Vagal Stimulation Research Articles

CSP2023: 449 - An international survey of experiences and attitudes towards Transauricular Vagus Nerve Stimulation for people with ME / CFS

CSP2023: 449 - An international survey of experiences and attitudes towards Transauricular Vagus Nerve Stimulation for people with ME / CFS

Transcutaneous auricular vagal nerve stimulation for consciousness recovery in patients with prolonged disorders of consciousness (TAVREC): study protocol for a multicenter, triple-blind, randomized controlled trial in China

IntroductionProlonged disorders of consciousness (pDoC) are a catastrophic condition following brain injury with few therapeutic options. Transcutaneous auricular vagal nerve stimulation (taVNS), a safe, non-invasive intervention modulating thalamo-cortical connectivity and...

Dual-mode electromagnetic-triboelectric-piezoelectric multifunctional self-charging energy system for efficient capture of kinetic energy

This study presents an innovative dual-mode electromagnetic-triboelectric-piezoelectric multifunctional self-charging energy system (MS-CES) that integrates two different operating modes of electromagnetic generators for contact-separation (CS-EMG) and non-contact (NC-EMG), as well as a triboelectric nanogenerator (TENG) and a piezoelectric nanogenerator (PENG). The system has an energy management circuit that efficiently captures and converts kinetic energy from the environment. We investigate the output performance of each unit of the MS-CES under different vibration frequencies and amplitudes. The units work together through a compact mechanical structure design to achieve high voltage output while shortening charging time based on improved space utilization, thus gaining more efficient energy storage. Polyacrylonitrile (PAN) powder and barium titanate (BTO) composite nanofibre membrane (PAN/BTO) as PENG material further enhances the system's output performance. The system provides a continuous power source for the vibration sensors. It enables human-computer interaction with mobile phones and computers via Bluetooth modules, enabling real-time monitoring and analysis of vibration parameters. Furthermore, we have validated the feasibility of using the MS-CES to power a noninvasive vagus nerve stimulation device, providing new technological means for monitoring and treatment in the medical field.

Neurorehabilitation with vagus nerve stimulation: a systematic review.

To systematically review vagus nerve stimulation (VNS) studies to present data on the safety and efficacy on motor recovery following stroke, traumatic brain injury (TBI), and spinal cord injury (SCI). Data sources: PubMed, EMBASE, SCOPUS, and Cochrane. Clinical trials of VNS in animal models and humans with TBI and SCI were included to evaluate the effects of pairing VNS with rehabilitation therapy on motor recovery. Two reviewers independently assessed articles according to the evaluation criteria and extracted relevant data electronically. Twenty-nine studies were included; 11 were animal models of stroke, TBI, and SCI, and eight involved humans with stroke. While there was heterogeneity in methods of delivering VNS with respect to rehabilitation therapy in animal studies and human non-invasive studies, a similar methodology was used in all human-invasive VNS studies. In animal studies, pairing VNS with rehabilitation therapy consistently improved motor outcomes compared to controls. Except for one study, all human invasive and non-invasive studies with controls demonstrated a trend toward improvement in motor outcomes compared to sham controls post-intervention. However, compared to non-invasive, invasive VNS, studies reported severe adverse events such as vocal cord palsy, dysphagia, surgical site infection, and hoarseness of voice, which were found to be related to surgery. Our review suggests that VNS (non-invasive or invasive) paired with rehabilitation can improve motor outcomes after stroke in humans. Hence, VNS human studies are needed in people with TBI and SCI. There are risks related to device implantation to deliver invasive VNS compared to non-invasive VNS. Future human comparison studies are required to study and quantify the efficacy vs. risks of paired VNS delivered via different methods with rehabilitation, which would allow patients to make an informed decision. https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=330653.

