Vagus Nerve Stimulation Therapy Research Articles

Vagus Nerve Stimulation Paired With Rehabilitation for Chronic Stroke: Characterizing Responders.

Implantable vagus nerve stimulation (VNS) paired with volitional upper extremity rehabilitation can improve impairment and function among moderately to severely impaired, chronic stroke survivors. This study is a retrospective analysis of the in-clinic rehabilitation phase of the blinded, placebo-controlled, randomized pivotal VNS-REHAB trial to determine whether dosing parameters during in-clinic paired VNS therapy were associated with responder status and whether covariates might impact that determination. Data were limited to 53 participants in the active VNS group who had received VNS implants prior to undergoing 6weeks of in-clinic rehabilitation paired with VNS. Tasks were standardized across all participants. Dosing parameters included number of stimulations and task time. The primary outcome was the Fugl-Meyer Upper Extremity Assessment (FMA-UE), evaluated at the end of 6weeks (Post-1). Participants were classified a priori as responders based on an improvement of≥6 points on the FMA-UE from baseline to Post-1. Dosing parameters were not associated with FMA-UE responder status at the end of 6weeks. Covariates including age, gender, paretic hand, baseline severity, and chronicity of stroke were also not significant associations of response. While responders to VNS could be defined, therapy dosing and participant attributes did not provide greater specification for association of responder status. Limitations of this study include small sample size and non-linearity of the FMA-UE. Future studies will include reassessing responder categorization using more linear scales and examining stroke lesion characteristics to determine whether these measures are more sensitive to dosing parameters. for more insights from the authors (see the Video, Supplemental Digital Content 1, available at: http://www.w3.org/1999/xlink).

Vagus Nerve Stimulation Therapy in Epilepsy: An Overview of Technical and Surgical Method, Patient Selection, and Treatment Outcomes.

Epilepsy affects over 65 million people worldwide. One-third of people with epilepsy do not respond to medication and may benefit from surgery. Vagus nerve stimulation (VNS) is the first neuromodulation therapy for the treatment of drug-resistant epilepsy. This method is used in combination with anti-seizure medications in adults and in the pediatric population. VNS has also been demonstrated to have benefits for some epilepsy comorbidities, such as depression, and can be used in combination with other neuromodulation therapies in epilepsy. The authors present an overview of VNS physiology, patient selection, surgery and risks, neuromodulation therapy, and application to epilepsy comorbidities.

Complications and Mortality Rate of Vagus Nerve Stimulation for Drug-Resistant Epilepsy.

The goal of this study is to evaluate the complications and mortality associated with vagus nerve stimulation (VNS). We retrospectively reviewed medical records of patients who underwent VNS implantation for the treatment of drug-resistant epilepsy (DRE) between 2000 and 2023. The mean follow-up time was 10.6 years, ranging from three months to 22 years. In total, 55 adult and pediatric patients received VNS therapy with 117 procedures performed over 23 years. The most common early complications were hoarseness and cough which were reported in eight adult patients (6.8%). Four children with intellectual disability (ID) had infection (3.4%), eight patients had lead breakage (6.8%), and two had device migration (1.7%). Fourof all patients (7.3%) demonstrated late complications due to chronic nerve stimulation including vocal cord dysfunction, late-onset severe AV block, and obstructive sleep apnea (OSA). Three patients (5.5%) had VNS deactivated permanently due to complications and/or lack of efficacy. Two patients died from probable sudden unexpected death in epilepsy (SUDEP) with an incidence of 3.4/1000 person-years. VNS therapy is safe over long-term follow-up but not without risks. Most post-operative complications are minor and transient for adults. Children with ID tend to have infection and device migration. Late-onset cardiac complications and OSA can develop in some patients during VNS therapy and should not be overlooked. The SUDEP rate may decrease with VNS therapy over time.

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.

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.

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.

