Neuromodulation Devices Research Articles

Two-year efficacy and safety outcomes of the pivotal OASIS Study using the Revi® System for treatment of urgency urinary incontinence.

The BlueWind Medical Device, Revi®, is a novel implantable tibial neuromodulation system powered by an external, battery-operated wearable that facilitates individually tailored stimulation to provide treatment for urgency urinary incontinence (i.e., overactive bladder wet). The Revi System is the first FDA-cleared implantable neuromodulation device which can be used without prior failure with more conservative treatment options. Two-year follow-up results of the OASIS Study are presented. The Revi System was implanted in 151 female participants. The primary efficacy and safety endpoints were assessed at 6- and 12-months, after which participants either consented to extend follow-up for long-term assessment of treatment durability and safety, or they chose to exit the study. Ninety-seven participants completed the 24-month assessment, and of these, 79% were therapy responders (≥ 50% reduction in urgency urinary incontinence episodes (UUIE), demonstrated on a 3-day voiding diary). Importantly, therapeutic response was durable, with comparable effectiveness at 6-, 12-, and 24-months (response rates of 78%, 82%, and 79%, respectively). Participants that completed both the 6- and 24-month assessment had similar demographics and treatment results at the 6-month visit, indicating that these results at 24-months are representative of the overall study population.In addition, high satisfaction and patient impression of improvement were reported, with 97% (88/91) of the participants satisfied with the therapy and 80% (78/97) feeling "much better" or "very much better". There were no serious adverse events related to the device or the procedure through 24 months. Two-year results demonstrate durable efficacy, high patient satisfaction, and a very favorable safety profile.

Advances in Therapy for Refractory Epilepsy.

Drug-resistant epilepsy (DRE) is defined as failure to achieve sustained seizure control with adequate trials of two appropriate antiseizure medications (ASMs). DRE affects one-third of patients with epilepsy and is associated with significant morbidity and mortality. Newer ASMs provide pharmacological therapy that is better tolerated but not necessarily more effective than older ASMs. Resective brain surgery is the gold standard to treat DRE and achieve seizure freedom, with laser ablation offering an alternative with less morbidity but lower effectiveness. For patients who are not candidates for resection or ablation, multiple neuromodulation options can reduce seizure burden. These neuromodulation devices have shown comparable effectiveness in randomized clinical trials, but the results vary in open-label follow-up cohorts, as do the risks of complications and associated costs. Dietary therapies can help, particularly in pediatric genetic epilepsies. Innovative genetic therapy approaches are being pursued, offering the promise of precision medicine.

Neuromorphic neuromodulation: Towards the next generation of closed-loop neurostimulation.

Neuromodulation techniques have emerged as promising approaches for treating a wide range of neurological disorders, precisely delivering electrical stimulation to modulate abnormal neuronal activity. While leveraging the unique capabilities of AI holds immense potential for responsive neurostimulation, it appears as an extremely challenging proposition where real-time (low-latency) processing, low-power consumption, and heat constraints are limiting factors. The use of sophisticated AI-driven models for personalized neurostimulation depends on the back-telemetry of data to external systems (e.g. cloud-based medical mesosystems and ecosystems). While this can be a solution, integrating continuous learning within implantable neuromodulation devices for several applications, such as seizure prediction in epilepsy, is an open question. We believe neuromorphic architectures hold an outstanding potential to open new avenues for sophisticated on-chip analysis of neural signals and AI-driven personalized treatments. With more than three orders of magnitude reduction in the total data required for data processing and feature extraction, the high power- and memory-efficiency of neuromorphic computing to hardware-firmware co-design can be considered as the solution-in-the-making to resource-constraint implantable neuromodulation systems. This perspective introduces the concept of Neuromorphic Neuromodulation, a new breed of closed-loop responsive feedback system. It highlights its potential to revolutionize implantable brain-machine microsystems for patient-specific treatment.

The Utilization of Blockchain for Data Security for the Chronic Pain Physician.