Distal Versus Proximal Arm Improvement After Paired Vagus Nerve Stimulation Therapy After Chronic Stroke

ObjectiveTo evaluate differences in upper-extremity (UE) segment-specific (proximal or distal segment) recovery after vagus nerve stimulation (VNS) paired with UE rehabilitation (Paired-VNS) compared with rehabilitation with sham-VNS (Control). We also assessed whether gains in specific UE segments predicted clinically meaningful improvement. DesignThis study reports on a secondary analysis of Vagus nerve stimulation paired with rehabilitation for UE motor function after chronic ischemic stroke (VNS-REHAB), a randomized, triple-blinded, sham-controlled pivotal trial. A Rasch latent regression was used to determine differences between Paired-VNS and Controls for distal and proximal UE changes after in-clinic therapy and 3 months later. Subsequently, we ran a random forest model to assess candidate predictors of meaningful improvement. Each item of the Fugl-Meyer Assessment-Upper Extremity (FMA-UE) and Wolf Motor Function Test (WMFT) was evaluated as a predictor of response to treatment. SettingNineteen stroke rehabilitation centers in the USA and UK. ParticipantsDataset included 108 participants (N=108) with chronic ischemic stroke and moderate-to-severe UE impairments. InterventionsNot applicable. Main Outcome MeasuresFMA-UE and WMFT. ResultsDistal UE improvement was significantly greater in the Paired-VNS group than in Controls immediately after therapy (95% confidence interval, 0.27-0.73; P≤.001) and after 3 months (95% confidence interval, 0.16-0.75; P=.003). Both groups showed similar improvement in proximal UE at both time points. A subset of both distal and proximal items from the FMA-UE and WMFT were predictors of meaningful improvement. ConclusionsPaired-VNS improved distal UE impairment in chronic stroke to a greater degree than intensive rehabilitation alone. Proximal improvements were equally responsive to either treatment. Given that meaningful UE recovery is predicted by improvements across both proximal and distal segments, Paired-VNS may facilitate improvement that is otherwise elusive.

Comparison of the efficacy of auricular vagus nerve stimulation and conventional low back rehabilitation in patients with chronic low back pain

BackgroundIn recent years, human and animal studies have provided increasing evidence that vagus nerve stimulation (VNS) can produce analgesic effects as well as alleviating resistant epilepsy and depression. Our study was designed to compare the efficacy of transcutaneous auricular vagus nerve stimulation with conventional low back rehabilitation in patients with chronic low back pain (CLBP). MethodsSixty patients with LBP were randomly divided into two groups. Group 1 received conventional rehabilitation and home exercise, and Group 2 received transcutaneous auricular VNS and home exercise. Both groups received treatment five days a week for three weeks. Trunk mobility (Modified Schober test, fingertip-to-floor test), muscle strength (CSMI-Cybex Humac-Norm isokinetic dynamometer and Lafayette manual muscle strength measuring device), trunk endurance, balance tests, Visual Analog Scale, Beck Depression Scale, Pittsburgh Sleep Quality Index, Oswestry Disability Index were evaluated. ResultsAt the end of three weeks, within-group assessment results showed positive effects on mobility, functional status, depression and sleep in all groups (p < 0.05). Pain level, endurance time and flexion trunk muscle strength results showed more improvement in Group 2 (p < 0.05). Some parameters of isokinetic lower extremity quadriceps muscle strength and fall risk scores showed a significant improvement in Group 1 (p < 0.05). DiscussionVNS has been observed to be more effective on pain, trunk muscle strength and endurance duration and sleep status. Auricular VNS may be included in the treatment of patients with CLBP in whom conventional physical therapy is inadequate or not applicable.

Transcutaneous Auricular Vagal Nerve Stimulation in Healthy Non-Sedated Horses: A Feasibility Study.

This study aimed to evaluate the feasibility of transcutaneous auricular vagal nerve stimulation (tAVNS) in healthy horses and its effect on heart rate variability (HRV). The study comprised three phases: the selection of mares, their acclimatization to the tAVNS, and the stimulation phase. Stimulation was performed with two electrodes positioned on the right pinna. The settings were 0.5 mA, 250 μs, and 25 Hz for pulse amplitude, pulse width, and pulse frequency, respectively. HRV was analysed before (B1), during (T), and after (B2) the tAVNS. From the 44 mares initially included, only 7 completed the three phases. In these mares, the heart rate (HR) was significantly lower, and frequency domain parameters showed an increased parasympathetic tone in B2 compared with B1. However, in 3/7 mares, the HR was significantly higher during T compared with B1 and B2, compatible with a decreased parasympathetic tone, while in 4/7 mares, the HR was significantly lower and the parasympathetic nervous system index was significantly higher during T and B2 compared with B1. The tAVNS is an economical and easy procedure to perform and has the potential to stimulate vagal activity; however, it was poorly tolerated in the mares included in this study.

