Transcutaneous auricular vagus nerve stimulation enhances learning of novel letter-sound relationships in adults.

BACKGROUND: Reading is a critical skill in modern society but is significantly more difficult to acquire during adulthood. Many adults are required to learn a new orthography after this window closes for personal or vocational reasons and while many programs and training methods exist for learning to read in adulthood, none result in native-like fluency. Implantable cervical vagus nerve stimulation is capable of driving neural plasticity but is invasive and not practical as a reading intervention. OBJECTIVE: The goal of the current study was to evaluate whether non-invasive transcutaneous auricular vagus nerve stimulation (taVNS) is effective at enhancing novel orthography acquisition in young adults. METHODS: We enrolled 37 typically developing participants and randomly assigned them to a computer control, device sham control, earlobe stimulation control, or experimental transcutaneous auricular stimulation (taVNS) group. Participants then learned novel letter-sound correspondences in Hebrew over five training lessons. Performance was assessed using three measures to evaluate various aspects of reading: Letter ID, Automaticity, and Decoding. RESULTS: The taVNS group significantly outperformed the three control groups on both the Automaticity and Decoding tasks. There was no difference on the Letter ID task. CONCLUSIONS: These results demonstrate, for the first time, that taVNS is capable of improving aspects of reading acquisition in adults. These findings have potential implications for a wide range of cognitive tasks.

Flat electrode contacts for vagus nerve stimulation.

The majority of available systems for vagus nerve stimulation use helical stimulation electrodes, which cover the majority of the circumference of the nerve and produce largely uniform current density within the nerve. Flat stimulation electrodes that contact only one side of the nerve may provide advantages, including ease of fabrication. However, it is possible that the flat configuration will yield inefficient fiber recruitment due to a less uniform current distribution within the nerve. Here we tested the hypothesis that flat electrodes will require higher current amplitude to activate all large-diameter fibers throughout the whole cross-section of a nerve than circumferential designs. Computational modeling and in vivo experiments were performed to evaluate fiber recruitment in different nerves and different species using a variety of electrode designs. Initial results demonstrated similar fiber recruitment in the rat vagus and sciatic nerves with a standard circumferential cuff electrode and a cuff electrode modified to approximate a flat configuration. Follow up experiments comparing true flat electrodes to circumferential electrodes on the rabbit sciatic nerve confirmed that fiber recruitment was equivalent between the two designs. These findings demonstrate that flat electrodes represent a viable design for nerve stimulation that may provide advantages over the current circumferential designs for applications in which the goal is uniform activation of all fascicles within the nerve.

No modulation of pupil size and event-related pupil response by transcutaneous auricular vagus nerve stimulation (taVNS).

Transcutaneous auricular vagus nerve stimulation (taVNS) bears therapeutic potential for a wide range of medical conditions. However, previous studies have found substantial interindividual variability in responsiveness to taVNS, and no reliable predictive biomarker for stimulation success has been developed so far. In this study, we investigate pupil size and event-related pupil response as candidate biomarkers. Both measures have a direct physiological link to the activity of the locus coeruleus (LC), a brainstem structure and the main source of norepinephrine in the brain. LC activation is considered one of the key mechanisms of action of taVNS, therefore, we expected a clear increase of the pupillary measures under taVNS compared to sham (placebo) stimulation, such that it could serve as a prospective predictor for individual clinical and physiological taVNS effects in future studies. We studied resting pupil size and pupillary responses to target stimuli in an auditory oddball task in 33 healthy young volunteers. We observed stronger pupil responses to target than to standard stimuli. However, and contrary to our hypothesis, neither pupil size nor the event-related pupil response nor behavioral performance were modulated by taVNS. We discuss potential explanations for this negative finding and its implications for future clinical investigation and development of taVNS.

Implantable Electronic Stimulation Devices from Head to Sacrum: Imaging Features and Functions.