The COVID-19 pandemic accelerated the surge in medical data utilization, notably impacting chronic pain management given its enormous economist cost. While the collection and use of data enhances research and care quality, data exchange risks compromising integrity and privacy, exemplified by the Change Healthcare cyberattack. Here, we review the potential of blockchain for the utilization for cybersecurity in the healthcare system with an emphasis on the field of chronic pain. Blockchain technology emerges as a potential solution, offering decentralized, secure, and immutable data management. Blockchain ensures transparency, integrity, and data privacy, which is crucial in healthcare. Smart contracts may offer automated, secure management of implantable neuromodulation devices such as spinal cord stimulators and intrathecal pumps. Blockchain's potential in pharmaceutical supply chain integrity is exemplified in preliminary efforts ensuring that the medication retrieved by the patient is indeed the intended medication. Despite limitations such as speed of transactions, blockchain presents innovative avenues for healthcare security and quality improvement, necessitating further development for widespread implementation. Blockchain's applicability is not only applicable to chronic pain management, but can be used in medicine as a whole.

Indwelling Urological Device Biofilm Composition and Characteristics in the Presence and Absence of Infection

ObjectiveTo characterize microbial biofilms associated with different device types used in the urological field including ureteral stents, sacral neuromodulation (SNM) devices, penile prostheses, and artificial urinary sphincters (AUS). Materials and MethodsData from four studies, each reporting biofilm composition of a particular device type, were pooled and included for inter-device analysis. Studies recruited adults scheduled for ureteral stent, SNM, IPP, or AUS removal/revision. Device (n=115) biofilms and controls were analyzed with multi-omics approaches, and compositions were compared across device types and clinical factors. ResultsMicrobiota present on each device type was distinct from that of perineal, rectal, or urine flora (p<0.01). Biofilm microbial counts (p<0.001) and diversity (p=0.024) differed by device type. Ureteral stents had greater microbial counts than other device types (p<0.001). Staphylococcus, Pseudomonas, Lactobacillus, Ureaplasma were commonly detected across devices. Device biofilms harbored a greater proportion of Proteobacteria phylum, and the rectal, perineal, and urine flora harbored a greater proportion of Firmicutes. Unique microbe-metabolite interaction networks were identified in presence and absence of infection. Antibiotic resistance genes including sul2 (sulfonamide resistance) and rpoB (rifampin resistance) were detected in biofilms across device types. Biofilm reconstitution in vitro differed by device type from which strains were isolated. ConclusionsUreteral stents, sacral neuromodulation devices, penile prostheses, and artificial urinary sphincters harbored unique microbial and metabolite profiles that differed from those of skin, urine, and rectal flora. The findings of this study set the groundwork for investigation of novel strategies to reduce device-associated infection risk within and outside urology. Data availability statementData are available from corresponding author upon reasonable request.

The safety and efficacy of antibiotic-impregnated envelopes in neuromodulation device implantation: a systematic review and meta-analysis protocol

The safety and efficacy of antibiotic-impregnated envelopes in neuromodulation device implantation: a systematic review and meta-analysis protocol

ID: 332765 CARSS: an open-source closed-loop implantable neuromodulation device platform for bioelectronic medicine

ID: 332765 CARSS: an open-source closed-loop implantable neuromodulation device platform for bioelectronic medicine

Evidence-based review and frontiers of migraine therapy.

Cyclic vomiting syndrome (CVS) is identified as one of the "episodic syndromes that may be associated with migraine," along with benign paroxysmal torticollis, benign paroxysmal vertigo, and abdominal migraine. It has been proposed that CVS and migraine may share pathophysiologic mechanisms of hypothalamic activation and altered dopaminergic signaling, and impaired sensorimotor intrinsic connectivity. The past decade has brought groundbreaking advances in the treatment of migraine and other headache disorders. While many of these therapies have yet to be studied in episodic syndromes associated with migraine including CVS and abdominal migraine, the potential shared pathophysiology among these conditions suggests that use of migraine-specific treatments may have a beneficial role even in those for whom headache is not the primary symptom. This manuscript highlights newer therapies in migraine. Calcitonin gene-related peptide (CGRP) and its relation to migraine pathophysiology and the therapies that target the CGRP pathway, as well as a 5HT1F receptor agonist and neuromodulation devices used to treat migraine are briefly discussed as they may potentially prove to be useful in the future treatment of CVS.

