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Objective . Direct current (DC) electrical block of peripheral nerve conduction shows promise for clinical applications to treat spasticity, pain, and cardiac arrhythmias. Most previous work has used invasive nerve cuffs. Here we investigate the potential of non-invasive transcutaneous DC motor block (tDCB). Approach . In anesthetized rats, force output from the tibialis and peroneus muscles was measured in response to stimulation proximally on the sciatic nerve. DC blocking waveforms were delivered via a surface electrode placed distally on the skin over the common peroneal nerve. The efficacy of the block was observed as the reduction/abolition of muscle force. Experiments using this model were performed with two different electrode types. A range of DC amplitudes and durations were used to elucidate the temporal properties of block. Main results . Higher levels of DC resulted in a larger block percentage. The amount of time needed to induce block depended on the level of DC, with smaller amplitudes resulting in longer induction times. When block was applied for a longer period of time (120s), the block was sustained following DC delivery. This 'recovery period' was longer for higher amplitudes of block. In addition to the block thresholds and temporal effects, two additional evaluations were made: In some animals the efficacy of tDCB to block tetanic muscle contractions was successfully verified. Finally, the effect of tDCB on the stability of nerve conduction was verified using a second distal electrode for comparison. Significance . In this study, tDCB has been shown to reversibly block action potentials in peripheral motor nerves. A subthreshold amplitude applied for a longer duration could produce complete or partial block following a brief induction time. Also, a higher amplitude was associated with a longer recovery time. These temporal properties are important considerations for potential clinical applications., (© 2025 IOP Publishing Ltd. All rights, including for text and data mining, AI training, and similar technologies, are reserved.)

Objective: Direct electrical neurostimulation using continuous sinusoidal low frequency alternating currents (LFAC) is an emerging modality for neuromodulation. As opposed to the traditional rectangular pulse stimulation, there is limited background on the characteristics of peripheral nerves responses to sinusoidal LFAC stimulation; especially within the low frequency range (<50 Hz). In this study, we demonstrate LFAC activation as a means to activate motor nerves by direct bipolar nerve stimulation via cuff electrodes, and characterize the factors of activation. We study and quantify the effects of sinusoidal frequency and electrode geometry on the motor nerve activation threshold in-vivo and in computational models, in-silico . Approach: Acute in-vivo experiments ( N = 34) were conducted on isoflurane-anaesthetized rats. A pure tone continuous sinusoidal current was applied to the rat sciatic nerve in bipolar configurations via bipolar or tripolar nerve cuff electrodes (different contact separations). LFAC activation thresholds were quantified by measuring the electromyogram (EMG) response of the triceps surae muscles and the induced twitch force to LFAC stimulation at six frequencies (1, 2, 3, 4, 8, and 20 Hz). Computationally, we utilized a volume conductor model of a bipolar cuff electrode around a single rat-size fascicle and projected the potentials to the McIntyre-Richardson-Grill models of myelinated motor nerve fibers. We compared the in-silico responses of a range of fiber diameters (5.7 to 16 µ m) to LFAC stimulation and their activation thresholds to the in-vivo findings. Main results : Sinusoidal LFAC stimulation elicited motor nerve activity in-vivo and in-silico , with a remarkable convergence of the in-silico predictions to the in-vivo observations. The EMG activity showed that muscle responses to LFAC stimulation were phase-locked to the sinusoidal cycle but exhibited two distinct activation modes. These modes were classified as burst and unitary, indicating the presence of two distinct patterns of muscle activation during LFAC stimulation. The LFAC motor activation threshold was significantly dependent on frequency and influenced by the contact separation of the cuff electrode, with a greater extent of reduction at a higher frequency or wider separation. Moreover, the order of fiber recruitment was suggested to be normal-physiological (small-to-large caliber) given the nature of the induced EMG activity and in-silico predictions. Significance : These findings provide significant insights into the nature of sinusoidal LFAC stimulation, at the explored range of frequency, and the expected mammalian peripheral motor nerve responses to LFAC. The characteristics of sinusoidal LFAC stimulation would facilitate selectivity approaches in a broader range of therapeutic and rehabilitative neuromodulation applications., (Creative Commons Attribution license.)

