Vagal Stimulation Research Articles

Slow-Paced Breathing Intervention in Healthcare Workers Affected by Long COVID: Effects on Systemic and Dysfunctional Breathing Symptoms, Manual Dexterity and HRV.

Many COVID-19 survivors still experience long-term effects of an acute infection, most often characterised by neurological, cognitive and psychiatric sequelae. The treatment of this condition is challenging, and many hypotheses have been proposed. Non-invasive vagus nerve stimulation using slow-paced breathing (SPB) could stimulate both central nervous system areas and parasympathetic autonomic pathways, leading to neuromodulation and a reduction in inflammation. The aim of the present study was to evaluate physical, cognitive, emotional symptoms, executive functions and autonomic cardiac modulation after one month of at-home slow breathing intervention. 6655 healthcare workers (HCWs) were contacted via a company email in November 2022, of which N = 58 HCWs were enrolled as long COVID (cases) and N = 53 HCWs as controls. A baseline comparison of the two groups was performed. Subsequently each case was instructed on how to perform a resonant SPB using visual heart rate variability (HRV) biofeedback. They were then given a mobile video tutorial breathing protocol and asked to perform it three times a day (morning, early afternoon and before sleep). N = 33 cases completed the FU. At T0 and T1, each subject underwent COVID-related, psychosomatic and dysfunctional breathing questionnaires coupled with heart rate variability and manual dexterity assessments. After one month of home intervention, an overall improvement in long-COVID symptoms was observed: confusion/cognitive impairment, chest pain, asthenia, headache and dizziness decreased significantly, while only a small increase in manual dexterity was found, and no relevant changes in cardiac parasympathetic modulation were observed.

Mixing transcutaneous vagal nerve stimulation and galvanic cutaneous stimulation to decrease simulator adaptation syndrome.

Simulator Adaptation Syndrome arises from a perceptual discordance between expected and actual motion, giving rise to symptoms such as nausea and disorientation. This research focused on determining the benefit of Transcutaneous Vagal Nerve Stimulation (tVNS) and Galvanic Cutaneous Stimulation (GCS), where both were applied in conjunction, as compared to their administration in isolation, to decrease Simulator Adaptation Syndrome (SAS). A driving simulation study was proposed where SAS, body balance, and driving performance were measured. These measurements were taken during seven different stimulation scenarios with a baseline condition without stimulation compared against tVNS and GCS conditions. The main result showed that the combination of tVNS and GCS reduced SAS and improved body balance and driving performance more successfully than their administration in isolation. Similar neuromodulation in the temporoparietal junction is proposed to mitigate SAS for GCS and tVNS (although additional explanations are discussed). Applying both techniques simultaneously is encouraged to decrease SAS in future interventions.

Ultrasound stimulation of the vagus nerve as a treatment modality for anxiety.

Anxiety is an increasingly prevalent mental disorder, causing widespread hardship and interfering with society's economic progression. Standard treatments include various talk therapies with poor prognoses or drug interventions with complex side effects, both introducing unnecessary burdens to patients. To remedy this, non-invasive ultrasound stimulation to the vagus nerve is a novel, low-cost treatment that is showing promise. Although vagus nerve stimulation is already approved for epilepsy and other conditions, it requires regular maintenance. In contrast, studies using non-invasive ultrasound stimulation have shown preliminary positive results in affecting vagal activity with minimal drawbacks. This review covers a variety of studies investigating the effects of ultrasound stimulation on the vagus nerve. With rising levels of anxiety with each generation, there is a pressing need for more innovative and diverse treatments with fewer costs and more benefits.

Baseline characteristics and predictors for early implantation of vagus nerve stimulation therapy in people with drug-resistant epilepsy: Observations from an international prospective outcomes registry (CORE-VNS).