Neuromodulation guide for the non-neuromodulator clinician: What it is and how it can benefit patients?

Neuromodulation is being utilized across a variety of medical subspecialties to treat both painful and non-painful medical conditions. However, publications on neuromodulation topics infrequently occur in journals targeting generalists and medical specialties outside of pain medicine and neurosurgery. This study reviewed implantable neuromodulation devices, their respective Food and Drug Administration-approved indications for use, as well as off-label usage, and the associated potential risks and benefits for each device. PubMed and Medline databases were queried for systematic reviews with or without meta-analyses and randomized controlled trials of implantable neuromodulation devices. The literature review resulted in 106 studies eligible for inclusion, and 67 were included in the final review. In conclusion, as the clinical volume of neuromodulation continues to grow, supporting and educating medical professionals who care for patients that receive implanted neuromodulation devices is paramount. It is likely the use of neuromodulation will continue to expand across all medical subspecialties, and as such, every clinician should have a baseline understanding of this treatment.

Long-term explantation risk in patients with chronic pain treated with spinal cord or dorsal root ganglion stimulation

ObjectiveTo investigate long-term explantation risks and causes for the explantation of neuromodulation devices for the treatment of chronic pain from different manufacturers.MethodsThis retrospective analysis included patients implanted with a system...

A Review of Remote Monitoring in Neuromodulation for Chronic Pain Management.

Neuromodulation techniques have emerged as promising strategies for managing chronic pain. These techniques encompass various modalities of nerve stimulation, including Spinal Cord Stimulation (SCS), Dorsal Root Ganglion Stimulation (DRG-S), and Peripheral Nerve Stimulation (PNS). Studies consistently demonstrate significant improvements in pain intensity, quality of life, and reduced opioid usage among patients treated with these modalities. However, neuromodulation presents challenges, such as the need for frequent in-person follow-up visits to ensure proper functionality of the implanted device. Our review explored factors impacting compliance in current neuromodulation users and examined how remote monitoring can mitigate some of these challenges. We also discuss outcomes of recent studies related to remote monitoring of neuromodulation. While remote monitoring capabilities for neuromodulation devices is an emerging development, there are promising results supporting its role in improving outcomes for chronic pain patients. Higher patient satisfaction, improved pain control, and reduced caretaker burdens have been observed with the use of remote monitoring. This review discusses the current challenges with neuromodulation therapy and highlights the role of remote monitoring. As the field continues to evolve, understanding the importance of remote monitoring for neuromodulation is crucial for optimizing pain management outcomes.

Contact Dermatitis From Biomedical Devices, Implants, and Metals—Trouble From Within

Allergic contact dermatitis is characterized by its appearance of red, raised and infiltrated, scaling or scabbed skin and intense pruritus, and distinguished from irritant contact dermatitis by its specific immune process and histopathology. Many contact allergens are low molecular weight chemicals including metals such as nickel, cobalt, and chromium, preservatives, and adhesives. When such materials are used internally in biomedical devices, they are similarly capable of causing sensitization and an inflammatory response. Sometimes the reaction remains internal, and presents as swelling, pain, stiffness, decreased range of motion, and internal itching around the implant. Such reactions may, in some cases, also extend to include a localized or, rarely, systemic contact dermatitis indicative of the same process. This review will present an overview of reported skin and local internal reactions to orthopedic implants, which are the largest category of implanted internal metal devices. Immune reactions to smaller categories of medical appliances include cardiac devices and vascular stents, neuromodulation devices, diabetic appliances, Nuss bar surgery for pectus excavatum, and dental and spinal implants. We will review the available diagnostic tools, the consensus on interpretation, and reported strategies for treatment.