A predictive study of the efficacy of transcutaneous auricular vagus nerve stimulation in the treatment of major depressive disorder: An fMRI-based machine learning analysis

BackgroundIn order to improve taVNS efficacy, the usage of fMRI to explore the predictive neuroimaging markers would be beneficial for screening the appropriate MDD population before treatment. MethodsA total of 86 MDD patients were recruited in this study, and all subjects were conducted with the clinical scales and resting-state functional magnetic resonance imaging (fMRI) scan before and after 8 weeks’ taVNS treatment. A two-stage feature selection strategy combining Machine Learning and Statistical was used to screen out the critical brain functional connections (FC) that were significantly associated with efficacy prediction, then the efficacy prediction model was constructed for taVNS treating MDD. Finally, the model was validated by separated the responding and non-responding patients. ResultsThis study showed that taVNS produced promising clinical efficacy in the treatment of mild and moderate MDD. Eleven FCs were selected out and were found to be associated with the cortico-striatal-pallidum-thalamic loop, the hippocampus and cerebellum and the HAMD-17 scores. The prediction model was created based on these FCs for the efficacy prediction of taVNS treatment. The R-square of the conducted regression model for predicting HAMD-17 reduction rate is 0.44, and the AUC for classifying the responding and non-responding patients is 0.856. ConclusionThe study demonstrates the validity and feasibility of combining neuroimaging and machine learning techniques to predict the efficacy of taVNS on MDD, and provides an effective solution for personalized and precise treatment for MDD.

Effects of Auricular Vagus Nerve Stimulation on Cardio-Respiratory Functions After Aerobic Exercise

The aim of our study is to find out whether the return rate of parasympathetic activity (PA) can be accelerated with auricular transcutaneous vagus nerve stimulation (TVNS). Pulmonary function test, ANS activity, pulse and blood pressure measurements were made. Individuals ran for 15 minutes. Those in the TVNS group received 5 minutes of auricular VNS. In the control group, headphones were attached but no current was given. After the end of their procedures, they were compared with pre-exercise. In the TVNS group, the pulse parameter was higher than in the initial measurement (p=0.001). There was a significant (p=0.007) rise in the FEV1 value in the VNS group. The sympathetic nervous system (SNS) index (p&amp;lt;0.05) increased in both groups when compared to the initial measurement, although there was no significant difference in the index values between the groups. The TVNS group showed an increase from the first measurement (p&amp;lt;0.05), but there was no significant difference in the parasympathetic nervous system (PNS) Index between the groups (p&amp;gt;0.05). The groups' values for the first and second measures were equal (p&amp;gt;0.05), and the root mean square of the successive differences (RMSSD) values did not reveal a significant difference. TVNS can improve respiratory parameters in healthy individuals in the acute period after exercise, and it seems that it can also increase activation in both the sympathetic and parasympathetic system. It can be stated that TVNS may lead to variable results in different circumstances in sports

P.036 Vagal nerve stimulation in three cases of continuous spike and wave in slow-wave sleep

Background: Continuous spike and waves during slow-wave sleep (CSWS) is a childhood-onset epileptic encephalopathy that is characterized by clinical seizures, electrical status epilepticus during sleep (ESES), and neurocognitive regression. Early intervention can preserve neurocognitive development, and vagus nerve stimulator (VNS) therapy had positive outcomes in the few previously reported case reports. We present three patients with intractable CSWS unresponsive to medications, who had a positive response to VNS therapy. Methods: Review of clinical records of three pediatric patients diagnosed with CSWS were compared for selected clinical outcomes and electrographic data both prior to and in the years following the initiation of VNS therapy. Results: Three patients now aged 13, 16 and 20 years, were treated with VNS following intolerance and a lack of response to multiple medications (5-9) for CSWS. The ketogenic diet was not an option. The CSWS resolved in all three patients, resulting in improved cognitive function. Patient 3 had resurgence of CSWS on EEG when the VNS settings inadvertently reset to the factory settings and improved with adjustment in the cycling. Conclusions: In patients who are unresponsive to medication, VNS provides an alternative option for resolving CSWS to preserve and, in some cases, potentially restore neurocognitive function.

