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As an innovative neural modulation technique, the transcranial magneto-acousto-electric (MAE) stimulation (TMAES) realizes the synergistic regulation of neuronal discharge through the ultrasonic mechanical and inductive electric effects, offering significant prospects in biomedical applications. However, the stimulation accuracy is still limited by the unidirectional distribution of MAE field intensity. A method of constructing center-converging MAE field by coupling the helical wave fronts of focused acoustic-vortex (FAV) beams with a coaxial magnetic field is proposed. By describing FAVs with Laguerre–Gaussian functions, the theory of MAE field construction is derived in explicit formulae and the spatiotemporal characteristics of MAE fields in the focal region are analyzed. It is theoretically and experimentally demonstrated that the MAE field generated by the FAV of lth order is determined by those of (l − 1)th and (l + 1)th orders. The center-converging phase-rotating MAE field can only be generated by the FAV of first order, maintaining a constant peak intensity at the vortex center. Experimental distributions of MAE fields for FAVs of different orders show good agreements with numerical simulations. With the peak pressure of 0.86 MPa and the magnetic intensity of 0.3 T, the peak intensity of 62.1 mV/m reaching the electric stimulation threshold is achieved. The center-converging MAE field constructed by FAV may develop a new synergistic neural modulation scheme for TMAES with enhanced precision and flexibility while ensuring safety and efficacy, thereby exhibiting significant scientific and practical implications. [ABSTRACT FROM AUTHOR]

Paired vagus nerve stimulation (VNS) has emerged as a promising strategy to potentiate recovery after neurological injury. This approach, which combines short bursts of electrical stimulation of the vagus nerve with rehabilitation exercises, received approval from the US Food and Drug Aministration in 2021 as the first neuromodulation‐based therapy for chronic stroke. Because this treatment is increasingly implemented in clinical practice, there is a need to take stock of what we know about this approach and what we have yet to learn. Here, we provide a survey on the foundational basis of VNS therapy for stroke and offer insight into the mechanisms that underlie potentiated recovery, focusing on the principles of neuromodulatory reinforcement. We discuss the current state of observations regarding synaptic reorganization in motor networks that are enhanced by VNS, and we propose other prospective loci of neuromodulation that should be evaluated in the future. Finally, we highlight the future opportunities and challenges to be faced as this approach is increasingly translated to clinical use. Collectively, a clearer understanding of the mechanistic basis of VNS therapy may reveal ways to maximize its benefits. [ABSTRACT FROM AUTHOR]

Temporal interference (TI) stimulation is a popular non-invasive neurostimulation technique that utilizes the following salient neural behavior: pure sinusoid (generated in off-target brain regions) appears to cause no stimulation, whereas modulated sinusoid (generated in target brain regions) does. To understand its effects and mechanisms, we examine responses of different cell types, excitatory pyramidal (Pyr) and inhibitory parvalbumin-expressing (PV) neurons, to pure and modulated sinusoids, in intact network as well as in isolation. In intact network, we present data showing that PV neurons are much less likely than Pyr neurons to exhibit TI stimulation. Remarkably, in isolation, our data shows that almost all Pyr neurons stop exhibiting TI stimulation. We conclude that TI stimulation is largely a network phenomenon. Indeed, PV neurons actively inhibit Pyr neurons in the off-target regions due to pure sinusoids (in off-target regions) generating much higher PV firing rates than modulated sinusoids in the target regions. Additionally, we use computational studies to support and extend our experimental observations. Excitatory-inhibitory network interactions reveal the mechanisms underlying non-invasive temporal interference stimulation of the cortex. [ABSTRACT FROM AUTHOR]

Introduction: Maximal voluntary isometric contractions (MVICs) as a fatiguing modality have been widely studied, but little attention has been given to the influence of the rate of torque development. Given the established differences in motor command and neuromuscular activation between ramp and rapid MIVCs, it is likely performance fatigue differs as well as the underlying physiological mechanisms. Purpose: To compare responses for rapid and maximal torque following ramp and rapid MVICs, and the corresponding neuromuscular and corticospinal alterations. Methods: On separate visits, twelve healthy males (22.8 ± 2.5 years) performed fatiguing intermittent MVICs of the knee extensors with either 2 s (RAMP) or explosive (RAPID) ramp-ups until a 50% reduction in peak torque was achieved. Before and after each condition, maximal and rapid torque measures were determined from an MVIC. Additionally, peripheral (twitch parameters) and central (voluntary activation) fatigue, as well as rapid muscle activation, and cortical-evoked twitch and electromyographic responses were recorded. Results: Maximal and late-phase rapid torque measures (p ≤ 0.001; η²p = 0.635–0.904) were reduced similarly, but early rapid torque capacity (0–50 ms) (p = 0.003; d = 1.11 vs. p = 0.054; d = 0.62) and rapid muscle activation (p = 0.008; d = 1.07 vs. p = 0.875; d = 0.06) decreased more after RAMP. Changes in peripheral fatigue, as indicated by singlet and doublet contractile parameters (p < 0.001 for all; η²p = 0.752–0.859), and nerve-evoked voluntary activation (p < 0.001; η²p = 0.660) were similar between conditions. Corticospinal inhibition (via silent period) was only increased after RAPID (p = 0.007; d = 0.94 vs. p = 0.753; d = 0.09), whereas corticospinal voluntary activation and excitability were unchanged. Conclusion: Ramp, fatiguing MVICs impaired early rapid torque capacity more than rapid MVICs, and this was accompanied by decrements in rapid muscle activation. Responses for peripheral and central fatigue (nerve and cortical stimulation) were largely similar between conditions, except that rapid MVICs increased corticospinal inhibition. [ABSTRACT FROM AUTHOR]

Introduction: For patients with drug-resistant epilepsy, successful localization and surgical treatment of the epileptogenic zone (EZ) can bring seizure freedom. However, surgical success rates vary widely because there are currently no clinically validated biomarkers of the EZ. Highly epileptogenic regions often display increased levels of cortical excitability, which can be probed using single-pulse electrical stimulation (SPES), where brief pulses of electrical current are delivered to brain tissue. It has been shown that high-amplitude responses to SPES can localize EZ regions, indicating a decreased threshold of excitability. However, performing extensive SPES in the epilepsy monitoring unit (EMU) is time-consuming. Thus, we built patient-specific in silico dynamical network models from interictal intracranial EEG (iEEG) to test whether virtual stimulation could reveal information about the underlying network to identify highly excitable brain regions similar to physical stimulation of the brain. Methods: We performed virtual stimulation in 69 patients that were evaluated at five centers and assessed for clinical outcome 1 year post surgery. We further investigated differences in observed SPES iEEG responses of 14 patients stratified by surgical outcome. Results: Clinically-labeled EZ cortical regions exhibited higher excitability from virtual stimulation than non-EZ regions with most significant differences in successful patients and little difference in failure patients. These trends were also observed in responses to extensive SPES performed in the EMU. Finally, when excitability was used to predict whether a channel is in the EZ or not, the classifier achieved an accuracy of 91%. Discussion: This study demonstrates how excitability determined via virtual stimulation can capture valuable information about the EZ from interictal intracranial EEG. [ABSTRACT FROM AUTHOR]

Objective To investigate the predictive value of thoracic sympathetic ganglion block (TSGB) in response to ketamine infusion therapy (KIT) and spinal-cord stimulation (SCS) in patients with chronic upper-extremity pain including complex regional pain syndrome (CRPS). Design Retrospective Setting Tertiary hospital single-center Subjects Patients who underwent TSGB receiving KIT or SCS within a 3-year window. Methods Positive TSGB outcomes were defined as ≥2 0–10 Numerical Rating Scale (NRS) score reduction at 2 weeks post-procedure. Positive KIT and SCS outcomes were determined by ≥2 NRS score reduction at 2–4 weeks post-KIT and ≥4 NRS score reduction at 2–4 weeks post-SCS implantation, respectively. Results Among 207 patients who underwent TSGB, 38 received KIT and 34 underwent SCS implantation within 3 years post-TSGB; 33 patients receiving KIT and 32 patients receiving SCS were included. Among 33 patients who received KIT, 60.6% (n  = 20) reported a ≥ 2 0–10 NRS pain-score reduction. Positive response to TSGB occurred in 70.0% (n  = 14) KIT responders, significantly higher than that in 30.8% (n  = 4) KIT non-responders. Multivariable analysis revealed a positive association between positive responses to TSGB and KIT (OR 7.004, 95% CI 1.26–39.02). Among 32 patients who underwent SCS implantation, 68.8% (n  = 22) experienced short-term effectiveness. Positive response to TSGB was significantly higher in SCS responders (45.5%, n  = 10) than in non-responders (0.0%). However, there were no associations between pain reduction post-TSGB and that post-KIT or post-SCS. Conclusions A positive response to TSGB is a potential predictor for positive KIT and SCS outcomes among patients with chronic upper-extremity pain, including CRPS. [ABSTRACT FROM AUTHOR]

