Vagal Stimulation Research Articles

Sinus arrest during thoracic drain placement in a dog

AbstractA 5‐year‐old female neutered Podenco Canario dog presented with a moderate pleural effusion and subsequently underwent placement of bilateral thoracic drains. Pre‐medication consisted of intravenous medetomidine (2 µg/kg) and methadone (0.2 mg/kg), followed by induction with propofol (2.1 mg/kg, via intravenous administration). Anaesthesia was maintained with isoflurane in 100% oxygen. The modified Seldinger technique was used to place bilateral small‐bore, wire‐guided thoracic drains. During placement of the first chest drain, the dog developed sinus arrest. It is suspected that there was direct vagal nerve stimulation by the guide wire during placement, leading to severe bradycardia and subsequent sinus arrest that was responsive to atropine. It is important to note that the definitive cause of the transient cardiac arrest could not be ascertained. It is possible that this is a rare complication of thoracic drain placement, warranting further research in this area.

Efficacy and acceptability of noninvasive brain stimulation for treating posttraumatic stress disorder symptoms: A network meta-analysis of randomized controlled trials.

Despite its high lifetime prevalence rate and the elevated disability caused by posttraumatic stress disorder (PTSD), treatments exhibit modest efficacy. In consideration of the abnormal connectivity between the dorsolateral prefrontal cortex (DLPFC) and amygdala in PTSD, several randomized controlled trials (RCTs) addressing the efficacy of different noninvasive brain stimulation (NIBS) modalities for PTSD management have been undertaken. However, previous RCTs have reported inconsistent results. The current network meta-analysis (NMA) aimed to compare the efficacy and acceptability of various NIBS protocols in PTSD management. We systematically searched ClinicalKey, Cochrane Central Register of Controlled Trials, Embase, ProQuest, PubMed, ScienceDirect, Web of Science, and ClinicalTrials.gov to identify relevant RCTs. The targeted RCTs was those comparing the efficacy of NIBS interventions, such as transcranial direct current stimulation (tDCS), repetitive transcranial magnetic stimulation (rTMS), and transcutaneous cervical vagal nerve stimulation, in patients with PTSD. The NMA was conducted using a frequentist model. The primary outcomes were changes in the overall severity of PTSD and acceptability (to be specific, rates of dropouts for any reason). We identified 14 RCTs that enrolled 686 participants. The NMA demonstrated that among the investigated NIBS types, high-frequency rTMS over bilateral DLPFCs was associated with the greatest reduction in overall PTSD severity. Further, in comparison with the sham controls, excitatory stimulation over the right DLPFC with/without excitatory stimulation over left DLPFC were associated with significant reductions in PTSD-related symptoms, including depression and anxiety symptoms, and overall PTSD severity. This NMA demonstrated that excitatory stimulation over the right DLPFC with or without excitatory stimulation over left DLPFC were associated with significant reductions in PTSD-related symptoms. PROSPERO CRD42023391562.

First outcomes of a therapeutic platform for drug resistant epilepsy based on transcutaneous electrical vagus nerve stimulation

Aim: The aim of this paper is to discuss the main features and first outcomes of a therapeutic platform proposed to implement a public health therapeutic service for patients suffering refractory epilepsy. Methods: The proposal is a three-layer system composed by a new portable therapy device and two software applications. The therapy is transcutaneous electrical vagus nerve stimulation, known as tVNS. The primary layer is composed of tVNS devices, configured for each patient according to the instructions provided by the specialists. The middle layer is named “hospital data collector” (HDC), its main tasks are the patient enrollment, the device setup, and the database maintenance to store therapeutic parameters and session events together with the information cited previously. Each hospital center runs a HDC that is connected to a cloud application named “system cloud application (SCA)” which concentrates all the data supplied by the HDCs. Artificial intelligence methods are integrated in the SCA to predict the treatment effectiveness for every new patient based on the accumulated knowledge from the enrolled previously. Results: A version of the proposed system is running at the Institute of Neurology and Neurosurgery. The sensitivity of the therapeutic device with the proposed treatment protocol reaches 83.33% in the 18-patient pilot trial carried out. Conclusions: The proposed approach seems a useful therapeutic tool based on the pilot trial outcomes. The developed device is comfortable and suitable for the intended use. The proposed system has created the essential conditions to feed and grow a knowledge, a basic element to predict the treatment effectiveness for each new patient. It is a promising option for a refractory epilepsy therapy service.