Characterization of an Algorithm for Autonomous, Closed-Loop Neuromodulation During Motor Rehabilitation

Background Recent evidence demonstrates that manually triggered vagus nerve stimulation (VNS) combined with rehabilitation leads to increased recovery of upper limb motor function after stroke. This approach is premised on studies demonstrating that the timing of stimulation relative to movements is a key determinant in the effectiveness of this approach. Objective The overall goal of the study was to identify an algorithm that could be used to automatically trigger VNS on the best movements during rehabilitative exercises while maintaining a desired interval between stimulations to reduce the burden of manual stimulation triggering. Methods To develop the algorithm, we analyzed movement data collected from patients with a history of neurological injury. We applied 3 different algorithms to the signal, analyzed their triggering choices, and then validated the best algorithm by comparing triggering choices to those selected by a therapist delivering VNS therapy. Results The dynamic algorithm triggered above the 95th percentile of maximum movement at a rate of 5.09 (interquartile range [IQR] = 0.74) triggers per minute. The periodic algorithm produces stimulation at set intervals but low movement selectivity (34.05%, IQR = 7.47), while the static threshold algorithm produces long interstimulus intervals (27.16 ± 2.01 seconds) with selectivity of 64.49% (IQR = 25.38). On average, the dynamic algorithm selects movements that are 54 ± 3% larger than therapist-selected movements. Conclusions This study shows that a dynamic algorithm is an effective strategy to trigger VNS during the best movements at a reliable triggering rate.

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.

Compatibility of Standard Vagus Nerve Stimulation and Investigational Microburst Vagus Nerve Stimulation Therapy with fMRI.

Vagus nerve stimulation devices are conditionally approved for MR imaging with stimulation turned off, and the requirement to modify the stimulation settings may be a barrier to scanning in some radiology practices. There is increasing interest in studying the effects of stimulation during MR imaging/fMRI. This study evaluated the safety of standard and investigational microburst vagus nerve stimulation therapies during MR imaging/fMRI. A prospective, multicenter study was conducted in patients with an investigational vagus nerve stimulation device that delivered either standard or investigational microburst vagus nerve stimulation. Thirty participants underwent sequential MR imaging and fMRI scans, encompassing 188 total hours of scan time (62.7 hours with standard vagus nerve stimulation and 125.3 hours with investigational microburst vagus nerve stimulation). No adverse events were reported with active stimulation during MR imaging or during 12 months of follow-up. Our results support the safety of standard and investigational microburst vagus nerve stimulation therapy during MR imaging and fMRI scans.

Vagus nerve stimulation alleviates cardiac dysfunction and inflammatory markers during heart failure in rats

Vagus nerve stimulation (VNS) is under clinical investigation as a therapy for heart failure with reduced ejection fraction (HFrEF). This study aimed to investigate its therapeutic effects on three main components of heart failure: cardiac function, cardiac remodeling and central neuroinflammation using a pressure overload (PO) rat model. Male Sprague-Dawley rats were divided into four groups: PO, PO + VNS, PO + VNS sham, and controls. All rats, except controls, underwent a PO surgery to constrict the thoracic aorta (~50 %) to induce HFrEF. Open loop VNS therapy was continuously administered to PO + VNS rats at 20 Hz, 1.0 mA for 60 days. Evaluation of cardiac function and structure via echocardiograms showed decreases in stroke volume and relative ejection fraction and increases in the internal diameter of the left ventricle during systole and diastole in PO rats (p < 0.05). However, these PO-induced adverse changes were alleviated with VNS therapy. Additionally, PO rats exhibited significant increases in myocyte cross sectional areas indicating hypertrophy, along with significant increases in myocardial fibrosis and apoptosis, all of which were reversed by VNS therapy (p < 0.05). Furthermore, VNS mitigated microglial activation in two central autonomic nuclei: the paraventricular nucleus of the hypothalamus and locus coeruleus. These findings demonstrate that when VNS therapy is initiated at an early stage of HFrEF progression (<10 % reduction in relative ejection fraction), the supplementation of vagal activity is effective in restoring multi organ homeostasis in a PO model.

Characterization of Vagus Nerve Stimulation (VNS) Dose-Dependent Effects on EEG Power Spectrum and Synchronization.

This study investigates the dose-dependent EEG effects of Vagus Nerve Stimulation (VNS) in patients with drug-resistant epilepsy. This research examines how varying VNS intensities impacts EEG power spectrum and synchronization in a cohort of 28 patients. Patients were categorized into responders, partial-responders, and non-responders based on seizure frequency reduction. The methods involved EEG recordings at incremental VNS intensities, followed by spectral and synchronization analysis. The results reveal significant changes in EEG power, particularly in the delta and beta bands across different intensities. Notably, responders exhibited distinct EEG changes compared to non-responders. Our study has found that VNS intensity significantly influences EEG power topographic allocation and brain desynchronization, suggesting the potential use of acute dose-dependent effects to personalized VNS therapy in the treatment of epilepsy. The findings underscore the importance of individualized VNS dosing for optimizing therapeutic outcomes and highlight the use of EEG metrics as an effective tool for monitoring and adjusting VNS parameters. These insights offer a new avenue for developing individualized VNS therapy strategies, enhancing treatment efficacy in epilepsy.