Purpose: This study aimed to assess the clinical effectiveness and safety of percutaneous endoscopic interlaminar discectomy (PEID) in the management of high-grade migrated Lumbar disc herniation (LDH). Methods: A total of 328 patients who underwent PEID for high-grade migrated LDH between May 2020 and January 2023 in our hospital were selected. Patients were categorized into high-grade migrated group and low-grade migrated group according to preoperative MRI findings. The preoperative and postoperative evaluations of clinical outcomes, such as Visual Analogue Scale (VAS) for lower backs and legs, Oswestry Disability Index (ODI), and modified MacNab criteria for surgical success, were compared between groups. Results: No statistically significant differences were found in hospitalization time, surgery time, intraoperative hemorrhage, number of intraoperative fluoroscopies, or incision length between the two groups. The lower back and leg VAS scores and ODI exhibited a statistically significant decrease in both groups across all postoperative time intervals. However, the difference between the two groups was not statistically significant. Postoperative nerve root stimulation symptoms were reported in two and three cases in the high-grade migrated group and low-grade migrated group, respectively. One patient in the high-grade migrated group underwent reoperation due to re-herniation at the same segment. There was no significant difference in the rate of excellent-good cases between the two groups, with an overall rate of 94.7%. Conclusion: In treating high-grade migrated disc herniation, PEID offers advantages such as reduced trauma, small incision, quicker recovery and satisfactory clinical safety and efficacy. [ABSTRACT FROM AUTHOR]

• Ophthalmoparesis has not been previously described in anti-HMGCR antibody-associated myopathies and two cases are presented. • Other causes of ophthalmoparesis and proximal weakness were extensively ruled out. • Consider anti-HMGCR antibody-associated myopathies in patients with proximal weakness, elevated creatine kinase, and ophthalmoparesis. We describe two anti-3‑hydroxy-3-methyl-glutaryl-coenzyme A reductase (HMGCR) antibody-positive patients with treatment-responsive ophthalmoparesis. Patient 1 was a 53-year-old male with progressive proximal limb weakness, dysphagia, ptosis, and diplopia over 6 weeks and creatine kinase (CK) of 3,512 units/L. Patient 2 was a 55-year-old female with progressive proximal weakness, dysarthria, ptosis, diplopia, and dyspnea over 2 weeks with CK of 31,998 units/L. Both patients had normal thyroid studies and repetitive nerve stimulation, myopathic electromyography with fibrillation potentials, magnetic resonance imaging demonstrating abnormal enhancement of extraocular muscles, muscle biopsy showing necrotic myofibers, and positive anti-HMGCR antibodies. Patient 1 also had weakly positive anti-PM/Scl antibodies. Immunomodulatory therapies led to resolution of oculobulbar weakness and normalization of CK levels in both patients, while limb weakness resolved completely in patient 1 and partially in patient 2. These cases expand the phenotypic spectrum of anti-HMGCR antibody-associated myopathies to include subacute ophthalmoparesis with limb-girdle weakness and markedly elevated CK. [ABSTRACT FROM AUTHOR]

Background: Apoptosis is an important pathologic mechanism of erectile dysfunction after radical prostatectomy. Studies have shown that programmed cell death factor 4 is connected to the modulation of apoptosis in many cells. However, the programmed cell death factor 4 function in the cavernous nerve injury erectile dysfunction is unclear. Objective: This investigation aimed to explore the programmed cell death factor 4 function in erectile dysfunction in rats with bilateral cavernous nerve crush. Materials and methods: The experiment used 30 male Sprague Dawley rats (18 months old) that were screened for normal erectile function by the apomorphine test. Ten rats were randomized into Sham and bilateral cavernous nerve crush groups to detect changes in programmed cell death factor 4 expression. The remaining 20 rats were distributed at random to four groups: the Sham group treated by sham surgery, the phosphate‐buffered saline group, the lentivirus containing negative control short hairpin RNA group, and the lentivirus containing short hairpin RNA targeting programmed cell death factor 4 group underwent bilateral cavernous nerve crush and were afterward administered intracavernous injections of phosphate‐buffered saline, lentivirus containing negative control short hairpin RNA, or lentivirus containing short hairpin RNA targeting programmed cell death factor 4. Electrical stimulation of the cavernous nerve was conducted 2 weeks later for penile erectile function assessment. The cavernous tissue was collected for histological analysis and western blotting. Results: The apoptosis level in rat corpus cavernosum was elevated, and programmed cell death factor 4 expression was increased after bilateral cavernous nerve crush. Knockdown of programmed cell death factor 4 significantly improved erectile function in bilateral cavernous nerve crush rats. Furthermore, lentivirus containing short hairpin RNA targeting programmed cell death factor 4 treatment raised smooth muscle content and attenuated cavernous fibrosis and apoptotic levels. Additionally, programmed cell death factor 4 was found to mediate the PI3K/AKT pathway. Discussion and conclusion: Elevated programmed cell death factor 4 expression may be an important pathogenetic mechanism for erectile dysfunction after bilateral cavernous nerve crush, and the knockdown of programmed cell death factor 4 enhanced erectile function in 18‐month‐old rats after cavernous nerve damage. The potential mechanism may be the stimulation of the PI3K/AKT pathway to attenuate the cavernous apoptosis level. [ABSTRACT FROM AUTHOR]

Background We previously reported that normalization of motor evoked potential (MEP) monitoring amplitude by compound muscle action potential (CMAP) after peripheral nerve stimulation prevented the expression of anesthetic fade (AF), suggesting that AF might be due to reduced synaptic transfer in the neuromuscular junction. Methods We calculated the time at which AF began for each of craniotomy and spinal cord surgery, and examined whether AF was avoided by CMAP after peripheral nerve stimulation normalization in each. Similar studies were also made with respect to the upper and lower limb muscles. Results AF was observed in surgery lasting 160 minutes for craniotomy and 260 minutes or more for spinal surgery, and 195 minutes in the upper limb muscles and 135 minutes in the lower limb muscles. In all the series, AF could be avoided by CMAP after peripheral nerve stimulation normalization. Conclusion AF of MEP occurred in both craniotomy and spinal cord surgery, and it was also corrected by CMAP after peripheral nerve stimulation. AF is considered to be mainly due to a decrease in synaptic transfer of the neuromuscular junction due to the accumulation of propofol because of the avoidance by CMAP normalization. However, it may be partially due to a decrease in the excitability of pyramidal tracts and α-motor neurons, because AF occurred earlier in the lower limb muscles than in the upper limb muscles. [ABSTRACT FROM AUTHOR]

The restoration of adequate function and sensation in nerves following an injury is often insufficient. Electrical stimulation (ES) applied during nerve repair can promote axon regeneration, which may enhance the likelihood of successful functional recovery. However, increasing operation time and complexity are associated with limited clinical use of ES. This study aims to better assess whether short-duration ES types (voltage mode vs. current mode) are able to produce enhanced regenerative activity following peripheral nerve repair in rat models. Wistar rats were randomly divided into 3 groups: no ES (control), 30-minute ES with a current pulse, and 30-minute ES with a voltage pulse. All groups underwent sciatic nerve transection and repair using a silicone tube to bridge the 6-mm gap between the stumps. In the 2 groups other than the control, ES was applied after the surgical repair. Outcomes were evaluated using electrophysiology, histology, and serial walking track analysis. Biweekly walking tracks test over 12 weeks revealed that subjects that underwent ES experienced more rapid functional improvement than subjects that underwent repair alone. Electrophysiological analysis of the newly intratubular sciatic nerve at week 12 revealed strong motor function recovery in rats that underwent 30-minute ES. Histologic analysis of the sciatic nerve and its tibial branch at 12 weeks demonstrated robust axon regrowth in all groups. Both types of short-duration ES applied during nerve repair can promote axon regrowth and enhance the chances of successful functional recovery. [ABSTRACT FROM AUTHOR]

Objectives: Gastroparesis that is refractory to standard dietary and medical management may benefit from surgical treatment with gastric electrical neurostimulation, which has shown promise in reducing symptoms of the disease. Pyloroplasty may serve an adjunctive role to a gastric stimulator, but the precise benefit remains unclear. The present study compares reported rates of symptom improvement following gastric neurostimulator implantation with and without pyloroplasty. Materials and methods: A single center retrospective analysis of consecutive patients who received operative management for symptom refractory gastroparesis from 1 January 2020 to 31 December 2021 was performed. Subjects were assigned to cohorts based on treatment with gastric electrical stimulation alone (GES-only) or combined with pyloroplasty (GES + PP). A survey-based assessment was administered post-operatively that evaluated cardinal symptoms of gastroparesis (nausea, vomiting, early satiety) before and after treatment. Results: In total, 42 patients (15 GES-only, 27 GES + PP) were included in the study. Both groups reported a high degree of improvement in global symptom control following surgery (93% vs 81%) with no differences between treatment cohorts (p = 0.09). Early satiety demonstrated better improvement in patients who received gastric stimulation alone (p = 0.012). Subgroup analysis of diabetic gastroparesis patients showed a 2.2% decrease in hemoglobin A1c levels in the GES + PP group (p-0.034). Conclusions: Symptom reduction in refractory gastroparesis appears to improve after placement of a gastric neurostimulator with or without the addition of a pyloroplasty procedure. [ABSTRACT FROM AUTHOR]