Transcutaneous auricular vagus nerve stimulation modifies cortical excitability in middle-aged and older adults.

There is a growing interest in the clinical application of transcutaneous auricular vagus nerve stimulation (taVNS). However, its effect on cortical excitability, and whether this is modulated by stimulation duration, remains unclear. We evaluated whether taVNS can modify excitability in the primary motor cortex (M1) in middle-aged and older adults and whether the stimulation duration moderates this effect. In addition, we evaluated the blinding efficacy of a commonly reported sham method. In a double-blinded randomized cross-over sham-controlled study, 23 healthy adults (mean age 59.91 ± 6.87 years) received three conditions: active taVNS for 30 and 60 min and sham for 30 min. Single and paired-pulse transcranial magnetic stimulation was delivered over the right M1 to evaluate motor-evoked potentials. Adverse events, heart rate and blood pressure measures were evaluated. Participant blinding effectiveness was assessed via guesses about group allocation. There was an increase in short-interval intracortical inhibition (F = 7.006, p = .002) and a decrease in short-interval intracortical facilitation (F = 4.602, p = .014) after 60 min of taVNS, but not 30 min, compared to sham. taVNS was tolerable and safe. Heart rate and blood pressure were not modified by taVNS (p > .05). Overall, 96% of participants detected active stimulation and 22% detected sham stimulation. taVNS modifies cortical excitability in M1 and its effect depends on stimulation duration in middle-aged and older adults. taVNS increased GABAAergic inhibition and decreased glutamatergic activity. Sham taVNS protocol is credible but there is an imbalance in beliefs about group allocation.

Long-Term Immunomodulatory Impact of VNS on Peripheral Cytokine Profiles and Its Relationship with Clinical Response in Difficult-to-Treat Depression (DTD)

Vagus nerve stimulation (VNS) represents a long-term adjunctive treatment option in patients with difficult-to-treat depression (DTD). Anti-inflammatory effects have been discussed as a key mechanism of action of VNS. However, long-term investigations in real-world patients are sparse. In this naturalistic observational study, we collected data on cytokines in peripheral blood in n = 6 patients (mean age 47.8) with DTD and VNS treatment at baseline and at 6 months follow-up. We have identified clusters of peripheral cytokines with a similar dynamic over the course of these 6 months using hierarchical clustering. We have investigated cytokine changes from baseline to 6 months as well as the relationship between the cytokine profile at 6 months and long-term response at 12 months. After 6 months of VNS, we observed significant correlations between cytokines (p < 0.05) within the identified three cytokine-pairs which were not present at baseline: interleukin (IL)-6 and IL-8; IL-1β and TNF-α; IFN-α2 and IL-33. At 6 months, the levels of all the cytokines of interest had decreased (increased in non-responders) and were lower (5-534 fold) in responders to VNS than in non-responders: however, these results were not statistically significant. VNS-associated immunomodulation might play a role in long-term clinical response to VNS.

Effect of transcranial direct current stimulation combined with transcutaneous auricular vagus nerve stimulation on poststroke cognitive impairment: a study protocol for a randomised controlled trial

IntroductionPoststroke cognitive impairment is a common complication in stroke survivors, seriously affecting their quality of life. Therefore, it is crucial to improve cognitive function of patients who had a stroke....

Clinical-functional correlation with brain volumetry in severe perinatal asphyxia: a case report