P.034 Cost-effectiveness of treatment strategies for medically refractory pediatric epilepsy: a systematic review

Background: Medically refractory pediatric epilepsy is a disorder that can cause significant financial and physical burden. Although multiple treatments exist, cost-effectiveness remains unclear. We conducted a systematic review to assess cost-effectiveness of treatments for medically refractory pediatric epilepsy and to summarize key issues and areas for further inquiry. Methods: We searched MEDLINE and 6 other databases up to July 2022. We included partial and full economic evaluations (EEs) on treatments for medically refractory pediatric epilepsy. Pairs of reviewers independently screened the literature, extracted data, and assessed quality using the 24-item Consolidated Health Economic Evaluation Reporting Standards (CHEERS) checklist. We extracted data on study characteristics, health outcomes, model design, costs, and treatment characteristics. Results: We identified 37 eligible studies for analysis, 19 of which were partial EEs and 18 were full EEs. Study quality, outcomes reported, treatment comparators, and factors included in cost calculations were common influential factors in study results. Vagus nerve stimulation and cannabinoid oil were the most consistently cost-effective, in 6 of 7 and 1 of 2 studies, respectively. Other treatments were inconsistently cost-effective. Conclusions: The cost-effectiveness of treatments for medically refractory pediatric epilepsy was not definitive. Consistency in study design and inputs is necessary for future comparison of epilepsy treatment.

Sinus nodal denervation by targeting the superior paraseptal ganglionated plexus: randomized comparison of right-atrial and bi-atrial cardioneuroablation guided by ablation index

Abstract Background Radiofrequency (RF) catheter ablation of superior paraseptal ganglionic plexus (SPSGP) that significantly suppresses the vagal modulation of the sinus node is used for the treatment of functional bradyarrhythmias. A reasonable effect can be achieved by targeting this plexus from the endocardial aspect of both the right and left atria. Purpose The study aimed to compare the acute efficacy of unifocal right-atrial (RA) and comparably extensive bi-atrial (BA) ablation of SPSGP for sinus nodal denervation as assessed by intraprocedural extracardiac vagus nerve stimulation (ECVS). Methods A population of 22 patients (age: 43±9 years, 55% males) undergoing cardioneuroablation (CAN) for functional bradyarrhythmias were randomized 1:1 to two ablation strategies that included: [1] single RF lesion at the very posterior site of the junction between right atrium and superior vena cava with ablation index (AI) = 800 (RA group) and [2] the same but twice smaller RF lesion (AI = 400) complemented with strictly contralateral left-atrial lesion (AI = 400) at the anterior vestibulum of right superior pulmonary vein (BA group). The effect of ablation was investigated by the post-ablation change in sinus rate and the attenuation of the response of the sinus node to ECVS (frequency: 50 Hz, pulse width: 0.05 ms, output: 1 V/kg [&amp;lt;70V], duration: 5 s) via the right internal jugular vein. Results Per-protocol ablation resulted in sinus acceleration by 9±15 bpm vs. 15±16 bpm (P=0.40) in RA vs. BA groups, respectively. Inducible sinus arrests were shortened by 4.7±4.2 s vs. 6.2±1.5 s (P=0.27) and reached the post-ablation level of 3.0±3.7 s vs. 1.0±0.3 s (P=0.08) in RA vs. BA groups, respectively. The results are also displayed in the Figure as medians, interquartile range (boxes) and total range (whiskers). Complete sinus nodal denervation was achieved in 8/11=73% vs. 11/11=100% patients (Fisher exact test P=0.21) in RA vs. BA groups, respectively. Practically 100% denervation efficacy in the BA group contrasted with 3 patients in the RA group in whom ablation had virtually no effect on ECVS-based indices (duration of post-ablation sinus arrests: 11.2, 8.7, and 5.2 s). Acute effects did not change substantially during the waiting period of 20±5 min. Conclusions In this small study with acute procedural endpoints, unifocal RA ablation of SPSGP appeared numerically less effective for sinus nodal denervation than comparably extensive BA ablation although the difference was formally non-significant. The ECVS-based outcome measure was valuable in detecting the differences between study groups. Change in sinus rate was not a reliable marker of sinus nodal denervation.