Congenital myasthenic syndromes (CMS) are a group of genetic disorders characterized by impaired neuromuscular transmission. CMS typically present at a young age with fatigable muscle weakness, often with an abnormal response after repetitive nerve stimulation (RNS). Pharmacologic treatment can improve symptoms, depending on the underlying defect. Prevalence is likely underestimated. This study reports on patients with CMS followed in Belgium in 2022. Data were gathered retrospectively from the medical charts. Only likely pathogenic and pathogenic variants were included in the analysis. We identified 37 patients, resulting in an estimated prevalence of 3.19 per 1,000,000. The patients harbored pathogenic variants in CHRNE , RAPSN , DOK7 , PREPL , CHRNB1 , CHRNG , COLQ , MUSK , CHRND , GFPT1, and GMPPB. CHRNE was the most commonly affected gene. Most patients showed disease onset at birth, during infancy, or during childhood. Symptom onset was at adult age in seven patients, caused by variants in CHRNE , DOK7 , MUSK , CHRND, and GMPPB. Severity and distribution of weakness varied, as did the presence of respiratory involvement, feeding problems, and extraneuromuscular manifestations. RNS was performed in 23 patients of whom 18 demonstrated a pathologic decrement. Most treatment responses were predictable based on the genotype. This is the first pooled characterization of patients with CMS in Belgium. We broaden the phenotypical spectrum of pathogenic variants in CHRNE with adult-onset CMS. Systematically documenting larger cohorts of patients with CMS can aid in better clinical characterization and earlier recognition of this rare disease. We emphasize the importance of establishing a molecular genetic diagnosis to tailor treatment choices. [ABSTRACT FROM AUTHOR]

Electromagnetic stimulation of the phrenic nerve induces diaphragm contractions, but no coils for clinical use have been available. We recently demonstrated the feasibility of ventilation using bilateral transcutaneous noninvasive electromagnetic phrenic nerve stimulation (NEPNS) before surgery in lung-healthy patients with healthy weight in a dose-dependent manner. Is NEPNS feasible in critically ill patients in an ICU setting? This feasibility nonrandomized controlled study aimed to enroll patients within 36 h of intubation who were expected to remain ventilated for ≥ 72 h. The intervention group received 15-min bilateral transcutaneous NEPNS bid, whereas the control group received standard care. If sufficient, NEPNS was used without pressure support to ventilate the patient; pressure support was added if necessary to ventilate the patient adequately. The primary outcome was feasibility, measured as time to find the optimal stimulation position. Further end points were sessions performed according to the protocol or allowing a next-day catch-up session and tidal volume achieved with stimulation reaching only 3 to 6 mL/kg ideal body weight (IBW). A secondary end point was expiratory diaphragm thickness measured with ultrasound from days 1 to 10 (or extubation). The revised European Union regulation mandated reapproval of medical devices, prematurely halting the study. Eleven patients (five in the intervention group, six in the control group) were enrolled. The median time to find an adequate stimulation position was 23 s (interquartile range, 12-62 s). The intervention bid was executed in 87% of patients, and 92% of patients including a next-day catch-up session. Ventilation with 3 to 6 mL/kg IBW was achieved in 732 of 1,701 stimulations (43.0%) with stimulation only and in 2,511 of 4,036 stimulations (62.2%) with additional pressure support. A decrease in diaphragm thickness was prevented by bilateral NEPNS (P =.034) until day 10. Bilateral transcutaneous NEPNS was feasible in the ICU setting with the potential benefit of preventing diaphragm atrophy during mechanical ventilation. NEPNS ventilation effectiveness needs further assessment. ClinicalTrials.gov ; No.: NCT05238753 ; URL: www.clinicaltrials.gov [ABSTRACT FROM AUTHOR]

This article provides an overview of the advancements and practical applications of magnetic resonance imaging (MRI) in diagnosing and treating musculoskeletal disorders. It discusses the benefits of MRI, including its excellent soft tissue contrast and multiplanar capabilities, as well as the technical developments that have improved its resolution and acquisition time. The article also acknowledges the challenges and limitations of MRI, such as long acquisition times and difficulties imaging tissues near hardware. It emphasizes the importance of considering practicality and feasibility in clinical settings, while also addressing various aspects of MRI imaging, including reducing distortion artifacts, patient safety considerations, workflow efficiency, and the need for increased access to MRI scanners, particularly in low- and middle-income countries. The authors call for ongoing research and technological advancements to further enhance the field of MRI imaging. [Extracted from the article]

• The interhemispheric connection between primary somatosensory areas can be probed by using bilateral median nerve stimulation. • N20 potentials and the late component of the high-frequency oscillations vary significantly across interstimulus intervals. • Findings suggest interhemispheric interaction between the primary somatosensory cortices, through corpus callosum. This study aimed at investigating the effect of median nerve stimulation on ipsilateral cortical potentials evoked by contralateral median nerve electrical stimulation. We recorded somatosensory-evoked potentials (SEPs) from the left parietal cortex in 15 right-handed, healthy subjects. We administered bilateral median nerve stimulation, with the ipsilateral stimulation preceding the stimulation on the contralateral by intervals of 5, 10, 20, or 40 ms. We adjusted these intervals based on each individual's N20 latency. As a measure of S1 excitability, the amplitude of the N20 and the area of the High Frequency Oscillation (HFO) burst were analyzed for each condition. The results revealed significant inhibition of N20 amplitude by ipsilateral median nerve stimulation at interstimulus intervals (ISIs) between 5 and 40 ms. Late HFO burst was suppressed at short ISIs of 5 and 10 ms, pointing to a transcallosal inhibitory effect on S1 intracortical circuits. Findings suggest interhemispheric interaction between the primary somatosensory areas, supporting the existence of transcallosal transfer of tactile information. This study provides valuable insights into the interhemispheric connections between primary sensory areas and underscore the potential role of interhemispheric interactions in somatosensory processing. [ABSTRACT FROM AUTHOR]

Drug-resistant epilepsy (DRE) poses significant challenges in terms of effective management and seizure control. Neuromodulation techniques have emerged as promising solutions for individuals who are unresponsive to pharmacological treatments, especially for those who are not good surgical candidates for surgical resection or laser interstitial therapy (LiTT). Currently, there are three neuromodulation techniques that are FDA-approved for the management of DRE. These include vagus nerve stimulation (VNS), deep brain stimulation (DBS), and responsive neurostimulation (RNS). Device selection, optimal time, and DBS and RNS target selection can also be challenging. In general, the number and localizability of the epileptic foci, alongside the comorbidities manifested by the patients, substantially influence the selection process. In the past, the general axiom was that DBS and VNS can be used for generalized and localized focal seizures, while RNS is typically reserved for patients with one or two highly localized epileptic foci, especially if they are in eloquent areas of the brain. Nowadays, with the advance in our understanding of thalamic involvement in DRE, RNS is also very effective for general non-focal epilepsy. In this review, we will discuss the underlying mechanisms of action, patient selection criteria, and the evidence supporting the use of each technique. Additionally, we explore emerging technologies and novel approaches in neuromodulation, such as closed-loop systems. Moreover, we examine the challenges and limitations associated with neuromodulation therapies, including adverse effects, complications, and the need for further long-term studies. This comprehensive review aims to provide valuable insights on present and future use of neuromodulation. [ABSTRACT FROM AUTHOR]

Transcranial Motor Evoked Potentials (TcMEPs) can improve intraoperative detection of femoral plexus and nerve root injury during lumbosacral spine surgery. However, even under ideal conditions, TcMEPs are not completely free of false-positive alerts due to the immobilizing effect of general anesthetics, especially in the proximal musculature. The application of transcutaneous stimulation to activate ventral nerve roots directly at the level of the conus medularis (bypassing the brain and spinal cord) has emerged as a method to potentially monitor the motor component of the femoral plexus and lumbosacral nerves free from the blunting effects of general anesthesia. To evaluate the reliability and efficacy of transabdominal motor evoked potentials (TaMEPs) compared to TcMEPs during lumbosacral spine procedures. We present the findings of a single-center 12-month retrospective experience of all lumbosacral spine surgeries utilizing multimodality intraoperative neuromonitoring (IONM) consisting of TcMEPs, TaMEPs, somatosensory evoked potentials (SSEPs), electromyography (EMG), and electroencephalography. Two hundred and twenty patients having one, or a combination of lumbosacral spine procedures, including anterior lumbar interbody fusion (ALIF), lateral lumbar interbody fusion (LLIF), posterior spinal fusion (PSF), and/or transforaminal lumbar interbody fusion (TLIF). Intraoperative neuromonitoring data was correlated to immediate postoperative neurologic examinations and chart review. Baseline reliability, false positive rate, true positive rate, false negative rate, area under the curve at baseline and at alerts, and detection of preoperative deficits of TcMEPs and TaMEPs were compared and analyzed for statistical significance. The relationship between transcutaneous stimulation voltage level and patient BMI was also examined. TaMEPs were significantly more reliable than TcMEPs in all muscles except abductor hallucis. Of the 27 false positive alerts, 24 were TcMEPs alone, and 3 were TaMEPs alone. Of the 19 true positives, none were detected by TcMEPs alone, 3 were detected by TaMEPs alone (TcMEPs were not present), and the remaining 16 true positives involved TaMEPs and TcMEPs. TaMEPs had a significantly larger area under the curve (AUC) at baseline than TcMEPs in all muscles except abductor hallucis. The percent decrease in TcMEP and TaMEP AUC during LLIF alerts was not significantly different. Both TcMEPs and TaMEPs reflected three preexisting motor deficits. Patient BMI and TaMEP stimulation intensity were found to be moderately positively correlated. These findings demonstrate the high reliability and predictability of TaMEPs and the potential added value when TaMEPs are incorporated into multimodality IONM during lumbosacral spine surgery. [ABSTRACT FROM AUTHOR]

Objective: To assess the efficacy of microcurrent electrical nerve stimulation (MENS) therapy in treating myofascial pain of the masticatory muscles. Methods: In this systematic review and meta-analysis, the efficacy of MENS was evaluated, with the primary outcome being the reduction in pain on palpation of the masticatory muscles. Results: Four independent comparisons based on three studies were included in the meta-analysis (n = 140). In comparison to placebo and other therapies, treatment with MENS showed an improved mean reduction in pain of −0.57 points (CI: −0.91 to −0.23 points, I2 = 83.7%). Conclusion: Evidence from this meta-analysis shows that MENS is an effective non-invasive treatment that can be used to reduce pain in patients with myofascial pain of the masticatory muscle; however, the study was limited by the small number of articles relevant to the research question as well as variability between the selected studies. [ABSTRACT FROM AUTHOR]