Evaluating Commercial Electrical Neuromodulation Devices with Low-Cost Neural Phantoms

Non-invasive transcranial electrical stimulation is a category of neuromodulation techniques used for various disorders. Although medically approved devices exist, the variety of consumer electrical stimulation devices is increasing. Because clinical trials and animal tests are costly and risky, using a brain phantom can provide preliminary experimental validation. However, existing brain phantoms are often costly or require excessive preparation time, precluding their use for rapid, real-time optimization of stimulation settings. A limitation of direct electric fields in a phantom is the lack of 3D spatial resolution. Using well-researched modalities such as transcranial direct current stimulation (tDCS) and newer modalities such as amplitude-modulated transcranial pulsed-current stimulation (am-tPCS), a range of materials was tested for use as electrical phantoms. Based on cost, preparation time, and efficiency, ground beef and agar gel with a 10% salt mix were selected. The measured values for the total dosages were 0.55 W-s for am-tPCS and 0.91 W-s for tDCS. Due to a low gain on the recording electrodes, the signal efficiency measured against the power delivered was 4.2% for tDCS and 3.1% for am-tPCS. Issues included electrodes shifting in the soft material and the low sensitivity of the recording electrodes. Despite these issues, the effective combination of the phantom and recording methodologies can enable low costs and the rapid testing, experimentation, and verification of consumer neuromodulation devices in three dimensions. Additionally, the efficiency factors (EFs) between the observed dosage and the delivered dosage could streamline the comparison of experimental configurations. As demonstrated by comparing two types of electrical neuromodulation devices across the 3D space of a phantom, EFs can be used in conjunction with a cost-effective, time-expedient phantom to rapidly iterate and optimize stimulation parameters.

Capacitive Neuromodulation via Material-Based Passive Interaction: Efficacy in Motor Function Improvement in Parkinson Disease.

A non-invasive and non-pharmacological approach is evaluated for the proprioceptive and postural improvement of PD subjects. The authors evaluated the effectiveness of a class I medical device according to EU regulation 745/2017 designed to develop the mechanism of action based on the modulation of action potentials, which occurs in prevalent pathways of the afferent peripheral nervous system efferent in subjects with spasticity. The present observational study, structured in a double-blind randomized manner, therefore, had the main aim of evaluating the ability of the device to improve on the motor and proprioceptive function of PD patients. This study was based on the instrumented gait analysis performed according to the Timed Up and Go (TUG) test procedure, as well as using a fall risk assessment in accordance with the Berg Balance Scale (BBS) procedures. This study involved 25 participants in the active group (no placebo) and 25 in the non-active group (placebo), the latter to whom non-functional devices were applied, but in every respect identical to the functional devices applied to the 25 patients in the no placebo group. Data analysis was conducted using statistical methodologies for statistics, the statistical significance of the results for the observed samples and the interdependence between the measured variables. The study of the mechanism of action based on the remodulation of action potentials was preliminary conducted through numerical modeling of the Hodgkin-Huxley axon, modified by introducing the influence of the capacitive device applied in clinical tests into the validated model to target the dielectric properties of materials constituting the passive sensor. The use of the neuromodulation device promises observable improvements in motor function among PD patients, including increased limb mobility and greater postural stability.

Implantation of Optoelectronic Devices in the Rodent Spinal Cord.

Neuromodulation can provide diagnostic, modulatory, and therapeutic applications. While extensive work has been conducted in the brain, modulation of the spinal cord remains relatively unexplored. The inherently delicate and mobile spinal cord tissue imposes constraints that make the precise implantation of neural probes challenging. Despite recent advances in neuromodulation devices, particularly flexible bioelectronics, opportunities to expand their use in the spinal cord have been limited by the surgical complexities of device implantation. Here, we provide a series of surgical protocols tailored specifically for the implantation of a custom-made optoelectronic device that interfaces with the spinal cord in rodents. The steps to place and anchor an optical shank on a specific segment of the spinal cord via two different surgical implantation methods are detailed here. These methods are optimized for a diverse range of devices and applications, which may or may not require direct contact with the spinal cord for optical stimulation. To elucidate the methodology, the vertebral anatomy is referenced first to identify prominent landmarks before making a skin incision. The surgical steps to secure an optical shank over the cervical spine in rodents are demonstrated. Procedures are then outlined for securing the optoelectronic device connected to the optical shank in a subcutaneous space away from the spinal cord, minimizing unnecessary direct contact. Behavioral studies comparing animals receiving the implants to those undergoing sham surgeries indicate that the optical shanks did not adversely affect hindlimb or forelimb function seven days post-implantation. The present work broadens the neuromodulation toolkit for use in future studies aimed at investigating various spinal cord interventions.