Electronic stimulation devices are implanted in various locations in the body to decrease pain, modulate nerve function, or stimulate various end organs. The authors describe these devices using a craniocaudal approach, first describing deep brain stimulation (DBS) devices and ending with sacral nerve stimulation (SNS) devices. The radiology-relevant background information for each device and its imaging appearance are also described. These devices have a common design theme and include the following components: (a) a pulse generator that houses the battery and control electronics, (b) an insulated lead or wire that conveys signals to the last component, which is (c) an electrode that contacts the end organ and senses and/or acts on the end organ. DBS electrodes are inserted into various deep gray nuclei, most commonly to treat the symptoms of movement disorders. Occipital, trigeminal, and spinal nerve stimulation devices are used as second-line therapy to control craniofacial or back pain. For cardiac devices, the authors describe two newer devices, the subcutaneous implantable cardioverter defibrillator and the leadless pacemaker, both of which avoid complications related to having leads threaded through the venous system. Diaphragmatic stimulation devices stimulate the phrenic nerve to restore diaphragmatic movement. Gastric electrical stimulation devices act on various parts of the stomach for the treatment of gastroparesis or obesity. Finally, SNS devices are used to modulate urinary and defecatory functions. Common complications diagnosed at imaging include infection, hematoma, lead migration, and lead breakage. Understanding the components, normal function, and normal imaging appearance of each device allows the radiologist to identify complications. ©RSNA, 2019.

ReStore: A wireless peripheral nerve stimulation system.

BACKGROUND: The growing use of neuromodulation techniques to treat neurological disorders has motivated efforts to improve on the safety and reliability of implantable nerve stimulators. NEW METHOD: The present study describes the ReStore system, a miniature, implantable wireless nerve stimulator system that has no battery or leads and is constructed using commercial components and processes. The implant can be programmed wirelessly to deliver charge-balanced, biphasic current pulses of varying amplitudes, pulse widths, frequencies, and train durations. Here, we describe bench and in vivo testing to evaluate the operational performance and efficacy of nerve recruitment. Additionally, we also provide results from a large-animal chronic active stimulation study assessing the long-term biocompatibility of the device. RESULTS: The results show that the system can reliably deliver accurate stimulation pulses through a range of different loads. Tests of nerve recruitment demonstrate that the implant can effectively activate peripheral nerves, even after accelerated aging and post-chronic implantation. Biocompatibility and hermeticity tests provide an initial indication that the implant will be safe for use in humans. COMPARISON WITH EXISTING METHOD(S): Most commercially available nerve stimulators include a battery and wire leads which often require subsequent surgeries to address failures in these components. Though miniaturized battery-less stimulators have been prototyped in academic labs, they are often constructed using custom components and processes that hinder clinical translation. CONCLUSIONS: The results from testing the performance and safety of the ReStore system establish its potential to advance the field of peripheral neuromodulation.

Electroceutical Targeting of the Autonomic Nervous System.

Autonomic nerves are attractive targets for medical therapies using electroceutical devices because of the potential for selective control and few side effects. These devices use novel materials, electrode configurations, stimulation patterns, and closed-loop control to treat heart failure, hypertension, gastrointestinal and bladder diseases, obesity/diabetes, and inflammatory disorders. Critical to progress is a mechanistic understanding of multi-level controls of target organs, disease adaptation, and impact of neuromodulation to restore organ function.

Autostimulation in Vagus Nerve Stimulator Treatment: Modulating Neuromodulation.

OBJECTIVES: Until now, the vagus nerve stimulation (VNS) treatment in epilepsy has consisted of two different modes: normal and magnet stimulation. A new vagus nerve stimulator model (106 AspireSR®, LivaNova, Houston, TX, USA) also allows automatic stimulation (AutoStim). The purpose of this study is to examine the effect of autostimulation on seizure frequencies together with energy consumption. MATERIALS AND METHODS: The study material consisted of 14 patients whose former stimulator model (102/103) was replaced with model 106. We calculated the theoretical charge (Q) in Coulombs for one day in both of those groups. We evaluated the follow-up data of the patients' seizure counts, with a mean follow-up time of 18.1 months (SD 8.1). RESULTS: The total charge, "VNS dose," was reduced with model 106 in comparison with models 102 or 103 (p = 0.001, Mann-Whitney test). The average charge (Qtotal ) for one day with AutoStim was 142.56 mC; without AutoStim, it was 321.09 mC. We were able to assess seizure diaries in 11 out of 14 patients. Four patients (36%) had >50% seizure reduction and two patients (18%) experienced a reduction in seizure severity with VNS with autostimulation. Five patients (46%) remained unchanged. In three out of four patients with improved seizure control, the duty cycle was maintained at the original level. The patients whose duty cycle was modified for a more prolonged OFF-time had unchanged seizure frequencies. CONCLUSION: VNS with AutoStim achieves maintenance of prior-established seizure control with markedly less energy consumption and can also improve seizure control as compared to former stimulator model.