Purpose: To demonstrate the performance of gradient array coils in minimizing switched‐gradient‐induced electric fields (E‐fields) and improving peripheral nerve stimulation (PNS) thresholds while generating gradient fields with adjustable linearity across customizable regions of linearity (ROLs). Methods: A body gradient array coil is used to reduce the induced E‐fields on the surface of a body model by modulating applied currents. This is achieved by performing an optimization problem with the peak E‐field as the objective function and current amplitudes as unknown variables. Coil dimensions and winding patterns are fixed throughout the optimization, whereas other engineering metrics remain adjustable. Various scenarios are explored by manipulating adjustable parameters. Results: The array design consistently yields lower E‐fields and higher PNS thresholds across all scenarios compared with a conventional coil. When the gradient array coil generates target gradient fields within a 44‐cm‐diameter spherical ROL, the maximum E‐field is reduced by 10%, 18%, and 61% for the X, Y, and Z gradients, respectively. Transitioning to a smaller ROL (24 cm) and relaxing the gradient linearity error results in further E‐field reductions. In oblique gradients, the array coil demonstrates the most substantial reduction of 40% in the Z–Y direction. Among the investigated scenarios, the most significant increase of 4.3‐fold is observed in the PNS thresholds. Conclusion: Our study demonstrated that gradient array coils offer a promising pathway toward achieving high‐performance gradient coils regarding gradient strength, slew rate, and PNS thresholds, especially in scenarios in which linear magnetic fields are required within specific target regions. [ABSTRACT FROM AUTHOR]

Introduction/Purpose: 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. Materials/Methods: 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. Results: 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. Conclusions: 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. [ABSTRACT FROM AUTHOR]

Highlights The experience of pain that is induced by extremely cold temperatures can exert a modulatory effect on motor cortex circuitry. Although it is known that immersion of a single limb in very cold water can increase corticomotor excitability it is unknown how afferent input to the cortex shapes excitatory and inhibitory processes. Therefore, the purpose of this study was to examine motor‐evoked potentials (MEP), short‐latency afferent inhibition (SAI) and long‐latency afferent inhibition (LAI) in response to immersion of a single hand in cold water. Transcranial magnetic stimulation (TMS) was used to assess MEPs, and peripheral nerve stimulation of the median nerve paired with TMS was used to measure SAI and LAI in motor circuits of the ipsilateral hemisphere. Measurements were obtained from electromyography (EMG) of the first dorsal interosseous (FDI) at baseline, during cold‐water immersion, and during recovery from cold‐water immersion. The intervention caused unconditioned MEPs to increase during exposure to the cold stimulus (P = 0.008) which then returned to baseline levels once the hand was removed from the cold water. MEP responses were decoupled from SAI responses, where SAI was reduced during exposure to the cold stimulus (P = 0.005) and remained reduced compared to baseline when the hand was removed from the cold water (P = 0.002). The intervention had no effect on LAI. The uncoupling of SAI from MEPs during the recovery period suggests that the mechanisms underlying the modulation of corticospinal excitability by sensory input may be distinct from those affecting intracortical inhibitory circuits. What is the central question of this study? Does immersion of a limb in very cold water influence corticospinal excitability and the level of afferent inhibition exerted on motor cortical circuits? What is the main finding and its importance? In additional to perception of temperature, immersion in 6°C water also induced perceptions of pain. Motor evoked potential (MEP) amplitude increased during immersion, and short‐latency afferent inhibition (SAI) of the motor cortex was reduced during immersion; however, these responses differed after the limb was removed from the cold stimulus, as MEPs returned to normal levels while SAI remained suppressed. What is the central question of this study?Does immersion of a limb in very cold water influence corticospinal excitability and the level of afferent inhibition exerted on motor cortical circuits?What is the main finding and its importance?In additional to perception of temperature, immersion in 6°C water also induced perceptions of pain. Motor evoked potential (MEP) amplitude increased during immersion, and short‐latency afferent inhibition (SAI) of the motor cortex was reduced during immersion; however, these responses differed after the limb was removed from the cold stimulus, as MEPs returned to normal levels while SAI remained suppressed. [ABSTRACT FROM AUTHOR]

Neuromodulation is a powerful tool for fundamental studies in neuroscience and potential treatments of neurological disorders. Both photoacoustic (PA) and photothermal (PT) effects are harnessed for non‐genetic high‐precision neural stimulation. Using a fiber‐based device excitable by a nanosecond pulsed laser and a continuous wave laser for PA and PT stimulation, respectively, PA and PT neuromodulation is systematically investigated at the single neuron level. These results show that to achieve the same level of neuron activation recorded by Ca2+ imaging, the laser energy needed for PA stimulation is 1/40 of that needed for PT stimulation. The threshold energy for PA stimulation is found to be further reduced in neurons overexpressing mechano‐sensitive channels, indicating direct involvement of mechano‐sensitive channels in PA stimulation. Electrophysiology study of single neurons upon PA and PT stimulation is performed by patch clamp recordings. Electrophysiological features induced by PA are distinct from those by PT, confirming that PA and PT stimulation operate through different mechanisms. These insights offer a foundation for the rational design of more efficient and safer non‐genetic neural modulation approaches. [ABSTRACT FROM AUTHOR]

Implantable devices interfacing with peripheral nerves exhibit limited longevity and resolution. Poor nerve-electrode interface quality, invasive surgical placement and development of foreign body reaction combine to limit research and clinical application of these devices. Here, we develop cuff implants with a conformable design that achieve high-quality and stable interfacing with nerves in chronic implantation scenarios. When implanted in sensorimotor nerves of the arm in awake rats for 21 days, the devices record nerve action potentials with fascicle-specific resolution and extract from these the conduction velocity and direction of propagation. The cuffs exhibit high biocompatibility, producing lower levels of fibrotic scarring than clinically equivalent PDMS silicone cuffs. In addition to recording nerve activity, the devices are able to modulate nerve activity at sub-nerve resolution to produce a wide range of paw movements. When used in a partial nerve ligation rodent model, the cuffs identify and characterise changes in nerve C fibre activity associated with the development of neuropathic pain in freely-moving animals. The developed implantable devices represent a platform enabling new forms of fine nerve signal sensing and modulation, with applications in physiology research and closed-loop therapeutics. Nerve interfaces have the potential to deliver therapythroughout the body by monitoring and modulating function via the peripheral nervous system. Here, the authors present an ultraconformable cuff capable of high-resolution recording and stimulation of nerve activity in freely-moving conditions. [ABSTRACT FROM AUTHOR]

Background: Gross motor function impairments and manual dexterity deficits are frequently observed in children and adolescents with Cerebral Palsy (CP), having a major impact on their activity level and autonomy. Improving manual dexterity and activity level of patients with CP is often the focus of rehabilitation. Novel and adjuvant treatment methods that could support the standard training also in chronic conditions are a research priority. The transcutaneous Vagus Nerve Stimulation (tVNS) is a non-invasive brain stimulation technique, which provides a bottom-up stimulation of subcortical and cortical brain structures, enhancing brain GABA and Noradrenaline levels. This technique may play a pivotal role in brain plasticity, which has not been tested in CP patients before. Methods: 44 children and adolescents with CP will be involved, treated in pairs in a randomized, double-blind, pre-post test study. The two groups will undergo the Hand-Arm Bimanual Intensive Therapy Including Lower Extremities (HABITILE) for 2 consecutive weeks, with 3  h daily sessions for 5  days per week, for an overall time interval of 30  h; the training will be combined with the application for 75  min/day of active or sham tVNS, in separate, randomly allocated groups. The primary outcome measure will include the scores at the Assisting Hand Assessment and Box and Block Test, and at an ad-hoc visuomotor task evaluating manual visuomotor control. Secondary outcomes will include the scores at the Children’s Hand Experience Questionnaire, Canadian Occupational Performance Measure, Melbourne Assessment of Unilateral Upper Limb Function, Gross Motor Function Measure, Vineland, Pediatric quality of life inventory. The evaluation points will include pre (T0), post (T1) and 3-month follow up (T2) assessments. Safety and tolerability will also be assessed. Results: The results of this trial will assess whether tVNS can effectively boost the effects of an intensive two-week bimanual training, in improving manual dexterity in children and adolescents with cerebral palsy, ensuring safety and tolerability throughout the intervention period. [ABSTRACT FROM AUTHOR]

Advanced artificial nerve conduits offer a promising alternative for nerve injury repair. Current research focuses on improving the therapeutic effectiveness of nerve conduits by optimizing scaffold materials and functional components. In this study, a novel poly(3,4‐ethylenedioxythiophene) (PEDOT)‐integrated fish swim bladder (FSB) is presented as a conductive nerve conduit with ordered topology and electrical stimulation to promote nerve regeneration. PEDOT nanomaterials and adhesive peptides (IKVAV) are successfully incorporated onto the decellularized FSB substrate through pre‐coating with polydopamine. The obtained PEDOT/IKVAV‐integrated FSB substrate exhibits outstanding mechanical properties, high electrical conductivity, stability, as well as excellent biocompatibility and bioadhesive properties. In vitro studies confirm that the PEDOT/IKVAV‐integrated FSB can effectively facilitate the growth and directional extension of pheochromocytoma 12 cells and dorsal root ganglion neurites. In addition, in vivo experiments demonstrate that the proposed PEDOT/IKVAV‐integrated FSB conduit can accelerate defective nerve repair and functional restoration. The findings indicate that the FSB‐derived conductive nerve conduits with multiple regenerative inducing signals integration provide a conducive milieu for nerve regeneration, exhibiting great potential for repairing long‐segment neural defects. [ABSTRACT FROM AUTHOR]