Removal Forces of a Helical Microwire Structure Electrode.

(1) Background: Medical devices, especially neuromodulation devices, are often explanted for a variety of reasons. The removal process imparts significant forces on these devices, which may result in device fracture and tissue trauma. We hypothesized that a device's form factor interfacing with tissue is a major driver of the force required to remove a device, and we isolated helical and linear electrode structures as a means to study atraumatic removal. (2) Methods: Ductile linear and helical microwire structure electrodes were fabricated from either Gold (Au) or Platinum-Iridium (Pt-Ir, 90-10). Removal forces were captured from synthetic gel models and following chronic implantation in rodent and porcine models. Devices were fully implanted in the animal models, requiring a small incision (<10 mm) and removal via tissue forceps. (3) Results: Helical devices were shown to result in significantly lower maximal removal forces in both synthetic gel and rodent studies compared to their linear counterparts. Chronically (1 yr.), the maximal removal force of helical devices remained under 7.30 N, for which the Platinum-Iridium device's tensile failure force was 32.90 ± 2.09 N, resulting in a safety factor of 4.50. (4) Conclusions: An open-core helical structure that can freely elongate was shown to result in reduced removal forces both acutely and chronically.

Patient Satisfaction With Long-term Sacral Neuromodulation for Fecal Incontinence: Experience From a Single Tertiary Center.

Sacral neuromodulation is an effective treatment for fecal incontinence in the long term. Efficacy is typically assessed using bowel diary, symptom severity, and quality-of-life questionnaires, and "success" is defined as more than 50% improvement in these measures. However, patient satisfaction may be a more meaningful and individualized measure of treatment efficacy. To assess patient-reported satisfaction with long-term sacral neuromodulation and compare it to the frequently applied efficacy measures. An observational study of a prospectively maintained database. A single tertiary pelvic floor referral unit. Data from 70 patients (68 women, median age 69 [60-74] years) were available. The median time since implantation was 11 (9-14) years. Nineteen patients reported inactive neuromodulation devices. Bowel diaries, the Manchester Health Questionnaire, and the St. Mark's Incontinence Score were recorded at baseline, after percutaneous nerve evaluation, and at the last follow-up. Patient-reported satisfaction, using a 0% to 100% visual analog scale, with treatment since implantation (overall) and in the 2 weeks preceding completion of the last outcome measures (current) were also assessed. Satisfaction was significantly higher in those with active sacral neuromodulation devices (75% vs 20%, p < 0.001) at follow-up. No significant relationships exist between symptom improvement using conventional measures and patient-reported satisfaction. Current satisfaction was not associated with changes in bowel diary data after percutaneous nerve evaluation. Despite improvements in the St. Mark's Incontinence Score and Manchester Health Questionnaire below the 50% improvement threshold used to define "success," patients reported high (80%) satisfaction. Retrospective design with gaps in the available data. High patient satisfaction with sacral neuromodulation can be achieved; however, the response to percutaneous nerve evaluation may not predict treatment satisfaction in the long term. The change in questionnaire results, which measure the use of compensatory behaviors and quality-of-life impact, may better correspond to treatment satisfaction. ANTECEDENTES:La neuromodulación sacra es un tratamiento eficaz para la incontinencia fecal a largo plazo. La eficacia suele evaluarse mediante cuestionarios sobre la frecuencia diaria intestinal, la gravedad de los síntomas o la calidad de vida, y el "éxito" se define como una mejoría >50% en estas medidas. Sin embargo, la satisfacción del paciente puede ser una medida más significativa e individualizada de la eficacia del tratamiento.OBJETIVO:Evaluar la satisfacción a largo plazo de los pacientes con la neuromodulación sacra y compararla con las medidas de eficacia aplicadas con frecuencia.DISEÑO:Estudio observacional de una base de datos mantenida prospectivamente.LUGAR:Unidad terciaria única de referencia de suelo pélvico.PACIENTES:Se dispuso de datos de 70 pacientes (68 mujeres, mediana de edad 69 [60-74]). La mediana de tiempo transcurrido desde la implantación fue de 11 (9-14) años. Diecinueve pacientes informaron de dispositivos de neuromodulación inactivos.PRINCIPALES MEDIDAS DE VALORACIÓN:Diarios intestinales, el Cuestionario de Salud de Manchester y la Puntuación de Incontinencia de St Marks registrados al inicio, tras la evaluación percutánea del nervio y en el último seguimiento. Los pacientes informaron de su satisfacción, utilizando una escala analógica visual de 0%-100%, con el tratamiento desde la implantación (global) y en las dos semanas anteriores a la realización de las últimas medidas de resultado (actual).RESULTADOS:La satisfacción fue significativamente mayor en los pacientes con dispositivos de neuromodulación sacra activos (75% frente a 20%, p < 0,001) durante el seguimiento. No existen relaciones significativas entre la mejoría de los síntomas mediante medidas convencionales y la satisfacción comunicada por el paciente. La satisfacción actual no se asoció con los cambios en los datos de la frecuencia diaria intestinal tras la evaluación percutánea de los nervios. A pesar de que las mejoras en la puntuación de incontinencia de St Mark y el Cuestionario de Salud de Manchester se situaron por debajo del umbral de mejora del 50% utilizado para definir el "éxito", los pacientes declararon un alto grado de satisfacción (80%).LIMITACIONES:Retrospectivo con lagunas en los datos disponibles.CONCLUSIONES:Puede lograrse una alta satisfacción de los pacientes con la neuromodulación sacra; sin embargo, la respuesta a la evaluación percutánea del nervio puede no predecir la satisfacción con el tratamiento a largo plazo. El cambio en los resultados del cuestionario, que mide el uso de conductas compensatorias y el impacto en la calidad de vida, puede corresponder mejor a la satisfacción con el tratamiento. (Traducción-Dr. Ingrid Melo ).