Cardioneuroablation guided by extracardiac vagal stimulation for cardioinhibitory vasovagal syncope

Abstract Introduction Vasovagal Syncope (VVS) is often linked to abnormal autonomic reflexes, with hypervagotonia identified as a key mechanism, especially in cases with pronounced cardioinhibition. Cardioneuroablation (CNA), which involves radiofrequency ablation of cardiac vagal ganglia, targets parasympathetic hyperactivity, offering a promising treatment for recurrent VVS. This study evaluates the effectiveness and safety of anatomically guided CNA, which may provide an alternative treatment option to pacemaker implantation for younger patients with severe cardioinhibitory VVS. Methods Consecutive patients between January 2019 and October 2023 who underwent CNA at two cardiology centers were enrolled. All patients had a history of recurrent syncope, predominantly cardioinhibitory and unresponsive to conventional treatments. Patients showed no signs of conduction system disease, evidenced by normal rate responses in treadmill stress tests and 24-hour Holter monitoring. Electroanatomic mapping of the left atrium and pulmonary veins was performed. Extracardiac vagal stimulation (ECVS) through the right internal jugular vein, with or without atrial pacing, was utilized to assess baseline responses of the sinus and atrioventricular (AV) nodes. The ablation strategy was tailored based on rhythm disturbances triggered by ECVS, using sequential and anatomically guided ablation of ganglionated parasympathetic plexuses. Radiofrequency ablation, conducted with an irrigated catheter, was guided by the ablation index. Acute success was defined as the absence or significant reduction of cardiac parasympathetic response to ECVS, indicated by the elimination of asystole, severe bradycardia, or AV block. The primary endpoint was syncope recurrence during follow-up. Results The study included 25 patients (16 males; mean age 36 ± 12 years). All had documented cardioinhibition, identified through ECG monitoring (N=12), implantable loop recorders (N=5), or head-up tilt tests (N=8). The average number of syncopal episodes per patient in the year preceding ablation was 2.7, ranging from 1 to 10. Ablation was acutely successful in all cases. Post-ablation, there were no immediate complications related to the procedure, except for one convulsion deemed unrelated. Over a mean follow-up of 17 ± 14 months, 23 patients remained syncope-free. Two patients experienced syncope recurrence; despite undergoing a repeat ablation, they eventually required pacemaker implantation. Conclusion The results of this study suggest that CNA guided by ECVS, may offer a promising treatment for patients with refractory cardioinhibitory VVS. While the procedure showed a high rate of acute success and a notable reduction in syncope recurrence, further research is warranted to fully establish its role as an alternative to pacemaker implantation.

Cardioneuroablation for asystolic reflex syncope with or without the use of extra cardiac vagal stimulation-one year follow-up results

Abstract Background Extra-Cardiac Vagal Stimulation (ECVS) during cardioneuroablation (CNA) has been introduced to confirm total vagal denervation – a clear intra-procedural end-point. However, whether the use of ECVS is associated with better outcome than simple intra-procedural assessment of CNA-induced changes in basic ECG parameters, has not been established. Purpose To compare one-year efficacy of CNA performed with versus without ECVS. Methods This retrospective analysis included 90 patients (age: 37±12 years, 39 males) divided into 2 groups: ECVS(+) (n=41, general anesthesia and total muscle relaxation, settings: 50 Hz, 0.05 ms, 1 V/kg (&amp;lt;70V) for 5 s) and ECVS(-) group (n=49, light sedation). CNA strategy was the same in all patients and was based on presumed anatomical localization of ganglionated plexi, combined with identification of ablation targets at sites with fragmented bipolar atrial electrograms. The end-point in the ECVS (+) group was complete vagal denervation, confirmed by ECVS, whereas in the ECVS (-) group - significant (&amp;gt;30%) acceleration of sinus rate. The primary endpoint was syncope recurrence during one-year follow-up. Results Both groups were comparable concerning clinical and demographic parameters. Primary endpoint occurred in 4 (10%) patients in the ECVS(+) group and in 7 (14%) patients in the ECVS(-) group (p=0.7481) (Figure). No complications were reported. Conclusions These preliminary results suggest that the use of ECVS only slightly improves the one-year CNA efficacy, however, prospective larger studies and longer follow-up are needed to confirm these initial findings.