Vagus nerve stimulation (VNS) Therapy is routinely indicated for people with drug-resistant epilepsy (DRE). We analyzed the baseline characteristics of individuals receiving the recently released VNS models and identified factors associated with early or late implantation. The Comprehensive Outcomes Registry of subjects with Epilepsy (CORE-VNS), a prospective observational study evaluating the clinical and psychosocial outcomes of VNS Therapy®, is following participants for up to 60 months after VNS implantation. In this analysis, we used Cox proportional hazards model to identify baseline characteristics associated with the time from diagnosis to first implantation. Of the 819 enrolled, 792 (96.7%) participants implanted with a VNS device were evaluated. 529 (64.6%) underwent the first implantation and 263 (32.1%) a re-implantation. Participants' median age at first implant was 24 years; 492 (62.1%) were ≥18 years old and 166 (20.3%) were < 12 years old. The average number of failed ASMs prior to VNS implantation was 7.1, and 145 (17.7%) had undergone previous epilepsy-related surgery. Epilepsy was classified as focal in 47.7% of participants, generalized in 16.1% and combined focal and generalized in 34.2%. Many of the participants (40.9%) had epilepsy of unknown etiology. The median time from diagnosis to first implantation was 10.33 years and was significantly shorter in participants with combined focal and generalized epilepsy compared to those with focal epilepsy alone, and in participants with genetic and immune epilepsy compared to those with unknown etiologies. In people with DRE, VNS Therapy is provided after multiple failures of ASMs and after failure of epilepsy surgery in one in six individuals. Time from diagnosis to first implantation is associated with epilepsy type and etiology, likely reflecting variable treatment pathways. Clearer guidelines on when and how non-drug therapies should be deployed in people with DRE related to different epilepsy factors are needed. Neuromodulation can be a very helpful treatment in people who have seizures that do not respond to medications. The most widely utilized neuromodulation therapy is vagus nerve stimulation (VNS). We present data from a large, global study to show that people use an average of seven anti-seizure medications before attempting VNS Therapy and that it takes about 10 years for people to get their first VNS implant. We advocate for clearer treatment guidelines on how and when to consider VNS Therapy in people with seizures that are resistant to medication.

Vagus nerve stimulation with a small total charge transfer improves motor behavior and reduces neuroinflammation in a mouse model of Parkinson's disease

Parkinson's disease (PD) is a common neurodegenerative disease characterized by the loss of dopaminergic (DA) neurons in the substantia nigra (SN). Conventional treatments are ineffective in reversing disease progression. Recently, the therapeutic and rehabilitation potential of vagus nerve stimulation (VNS) in PD has been explored. However, the underlying mechanisms remain largely unknown. In this study, we investigated the neuroprotective effects of VNS in a lateral lesioned mice model of PD. Excluding controls, experimental mice received cuff electrode implantation on the left vagus nerve and 6-hydroxydopamine administration into the bilateral striatum. After ten days, electrical stimulation was delivered for 11 consecutive days onto PD animals. Behavioral tests were performed after stimulation. The expression of TH, Iba-1, GFAP, adrenergic receptors and cytokines in the SN and striatum was detected by immunofluorescence or western blotting. The activity of noradrenergic neurons in the locus coeruleus (LC) was also measured. Our results suggest that VNS improved behavioral performance in rod rotation, open field tests and pole-climbing tests in PD mice, accompanied by a decrease in the loss of dopaminergic neurons in the SN and increased TH expression in the striatum. Neuroinflammation-related factors, such as GFAP, Iba-1, TNF-α and IL-1β were also suppressed in PD mice after VNS compared to those without treatment. Furthermore, the proportion of c-Fos-positive noradrenergic neurons in the LC increased when animals received VNS. Additionally, the expression of the adrenergic receptor of α1BR was also upregulated after VNS compared to PD mice. In conclusion, VNS has potential as a novel PD therapy for neuroprotective effects, and indicate that activation of norepinephric neurons in LC may plays an important role in VNS treatment for PD.

Expert opinion on use of vagus nerve stimulation therapy in the management of pediatric epilepsy: a Delphi consensus study

Purpose: To provide consensus-based recommendations for use of vagus nerve stimulation (VNS) therapy in the management of pediatric epilepsy. Methods: Delphi methodology with two rounds of online survey was used to build consensus. A steering committee developed 43 statements related to pediatric epilepsy and the use of VNS therapy, which were evaluated by a panel of 12 neurologists/neurosurgeons with expertise in pediatric epilepsy, who graded their agreement with each statement on a scale of 1 (“I do not agree at all”) to 5 (“I strongly agree”). For each statement, consensus was established if ≥70% of the agreement scores were 4 or 5 and <30% were 1 or 2 in the final survey. Results: Twenty-four statements regarding the need for seizure reduction in pediatric epilepsy, the recommended treatment algorithm, the benefits and safety of VNS therapy, management of side effects of VNS therapy, patient selection for VNS therapy, and the use, dosing, and titration of VNS therapy achieved consensus. VNS and other neuromodulation therapies should be considered for pediatric patients with drug-resistant epilepsy who are not candidates for resective surgery, or who do not remain seizure free after resective surgery. When VNS therapy is initiated, the target dose range should be achieved via the fastest and safest titration schedule for each patient. Scheduled programming can be helpful in dose titration. Conclusion: The expert consensus statements represent the panelists’ collective opinion on the best practice use of VNS therapy to optimize outcomes in the management of pediatric epilepsy.