Non-invasive vagus nerve stimulation therapy for severe pharmacoresistant restless legs syndrome: efficacy and tolerance at 6 months

Non-invasive vagus nerve stimulation therapy for severe pharmacoresistant restless legs syndrome: efficacy and tolerance at 6 months

Vagus nerve stimulation allows to cease maintenance electroconvulsive therapy in treatment-resistant depression: a retrospective monocentric case series.

The use of vagus nerve stimulation (VNS) to reduce or stop electroconvulsive therapy (ECT) in treatment-resistant depression seems promising. The aim of this study was to investigate the efficacy of VNS on the reduction of ECT sessions and mood stabilization. We conducted a monocentric retrospective case series of patients who suffered from treatment-resistant depression, treated with ECT and referred to our center for VNS. We investigated the number and the frequency of ECT sessions before and after VNS implantation. Secondary criteria consisted in the Montgomery Åsberg Depression Rating Scale (MADRS) score, number of medical treatments, dosage of the main treatment and length of hospital stays before and after VNS. Additionally, we sent an anonymous survey to psychiatrists and other physicians in our institution to investigate their knowledge and perception of VNS therapy to treat treatment-resistant depression. Seven patients benefited from VNS: six (86%) were female (mean age of 51.7 +/- 16.0 years at surgery), and five (71%) suffered from bipolar depression (three type I and two type II). All patients were followed up at least 2 years post-implantation (range: 27-68 months). Prior to VNS, six patients were treated by maintenance ECT. After VNS, three (43%) patients did not require maintenance ECT anymore, and three (43%) patients required less frequent ECT session with a mean 14.7 +/- 9.8 weeks between sessions after VNS vs. 2.9 +/- 0.8 weeks before VNS. At last follow-up, 4 (57%) patients had stopped ECT. Five (71%) patients implanted with VNS were good responders (50% decrease relative to baseline MADRS). According to the survey, psychiatrists had a significantly better perception and knowledge of ECT, but a worse perception and knowledge of VNS compared to other physicians. VNS is a good option for treatment-resistant depression requiring maintenance ECT dependence. Larger on-going studies will help broaden the implanted patients while strengthening psychiatrists' knowledge on this therapy.

Vagus Nerve Stimulation Therapy for Drug-Resistant Epilepsy in Children—A Literature Review

Vagus nerve stimulation (VNS) is a palliative treatment for drug-resistant epilepsy (DRE) that has been in use for over two decades. VNS suppresses epileptic seizures, prevents emotional disorders, and improves cognitive function and sleep quality, a parallel effect associated with the control of epileptic seizures. The seizure suppression rate with VNS increases monthly to annually, and the incidence of side effects reduces over time. This method is effective in treating DRE in children as well as adults, such as epilepsy associated with tuberous sclerosis, Dravet syndrome, and Lennox–Gastaut syndrome. In children, it has been reported that seizures decreased by &gt;70% approximately 8 years after initiating VNS, and the 50% responder rate was reported to be approximately 70%. VNS regulates stimulation and has multiple useful systems, including self-seizure suppression using magnets, additional stimulation using an automatic seizure detection system, different stimulation settings for day and night, and an automatic stimulation adjustment system that reduces hospital visits. VNS suppresses seizures and has beneficial behavioral effects in children with DRE. This review describes the VNS system, the mechanism of the therapeutic effect, the specific stimulation adjustment method, antiepileptic effects, and other clinical effects in patients with childhood DRE.

Vagus nerve stimulation: Potential for treating chronic wounds.