Transcutaneous auricular vagus nerve stimulation may benefit from the addition of N-acetylcysteine to facilitate motor learning in infants of diabetic mothers failing oral feeds.

This study aims to determine if pretreating with enteral N-acetylcysteine (NAC) improves CNS oxidative stress and facilitates improvement in oromotor skills during transcutaneous auricular nerve stimulation (taVNS) paired with oral feedings in infants of diabetic mothers (IDMs) who are failing oral feeds. We treated 10 IDMs who were gastrostomy tube candidates in an open-label trial of NAC and taVNS paired with oral feeding. NAC (75 or 100 mg/kg/dose) was given by nasogastric (NG) administration every 6 h for 4 days, then combined with taVNS paired with 2 daily feeds for another 14 days. NAC pharmacokinetic (PK) parameters were determined from plasma concentrations at baseline and at steady state on day 4 of treatment in conjunction with magnetic resonance spectroscopic (MRS) quantification of CNS glutathione (GSH) as a marker of oxidative stress. We compared increases in oral feeding volumes before and during taVNS treatment and with a prior cohort of 12 IDMs who largely failed to achieve full oral feeds with taVNS alone. NAC 100 mg/kg/dose every 6 h NG resulted in plasma [NAC] that increased [GSH] in the basal ganglia with a mean of 0.13 ± 0.08 mM (p = 0.01, compared to baseline). Mean daily feeding volumes increased over 14 days of NAC + taVNS compared to the 14 days before treatment and compared to the prior cohort of 12 IDMs treated with taVNS alone. Seven IDMs reached full oral feeds sufficient for discharge, while three continued to have inadequate intake. In IDM failing oral feeds, NAC 100 mg/kg/dose every 6 h NG for 4 days before and during taVNS paired with oral feeding increased CNS GSH, potentially mitigating oxidative stress, and was associated with improving functional feeding outcomes compared to taVNS alone in a prior cohort. This represents a novel approach to neuromodulation and supports the concept that mitigation of ongoing oxidative stress may increase response to taVNS paired with a motor task.

Retention rate of vagus nerve stimulation for the treatment of drug-resistant epilepsy: A single-centre, retrospective study.

The aim of this single-centre, retrospective, observational study was to evaluate long-term effectiveness of vagus nerve stimulation (VNS) in drug-resistant epilepsy (DRE) by using retention rate as a surrogate measure for seizure reduction. We included all patients with DRE, treated at the adult neurology department of the University Hospitals Leuven and who started VNS therapy from January 1, 1994, until May 1, 2021, with follow-up data cutoff on January 1, 2023. Retention rate of VNS was defined as the percentage of patients who maintain VNS at established time points. We estimated cumulative retention rate and battery replacement rate and correlated these with seizure reduction, using Kaplan-Meier analysis. Statistical analysis of potential predictors of VNS outcome (age, sex and epilepsy duration at implantation) was performed using mono- and multivariate analyses. VNS was started in 110 patients with DRE, with a mean follow-up of 8.7 years (SD 6.5). VNS was discontinued in 55 patients (50%), with ineffectiveness as the main reason for discontinuation (98%). The battery was replaced at least once in 42 patients (38%). Estimated retention rates were 70%, 52%, 45% and 33% after 5, 10, 15 and 20 years, respectively. Estimated first battery replacement rates were 16%, 42% and 47% after 5, 10 and 15 years, respectively. Both estimates showed a statistically significant correlation with seizure reduction. No independent predictors of long-term outcome of VNS were found. This is the first long-term study using retention rate of VNS to assess effectiveness. VNS is a well-tolerated therapy, but retention rates decline with long follow-up.

Importance of cardiac-synchronized vagus nerve stimulation parameters on the provoked chronotropic response for different levels of cardiac innervation.