Objectives: To examine the pain conditions that have been studied using transcutaneous auricular vagus nerve stimulation (taVNS), the various methods and dosage configurations used, as well as identify current gaps in the literature., Design: Scoping review with the literature search and reporting guided by the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement-extension for scoping reviews., Review Methods: A systematic search was conducted across four databases-Pubmed/Medline (n = 24), PsycInfo (n = 218), CINAHL (n = 114), and Scopus (n = 52)-comprising a total of 408 publications from peer-reviewed journals. The MeSH terms used for the search were: "transcutaneous nerve stimulation AND vagus nerve stimulation" along with "transcutaneous vagus nerve stimulation OR taVNS AND pain" with filters placed for clinical trials published between 2014 to March 2024., Results: A total of 26 publications met eligibility for inclusion in this scoping review. The most common types of pain that have been used to evaluate the efficacy of taVNS include episodic migraine without aura, rheumatoid arthritis, fibromyalgia, irritable bowel syndrome, and chronic low back pain. The device type and settings, dosage, and placement of electrodes varied across studies. Identified research gaps include the need to determine optimal dosage for the pain condition under study, inclusion of measures to evaluate intervention fidelity, long-term outcomes and symptoms that co-occur with pain, and subanalyses to examine outcomes among various sociodemographic variables., Conclusions: There is increasing evidence supporting the potential of taVNS in pain management. Further research is necessary to comprehensively evaluate its efficacy, underlying mechanisms, and to optimize its clinical application., Nursing Practice Implications: The findings indicate a growing body of evidence for effective use of taVNS for pain management, along with reducing co-occurring symptoms, such as depression. Nurses should be knowledgeable about this treatment option and collaborate with other healthcare professionals to develop best practices for the use of this technology in practice., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Inc.)

Background: Peripheral nerve stimulation (PNS) has emerged as a minimally invasive percutaneous procedure addressing neuropathic pain. However, the percutaneous cylindrical lead ultrasound-guided implantation procedure requires expertise that limits widespread PNS utilization. To overcome these challenges, a microinvasive endoscopy device has very recently been developed, enhancing the precision of PNS implantation by providing accurate visualization of the targeted nerve. We aimed to determine the feasibility, safety, clinical effectiveness, and energy consumption of PNS therapy by means of ultrasound guidance combined with microendoscopy., Materials and Methods: This is a retrospective, single-center, single-arm study. Patient recruitment was performed in February and March 2023. Patients with >12 months of upper or lower limb pain presenting with pain >5 of 10 that was refractory to conventional treatments were eligible. Safety was assessed by collecting adverse events and complications related to the PNS implantation with microendoscopy. The Multidimensional Clinical Response Index (MCRI), pain intensity (visual analog scale [VAS]), pain surface (PRISMap Software, PRISMATICS lab, CHU de Poitiers, Poitiers, France), quality of life (EuroQoL 5 dimensions 5 levels [EQ5D-5L]), functional disability (Oswestry Disability Index [ODI]), anxiety and depression (Hospital Anxiety and Depression Scale), and energy consumption were assessed at baseline and at one and three months., Results: Six patients received PNS, which was implanted through ultrasound guidance combined with microendoscopy. No adverse event was reported during the three-month follow-up. Clinical outcomes (MCRI, VAS, ODI, EQ5D-5L) significantly increased at one- and three-month follow-up. Energy consumption was, on average, 2.6 ± 1.1 μC.s -1 at one-month and 3.3 ± 2.0 μC.s -1 at three-month follow-up., Conclusions: Implanted PNS by means of ultrasound combined with microendoscopy was safe and provided clinical benefits with very low energy consumption (15-440 times less than spinal cord stimulation) in patients with upper or lower limb neuropathic pain. Microendoscopy would offer extended PNS indications, overcoming limitations associated with ultrasound alone. Future research is nonetheless needed to provide stronger evidence through randomized controlled trial design., Competing Interests: Conflict of Interest Philippe Rigoard reports grants and speaker fees from Quantel Medical, Medtronic, Abbott, and Boston Scientific. Maarten Moens reports speaker fees from Medtronic, Saluda, and Nevro. Lisa Goudman reports speaker fees from Medtronic, Nevro, and Saluda. Romain David and Manon Duraffourg have received consulting fees from Boston Scientific. Sam Eldabe reports consulting agreements from Mainstay Medical and Medtronic, institutional research grants from Medtronic, and other from Abbott. Denys Fontaine is a consultant for Medtronic, Abbott, and Boston and received research grants from Medtronic and Abbott. Bénédicte Bouche reports speaking fees from Boston Scientific and Medtronic. The remaining authors reported no conflict of interest., (Copyright © 2024 International Neuromodulation Society. Published by Elsevier Inc. All rights reserved.)