Vagus nerve stimulation (VNS) has been approved as a treatment for various conditions, including drug-resistant epilepsy, migraines, chronic cluster headaches and treatment-resistant depression. It is known to have anti-inflammatory, anti-nociceptive and anti-adrenergic effects, and its therapeutic potential for diverse pathologies is being investigated. VNS can be achieved through invasive (iVNS) or non-invasive (niVNS) means, targeting different branches of the vagus nerve. iVNS devices require surgical implantation and have associated risks, while niVNS devices are generally better tolerated and have a better safety profile. Studies have shown that both iVNS and niVNS can reduce inflammation and pain perception in patients with acute and chronic conditions. VNS devices, such as the VNS Therapy System and MicroTransponder Vivistim, have received Food and Drug Administration approval for specific indications. Other niVNS devices, like NEMOS and gammaCore, have shown effectiveness in managing epilepsy, pain and migraines. VNS has also demonstrated potential in autoimmune disorders, such as rheumatoid arthritis and Crohn's disease, as well as neurological disorders like epilepsy and migraines. In addition, VNS has been explored in cardiovascular disorders, including post-operative atrial fibrillation and myocardial ischemia-reperfusion injury, and has shown positive outcomes. The mechanisms behind VNS's effects include the cholinergic anti-inflammatory pathway, modulation of cytokines and activation of specialised pro-resolving mediators. The modulation of inflammation by VNS presents a promising avenue for investigating its potential to improve the healing of chronic wounds. However, more research is needed to understand the specific mechanisms and optimise the use of VNS in wound healing. Ongoing clinical trials may support the use of this modality as an adjunct to improve healing.

Effectiveness of transcutaneous vagus nerve stimulation (tVNS) on salicylate-induced tinnitus

IntroductionTinnitus is the most common symptom of auditory system disorders. It affects the quality of life of millions of people, but it is still incurable in most cases. Vagus nerve stimulation (VNS) therapy is a potential new treatment for subjective tinnitus. In this study, transcutaneous vagus nerve stimulation (tVNS) combined with tones was utilized to treat salicylate-induced tinnitus since salicylate is a reliable and convenient approach for rapidly inducing tinnitus. MethodsWistar rats were divided into acoustic stimulation alone (AS, n = 6), tVNS alone (n = 6), and tVNS with AS (n = 6) groups for behavioral and electrophysiological tests. They were assessed by auditory brainstem response (ABR), prepulse inhibition (PPI), gap prepulse inhibition of the acoustic startle (GPIAS), social interactions, and aggressive behavior tests at baseline and seven days’ post-salicylate (175 mg/kg, twice a day) injection. ResultsThe inhibition percentage of the GPIAS test was significantly reduced post-salicylate injection in the tVNS and AS alone groups, while it was not significant in the tVNS with AS group. There was no significant difference in the mean percentage of the GPIAS test between the tVNS groups (with or without AS) after salicylate injections. Social interactions were significantly different in the AS alone group pre- and post-salicylate injections, but they were not significant in other groups. Moreover, the results of aggressive behavior tests showed significantly increased post-salicylate injections in the AS alone group, while they were not significant in the tVNS groups (with or without AS). ConclusionsThe current study revealed that the application of tVNS alone produced improved social interaction and mood and alleviated salicylate-induced tinnitus severity. Moreover, combining tVNS with acoustic stimulation can prevent salicylate-induced tinnitus.

Vagus nerve stimulation for the treatment of narcolepsy

Background and objectiveNo study on neurostimulation in narcolepsy is available until now. Arousal- and wake-promoting effects of vagus nerve stimulation (VNS) have been demonstrated in animal experiments and are well-known as side effects of VNS therapy in epilepsy and depression. The objective was to evaluate the therapeutic effect of VNS on daily sleepiness and cataplexies in narcolepsy. MethodsIn our open-label prospective comparative study, we included narcolepsy patients who were treated with VNS because of depression or epilepsy and compared them to controls without narcolepsy treated with VNS for depression or epilepsy (18 patients in each group, aged 31.5 ± 8.2 years). We evaluated daily sleepiness (Epworth Sleepiness Scale, ESS) and the number of cataplexies per week before the implantation of VNS and at three and six month follow-ups. ResultsCompared to baseline (ESS: 15.9 ± 2.5) patients with narcolepsy showed a significant improvement on ESS after three months (11.2 ± 3.3, p < 0.05) and six months (9.6 ± 2.8, p < 0.001) and a trend to reduction of cataplexies. No significant ESS-improvement was observed in patients without narcolepsy (14.9 ± 3.9, 13.6 ± 3.7, 13.2 ± 3.5, p = 0.2 at baseline, three and six months, correspondingly). Side effects did not differ between the study groups. ConclusionIn this first evaluation of VNS in narcolepsy, we found a significant improvement of daily sleepiness due to this type of neurostimulation. VNS could be a promising non-medical treatment in narcolepsy.