Transcutaneous auricular vagus nerve stimulation improves cognitive decline by alleviating intradialytic cerebral hypoxia in hemodialysis patients: A fNIRS pilot study

Cognitive impairment is common in hemodialysis patients, possibly due to inadequate cerebral blood flow during hemodialysis. No effective non-pharmacological interventions are available. This study investigates the impact of hemodialysis-induced cerebral hypoxia on cognitive decline in hemodialysis patients and the potential of transcutaneous auricular vagus nerve stimulation (taVNS) as a non-pharmacological intervention. A randomized controlled trial with 36 participants showed that cognitive performance and cerebral oxygenation in the dorsolateral prefrontal cortex (DLPFC) significantly declined in the sham group. In contrast, taVNS improved cognitive function by increasing cerebral oxygenation, with significant correlations to reaction times and MoCA scores. The study suggests that Hemodialysis-induced cerebral hypoxia may contribute to persistent cognitive decline in MHD patients. However, taVNS could be an effective intervention to prevent cognitive impairment in hemodialysis patients by alleviating cerebral hypoxia.

Transcutaneous vagus nerve stimulation effects on chronic pain: systematic review and meta-analysis.

Chronic pain is one of the major causes of disability with a tremendous impact on an individual's quality of life and on public health. Transcutaneous vagus nerve stimulation (tVNS) is a safe therapeutic for this condition. We aimed to evaluate its effects in adults with chronic pain. A comprehensive search was performed, including randomized controlled trials published until October 2023, which assessed the effects of noninvasive tVNS. Cohen's d effect size and 95% confidence intervals (CIs) were calculated, and random-effects meta-analyses were performed. Fifteen studies were included. The results revealed a mean effect size of 0.41 (95% CI 0.17-0.66) in favor of tVNS as compared with control, although a significant heterogeneity was observed (χ2 = 21.7, df = 10, P = 0.02, I 2 = 53.9%). However, when compared with nonactive controls, tVNS shows a larger effect size (0.79, 95% CI 0.25-1.33), although the number of studies was small (n = 3). When analyzed separately, auricular tVNS and cervical tVNS against control, it shows a significant small to moderate effect size, similar to that of the main analysis, respectively, 0.42 (95% CI 0.08-0.76, 8 studies) and 0.36 (95% CI 0.01-0.70, 3 studies). No differences were observed in the number of migraine days for the trials on migraine. This meta-analysis indicates that tVNS shows promise as an effective intervention for managing pain intensity in chronic pain conditions. We discuss the design of future trials to confirm these preliminary results, including sample size and parameters of stimulation.

Vagal sensory neuron-derived FGF3 controls insulin secretion

Vagal nerve stimulation has emerged as a promising modality for treating a wide range of chronic conditions, including metabolic disorders. However, the cellular and molecular pathways driving these clinical benefits remain largely obscure. Here, we demonstrate that fibroblast growth factor 3 (Fgf3) mRNA is upregulated in the mouse vagal ganglia under acute metabolic stress. Systemic and vagal sensory overexpression of Fgf3 enhanced glucose-stimulated insulin secretion (GSIS), improved glucose excursion, and increased energy expenditure and physical activity. Fgf3-elicited insulinotropic and glucose-lowering responses were recapitulated when overexpression of Fgf3 was restricted to the pancreas-projecting vagal sensory neurons. Genetic ablation of Fgf3 in pancreatic vagal afferents exacerbated high-fat diet-induced glucose intolerance and blunted GSIS. Finally, electrostimulation of the vagal afferents enhanced GSIS and glucose clearance independently of efferent outputs. Collectively, we demonstrate a direct role for the vagal afferent signaling in GSIS and identify Fgf3 as a vagal sensory-derived metabolic factor that controls pancreatic β-cell activity.

Presurgical Use of Cenobamate for Adult and Pediatric Patients Referred for Epilepsy Surgery: Expert Panel Recommendations.