ABSTRACT Photobiomodulation (PBM) using 830 nm light‐emitting diode (LED) benefits tissue regeneration, wound healing and neural stimulation. However, there is not much exploration of its effect on melanocytes and ex vivo skin model. This study aims to investigate the mechanism behind the anti‐melanogenic activity of 830 nm LED and provides evidence for its activity in human ex vivo skin model. Our results showed that 830 nm LED at fluences ranging from 5 to 20 J/cm2 inhibited melanosome maturation and reduced melanin content, tyrosinase activity and melanogenesis‐related proteins. 830 nm LED inhibited the phosphorylation of AKT and its downstream FOXO3a, leading to nuclear translocation of FOXO3a. Furthermore, FOXO3a knockdown and AKT activator like SC79 could reverse the melanogenesis inhibition phenotype induced by 830 nm LED. In human ex vivo skin model, Fontana–Masson staining revealed a decrease in epidermal basal pigmentation after 830 nm LED irradiation. Taken together, 830 nm LED demonstrated the anti‐melanogenic activity via FOXO3a. [ABSTRACT FROM AUTHOR]

Background: Micro-RNAs could provide great insights about the neuropathological mechanisms associated with osteoarthritis (OA) pain processing. Using the validated Montreal Induction of Rat Arthritis Testing (MIRAT) model, this study aimed to characterize neuroepigenetic markers susceptible to correlate with innovative pain functional phenotype and targeted neuropeptide alterations. Methods: Functional biomechanical, somatosensory sensitization (peripheral--via tactile paw withdrawal threshold; central--via response to mechanical temporal summation), and diffuse noxious inhibitory control (via conditioned pain modulation) alterations were assessed sequentially in OA (n = 12) and Naïve (n = 12) rats. Joint structural, targeted spinal neuropeptides and differential expression of spinal cord micro-RNAs analyses were conducted at the sacrifice (day (D) 56). Results: The MI-RAT model caused important structural damages (reaching 35.77% of cartilage surface) compared to the Naïve group (P < 0.001). This was concomitantly associated with nociceptive sensitization: ipsilateral weight shift to the contralateral hind limb (asymmetry index) from -55.61% ± 8.50% (D7) to -26.29% ± 8.50% (D35) (P < 0.0001); mechanical pain hypersensitivity was present as soon as D7 and persisting until D56 (P < 0.008); central sensitization was evident at D21 (P = 0.038); pain endogenous inhibitory control was distinguished with higher conditioned pain modulation rate (P < 0.05) at D7, D21, and D35 as a reflect of filtrated pain perception. Somatosensory profile alterations of OA rats were translated in a persistent elevation of pro-nociceptive neuropeptides substance P and bradykinin, along with an increased expression of spinal miR-181b (P = 0.029) at D56. Conclusion: The MI-RAT OA model is associated, not only with structural lesions and static weight-bearing alterations, but also with a somatosensory profile that encompasses pain centralized sensitization, associated to active endogenous inhibitory/facilitatory controls, and corresponding neuropeptidomic and neuroepigenetic alterations. This preliminary neuroepigenetic research confirms the crucial role of pain endogenous inhibitory control in the development of OA chronic pain (not only hypersensitivity) and validates the MI-RAT model for its study. [ABSTRACT FROM AUTHOR]

Objective: In addition to the well-established advantage that strengthened pelvic musculature increases urethral resistance in stress urinary incontinence (SUI) patients, intra-vaginal electrical stimulation (iVES) has been shown in preclinical studies to improve bladder capacity via the pudendal-hypogastric mechanism. This study investigated whether iVES also benefits bladder storage in SUI patients by focusing on compliance, a viscoelastic parameter critically defining the bladder's storage function, in a clinical study. Moreover, the potential involvement of stimulation-induced neuromodulation in iVESmodified compliance was investigated by comparing the therapeutic outcomes of SUI patients treated with iVES to those who underwent a trans-obturator tape (TOT) implantation surgery, where a mid-urethral sling was implanted without electric stimulation. Patients and methods: Urodynamic and viscoelastic data were collected from 21 SUI patients treated with a regimen combining iVES and biofeedbackassisted pelvic floor muscle training (iVES-bPFMT; 20-min iVES and 20-min bPFMT sessions, twice per week, for 3 months). This regimen complied with ethical standards. Data from 21 SUI patients who received TOT implantation were retrospectively analyzed. Mean compliance (Cm), infused volume (Vinf), and threshold pressure (Pthr) from the pressure-flow/volume investigations were assessed. Results: Compared with the pretreatment control, iVES-bPFMT consistently and significantly increased Cm (18/21; 85%, p = 0.017, N = 21) and Vinf (16/21; 76%, p = 0.046; N = 21) but decreased Pthr (16/21; 76%, p = 0.026, N = 21). In contrast, TOT implantation did not result in consistent or significant changes in Cm, Vinf, or Pthr (p = 0.744, p = 0.295, p = 0.651, respectively; all N = 21). Conclusion: Our results provide viscoelastic and thermodynamic evidence supporting an additional benefit of iVES-bPFMT to bladder storage in SUI patients by modifying bladder compliance, possibly due to the potentiated hypogastric tone, which did not occur in TOT-treated SUI patients. [ABSTRACT FROM AUTHOR]

Background: Over the last three decades, the number of randomized controlled trials (RCTs) using stimulation of auricular vagal sensory nerves by means of electrical stimulation, auricular acupuncture, or acupressure to support weight loss has increased markedly. This systematic review focuses on the effects of auricular stimulation (AS) on anthropometric parameters and obesity-related blood chemistry. Methods and analysis: The following databases were searched until November 2021: MEDLINE (PubMed), EMBASE, Cochrane Central Register of Controlled Trials (CENTRAL), ISI Web of Science, and Scopus Database. Data collection and analysis were conducted by two reviewers independently. Quality and risk assessment of included studies was performed using the risk of bias tool of the Cochrane Handbook, and the meta-analysis of the effect of the most frequently assessed biomarkers was conducted using the statistical software RevMan. Results: The full texts of 1,274 studies were screened; 22 contained data on obesity-related outcomes, and 15 trials with 1,333 patients were included in the meta-analysis. The overall quality of the included trials was moderate. AS significantly reduced body mass index (BMI) (mean difference (MD) = -0.38 BMI points, 95% CI (-0.55 to -0.22), p < 0.0001), weight (MD = -0.66 kg, 95% CI (-1.12 to -0.20), p = 0.005), waist circumference (MD = -1.44 cm, 95% CI (-2.69 to -0.20), p = 0.02), leptin, insulin, and HOMA insulin resistance compared to controls. No significant reduction was found in body fat, hip circumference, ratio of waist/hip circumference, cholesterol, LDL, triglycerides, adiponectin, ghrelin, and glucose levels. The AS was safe throughout the trials, with only minor adverse reactions. Conclusion: The study results suggest that a reduction of weight and BMI can be achieved by AS in obese patients; however, the size of the effect does not appear to be of clinical relevance. The effects might be underestimated due to active sham trials. [ABSTRACT FROM AUTHOR]

Verbal working memory (vWM) is an essential limited‐capacity cognitive system that spans the fronto‐parietal network and utilizes the subprocesses of encoding, maintenance, and retrieval. With the recent widespread use of noninvasive brain stimulation techniques, multiple recent studies have examined whether such stimulation may enhance cognitive abilities such as vWM, but the findings to date remain unclear in terms of both behavior and critical brain regions. In the current study, we applied high‐definition direct current stimulation to the left and right parietal cortices of 39 healthy adults in three separate sessions (left anodal, right anodal, and sham). Following stimulation, participants completed a vWM task during high‐density magnetoencephalography (MEG). Significant neural responses at the sensor‐level were imaged using a beamformer and whole‐brain ANOVAs were used to identify the specific neuromodulatory effects of the stimulation conditions on neural responses serving distinct phases of vWM. We found that right stimulation had a faciliatory effect relative to left stimulation and sham on theta oscillations during encoding in the right inferior frontal, while the opposite pattern was observed for left supramarginal regions. Stimulation also had a faciliatory effect on theta in occipital regions and alpha in temporal regions regardless of the laterality of stimulation. In summary, our data suggest that parietal HD‐tDCS both facilitates and interferes with neural responses underlying both the encoding and maintenance phases of vWM. Future studies are warranted to determine whether specific tDCS parameters can be tuned to accentuate the facilitation responses and attenuate the interfering aspects. [ABSTRACT FROM AUTHOR]