BackgroundHypoxic-ischemic encephalopathy (HIE) appears in neurological conditions where some brain areas are likely to be injured, such as deep grey matter, basal ganglia area, and white matter subcortical periventricular áreas. Moreover, modeling these brain areas in a newborn is challenging due to significant variability in the intensities associated with HIE conditions. This paper aims to evaluate functional measurements and 3D machine learning models of a given HIE case by correlating the affected brain areas with the pathophysiology and clinical neurodevelopmental.Case presentationA comprehensive analysis of a term infant with perinatal asphyxia using longitudinal 3D brain information from Machine Learning Models is presented. The clinical analysis revealed the perinatal asphyxia diagnosis with APGAR <5 at 5 and 10 minutes, umbilical arterial pH of 7.0 BE of -21.2 mmol / L), neonatal seizures, and invasive ventilation mechanics. Therapeutic interventions: physical, occupational, and language neurodevelopmental therapies. Epilepsy treatment: vagus nerve stimulation, levetiracetam, and phenobarbital. Furthermore, the 3D analysis showed how the volume decreases due to age, exhibiting an increasing asymmetry between hemispheres. The results of the basal ganglia area showed that thalamus asymmetry, caudate, and putamen increase over time while globus pallidus decreases. Clinical outcomes: spastic cerebral palsy, microcephaly, treatment-refractory epilepsy.ConclusionsSlight changes in the basal ganglia and cerebellum require 3D volumetry for detection, as standard MRI examinations cannot fully reveal their complex shape variations. Quantifying these subtle neurodevelopmental changes helps in understanding their clinical implications. Besides, neurophysiological evaluations can boost neuroplasticity in children with neurological sequelae by stimulating new neuronal connections.

Vagus Nerve Stimulation for Epilepsy During Pregnancy (P7-1.012)

Vagus Nerve Stimulation for Epilepsy During Pregnancy (P7-1.012)

Efficiency and Safety of Vagus Nerve Stimulation in Intractable Epilepsy: An Updated Systematic Review and Meta-analysis (P7-1.014)

Efficiency and Safety of Vagus Nerve Stimulation in Intractable Epilepsy: An Updated Systematic Review and Meta-analysis (P7-1.014)

Research progress on the improvement of cardiovascular diseases through the autonomic nervous system regulation of the NLRP3 inflammasome pathway

Cardiovascular disease stands as a leading global cause of mortality. Nucleotide-binding Oligomerization Domain-like Receptor Protein 3 (NLRP3) inflammasome is widely acknowledged as pivotal factor in specific cardiovascular disease progression, such as myocardial infarction, heart failure. Recent investigations underscore a close interconnection between autonomic nervous system (ANS) dysfunction and cardiac inflammation. It has been substantiated that sympathetic nervous system activation and vagus nerve stimulation (VNS) assumes critical roles withinNLRP3 inflammasome pathway regulation, thereby contributing to the amelioration of cardiac injury and enhancement of prognosis in heart diseases. This article reviews the nexus between NLRP3 inflammasome and cardiovascular disorders, elucidating the modulatory functions of the sympathetic and vagus nerves within the ANS with regard to NLRP3 inflammasome. Furthermore, it delves into the potential therapeutic utility of NLRP3 inflammasome to be targeted by VNS. This review serves as a valuable reference for further exploration into the potential mechanisms underlying VNS in the modulation of NLRP3 inflammasome.

Neurostimulation for treatment of post-stroke impairments.

Neurostimulation, the use of electrical stimulation to modulate the activity of the nervous system, is now commonly used for the treatment of chronic pain, movement disorders and epilepsy. Many neurostimulation techniques have now shown promise for the treatment of physical impairments in people with stroke. In 2021, vagus nerve stimulation was approved by the FDA as an adjunct to intensive rehabilitation therapy for the treatment of chronic upper extremity deficits after ischaemic stroke. In 2024, pharyngeal electrical stimulation was conditionally approved by the UK National Institute for Health and Care Excellence for neurogenic dysphagia in people with stroke who have a tracheostomy. Many other approaches have also been tested in pivotal device trials and a number of approaches are in early-phase study. Typically, neurostimulation techniques aim to increase neuroplasticity in response to training and rehabilitation, although the putative mechanisms of action differ and are not fully understood. Neurostimulation techniques offer a number of practical advantages for use after stroke, such as precise dosing and timing, but can be invasive and costly to implement. This Review focuses on neurostimulation techniques that are now in clinical use or that have reached the stage of pivotal trials and show considerable promise for the treatment of post-stroke impairments.