Sacral neuromodulation device biofilm differs in the absence and presence of infection, harbors antibiotic resistance genes, and is reproducible in vitro.

Sacral neuromodulation (SNM) is effective therapy for overactive bladder refractory to oral therapies, and non-obstructive urinary retention. A subset of SNM devices is associated with infection requiring surgical removal. We sought to compare microbial compositions of explanted devices in the presence and absence of infection, by testing phase, and other clinical factors, and to investigate antibiotic resistance genes present in the biofilms. We analyzed resistance genes to antibiotics used in commercially-available anti-infective device coating/pouch formulations. We further sought to assess biofilm reconstitution by material type and microbial strain in vitro using a continuous-flow stir tank bioreactor, which mimics human tissue with an indwelling device. We hypothesized that SNM device biofilms would differ in composition by infection status, and genes encoding resistance to rifampin and minocycline would be frequently detected. Patients scheduled to undergo removal or revision of SNM devices were consented per IRB-approved protocol (IRB 20-415). Devices were swabbed intraoperatively upon exposure, with controls and precautions to reduce contamination of the surrounding field. Samples and controls were analyzed with next-generation sequencing and RT-PCR, metabolomics, and culture-based approaches. Associations between microbial diversity or microbial abundance, and clinical variables were then analyzed using t-tests and ANOVA. Reconstituted biofilm deposition in vitro using the bioreactor was compared by microbial strain and material type using plate-based assays and scanning electron microscopy. Thirty seven devices were analyzed, all of which harbored detectable microbiota. Proteobacteria, Firmicutes and Actinobacteriota were the most common phyla present overall. Beta-diversity differed in the presence versus absence of infection (p = 0.014). Total abundance, based on normalized microbial counts, differed by testing phase (p < 0.001), indication for placement (p = 0.02), diabetes mellitus (p < 0.001), cardiac disease (p = 0.008) and history of UTI (p = 0.008). Significant microbe-metabolite interaction networks were identified overall and in the absence of infection. 24% of biofilms harbored the tetA tetracycline/minocycline resistance gene and 53% harbored the rpoB rifampin resistance gene. Biofilm was reconstituted across tested strains and material types. Ceramic and titanium did not differ in biofilm deposition for any tested strain. All analyzed SNM devices harbored microbiota. Device biofilm composition differed in the presence and absence of infection and by testing phase. Antibiotic resistance genes including to rifampin and tetracycline/minocycline, which are used in commercially-available anti-infective pouches, were frequently detected. Isolated organisms from SNM devices demonstrated the ability to reconstitute biofilm formation in vitro. Biofilm deposition was similar between ceramic and titanium, materials used in commercially-available SNM device casings. The findings and techniques used in this study together provide the basis for the investigation of the next generation of device materials and coatings, which may employ novel alternatives to traditional antibiotics. Such alternatives might include bacterial competition, quorum-sensing modulation, or antiseptic application, which could reduce infection risk without significantly selecting for antibiotic resistance.