Background: Satellite glial cells (SGCs) in the dorsal root ganglia (DRG) play a pivotal role in the formation of neuropathic pain (NP). Sciatic nerve stimulation (SNS) neuromodulation was reported to alleviate NP and reduce neuroinflammation. However, the mechanisms underlying SNS in the DRG remain unclear. This study aimed to elucidate the mechanism of electric stimulation in reducing NP, focusing on the DRG. Methods: L5 nerve root ligation (NRL) NP rat model was studied. Ipsilateral SNS performed 1 day after NRL. Behavioral tests were performed to assess pain phenotypes. NanoString Ncounter technology was used to explore the differentially expressed genes and cellular pathways. Activated SGCs were characterized in vivo and in vitro. The histochemical alterations of SGCs, macrophages, and neurons in DRG were examined in vivo on post-injury day 8. Results: NRL induced NP behaviors including decreased pain threshold and latency on von Frey and Hargreaves tests. We found that following nerve injury, SGCs were hyperactivated, neurotoxic and had increased expression of NP-related ion channels including TRPA1, Cx43, and SGC-neuron gap junctions. Mechanistically, nerve injury induced reciprocal activation of SGCs and M1 macrophages via cytokines including IL-6, CCL3, and TNF-α mediated by the HIF-1α-NF-κB pathways. SNS suppressed SGC hyperactivation, reduced the expression of NP-related ion channels, and induced M2 macrophage polarization, thereby alleviating NP and associated neuroinflammation in the DRG. Conclusions: NRL induced hyperactivation of SGCs, which had increased expression of NP-related ion channels. Reciprocal activation of SGCs and M1 macrophages surrounding the primary sensory neurons was mediated by the HIF-1α and NF-κB pathways. SNS suppressed SGC hyperactivation and skewed M1 macrophage towards M2. Our findings establish SGC activation as a crucial pathomechanism in the gliopathic alterations in NP, which can be modulated by SNS neuromodulation. [ABSTRACT FROM AUTHOR]

Transcutaneous auricular vagus nerve stimulation (taVNS) targets subcutaneous axons in the auricular branch of the vagus nerve at the outer ear. Its non‐invasive nature makes it a potential treatment for various disorders. taVNS induces neuromodulatory effects within the nucleus of the solitary tract (NTS), and due to its widespread connectivity, the NTS acts as a gateway to elicit neuromodulation in both higher‐order brain regions and other brainstem nuclei (e.g. spinal trigeminal nucleus; Sp5). Our objective was to examine stimulation parameters on single‐neuron electrophysiological responses in α‐chloralose‐anaesthetized Sprague–Dawley rats within NTS and Sp5. taVNS was also compared to traditional cervical VNS (cVNS) on single neuronal activation. Specifically, electrophysiological extracellular recordings were evaluated for a range of frequency and intensity parameters (20–250 Hz, 0.5–1.0 mA). Neurons were classified as positive, negative or non‐responders based on increased activity, decreased activity or no response during stimulation, respectively. Frequency‐dependent analysis showed that 20 and 100 Hz generated the highest proportion of positive responders in NTS and Sp5 with 1.0 mA intensities eliciting the greatest magnitude of response. Comparisons between taVNS and cVNS revealed similar parameter‐specific activation for caudal NTS neuronal populations; however, individual neurons showed different activation profiles. The latter suggests that cVNS and taVNS send afferent input to NTS via different neuronal pathways. This study demonstrates differential parameter‐specific taVNS responses and begins an investigation of the mechanisms responsible for taVNS modulation. Understanding the neuronal pathways responsible for eliciting neuromodulatory effects will enable more tailored taVNS treatments in various clinical disorders. Key points: Transcutaneous auricular vagus nerve stimulation (taVNS) offers a non‐invasive alternative to invasive cervical vagus nerve stimulation (cVNS) by activating vagal afferents in the ear to induce neuromodulation.Our study evaluated taVNS effects on neuronal firing patterns in the nucleus of the solitary tract (NTS) and spinal trigeminal nucleus (Sp5) and found that 20 and 100 Hz notably increased neuronal activity during stimulation in both nuclei.Increasing taVNS intensity not only increased the number of neurons responding in Sp5 but also increased the magnitude of response, suggesting a heightened sensitivity to taVNS compared to NTS.Comparisons between cVNS and taVNS revealed similar overall activation but different responses on individual neurons, indicating distinct neural pathways.These results show parameter‐specific and nuclei‐specific responses to taVNS and confirm that taVNS can elicit responses comparable to cVNS at the neuronal level, but it does so through different neuronal pathways. [ABSTRACT FROM AUTHOR]

Diabetic Peripheral Neuropathy (DPN) is a prevalent and debilitating complication of diabetes, affecting a significant proportion of the diabetic population. Neuromodulation, an emerging therapeutic approach, has shown promise in the management of DPN symptoms. This systematic review aims to synthesize and analyze the current advancements in neuromodulation techniques for the treatment of DPN utilizing studies with preclinical animal models. A comprehensive search was conducted across multiple databases, including PubMed, Scopus, and Web of Science. Inclusion criteria were focused on studies utilizing preclinical animal models for DPN that investigated the efficacy of various neuromodulation techniques, such as spinal cord stimulation, transcranial magnetic stimulation, and peripheral nerve stimulation. The findings suggest that neuromodulation significantly alleviated pain symptoms associated with DPN. Moreover, some studies reported improvements in nerve conduction velocity and reduction in nerve damage. The mechanisms underlying these effects appeared to involve modulation of pain pathways and enhancement of neurotrophic factors. However, the review also highlights the variability in methodology and stimulation parameters across studies, highlighting the need for standardization in future research. Additionally, while the results are promising, the translation of these findings from animal models to human clinical practice requires careful consideration. This review concludes that neuromodulation presents a potentially effective therapeutic strategy for DPN, but further research is necessary to optimize protocols and understand the underlying molecular mechanisms. It also emphasizes the importance of bridging the gap between preclinical findings and clinical applications to improve the management of DPN in diabetic patients. [ABSTRACT FROM AUTHOR]

The development of noninvasive approaches to precisely control neural activity in mammals is highly desirable. Here, we used the ion channel transient receptor potential ankyrin-repeat 1 (TRPA1) as a proof of principle, demonstrating remote near-infrared (NIR) activation of endogenous neuronal channels in mice through an engineered nanoagonist. This achievement enables specific neurostimulation in nongenetically modified mice. Initially, target-based screening identified flavins as photopharmacological agonists, allowing for the photoactivation of TRPA1 in sensory neurons upon ultraviolet A/blue light illumination. Subsequently, upconversion nanoparticles (UCNPs) were customized with an emission spectrum aligned to flavin absorption and conjugated with flavin adenine dinucleotide, creating a nanoagonist capable of NIR activation of TRPA1. Following the intrathecal injection of the nanoagonist, noninvasive NIR stimulation allows precise bidirectional control of nociception in mice through remote activation of spinal TRPA1. This study demonstrates a noninvasive NIR neurostimulation method with the potential for adaptation to various endogenous ion channels and neural processes by combining photochemical toolboxes with customized UCNPs. [ABSTRACT FROM AUTHOR]

Little is known about the electrophysiologic activity of the intact human spinal cord during volitional movement. We analyzed epidural spinal recordings from a total of five human subjects of both sexes during a variety of upper extremity movements and found that these spinal epidural electrograms contain spectral information distinguishing periods of movement, rest, and sensation. Cervical epidural electrograms also contained spectral changes time-locked with movement. We found that these changes were primarily associated with increased power in the theta (4–8 Hz) band and feature increased theta phase to gamma amplitude coupling, and this increase in theta power can be used to topographically map distinct upper extremity movements onto the cervical spinal cord in accordance with established myotome maps of the upper extremity. Our findings have implications for the development of neurostimulation protocols and devices focused on motor rehabilitation for the upper extremity, and the approach presented here may facilitate spatiotemporal mapping of naturalistic movements. [ABSTRACT FROM AUTHOR]

Background: Transurethral resection of bladder tumor (TURBT) is usually done spinal anesthesia but it does not prevent the obturator reflex leading to bladder perforation, bleeding, or incompletely resection of resection of the tumor which could be prevented by obturator nerve block (ONB) in TURBT. Aims and Objectives: The aim of our study is to compare the effectiveness of ONB by peripheral nerve stimulator (PNS) and ultrasonography (USG) in TURBT and also compare morbidity between USG- and PNS-guided ONB in TURBT under spinal anesthesia. Materials and Methods: Sixty patients were randomly divided into two groups. Group (1) patients had a PNS-guided ONB and Group (2) patients had ONBguided ONB. The presence or absence of adductor muscles reflexes was recorded. Bladder perforation and bleeding during surgery were also recorded. Results: A success rate of 90% was achieved in the Group (2) compared to 66% in Group (1) which was clinically significant with P=0.049. Complete bladder perforation was detected in four patients in Group (1) whereas no perforation was observed in Group (2). Bleeding was observed in both groups but severe bleeding was present in five patients in Group (1) and required a blood transfusion. Conclusion: We concluded that USG-guided ONB is more efficient and safer as compared to PNS-guided ONB. [ABSTRACT FROM AUTHOR]

Heteronymous inhibition between lower limb muscles is primarily attributed to recurrent inhibitory circuits in humans but could also arise from Golgi tendon organs (GTOs). Distinguishing between recurrent inhibition and mechanical activation of GTOs is challenging because their heteronymous effects are both elicited by stimulation of nerves or a muscle above motor threshold. Here, the unique influence of mechanically activated GTOs was examined by comparing the magnitude of heteronymous inhibition from quadriceps (Q) muscle stimulation onto ongoing soleus electromyographic at five Q stimulation intensities (1.5–2.5× motor threshold) before and after an acute bout of stimulation‐induced Q fatigue. Fatigue was used to decrease Q stimulation evoked force (i.e., decreased GTO activation) despite using the same pre‐fatigue stimulation currents (i.e., same antidromic recurrent inhibition input). Thus, a decrease in heteronymous inhibition after Q fatigue and a linear relation between stimulation‐evoked torque and inhibition both before and after fatigue would support mechanical activation of GTOs as a source of inhibition. A reduction in evoked torque but no change in inhibition would support recurrent inhibition. After fatigue, Q stimulation‐evoked knee torque, heteronymous inhibition magnitude and inhibition duration were significantly decreased for all stimulation intensities. In addition, heteronymous inhibition magnitude was linearly related to twitch‐evoked knee torque before and after fatigue. These findings support mechanical activation of GTOs as a source of heteronymous inhibition along with recurrent inhibition. The unique patterns of heteronymous inhibition before and after fatigue across participants suggest the relative contribution of GTOs, and recurrent inhibition may vary across persons. [ABSTRACT FROM AUTHOR]