Medical Devices for the Management of Patients with Epilepsy

The increasing number of medical devices developed and marketed towards management of patients with epilepsy reflects the growing interest in translating technological advances and knowledge about epilepsy into better healthcare for this population. The objective of this narrative literature review is to analyze the available options of medical devices for detecting, treating, and recording epileptic seizures, and their potential clinical application. The included articles were selected from the PubMed database using the query “(Epilepsy[MeSH Terms]) AND (SUDEP)) AND (Medical Device)) AND (English[Language])”. The detection of epileptic seizures is essential for early intervention and to optimize the therapy for each patient. In outpatient settings, this detection is further challenging due to their unpredictability. Traditionally electroencephalography is the direct detection method used in a hospital environment. Indirect methods, such as electrocardiogram, photoplethysmography, oximeter, electrodermal activity, accelerometer, and electromyography, have shown potential for detecting seizures in the outpatient setting. Several medical devices have been developed based on the mentioned methods, with the aim of providing patients with solutions they can use in their daily lives. Behind-the-ear EEG, wristbands, armbands and bed sensors are some of the designs available. Equipped with different features, these devices can answer the need for early seizure detection and improve patients’ and caregivers’ quality of life. There are also devices available for the treatment of epileptic seizures. Through neuromodulation techniques such as vagus nerve stimulation, deep brain stimulation, and responsive neurostimulation, these devices are presented as solutions for patients with refractory epilepsy not eligible for ressective surgery. Patients with epilepsy have several apps available online for proper recording of seizures. These apps help doctors optimize therapy based on clinical evolution. The wide range of devices available creates the opportunity to personalize the approach to patient’s specific needs. Understanding each device’s characteristics can help clinicians improve management of patients with epilepsy.

241 Disparities in Access to Epilepsy Surgery Care in Children With Drug Resistant Epilepsy: Implications For Long-Term Survival Outcomes

INTRODUCTION: Our recent publication in Lancet Child and Adolescent Health examined long-term survival rates for pediatric patients with drug-resistant epilepsy (DRE) treated with antiseizure medications (ASMs) only, ASMs plus vagus nerve stimulation (VNS), and ASMs plus cranial epilepsy surgery in a large United States (US) administrative database. The difference in survival probabilities was statistically significant (p &lt; .001). Adjusted probabilities of survival beyond 10 years were 89.27% for the ASMs only cohort (95%CI, 87.71%-90.85%), 92.65% for VNS cohort (95%CI, 90.62%-94.72%), and 98.45% for cranial surgery cohort (95%CI, 97.53%-99.38%). METHODS: Patients aged 0-17 years with DRE between 01/01/2004-31/12/2020 were identified from the Pediatric Health Information System data set across 49 US pediatric hospitals. Patients treated with ASMs only or ASMs plus VNS or ASMs plus cranial epilepsy surgery were included. Chi-square tests determined associations between treatment time and preoperative factors such as treatment type, age, sex, race/ethnicity, insurance type, geographic region, epilepsy type, and medical complexity (presence of pediatric complex chronic conditions [PCCCs]). RESULTS: 18,292 total patients were included: 10,240 patients treated with ASMs only, 5,019 patients with ASMs plus VNS, 3,033 patients with ASMs plus cranial epilepsy surgery. There were significant differences in age, geographic region, race/ethnicity, presence of PCCCs, diagnosis, and insurance type (p &lt; 0.001). Those treated surgically, either with VNS implantation or cranial epilepsy surgery, were 2 years older than ASMs only. ASMs only patients were less ikely to be reported as non-Hispanic white (51.78%), less likely have a focal/partial epilepsy diagnosis (8.74%), and less likely carry private medical insurance (35.82%). CONCLUSIONS: We show a link of disparities in pediatric epilepsy surgery care and survival outcomes. Focused strategies are needed to expand access to comprehensive epilepsy care with neurosurgical evaluation and offerings when appropriate.