Auricular vagal nerve stimulation in peripheral arterial disease patients.

BACKGROUND: Auricular nerve stimulation has been proven effective in different diseases. We investigated if a conservative therapeutic alternative for claudication in peripheral arterial occlusive disease (PAD) via electroacupuncture of the outer ear can be established. PATIENTS AND METHODS: In this prospective, double-blinded trial an ear acupuncture using an electroacupuncture device was carried out in 40 PAD patients in Fontaine stage IIb. Twenty patients were randomized to the verum group using a fully functional electroacupuncture device, the other 20 patients received a sham device (control group). Per patient, eight cycles (1 cycle = 1 week) of electroacupuncture were performed. The primary endpoint was defined as a significantly more frequent doubling of the absolute walking distance after eight cycles in the verum group compared to controls in a standardized treadmill testing. Secondary endpoints were a significant improvement of the total score of the Walking Impairment Questionnaire (WIQ) as well as improvements in health related quality of life using the Short Form 36 Health Survey (SF-36). RESULTS: There were no differences in baseline characteristics between the two groups. The initial walking distance significantly increased in both groups (verum group [means]: 182 [95 % CI 128-236] meters to 345 [95 % CI 227-463] meters [+ 90 %], p < 0.01; control group [means]: 159 [95 % CI 109-210] meters to 268 [95 % CI 182-366] meters [+ 69 %], p = 0.01). Twelve patients (60 %) in the verum group and five patients (25 %) in controls reached the primary endpoint of doubling walking distance (p = 0.05). The total score of WIQ significantly improved in the verum group (+ 22 %, p = 0.01) but not in controls (+ 8 %, p = 0.56). SF-36 showed significantly improvements in six out of eight categories in the verum group and only in one of eight in controls. CONCLUSIONS: Electroacupuncture of the outer ear seems to be an easy-to-use therapeutic option in an age of increasingly invasive and mechanically complex treatments for PAD patients.

Neurostimulation Devices for the Treatment of Neurologic Disorders.

Rapid advancements in neurostimulation technologies are providing relief to an unprecedented number of patients affected by debilitating neurologic and psychiatric disorders. Neurostimulation therapies include invasive and noninvasive approaches that involve the application of electrical stimulation to drive neural function within a circuit. This review focuses on established invasive electrical stimulation systems used clinically to induce therapeutic neuromodulation of dysfunctional neural circuitry. These implantable neurostimulation systems target specific deep subcortical, cortical, spinal, cranial, and peripheral nerve structures to modulate neuronal activity, providing therapeutic effects for a myriad of neuropsychiatric disorders. Recent advances in neurotechnologies and neuroimaging, along with an increased understanding of neurocircuitry, are factors contributing to the rapid rise in the use of neurostimulation therapies to treat an increasingly wide range of neurologic and psychiatric disorders. Electrical stimulation technologies are evolving after remaining fairly stagnant for the past 30 years, moving toward potential closed-loop therapeutic control systems with the ability to deliver stimulation with higher spatial resolution to provide continuous customized neuromodulation for optimal clinical outcomes. Even so, there is still much to be learned about disease pathogenesis of these neurodegenerative and psychiatric disorders and the latent mechanisms of neurostimulation that provide therapeutic relief. This review provides an overview of the increasingly common stimulation systems, their clinical indications, and enabling technologies.

Two-Year Outcomes of Vagal Nerve Blocking (vBloc) for the Treatment of Obesity in the ReCharge Trial.