Cenobamate has demonstrated efficacy in patients with treatment-resistant epilepsy, including patients who continued to have seizures after epilepsy surgery. This article provides recommendations for cenobamate use in patients referred for epilepsy surgery evaluation. A panel of six senior epileptologists from the United States and Europe with experience in presurgical evaluation of patients with epilepsy and in the use of antiseizure medications (ASMs) was convened to provide consensus recommendations for the use of cenobamate in patients referred for epilepsy surgery evaluation. Many patients referred for surgical evaluation may benefit from ASM optimization; both ASM and surgical treatment should be individualized. Based on previous clinical studies and the authors' clinical experience with cenobamate, a substantial proportion of patients with treatment-resistant epilepsy can become seizure-free with cenobamate. We recommend a cenobamate trial and ASM optimization in parallel with presurgical evaluations. Cenobamate can be started before phase two monitoring, especially in patients who are found to be suboptimal surgery candidates. As neurostimulation therapies are generally palliative, we recommend trying cenobamate before vagus nerve stimulation (VNS), deep brain stimulation, or responsive neurostimulation (RNS). In surgically remediable cases (mesial temporal sclerosis, benign discrete lesion in non-eloquent cortex, cavernous angioma, etc.), cenobamate use should not delay imminent surgery; however, a patient may decide to defer or even cancel surgery should they achieve sustained seizure freedom with cenobamate. This decision should be made on an individual, case-by-case basis based on seizure etiology, patient preferences, potential surgical risks (mortality and morbidity), and likely surgical outcome. The addition of cenobamate after unsuccessful surgery or palliative neuromodulation may also be associated with better outcomes.

Deep brain stimulation versus vagus nerve stimulation for the motor function of poststroke hemiplegia: study protocol for a multicentre randomised controlled trial

IntroductionDeep brain stimulation (DBS) and vagus nerve stimulation (VNS) can improve motor function in patients with poststroke hemiplegia. No comparison study exists.Methods and analysisThis is a randomised, double-blind, controlled clinical...

First-aid knowledge and practices towards patients with epileptic seizures among the dental students in Saudi Arabia – A cross-sectional study

ABSTRACT Background: Dental care of patients with epilepsy and seizures must be performed by dentists who are familiar with these disorders. Improper training and incapability to manage medical emergencies, including epileptic seizures, may cause thoughtful consequences and legal actions. Therefore, dental students must have a proper knowledge of the disease and its consequences. They should have the ability to provide first-aid measures helping a patient experiencing an epileptic seizure in their clinics. This study aims to evaluate the first-aid knowledge and practices towards patients with epileptic seizures among the dental students in Saudi Arabia. Methods: A cross-sectional study was conducted targeting dental students in Saudi Arabia from 15 September 2022 to 15 December 2022 using convenience sampling. An online questionnaire was sent to the students via social media platforms for data collection. The data analysis was conducted using the Statistical Package for the Social Sciences (SPSS) version 16.0. Results: Of the 499 dental students included, 154 (30.86%) students had ever seen an epileptic patient in the clinics. About 16% of students did not know about performing cardiopulmonary resuscitation (CPR) on patients. The majority (66.5%) would call the ambulance after the patient’s seizure stops. About 82% of students prefer to call an ambulance if the patients face difficulty breathing or waking up after the seizure. More than 60% of students were taking precautions before treating an epilepsy patient. About 58.5% of the students were using local anaesthesia for an epilepsy patient. Nearly 41.9% do not have the confidence to treat an epilepsy patient. About 28.0% would swipe the vagus nerve stimulation (VNS) magnet over the left side of the chest. Of 154 students, who had ever seen epileptic patients, the majority (68.8%) refused to treat patients if they observe noncompliance with medication and follow-up among the patients who had any recent illness or seizures (16.2%). Conclusion: The undergraduate dental students had an intermediate knowledge regarding epilepsy and epileptic seizure first aid. However, some students lacked the confidence to deal with the epileptic cases in their clinics. Educational campaigns on epilepsy and first-aid courses targeting dental students are highly recommended.

Concurrent modulation of the brain-heart pathway: Unveiling potential antagonisms through transcranial magnetic stimulation and transcutaneous auricular vagus nerve stimulation integration

Concurrent modulation of the brain-heart pathway: Unveiling potential antagonisms through transcranial magnetic stimulation and transcutaneous auricular vagus nerve stimulation integration

Insula-Medial Prefrontal Cortex Functional Connectivity Modulated by Transcutaneous Auricular Vagus Nerve Stimulation: An fMRI Study.