Neuromodulation in Behavioral and Psychological Symptoms of Dementia (BPSD)

Behavioral and psychological symptoms of dementia (BPSD) affect up to 90% of people living with dementia and include agitation, hallucinations, delusions, sleep or mood changes. BPSD are challenging to treat and there are limited safe and effective pharmacologic treatments. Electroconvulsive therapy (ECT), transcranial magnetic stimulation (TMS), Deep Brain Stimulation (DBS), Vagal nerve stimulation (VNS), ketamine, and cannabinoids are interventions that have proven effectiveness for other psychiatric conditions including depression and psychosis. More recently, many of these have also been investigated for the treatment of BPSD.This presentation will review the current evidence for using ECT, TMS, ketamine, DBS, VNS, and cannabinoids for the treatment of BPSD. Out of these techniques, ECT has been the most studied and shows some benefit for the treatment of BPSD. TMS has also been studied in over 10 trials and most of these studies show an improvement in BPSD. The effect of TMS on apathy in dementia has been examined in multiple studies, the majority of which have shown benefit. DBS has shown some benefit for improving hallucinations in Parkinson disease dementia in one small RCT of six patients, and the procedure was well tolerated. VNS for BPSD has not been studied. Ketamine, in evidence from heterogeneous case reports, has shown to target three distinct behavioral disturbances, agitation, catatonia and depression, in dementia.Cannabinoids, particularly dronabinol and nabilone, have also been investigated in a number of RCTs and show mixed results for treating agitation in dementia. Sedation was the most common side effect reported but often did not result in discontinuation of therapy.In conclusion, neuromodulation has increasing evidence for the treatment of BPSD and most studies show good safety profiles. Larger and more rigorous trials are needed to further investigate the effectiveness, safety, and practicality of these interventions in this population. This presentation will summarize the effects of these various interventions, their side effects, doses used, and durations of treatment.

137 Light-mediated Vagus Nerve Stimulation Inhibits Pro-inflammatory Cytokine Production in Acute Endotoxemia

INTRODUCTION: Vagus nerve stimulation (VNS) is a form of neuromodulation being explored to treat chronic inflammatory conditions by activating the inflammatory reflex, an arc reducing proinflammatory cytokine release through efferent cholinergic signaling. Current VNS approaches are primarily invasive and use electricity, but alternatives may improve vagal fiber specificity and eliminate surgical risks. Red-light optogenetics, a biological tool utilizing red light-activatable channelrhodopsins (ReaChR), can selectively activate genetically-modified neurons transdermally with light. Here, we show that ReaChR activation of cholinergic vagal fibers reduces cytokine production in a model of acute inflammation. METHODS: Vagus nerve cholinergic fibers were selectively activated using ReaChR expressed on choline acetyltransferase-expressing (ChAT) fibers in transgenic ChAT-ReaChR mice. Sensory afferent vagal fibers were activated in a separate cohort of transient receptor potential vanilloid subfamily member 1 (TRPV1)-ReaChR mice. Lipopolysaccharide (LPS) was injected intraperitoneally under anesthesia to induce acute endotoxemia, as measured by elevated tumor necrosis factor-alpha (TNFa). A 635nm fiber optic was targeted onto an isolated, cervical vagus for optogenetic VNS post-LPS administration. RESULTS: Selective ReaChR activation of cholinergic fibers in the cervical vagus nerve stimulates the inflammatory reflex to inhibit splenic TNFa production to bacterial LPS (ChAT-ReaChR: 1.27 ± 1.44 pg/ug; control: 4.26 ± 0.97 pg/ug, p &lt; 0.001), but no significant differences were observed in serum (ChAT-ReaChR: 538 ± 216 pg/ml; littermate: 447 ± 206 pg/ml, p = 0.81). In contrast to efferent activation, ReaChR stimulation of afferent subsets (TRPV1+) failed to show cytokine regulation in splenic nor in serum .Approximate 20% baseline heart rate drop was seen during both ChAT+ and TRPV1+ fiber excitation, but only cholinergic activation sustained bradycardia throughout the stimulation period. CONCLUSIONS: Red-light optogenetic activation of cholinergic vagal fibers reduces splenic inflammatory cytokine production in murine endotoxemia and holds potential as a non-invasive, light-mediated VNS approach.