Transcutaneous spinal direct current stimulation (TSDCS) has the potential to modulate spinal circuits and induce functional changes in humans. Nevertheless, differences across studies on basic parameters used and obtained metrics represent a confounding factor. Computer simulations are instrumental in improving the application of the TSDCS technique. Their findings allow a better interpretation of the tissue conductivities heterogeneity. Emerging findings indicate the electric field is maximal in the segments located between the electrodes, and that factors such as the depth of the targeted area, and location of the electrodes on low conductive points, such as the spinous processes, may impact the electric field generated in the spinal cord, with consequences for thoracic versus lumbar or cervical applications. Recently, growing attention has been directed toward the importance of the TSDCS reference electrode's position and its influence on the current field properties at the targeted site. This review highlights the influence of dosage, polarity, and electrode position on the variety of TSDCS results in healthy and some clinical populations. Based on the available evidence, we suggest that although the current dosage appears to have a negligible effect, the variety of electrode montages and configurations of TSDCS can significantly impact the electric field distributions and potentially explain the conflicting results of experimental studies. Future human trials should systematically and thoughtfully evaluate the location of TSDCS electrodes based on the targeted neural structures.

Background: Percutaneous auricular nerve stimulation (neuromodulation) is an analgesic technique involving the percutaneous implantation of multiple leads at various points on/around the ear followed by the delivery of electric current using an external pulse generator. A device is currently available within the USA cleared to treat symptoms from opioid withdrawal, and multiple reports suggest a possible postoperative analgesic effect. The current randomized, controlled pilot study was undertaken to (1) determine the feasibility and optimize the protocol for a subsequent definitive clinical trial and (2) estimate the treatment effect of auricular neuromodulation on postoperative pain and opioid consumption following total knee arthroplasty., Methods: Within the recovery room following primary, unilateral, total knee arthroplasty, an auricular neuromodulation device (NSS-2 Bridge, Masimo, Irvine, California, USA) was applied using three percutaneous leads and one ground electrode. Participants were randomized to 5 days of either electrical stimulation or sham stimulation in a double-masked fashion. Participants were discharged with the stimulator in situ and removed the disposable devices at home. The dual primary treatment effect outcome measures were the cumulative opioid use (oral oxycodone) and the mean of the "average" daily pain measured with the Numeric Rating Scale for the first 5 postoperative days., Results: During the first five postoperative days, oxycodone consumption in participants given active stimulation (n=15) was a median (IQR) of 4 mg (2-12) vs 13 mg (5-23) in patients given sham (n=15) treatment (p=0.039). During this same period, the average pain intensity in patients given active stimulation was a median (IQR) of 2.5 (1.5-3.3) vs 4.0 (3.6-4.8) in those given sham (p=0.014). Awakenings due to pain over all eight postoperative nights in participants given active stimulation was a median (IQR) of 5 (3-8) vs 11 (4-14) in those given sham (p<0.001). No device-related localized cutaneous irritation, systemic side effects, or other adverse events were identified., Conclusions: Percutaneous auricular neuromodulation reduced pain scores and opioid requirements during the initial week after total knee arthroplasty. Given the ease of application as well as the lack of systemic side effects and reported complications, a definitive clinical trial appears warranted., Trial Registration Number: NCT05521516., Competing Interests: Competing interests: None declared., (© American Society of Regional Anesthesia & Pain Medicine 2025. Re-use permitted under CC BY-NC. No commercial re-use. Published by BMJ Group.)