Identification of metabolic biomarkers of chronic vagus nerve stimulation (VNS) in subjects with drug-resistant epilepsy (DRE).

Neuromodulation by means of vagus nerve stimulation (VNS) therapy, reduces seizure frequency and improves quality of life in subjects with drug-resistant epilepsy (DRE), yet its molecular mechanism remains unclear. This study investigates the impact of chronic VNS on lipid bioactive metabolites and fatty acids (FA) in the plasma and red blood cells of seven subjects with DRE. By measuring expression levels of peroxisome proliferator-activated receptor α (PPARα) and sirtuin1 (SIRT1) genes-key regulators in energy and lipid metabolism-and lipid profiles before and after various stages of VNS, this study identifies potential mechanisms by which VNS may reduce seizure frequency. Blood samples collected before VNS device implantation, after acute VNS stimulus, and following gradual intensity increments up to therapeutic levels revealed that VNS increases SIRT1 and PPARα expression and erythrocyte concentrations of PPARα ligands. Additionally, we observe reduced de novo lipogenesis biomarkers in erythrocytes, indicating that VNS may influence systemic lipid and energy metabolism. Our findings suggest that VNS could enhance neuronal function by modulating energy metabolism, thus potentially reducing seizure frequency in subjects with DRE. Future research targeting SIRT1 and PPARα may provide innovative therapeutic strategies for managing DRE. Plain Language Summary: The exact mechanism of VNS is still unknown. This study investigated the effects of VNS Therapy on energetic metabolism, suggesting possible novel biomarkers for DRE subjects and neuromodulation therapies.

Vagus Nerve Stimulation and Sacral Nerve Stimulation for Inflammatory Bowel Disease: A Systematic Review.

In this systematic review, we assessed the efficacy, potential mechanisms, and safety of two neuromodulation therapies in patients with inflammatory bowel disease (IBD), including Crohn's disease and ulcerative colitis. The first therapy is vagus nerve stimulation (VNS) utilizing implantable or transcutaneous electrodes, and the second is sacral nerve stimulation (SNS) using implantable or percutaneous electrodes. We conducted a systematic literature review following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The PubMed database was comprehensively searched, and studies were rigorously assessed for inclusion and exclusion criteria. Our analysis encompassed five clinical studies, three on VNS and two on SNS. Most investigated studies demonstrated significant beneficial effects on IBD symptoms, including disease activity, severity of intestinal lesions, and intestinal pain. When evaluating the impact on key IBD pathophysiologies, both VNS and SNS exhibited trends toward reducing biomarkers of intestinal mucosal inflammation and mitigating sympathetic dominance. Importantly, none of the evaluated neuromodulation methods resulted in long-term adverse effects. Cumulative evidence from the evaluated studies indicates that VNS and SNS therapies effectively alleviate IBD symptoms and may hold promise in addressing the underlying pathophysiologies of IBD, including intestinal mucosal inflammation and sympathetic dominance. Consequently, they represent valuable options for individualized IBD treatment.

Quantifying the effects of vagus nerve stimulation on gastric myoelectric activity in ferrets using an interpretable machine learning approach.

Vagus nerve stimulation (VNS) is a potential treatment option for gastrointestinal (GI) diseases. The present study aimed to understand the physiological effects of VNS on gastrointestinal (GI) function, which is crucial for developing more effective adaptive closed-loop VNS therapies for GI diseases. Electrogastrography (EGG), which measures gastric electrical activities (GEAs) as a proxy to quantify GI functions, was employed in our investigation. We introduced a recording schema that allowed us to simultaneously induce electrical VNS and record EGG. While this setup created a unique model for studying the effects of VNS on the GI function and provided an excellent testbed for designing advanced neuromodulation therapies, the resulting data was noisy, heterogeneous, and required specialized analysis tools. The current study aimed at formulating a systematic and interpretable approach to quantify the physiological effects of electrical VNS on GEAs in ferrets by using signal processing and machine learning techniques. Our analysis pipeline included pre-processing steps, feature extraction from both time and frequency domains, a voting algorithm for selecting features, and model training and validation. Our results indicated that the electrophysiological changes induced by VNS were optimally characterized by a distinct set of features for each classification scenario. Additionally, our findings demonstrated that the process of feature selection enhanced classification performance and facilitated representation learning.