488 National Trends in the Treatment of Refractory Epilepsy: A Nationwide Inpatient SampleBased Propensity Score Matching Analysis

INTRODUCTION: Epilepsy is considered one of the most prevalent and severe chronic neurological disorders worldwide. METHODS: Using the NIS database from 2010-2020, patients with focal intractable epilepsy who underwent Laser Interstitial Thermal Therapy (LITT), open surgical resection, Vagal Nerve Stimulation (VNS), or Responsive Neuro-Stimulation (RNS) were identified. Outcomes such as discharge disposition, length of stay, complications, and mortality were analyzed. Propensity score matching was used to compare outcomes between pre-pandemic and pandemic (first peak of COVID-19) periods. RESULTS: A total of 33,969 focal intractable epilepsy cases were found with 3,343 patients receiving different treatment modalities including surgical resection (77.83%), VNS (8.21%), RNS (7.83%), and LITT (6.13%). Most of these patients (89.32%) were treated during the pre-COVID pandemic era (2010-2019), while a minority (10.67%) underwent treatment during the COVID pandemic (2020). Among all treated patients, 2.7% had postoperative neurologic complications and 0.3% died. After propensity-score matching, 658 patients (329 in each group) were included. During the pandemic period, 7% presented with preoperative paralysis/aphasia, and 0.6% had subarachnoid hemorrhages, which was significantly higher than the pre-pandemic rate (1.8%; p &lt; 0.001). There were no statistical differences in neurologic complications, discharge disposition, or LOS between the pre-pandemic and pandemic periods. On the other hand, the mortality rate was slightly higher during the pandemic compared to the pre-pandemic period (N = 4; 1.2% vs. N = 1; 0.2%; p = 0.026). CONCLUSIONS: Our study shows an increase in the diagnosis of focal intractable epilepsy and a decrease in resections, while LITT and RNS usage is rising. Improving access to surgery and encouraging newer treatment modalities for DRE is crucial. Further research is needed to optimize patient outcomes and identify factors that influence treatment choices.

A LFP/AP Mode Reconfigurable Analog Front-End Combining an Electrical EEEG-iEEG Model for the Closed-Loop VNS.

This article presents a local field potential (LFP)/action potential (AP) mode reconfigurable analog front-end (AFE) dedicated for the closed-loop vagus nerve stimulator (VNS). It combines an inverse electrical model of the intracranial electroencephalogram (iEEG) conducting in the brain tissues and been recorded at scalp as the extended electroencephalogram (EEEG). The AFE contains a LFP/AP mode reconfigurable EEEG preamplifier, a tunable integrator to compensate the effect of either the recording electrodes or head tissues, and an adder. The LFP/AP mode reconfigurable EEEG preamplifier consists of a tunable chopper-stabilized amplifier (CSA) and a 2nd-order tunable low pass filter (LPF). For better separation of LFP and AP signals, a high-order DC servo loop (DSL) characterized as a 2nd-order DSL in parallel with a 1st-order DSL is exploited in the tunable CSA to achieve a tunable high-pass frequency with a stopband attenuation slope (SAS) of +40 dB/dec. In addition, the tunable LPF can obtain a tunable low-pass frequency with a SAS of -40 dB/dec and provide additional 20 dB gain for AP signals. Fabricated in a SMIC 180 nm CMOS technology, and in the LFP band (0.5 Hz-200 Hz) and AP band (300 Hz-5 kHz), the measured mid-band gains of the LFP/AP mode reconfigurable EEEG preamplifier are 39.6 dB and 59.5 dB, the input-referred noises (IRNs) are 2.2 μVrms and 6.3 μVrms, the DC/in-band input impedances are 1.27/1.26 GΩ and 0.3/0.22 GΩ, respectively. The power consumption per channel AFE is 6.3 μW, and the die area is 1.4 mm × 0.25 mm.

Does vibrotactile stimulation of the auricular vagus nerve enhance working memory? A behavioral and physiological investigation

BackgroundWorking memory is essential to a wide range of cognitive functions and activities. Transcutaneous auricular VNS (taVNS) is a promising method to improve working memory performance. However, the feasibility and scalability of electrical stimulation are constrained by several limitations, such as auricular discomfort and inconsistent electrical contact. ObjectiveWe aimed to develop a novel and practical method, vibrotactile taVNS, to improve working memory. Further, we investigated its effects on arousal, measured by skin conductance and pupil diameter. MethodThis study included 20 healthy participants. Behavioral response, skin conductance, and eye tracking data were concurrently recorded while the participants performed N-back tasks under three conditions: vibrotactile taVNS delivered to the cymba concha, earlobe (sham control), and no stimulation (baseline control). ResultsIn 4-back tasks, which demand maximal working memory capacity, active vibrotactile taVNS significantly improved the performance metric compared to the baseline but not to the sham. Moreover, we found that the reduction rate of with increasing task difficulty was significantly smaller during vibrotactile taVNS sessions than in both baseline and sham conditions. Arousal, measured as skin conductance and pupil diameter, declined over the course of the tasks. Vibrotactile taVNS rescued this arousal decline, leading to arousal levels corresponding to optimal working memory levels. Moreover, pupil diameter and skin conductance level were higher during high-cognitive-load tasks when vibrotactile taVNS was delivered to the concha compared to baseline and sham. ConclusionOur findings suggest that vibrotactile taVNS modulates the arousal pathway and could be a potential intervention for enhancing working memory.