Background/Objectives: Hypoglossal nerve stimulation (HNS) emerged as an alternative treatment for patients with obstructive sleep apnea (OSA) a decade ago. Long-term clinical trials and real-world data show that HNS treatment provides significant and sustained improvements in both OSA disease control and quality-of-life measures over time. Given the nature of HNS treatment, with the requirement of using an implantable neurostimulation system, patient safety is a critical domain in the assessment of this technology. The objective of this review was to evaluate adverse events (AEs) and complications with HNS therapy in a systematic review of published evidence. Methods: Medline, Cochrane, and Web of Science were systematically searched to identify randomized controlled and real-world observational studies reporting relevant outcomes with HNS therapy for treatment of OSA that included procedure-, device-, and treatment-related AEs. Results: Out of 418 articles screened, 27 were reviewed for eligibility, and 17 studies, the majority found to have low-to-moderate risk of bias, with data on 1962 patients were included for further analysis. Across included studies, reporting of AEs was heterogeneous with regard to the classifications used and the extent of reporting. Over an average follow-up duration of 17.5 ± 16.9 months, the pooled mortality rate was 0.01% (95% CI = 0.0 to 0.2%), with all reported deaths being unrelated to HNS treatment. The HNS system survival probability over the follow-up time of 60 months was 0.9834 (95% CI = 0.9768 to 0.9882), with infections and request for removal by patients being the most common indications. The pooled surgical revision rate was 0.08% (95% CI 0.0 to 0.2%). Most reported treatment-related side effects were transient stimulation-related discomfort (0.08%, 95% CI = 0.0 to 0.2%) and tongue abrasions (0.07%, 95% CI = 0.0 to 0.2%). Based on the systematic review, a standardized set of endpoints was defined, aiming to harmonize safety data relevant to HNS therapy. Conclusions: In this systematic review, HNS therapy for treatment of OSA is associated with a positive patient safety profile. AEs occur mainly at device implantation and during the treatment acclimatization period. Due to a lack of available evidence, partially implantable HNS systems are underrepresented in this review, which limits the generalizability of the results. Significant heterogeneity was found for adverse event reporting. A framework for reporting HNS outcomes that includes AEs and side effects is proposed to facilitate comparability of the reported data. [ABSTRACT FROM AUTHOR]

Postoperative pain is a major clinical problem imposing a significant burden on patients and society. In a survey 2 years after orthopedic surgery, 57%of patients reported persisting postoperative pain. However, only limited progress has been made in the development of safe and effective therapies to prevent the onset and chronification of pain after orthopedic surgery. We established a tibial fracturemouse model that recapitulates clinically relevant orthopedic trauma surgery, which causes changes in neuropeptide levels in dorsal root ganglia and sustained neuroinflammation in the spinal cord. Here, we monitored extended pain behavior in this model, observing chronic bilateral hindpaw mechanical allodynia in both male and female C57BL/6J mice that persisted for .3 months after surgery. We also tested the analgesic effects of a novel, minimally invasive, bioelectronic approach to percutaneously stimulate the vagus nerve (termed percutaneous vagus nerve stimulation [pVNS]). Weekly pVNS treatment for 30 minutes at 10 Hz for 3 weeks after the surgery strongly reduced pain behaviors comparedwith untreated controls. Percutaneous vagus nerve stimulation also improved locomotor coordination and accelerated bone healing. In the dorsal root ganglia, vagal stimulation inhibited the activation of glial fibrillary acidic protein-positive satellite cells but without affectingmicroglial activation. Overall, these data provide novel evidence supportive of theuseof pVN Stop revent post operative pain and inform translational studies to test antinociceptive effects of bioelectronic medicine in the clinic. [ABSTRACT FROM AUTHOR]

Prior studies suggest resistance exercise as a potential form of motor learning due to task-specific corticospinal responses observed in single sessions of motor skill and resistance training. While existing literature primarily focuses on upper limb muscles, revealing a task-dependent nature in eliciting corticospinal responses, our aim was to investigate such responses after a single session of lower limb motor skill and resistance training. Twelve participants engaged in a visuomotor force tracking task, self-paced knee extensions, and a control task. Corticospinal, spinal, and neuromuscular responses were measured using transcranial magnetic stimulation (TMS) and peripheral nerve stimulation (PNS). Assessments occurred at baseline, immediately post, and at 30-min intervals over two hours. Force steadiness significantly improved in the visuomotor task (P < 0.001). Significant fixed-effects emerged between conditions for corticospinal excitability, corticospinal inhibition, and spinal excitability (all P < 0.001). Lower limb motor skill training resulted in a greater corticospinal excitability compared to resistance training (mean difference [MD] = 35%, P < 0.001) and control (MD; 37%, P < 0.001). Motor skill training resulted in a lower corticospinal inhibition compared to control (MD; – 10%, P < 0.001) and resistance training (MD; – 9%, P < 0.001). Spinal excitability was lower following motor skill training compared to control (MD; – 28%, P < 0.001). No significant fixed effect of Time or Time*Condition interactions were observed. Our findings highlight task-dependent corticospinal responses in lower limb motor skill training, offering insights for neurorehabilitation program design. [ABSTRACT FROM AUTHOR]

The regenerative capacity of the peripheral nervous system is limited, and peripheral nerve injuries often result in incomplete healing and poor outcomes even after repair. Transection injuries that induce a nerve gap necessitate microsurgical intervention; however, even the current gold standard of repair, autologous nerve graft, frequently results in poor functional recovery. Several interventions have been developed to augment the surgical repair of peripheral nerves, and the application of functional biomaterials, local delivery of bioactive substances, electrical stimulation, and allografts are among the most promising approaches to enhance innate healing across a nerve gap. Biocompatible polymers with optimized degradation rates, topographic features, and other functions provided by their composition have been incorporated into novel nerve conduits (NCs). Many of these allow for the delivery of drugs, neurotrophic factors, and whole cells locally to nerve repair sites, mitigating adverse effects that limit their systemic use. The electrical stimulation of repaired nerves in the perioperative period has shown benefits to healing and recovery in human trials, and novel biomaterials to enhance these effects show promise in preclinical models. The use of acellular nerve allografts (ANAs) circumvents the morbidity of donor nerve harvest necessitated by the use of autografts, and improvements in tissue-processing techniques may allow for more readily available and cost-effective options. Each of these interventions aid in neural regeneration after repair when applied independently, and their differing forms, benefits, and methods of application present ample opportunity for synergistic effects when applied in combination. [ABSTRACT FROM AUTHOR]

Non-invasive neurostimulation, including bright light therapy (BLT), repetitive transcranial magnetic (rTMS) and transcranial direct current stimulation (tDCS), has been shown to alleviate depressive symptoms in major depressive disorder (MDD). However, the efficacy of these interventions in addressing sleep disturbances in MDD patients remains a subject of debate. We aimed to conduct a meta-analysis of available randomized controlled trials (RCTs) to assess the effectiveness of non-invasive neurostimulation in improving sleep disturbances and depressive symptoms in MDD patients. Systematic searches for relevant RCTs were conducted in the databases PubMed, Cochrane Library, Web of Science, EMBASE, Wanfang and China National Knowledge Infrastructure up to January 2024. Data on outcomes comparable across the studies were meta-analyzed using Review Manager 5.3 and Stata 14. The pooled results were reported as standardized mean differences (SMD) with their respective 95% confidence intervals (CI). Our analysis encompassed 15 RCTs involving 1348 patients. Compared to sham or no stimulation, non-invasive neurostimulation significantly improved sleep quality (SMD -0.74, 95%CI -1.15 to −0.33, p = 0.0004) and sleep efficiency (SMD 0.35, 95%CI 0.10 to 0.60, p = 0.006). It also significantly reduced severity of depressive symptoms (SMD -0.62, 95%CI -0.90 to −0.35, p < 0.00001). Subgroup analysis further demonstrated that patients experiencing sleep improvements due to neurostimulation showed a marked decrease in depressive symptoms compared to the control group (SMD = −0.90, 95% CI [-1.26, −0.54], p < 0.0001). Current evidence from RCTs suggests that neurostimulation can enhance sleep quality and efficiency in individuals with MDD, which in turn may be associated with mitigation of depressive symptoms. CRD42023423844. [ABSTRACT FROM AUTHOR]

Beyond motor deficits, spinocerebellar ataxia (SCA) patients also suffer cognitive decline and show socio-affective difficulties, negatively impacting on their social functioning. The possibility to modulate cerebello-cerebral networks involved in social cognition through cerebellar neurostimulation has opened up potential therapeutic applications for ameliorating social and affective difficulties. The present review offers an overview of the research on cerebellar neurostimulation for the modulation of socio-affective functions in both healthy individuals and different clinical populations, published in the time period 2000–2022. A total of 25 records reporting either transcranial magnetic stimulation (TMS) or transcranial direct current stimulation (tDCS) studies were found. The investigated clinical populations comprised different pathological conditions, including but not limited to SCA syndromes. The reviewed evidence supports that cerebellar neurostimulation is effective in improving social abilities in healthy individuals and reducing social and affective symptoms in different neurological and psychiatric populations associated with cerebellar damage or with impairments in functions that involve the cerebellum. These findings encourage to further explore the rehabilitative effects of cerebellar neurostimulation on socio-affective deficits experienced by patients with cerebellar abnormalities, as SCA patients. Nevertheless, conclusions remain tentative at this stage due to the heterogeneity characterizing stimulation protocols, study methodologies and patients' samples. [ABSTRACT FROM AUTHOR]