Transcutaneous auricular vagus nerve stimulation (taVNS) is an emerging neuromodulation technology that has been reported to be beneficial in the treatment of diseases by several studies, but its exact mechanism of action is still unclear. It has been demonstrated that taVNS can influence interoceptive signals. Notably, the processing of interoceptive signals is directly related to many diseases, such as depression, anxiety, and insomnia. The insula and the medial prefrontal cortex (MPFC) communicate during the bottom-up transmission of taVNS-induced signals, and both play a role in interoceptive signal processing. By focusing on the insula and MPFC, our research pioneers detail the potential interactions between interoceptive signal processing and the neuromodulation effects of taVNS, providing novel insights into the neurobiological mechanisms of taVNS. Two functional connectivity (FC) analyses (region of interest-based and seed-based) were used in this study. We observed that negative connectivity between the insula and the MPFC was significantly weakened following taVNS, while there were no statistical changes in the sham group. Our findings elucidate potential mechanisms linking vagal activity with intrinsic FC among specific brain regions and networks. Specifically, our results indicate that taVNS may enhance the ability to flexibly balance interoceptive awareness and cognitive experiences by modulating the FC between the insula and MPFC. The modulation effects may impact body-brain interactions, suggesting the mechanism of taVNS in therapeutic applications.

A commentary on ‘Transcutaneous auricular vagus nerve stimulation as a novel therapy connecting the central and peripheral systems: a review’

A commentary on ‘Transcutaneous auricular vagus nerve stimulation as a novel therapy connecting the central and peripheral systems: a review’

ID: 337509 A computational model of porcine vagus nerve stimulation and compound action potential sensing

ID: 337509 A computational model of porcine vagus nerve stimulation and compound action potential sensing

Anti-inflammatory Effects of Vagus Nerve Stimulation Are Mediated by the Notch Signaling Pathway during Sepsis-Associated AKI

Anti-inflammatory Effects of Vagus Nerve Stimulation Are Mediated by the Notch Signaling Pathway during Sepsis-Associated AKI

Effects of Non-invasive Vagus Nerve Stimulation on Inflammatory Markers in COVID-19 Patients: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Effects of Non-invasive Vagus Nerve Stimulation on Inflammatory Markers in COVID-19 Patients: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Autonomic Nervous System: A Therapeutic Target for Cardiac End-Organ Damage in Hypertension.

More than 1.5 billion people worldwide have arterial hypertension. Hypertension increases the risks of death and cardiovascular disease, such as atrial fibrillation and heart failure. The autonomic nervous system plays an essential role in hypertension development and disease progression. While lifestyle factors, such as obesity and obstructive sleep apnea, predispose to hypertension by increasing sympathetic activity, hypertension itself maintains the autonomic nervous imbalance, providing the substrate for atrial fibrillation and heart failure. Therefore, autonomic nervous system modulation either by direct targeting or indirect treatment of comorbidities has the potential to treat both hypertension and related atrial and ventricular end-organ damage. We discuss interventions for the modulation of the autonomic nervous system for hypertension and related cardiac end-organ damage, including pharmacological adrenergic beta-receptor blockade, renal denervation, carotid baroreceptor stimulation, low-level vagal stimulation, and ablation of ganglionated plexuses. In summary, the literature suggests that targeting the autonomic nervous system potentially represents a therapeutic approach to prevent atrial and ventricular end-organ damage in patients with hypertension. However, clinical trials specifically designed to test the effect of autonomic modulation on hypertension-mediated cardiac end-organ damage are scarce.

De novo Postoperative Postictal Psychosis Improved with Vagal Nerve Stimulation: A Case Report

Post-ictal psychosis can manifest in patients with intractable temporal lobe epilepsy following temporal lobectomy, presenting with psychiatric symptoms such as hallucinations, depression, and aggressive behavior. This case study details a 43-year-old male with refractory focal epilepsy who developed de novo post-ictal psychosis after undergoing left anterior temporal lobectomy and hippocampal ablation. Initially, the patient achieved seizure control, but later experienced recurrent focal seizures and subsequent post-ictal psychosis, characterized by aggression, paranoia, and hallucinations. Despite multiple hospitalizations and trials of antipsychotic medications, no improvement was observed. Following the placement of a vagal nerve stimulator, the patient’s psychotic episodes ceased, allowing for the discontinuation of antipsychotic medications. This case highlights the critical need for psychiatric monitoring in epilepsy patients post temporal lobectomy and underscores the potential of vagal nerve stimulator in managing peri-ictal psychotic episodes. Further research is essential to elucidate the mechanisms by which vagal nerve stimulator exerts its antipsychotic effects and to establish guidelines for its use in this patient population.