924 Corpus Callosotomy for Intractable Epilepsy: A Contemporary Series of Operative Factors and Overall Complication Rate

INTRODUCTION: Corpus callosotomy is an effective treatment for atonic seizures in medically refractory epilepsy. Recently, laser interstitial thermal therapy has been adapted as a less invasive method to achieve similar results, yet technical challenges associated with this nascent approach persist. A modern series of corpus callosotomies performed by open craniotomy is lacking in the literature, a fact which highlights the importance of establishing contemporary complication rates for this operation to compare with newer methodologies. METHODS: We retrospectively reviewed institutional data for patients who underwent first time open callosotomy from 2005 to 2022. Demographic and clinical variables were collected and analyzed with a focus on operative factors and complication rates. RESULTS: 105 patients were included in the study with a mean age of 9.39 years (0.67-24.17 years). 58.1% of patients were male (61), and one surgeon performed a majority (76.20%, 80) of the operations with two other surgeons performing the remainder (21.9% and 1.90%, respectively). In total, 63 complete, 31 subtotal (anterior 70-99%), and 1 posterior (40%) callosotomies were performed. Blood loss was available for 102/105 patients with a mean of 96.67 mL (10-500 mL), and mean operative time was calculated as 226.76 minutes (45-504 minutes) from 76/105 patients by excluding those patients who underwent concurrent vagal nerve stimulator placement or revision. Operative complication rate was determined to be 6.67% and was comprised of 3 pseudomeningoceles, 3 superficial wound infections, and 1 delayed intraparenchymal hemorrhage. No venous infarcts were observed on postoperative MRI. CONCLUSIONS: This the largest single center series of open callosotomy patients describes important updated metrics to help evaluate new techniques being developed for the surgical treatment of atonic seizures in medically intractable epilepsy.

Online Bayesian optimization of vagus nerve stimulation.

Objective.In bioelectronic medicine, neuromodulation therapies induce neural signals to the brain or organs, modifying their function. Stimulation devices capable of triggering exogenous neural signals using electrical waveforms require a complex and multi-dimensional parameter space to control such waveforms. Determining the best combination of parameters (waveform optimization or dosing) for treating a particular patient's illness is therefore challenging. Comprehensive parameter searching for an optimal stimulation effect is often infeasible in a clinical setting due to the size of the parameter space. Restricting this space, however, may lead to suboptimal therapeutic results, reduced responder rates, and adverse effects.Approach. As an alternative to a full parameter search, we present a flexible machine learning, data acquisition, and processing framework for optimizing neural stimulation parameters, requiring as few steps as possible using Bayesian optimization. This optimization builds a model of the neural and physiological responses to stimulations, enabling it to optimize stimulation parameters and provide estimates of the accuracy of the response model. The vagus nerve (VN) innervates, among other thoracic and visceral organs, the heart, thus controlling heart rate (HR), making it an ideal candidate for demonstrating the effectiveness of our approach.Main results.The efficacy of our optimization approach was first evaluated on simulated neural responses, then applied to VN stimulation intraoperatively in porcine subjects. Optimization converged quickly on parameters achieving target HRs and optimizing neural B-fiber activations despite high intersubject variability.Significance.An optimized stimulation waveform was achieved in real time with far fewer stimulations than required by alternative optimization strategies, thus minimizing exposure to side effects. Uncertainty estimates helped avoiding stimulations outside a safe range. Our approach shows that a complex set of neural stimulation parameters can be optimized in real-time for a patient to achieve a personalized precision dosing.