Background: There is growing interest in use of transcutaneous spinal stimulation (TSS) for people with neurologic conditions both to augment volitional control (by facilitating motoneuron excitability), and to decrease spasticity (by activating inhibitory networks). Various electrode montages are used during TSS, with little understanding of how electrode position influences spinal circuit activation. We sought to identify the thoracolumbar electrode montage associated with the most robust activation of spinal circuits by comparing posterior root-muscle reflexes (PRM reflexes) elicited by 6 montages. Additionally, we assessed tolerability of the stimulation during PRM reflex testing., Methods: Fifteen adults with intact neurological systems participated in this randomized crossover study. PRM reflexes were evoked transcutaneously using electrode montages with dorsal-ventral (DV) or dorsal-midline (DM) current flow. DV montages included: [1] cathode over T11/T12, anodes over iliac crests (DV-I), [2] cathode over T11/T12, anodes over umbilicus (DV-U), [3] dual paraspinal cathodes at T11/12, anodes over iliac crests (DV-PI), and [4] dual paraspinal cathodes at T11/12, anodes over umbilicus (DV-PU). DM montages included: [5] cathode over T11/12, anode 5 cm caudal (DM-C), and [6] cathode over T11/12, anode 5 cm rostral (DM-R). PRM reflex recruitment curves were obtained in the soleus muscle of both lower extremities., Results: Lower reflex thresholds (mA) for dominant (D) and nondominant (ND) soleus muscles were elicited in DV-U (D: 46.7[33.9, 59.4], ND: 45.4[32.5, 58.2]) and DV-I (D: 48.1[35.3, 60.8], ND: 45.4[32.5, 58.2]) montages compared to DV-PU (D: 64.3[51.4, 77.1], ND:61.7[48.8, 74.6]), DV-PI (D:64.9[52.1, 77.7], ND:61.4[48.5, 75.5]), DM-C(D:60.0[46.9, 73.1], ND:63.6[50.8, 76.5]), and DM-R(D:63.1[50.3, 76.0], ND:62.6[49.8, 75.5]). DV-U and DV-I montages demonstrated larger recruitment curve area than other montages. There were no differences in response amplitude at 120% of RT(1.2xRT) or tolerability among montages., Conclusions: Differences in spinal circuit recruitment are reflected in the response amplitude of the PRM reflexes. DV-I and DV-U montages were associated with lower reflex thresholds, indicating that motor responses can be evoked with lower stimulation intensity. DV-I and DV-U montages therefore have the potential for lower and more tolerable interventional stimulation intensities. Our findings optimize electrode placement for interventional TSS and PRM reflex assessments., Clinical Trial Number: NCT04243044., Competing Interests: Declarations. Ethics approval and consent to participate: This study was carried out with approval of the Shepherd Center Research Review Committee. All participants gave written informed consent prior to study enrollment in accordance with the Declaration of Helsinki. Consent for publication: All participants gave written informed consent for the publication of the study. Competing interests: Author ECF-F serves as a consultant to the medical device company ONWARD Inc., (© 2025. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Background: Kilohertz high-frequency alternating current (KHFAC) stimulation has demonstrated to induce rapid and reversible nerve blocks without causing nerve damage. Previous studies have explored frequency-dependent effects using a transcutaneous approach in humans from 5 to 20 kHz. Nevertheless, its application in humans is limited by the lack of stimulators approved for frequencies above 20 kHz. Therefore, this study aimed to assess the effects and safety of transcutaneous KHFAC stimulation using a novel prototype stimulator, comparing interventions at 30, 40, and 50 kHz to sham stimulation on experimental pain, sensory, motor, and neurophysiological outcomes., Methods: A randomized, double-blind, sham-controlled crossover study involving 34 healthy participants was conducted. Four interventions (30, 40, 50 kHz, and sham) were administered, and stimulation was applied for 20 min to the median nerve of the non-dominant hand. A prototype stimulator capable of delivering frequencies