-quality evidence. Thus, high-quality randomized controlled trials are needed to confirm the efficacy of VNS in DS.