Focal cooling: An alternative treatment for drug-resistant epilepsy in a mesial temporal lobe epilepsy primate model-A preliminary study.

Focal cooling is emerging as a relevant therapy for drug-resistant epilepsy (DRE). However, we lack data on its effectiveness in controlling seizures that originate in deep-seated areas like the hippocampus. We present a thermoelectric solution for focal brain cooling that specifically targets these brain structures. A prototype implantable device was developed, including temperature sensors and a cannula for penicillin injection to create an epileptogenic zone (EZ) near the cooling tip in a non-human primate model of epilepsy. The mesial temporal lobe was targeted with repeated penicillin injections into the hippocampus. Signals were recorded from an sEEG (Stereoelectroencephalography)lead placed 2 mm from the EZ. Once the number of seizures had stabilized, focal cooling was applied, and temperature and electroclinical events were monitored using a customized detection algorithm. Tests were performed on two Macaca fascicularis monkeys at three temperatures. Hippocampal seizures were observed 40-120 min post-injection, their duration and frequency stabilized at around 120 min. Compared to the control condition, a reduction in the number of hippocampal seizures was observed with cooling to 21°C (Control: 4.34 seizures, SD 1.704 per 20 min vs Cooling to 21°C: 1.38 seizures, SD 1.004 per 20 min). The effect was more pronounced with cooling to 17°C, resulting in an almost 80% reduction in seizure frequency. Seizure duration and number of interictal discharges were unchanged following focal cooling. After several months of repeated penicillin injections, hippocampal sclerosis was observed, similar to that recorded in humans. In addition, seizures were identified by detecting temperature variations of 0.3°C in the EZ correlated with the start of the seizures. In epilepsy therapy, the ultimate aim is total seizure control with minimal side effects. Focal cooling of the EZ could offer an alternative to surgery and to existing neuromodulation devices.

Mapping the Vagus Nerve with Anatomical Scaffolds

Phase 2 of the Stimulating Peripheral Activity to Relieve Conditions (SPARC) program ( https://commonfund.nih.gov/sparc ) aims to build a comprehensive map of the anatomy and functional connectivity of the human vagus nerve, allowing comparisons of inter-subject variability, and helping guide experiments on vagus nerve stimulation and the development of neuromodulation devices. Following approaches used in Phase 1 of the SPARC program, segmented nerve and fascicle data (using various imaging modalities) of vagus nerves from a large number of human subjects will be registered into an Anatomical Scaffold. This is a geometric model of the vagus nerve providing a common coordinate system across subjects. Registration is achieved by fitting a subject-specific vagus scaffold to digitized subject data, using standardized annotations for trunks, branches, fixed landmarks and orientation marks in the data and for the corresponding features of the Scaffold. We report here on progress and issues in the early stages of the study. A particular complication of the vagus is inter-subject variability. While the left and right vagus trunk are quite consistent across subjects, the number and locations of branches innervating a particular organ or target is quite different from one subject to another. This dictates generating a scaffold for each subject with its own unique branching structure. Once data is available for a reasonable number of subjects these will be remapped to a common or representative vagus scaffold. At the conclusion of this study all vagus imaging, plus derived data including the scaffold and embedded fascicles, their groupings and distributions will be freely available on the SPARC Portal ( https://sparc.science/ ). Mapping to a common scaffold allows these data to be compared and visualized at equivalent locations across all subjects in the study. This work is supported by the NIH SPARC program under award number OT3OD025347. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.