Purpose: Occipital neuralgia (ON) is a disabling problem within the pediatric population. Many of these patients fail medical therapies and continue to suffer without further surgical management. Occipital nerve stimulation (ONS) is used to treat ON in the adult population leading to a 72–89% reduction in pain; however, there are limited studies regarding its use in the pediatric population. In this study, we examined the outcomes of ONS in pediatric patients with medically refractory ON. Methods: We performed a chart review of pediatric patients at our institution who have undergone ONS for the same indications. Results: We identified 3 patients at our institution who underwent ONS trial and/or permanent implantation for ON. One patient had complete pain relief after the trial and declined permanent implantation. The other patient had fewer attacks compared to his pre-trial baseline and controlled them by adjusting his permanent implant stimulation settings. The last patient had near complete relief of her symptoms and no longer required any pain medication. Conclusion: Our study highlights the paucity of studies evaluating the utility of ONS in the pediatric ON population. Limited data from both the literature and our institution's experience reveal that pediatric patients may benefit from trial and/or permanent implantation of ONS for medically refractory ON pain. [ABSTRACT FROM AUTHOR]

Neuromodulation therapies offer an efficacious treatment alternative for patients with drug‐resistant epilepsy (DRE), particularly those unlikely to benefit from surgical resection. Here we present our retrospective single‐center case series of patients with pediatric‐onset DRE who underwent responsive neurostimulation (RNS) depth electrode implantation targeting the bilateral centromedian nucleus (CM) of the thalamus between October 2020 and October 2022. Sixteen patients were identified; seizure outcomes, programming parameters, and complications at follow‐up were reviewed. The median age at implantation was 13 years (range 3.6–22). Six patients (38%) were younger than 12 years of age at the time of implantation. Ictal electroencephalography (EEG) patterns during patients' most disabling seizures were reliably detected. Ten patients (62%) achieved 50% or greater reduction in seizure frequency at a median 1.3 years (range 0.6–2.6) of follow‐up. Eight patients (50%) experienced sensorimotor side effects, and three patients (19%) had superficial pocket infection, prompting the removal of the RNS device. Side effects of stimulation were experienced mostly in monopolar‐cathodal configuration and alleviated with programming change to bipolar configuration or low‐frequency stimulation. Closed‐loop neurostimulation using RNS targeting bilateral CM is a feasible and useful therapy for patients with pediatric‐onset DRE. [ABSTRACT FROM AUTHOR]

Objectives: A surgical "treatment gap" in pediatric epilepsy persists despite the demonstrated safety and effectiveness of surgery. For this reason, the national surgical landscape should be investigated such that an updated assessment may more appropriately guide health care efforts. Methods: In our retrospective cross‐sectional observational study, the National Inpatient Sample (NIS) database was queried for individuals 0 to <18 years of age who had an International Classification of Diseases (ICD) code for drug‐resistant epilepsy (DRE). This cohort was then split into a medical group and a surgical group. The former was defined by ICD codes for ‐DRE without an accompanying surgical code, and the latter was defined by DRE and one of the following epilepsy surgeries: any open surgery; laser interstitial thermal therapy (LITT); vagus nerve stimulation; or responsive neurostimulation (RNS) from 1998 to 2020. Demographic variables of age, gender, race, insurance type, hospital charge, and hospital characteristics were analyzed between surgical options. Continuous variables were analyzed with weight‐adjusted quantile regression analysis, and categorical variables were analyzed by weight‐adjusted counts with percentages and compared with weight‐adjusted chi‐square test results. Results: These data indicate an increase in epilepsy surgeries over a 22‐year period, primarily due to a statistically significant increase in open surgery and a non‐significant increase in minimally invasive techniques, such as LITT and RNS. There are significant differences in age, race, gender, insurance type, median household income, Elixhauser index, hospital setting, and size between the medical and surgical groups, as well as the procedure performed. Significance: An increase in open surgery and minimally invasive surgeries (LITT and RNS) account for the overall rise in pediatric epilepsy surgery over the last 22 years. A positive inflection point in open surgery is seen in 2005. Socioeconomic disparities exist between medical and surgical groups. Patient and hospital sociodemographics show significant differences between the procedure performed. Further efforts are required to close the surgical "treatment gap." [ABSTRACT FROM AUTHOR]

Objective: Short‐term outcomes of deep brain stimulation of the anterior nucleus of the thalamus (ANT‐DBS) were reported for people with drug‐resistant focal epilepsy (PwE). Because long‐term data are still scarce, the Medtronic Registry for Epilepsy (MORE) evaluated clinical routine application of ANT‐DBS. Methods: In this multicenter registry, PwE with ANT‐DBS were followed up for safety, efficacy, and battery longevity. Follow‐up ended after 5 years or upon study closure. Clinical characteristics and stimulation settings were compared between PwE with no benefit, improvers, and responders, that is, PwE with average monthly seizure frequency reduction rates of ≥50%. Results: Of 170 eligible PwE, 104, 62, and 49 completed the 3‐, 4‐, and 5‐year follow‐up, respectively. Most discontinuations (68%) were due to planned study closure as follow‐up beyond 2 years was optional. The 5‐year follow‐up cohort had a median seizure frequency reduction from 16 per month at baseline to 7.9 per month at 5‐year follow‐up (p <.001), with most‐pronounced effects on focal‐to‐bilateral tonic–clonic seizures (n = 15, 77% reduction, p =.008). At last follow‐up (median 3.5 years), 41% (69/170) of PwE were responders. Unifocal epilepsy (p =.035) and a negative history of epilepsy surgery (p =.002) were associated with larger average monthly seizure frequency reductions. Stimulation settings did not differ between response groups. In 179 implanted PwE, DBS‐related adverse events (AEs, n = 225) and serious AEs (n = 75) included deterioration in epilepsy or seizure frequency/severity/type (33; 14 serious), memory/cognitive impairment (29; 3 serious), and depression (13; 4 serious). Five deaths occurred (none were ANT‐DBS related). Most AEs (76.3%) manifested within the first 2 years after implantation. Activa PC depletion (n = 37) occurred on average after 45 months. Significance: MORE provides further evidence for the long‐term application of ANT‐DBS in clinical routine practice. Although clinical benefits increased over time, side effects occurred mainly during the first 2 years. Identified outcome modifiers can help inform PwE selection and management. [ABSTRACT FROM AUTHOR]

A brain‐to‐brain interface (BBI), defined as a combination of neuroimaging and neurostimulation methods to extract and deliver information between brains directly without the need for the peripheral nervous system, is a budding communication technique. A BBI system is made up of two parts known as the brain–computer interface part, which reads a sender's brain activity and digitalizes it, and the computer–brain interface part, which writes the delivered brain activity to a receiving brain. As with other technologies, BBI systems have gone through an evolutionary process since they first appeared. The BBI systems have been employed for numerous purposes, including rehabilitation for post‐stroke patients, communicating with patients suffering from amyotrophic lateral sclerosis, locked‐in syndrome and speech problems following stroke. Also, it has been proposed that a BBI system could play an important role on future battlefields. This technology was not only employed for communicating between two human brains but also for making a direct communication path among different species through which motor or sensory commands could be sent and received. However, the application of BBI systems has provoked significant challenges to human rights principles due to their ability to access and manipulate human brain information. In this study, we aimed to review the brain–computer interface and computer–brain interface technologies as components of BBI systems, the development of BBI systems, applications of this technology, arising ethical issues and expectations for future use. [ABSTRACT FROM AUTHOR]

Introduction: Further clinical validation is required to determine whether transcutaneous electrical acupoint stimulation (TEAS) can replace opioids and be used in combination with remimazolam for sedation during gastrointestinal endoscopy. Methods: A total of 108 outpatients who underwent diagnostic gastrointestinal endoscopy were randomly divided into three groups: fentanyl plus remimazolam group (group C), TEAS plus remimazolam group (group E), and placebo-TEAS plus remimazolam group (group P). The assessments of patient satisfaction, physician satisfaction, and pain scale score during the examination constituted the primary endpoints of the study. The secondary endpoints were the time of recovery, recovery of normal behavioral function and discharge, incidence of adverse reactions, and dose of remimazolam. Results: Compared with group C, group E had a greater median score for patient satisfaction at follow-up and a slightly lower median score for physician satisfaction. The pain score of group E was slightly greater than that of group C, but the difference was not significant. However, in group C, the incidence of hypoxemia, the rate of nausea and the severity of vertigo were greater, and the number of patients discharged and resuming normal behavioral function was greater than those in the other two groups. The dose of remimazolam in group C and group E was less than that in group P. Conclusions: TEAS combined with moderate sedation of remimazolam can provide an ideal sedative effect, which preferably suppresses discomfort caused by gastrointestinal endoscopy and has fewer sedation-related complications. Trial Registration: ID: NCT05485064; First registration (29/07/2022); Last registration (02/11/2022) (Clinical Trials.gov). [ABSTRACT FROM AUTHOR]