BACKGROUND: The ReCharge Trial demonstrated that a vagal blocking device (vBloc) is a safe and effective treatment for moderate to severe obesity. This report summarizes 24-month outcomes. METHODS: Participants with body mass index (BMI) 40 to 45 kg/m2, or 35 to 40 kg/m2 with at least one comorbid condition were randomized to either vBloc therapy or sham intervention for 12 months. After 12 months, participants randomized to vBloc continued open-label vBloc therapy and are the focus of this report. Weight loss, adverse events, comorbid risk factors, and quality of life (QOL) will be assessed for 5 years. RESULTS: At 24 months, 123 (76 %) vBloc participants remained in the trial. Participants who presented at 24 months (n = 103) had a mean excess weight loss (EWL) of 21 % (8 % total weight loss [TWL]); 58 % of participants had ≥5 % TWL and 34 % had ≥10 % TWL. Among the subset of participants with abnormal preoperative values, significant improvements were observed in mean LDL (-16 mg/dL) and HDL cholesterol (+4 mg/dL), triglycerides (-46 mg/dL), HbA1c (-0.3 %), and systolic (-11 mmHg) and diastolic blood pressures (-10 mmHg). QOL measures were significantly improved. Heartburn/dyspepsia and implant site pain were the most frequently reported adverse events. The primary related serious adverse event rate was 4.3 %. CONCLUSIONS: vBloc therapy continues to result in medically meaningful weight loss with a favorable safety profile through 2 years. TRIAL REGISTRATION: https://clinicaltrials.gov/ct2/show/NCT01327976.

Medical Devices; Neurological Devices; Classification of the External Vagal Nerve Stimulator for Headache. Final order.

The Food and Drug Administration (FDA or we) is classifying the external vagal nerve stimulator for headache into class II (special controls). The special controls that apply to the device type are identified in this order and will be part of the codified language for the external vagal nerve stimulator for headache's classification. We are taking this action because we have determined that classifying the device into class II (special controls) will provide a reasonable assurance of safety and effectiveness of the device. We believe this action will also enhance patients' access to beneficial innovative devices, in part by reducing regulatory burdens.

Extra-cardiac stimulators: what do cardiologists need to know?

For several decades, treating patients with pacemakers has been the privilege of cardiologists. However, in the last 30 years, researchers have found new targets for electrical stimulation in different clinical subspecialities, such as deep brain stimulation (for the treatment of Parkinson's disease, essential tremor, dystonia, and some psychiatric illnesses); spinal cord stimulation (for refractory angina, chronic pain, and peripheral artery disease); and sacral (for diverse urologic and proctologic conditions), vagal (for epilepsy), and phrenic nerve stimulation (for sleep apnoea). The purpose of this article is to familiarize cardiologists with these 'extra-cardiac pacemakers' and to discuss potential issues that must be addressed when these patients undergo cardiac procedures.

Interventional treatment of obesity and diabetes: An interim report on gastric electrical stimulation.

Gastric electrical stimulation has been applied to treat human obesity since 1995. Dilatation of the stomach causes a series of neural reflexes which result in satiation and satiety. In non-obese individuals food ingestion is limited in part by this mechanism. In obese individuals, satiation and satiety are defective and unable to limit energy intake and prevent excessive weight gain. Several gastric electrical stimulatory (GES) devices have been developed, tested in clinical trials and even approved for the treatment of obesity. The design and clinical utility of three devices (Transend®, Maestro® and DIAMOND®) that have been extensively studied are presented as well as that of a new device (abiliti®) which is in early development. The Transcend®, a low energy GES device, showed promising results in open label studies but failed to show a difference from placebo in decreasing weight in obese subjects. The results of the clinical trials in treating obese subjects with the Maestro®, a vagal nerve stimulator, were sufficient to gain approval for marketing the device. The DIAMOND®, a multi-electrode GES device, has been used to treat type 2 diabetes and an associated benefit is to reduce body weight and lower systolic blood pressure.

[Invasive neuromodulation in the treatment of drug-resistant epilepsies]. / Invazív neuromoduláció a gyógyszerrezisztens epilepsziák kezelésében.