The influence of vagus nerve stimulation (VNS) parameters on provoked cardiac effects in different levels of cardiac innervation is not well understood yet. This study examines the effects of VNS on heart rate (HR) modulation across a spectrum of cardiac innervation states, providing data for the potential optimization of VNS in cardiac therapies. Utilizing previously published data from VNS experiments on six sheep with intact innervation, and data of additional experiments in five rabbits post bilateral rostral vagotomy, and four isolated rabbit hearts with additionally removed sympathetic influences, the study explored the impact of diverse VNS parameters on HR. Significant differences in physiological threshold charges were identified across groups: 0.09 ± 0.06μC for intact, 0.20 ± 0.04μC for vagotomized, and 9.00 ± 0.75μC for isolated hearts. Charge was a key determinant of HR reduction across all innervation states, with diminishing correlations from intact (r = 0.7) to isolated hearts (r = 0.44). An inverse relationship was observed for the number of pulses, with its influence growing in conditions of reduced innervation (intact r = 0.11, isolated r = 0.37). Frequency and stimulation delay showed minimal correlations (r < 0.17) in all conditions. Our study highlights for the first time that VNS parameters, including stimulation intensity, pulse width, and pulse number, crucially modulate heart rate across different cardiac innervation states. Intensity and pulse width significantly influence heart rate in innervated states, while pulse number is key in denervated states. Frequency and delay have less impact impact across all innervation states. These findings suggest the importance of customizing VNS therapy based on innervation status, offering insights for optimizing cardiac neuromodulation.

Efficacy and safety of transcutaneous auricular vagus nerve stimulation (ta-VNS) in the treatment of tinnitus: protocol for an updated systematic review and meta-analysis

IntroductionWith an increasing incidence and significant effects on patients, tinnitus has become a major disease burden. There is a dearth of therapies with established efficacy for tinnitus. Transcutaneous auricular vagus...

Transcutaneous auricular vagus nerve stimulation enhances short-latency afferent inhibition via central cholinergic system activation

The present study examined the effects of transcutaneous auricular vagus nerve stimulation (taVNS) on short-latency afferent inhibition (SAI), as indirect biomarker of cholinergic system activation. 24 healthy adults underwent intermittent taVNS (30 s on/30 s off, 30 min) or continuous taVNS at a frequency of 25 Hz (15 min) along with earlobe temporary stimulation (15 min or 30 min) were performed in random order. The efficiency with which the motor evoked potential from the abductor pollicis brevis muscle by transcranial magnetic stimulation was attenuated by the preceding median nerve conditioning stimulus was compared before taVNS, immediately after taVNS, and 15 min after taVNS. Continuous taVNS significantly increased SAI at 15 min post-stimulation compared to baseline. A positive correlation (Pearson coefficient = 0.563, p = 0.004) was observed between baseline SAI and changes after continuous taVNS. These results suggest that 15 min of continuous taVNS increases the activity of the cholinergic nervous system, as evidenced by the increase in SAI. In particular, the increase after taVNS was more pronounced in those with lower initial SAI. This study provides fundamental insight into the clinical potential of taVNS for cholinergic dysfunction.

Educating the next generation of psychiatrists in the use of clinical neuromodulation therapies: what should all psychiatry residents know?

A variety of neuromodulation treatments are available today and more are on the way, but are tomorrow's psychiatrists prepared to incorporate these tools into their patients' care plans? This article addresses the need for training in clinical neuromodulation for general psychiatry trainees. To ensure patient access to neuromodulation treatments, we believe that general psychiatrists should receive adequate education in a spectrum of neuromodulation modalities to identify potential candidates and integrate neuromodulation into their multidisciplinary care plans. We propose curricular development across the four FDA-cleared modalities currently available in psychiatric practice: electroconvulsive therapy (ECT), transcranial magnetic stimulation (TMS), deep brain stimulation (DBS), and vagus nerve stimulation (VNS). With a focus on psychiatry residency training, the article delineates core learning components for each neuromodulation technique. For each modality, we review the clinical training status, the respective FDA-cleared indications, mechanisms of action, clinical indications and contraindications, adverse effects, informed consent process, dosing considerations, and clinical management guidelines. The approach outlined in this article aims to contribute to the development of a well-rounded generation of psychiatry trainees with the capacity to navigate the growing field of neuromodulation. Whether or not a psychiatrist specializes in delivering neuromodulation therapies themselves, it is incumbent on all psychiatrists to be able to identify patients who should be referred to neuromodulation therapies, and to provide comprehensive patient care before, during and after clinical neuromodulation interventions to optimize outcomes and prevent relapse.