Neuromodulation is one of the most developing new disciplines of medical science, which examines how electrical, chemical and mechanical interventions can modulate or change the functioning of the central and peripheral nervous system. Neuromodulation is a reversible form of therapy which uses electrical or mechanical stimulation or centrally-delivered drugs to modulate the abnormal function of the central nervous system in pain, spasticity, epilepsy, movement and psychiatric disorders, and certain cardiac, incontinency, visual and auditory diseases. Neuromodulation therapy has two major branches. Non-invasive neuromodulation includes transcranial magnetic simulation, direct current stimulation and transcutaneous electric nerve stimulation. Invasive neuromodulation includes deep brain stimulation, cortical stimulation, spinal cord stimulation, peripheral nerve stimulation, sacral nerve simulation, and subcutan stimulation. In this article the authors overview the apparently available neural interface technologies in epilepsy surgery.

Electrochemical and Electrophysiological Performance of Platinum Electrodes Within the Ninety-Nine-Electrode Stimulating Nerve Cuff.

The trend in neural prostheses using selective nerve stimulation for electrical stimulation therapies is headed toward single-part systems having a large number of working electrodes (WEs), each of which selectively stimulate neural tissue or record neural response (NR). The present article reviews the electrochemical and electrophysiological performance of platinum WE within a ninety-nine-electrode spiral cuff for selective nerve stimulation and recording of peripheral nerves, with a focus on the vagus nerve (VN). The electrochemical properties of the WE were studied in vitro using the electrochemical impedance spectroscopy (EIS) technique. The equivalent circuit model (ECM) of the interface between the WE and neural tissue was extracted from the EIS data and simulated in the time domain using a preset current stimulus. Electrophysiological performance of in-space and fiber-type highly selective vagus nerve stimulation (VNS) was tested using an isolated segment of a porcine VN and carotid artery as a reference. A quasitrapezoidal current-controlled pulse (stimulus) was applied to the VN or arterial segment using an appointed group of three electrodes (triplet). The triplet and stimulus were configured to predominantly stimulate B-fibers and minimize the stimulation of A-fibers. The EIS results revealed capacitive charge transfer predominance, which is a highly desirable property. Electrophysiological performance testing indicated the potential existence of certain parameters and waveforms of the stimulus for which the contribution of the A-fibers to the NR decreased slightly and that of the B-fibers increased slightly. Findings show that the design of the stimulating electrodes, based on the EIS and ECM results, could act as a useful tool for nerve cuff development.

Vagus nerve stimulation in neuropsychiatry: Targeting anatomy-based stimulation sites.

The vagus nerve (VN) is the longest cranial nerve, extending from the brain to the abdominal cavity. The VN consists of both afferent and efferent fibers (respectively 80% and 20%). Vagus nerve stimulation (VNS) is a neuromodulation strategy first developed in the 1980s for epilepsy. More recently, growing efforts in clinical research have been underscoring possible clinical benefits of VNS for different medical conditions such as epilepsy, major depression, anxiety disorders, and Tourette syndrome. Following the rational of VN anatomy and cranial innervation presented above, we hereby hypothesize that transcutaneously placing electrodes over the mastoid process could be a useful study protocol for future tVNS trials.

Increase of ventricular interval during atrial fibrillation by atrioventricular node vagal stimulation: chronic clinical atrioventricular-nodal stimulation download study.

BACKGROUND: Patients with a high ventricular rate during atrial fibrillation (AF) are at increased risk of receiving inappropriate implantable cardioverter defibrillator shocks. The objective was to demonstrate the feasibility of high frequency atrioventricular-nodal stimulation (AVNS) to reduce the ventricular rate during AF to prevent inappropriate implantable cardioverter defibrillator shocks. METHODS AND RESULTS: Patients with a new atrial lead placement as part of a cardiac resynchronization therapy and defibrillator implant and a history of paroxysmal or persistent AF were eligible. If proper atrial lead position was confirmed, AVNS software was uploaded to the cardiac resynchronization therapy device, tested, and optimized. AVNS was delivered via a right atrial pacing lead positioned in the posterior right atrium. Software allowed initiation of high frequency bursts triggered on rapidly conducted AF. Importantly, the efficacy was evaluated during spontaneous AF episodes between 1 and 6 months after implant. Forty-four patients were enrolled in 4 centers. Successful atrial lead placement occurred in 74%. Median implant time of the AVNS lead was 37 minutes. In 26 (81%) patients, manual AVNS tests increased the ventricular interval by >25%. Between 1 and 6 months, automatic AVNS activations occurred in 4 patients with rapidly conducted AF, and in 3 patients, AVNS slowed the ventricular rate out of the implantable cardioverter defibrillator shock zone. No adverse events were associated with the AVNS software. CONCLUSIONS: The present study demonstrated the feasibility of implementation of AVNS in a cardiac resynchronization therapy and defibrillator system. AVNS increased ventricular interval >25% in 81% of patients. AVNS did not influence the safety profile of the cardiac resynchronization therapy and defibrillator system. CLINICAL TRIAL REGISTRATION: clinicaltrials.gov; Unique Identifier: NCT01095952.

Implantation of a new Vagus Nerve Stimulation (VNS) Therapy® generator, AspireSR®: considerations and recommendations during implantation and replacement surgery--comparison to a traditional system.

INTRODUCTION: The most widely used neuro-stimulation treatment for drug-resistant epilepsy is Vagus Nerve Stimulation (VNS) Therapy®. Ictal tachycardia can be an indicator of a seizure and, if monitored, can be used to trigger an additional on-demand stimulation, which may positively influence seizure severity or duration. A new VNS Therapy generator model, AspireSR®, was introduced and approved for CE Mark in February 2014. In enhancement of former models, the AspireSR has incorporated a cardiac-based seizure-detection (CBSD) algorithm that can detect ictal tachycardia and automatically trigger a defined auto-stimulation. To evaluate differences in preoperative, intraoperative and postoperative handling, we compared the AspireSR to a conventional generator model (Demipulse®). METHOD: Between February and September 2014, seven patients with drug-resistant epilepsy and ictal tachycardia were implanted with an AspireSR. Between November 2013 and September 2014, seven patients were implanted with a Demipulse and served as control group. Operation time, skin incision length and position, and complications were recorded. Handling of the new device was critically evaluated. RESULTS: The intraoperative handling was comparable and did not lead to a significant increase in operation time. In our 14 operations, we had no significant short-term complications. Due to its larger size, patients with the AspireSR had significantly larger skin incisions. For optimal heart rate detection, the AspireSR had to be placed significantly more medial in the décolleté area than the Demipulse. The preoperative testing is a unique addition to the implantation procedure of the AspireSR, which may provide minor difficulties, and for which we provide several recommendations and tips. The price of the device is higher than for all other models. CONCLUSIONS: The new AspireSR generator offers a unique technical improvement over the previous Demipulse. Whether the highly interesting CBSD feature will provide an additional benefit for the patients, and will rectify the additional costs, respectively, cannot be answered in the short-term. The preoperative handling is straightforward, provided that certain recommendations are taken into consideration. The intraoperative handling is equivalent to former models-except for the placement of the generator, which might cause cosmetic issues and has to be discussed with the patient carefully. We recommend the consideration of the AspireSR in patients with documented ictal tachycardia to provide a substantial number of patients for later seizure outcome analysis.

A flexible platform for biofeedback-driven control and personalization of electrical nerve stimulation therapy.

Electrical vagus nerve stimulation is a treatment alternative for many epileptic and depressed patients whose symptoms are not well managed with pharmaceutical therapy. However, the fixed stimulus, open loop dosing mechanism limits its efficacy and precludes major advances in the quality of therapy. A real-time, responsive form of vagus nerve stimulation is needed to control nerve activation according to therapeutic need. This personalized approach to therapy will improve efficacy and reduce the number and severity of side effects. We present autonomous neural control, a responsive, biofeedback-driven approach that uses the degree of measured nerve activation to control stimulus delivery. We demonstrate autonomous neural control in rats, showing that it rapidly learns how to most efficiently activate any desired proportion of vagal A, B, and/or C fibers over time. This system will maximize efficacy by minimizing patient response variability and by minimizing therapeutic failures resulting from longitudinal decreases in nerve activation with increasing durations of treatment. The value of autonomous neural control equally applies to other applications of electrical nerve stimulation.