between 1 and 50 kHz, with a maximum peak-to-peak output current intensity of 400 mA was designed. The intensity applied during the stimulation was below motor threshold, evoking a 'strong but comfortable' tingling sensation. Primary outcomes included heat pain threshold (HPT), pressure pain threshold (PPT), and adverse effects. The secondary outcomes included static two-point discrimination sensitivity, isometric pinch strength, and median sensory nerve action potential (SNAP)., Results: Compared with the sham stimulation, all the active interventions exhibited a significantly greater increase in the PPT during and immediately after the stimulation, while only a significant increase was observed at 40 kHz (4.1 N/cm 2 ; 95%CI 0.3 to 7.9) at 15 min post-intervention. Compared to sham stimulation, the 40 kHz intervention had a significantly greater effect on the HPT at all time points, with the greatest difference (1.4 °C; 0.6 to 2.1) occurring immediately post-intervention. Adverse effects during active interventions included petechiae, erythema, and itching, which resolved at 24 h post-intervention. For secondary outcomes, only a significant reduction in the median SNAP velocity was observed in the sham stimulation group compared to the 50 kHz group., Conclusions: Active KHFAC stimulation, particularly at 40 kHz, delivered through a novel stimulator, effectively increased the PPT and HPT without affecting tactile or motor outcomes, inducing mild skin-related adverse effects. These findings have potential implications for people with pain-related pathologies., Trial Registration: NCT05230836., Competing Interests: Declarations Ethics approval and consent to participate Before the initiation of the study, the local research ethics committee (reference number: 805 − 24/11/2021) and the Spanish Agency of Medicines and Medical Devices (reference number: 965/22/EC-R) approved this study. All the participants gave and signed an informed consent to participate in this study. Consent for publication Not applicable. Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

This review discusses non-pharmacological, non-surgical interventions for action tremor, including essential tremor (ET). We review transcutaneous peripheral nerve stimulation (PNS), a variety of orthotic/mechanical devices, cooling and vibration strategies, and adaptive utensils, most of which are currently available. The PNS section discusses open loop (CALA-Trio) and closed loop systems (Felix™, NeuroAI™ and Motimove® systems). Orthotic devices which physically dampen tremor include Tremulo™, GyroGlove™, WOTAS exoskeleton, Magnetorheological Fluid-Based Exoskeleton System, Steadi-One® and Steadi-Two®, and Readi-Steady®. Adaptive devices include weighted spoons, deep cavity spoons, counter-balance utensils, and electrical actuator devices. Despite availability, most of these devices have limited to no published clinical trial data., Competing Interests: The authors have no competing interests to declare., (Copyright: © 2024 The Author(s).)

Purpose of Review: Neuromodulation approaches have been a part of a revolution in migraine therapies with multiple devices approved or in development. These devices vary in the nerve(s) being targeted, implantable versus noninvasive form factors as well as their effectiveness for acute pain reduction or migraine prevention. This review will summarize these recent advancements and approaches that are being developed which build upon prior work and improved technology that may help enhance the effectiveness as well as the patient experience., Recent Findings: Both noninvasive and implantable devices primarily targeting cranial nerves have shown the ability to help alleviate migraine symptoms. Multiple prospective and retrospective studies have demonstrated clinically meaningful reductions in headache intensity with noninvasive approaches, while prevention of migraine demonstrates more modest effects. Implantable neuromodulation technologies focusing on occipital and supraorbital stimulation have shown promise in migraine/headache prevention in chronic migraine patients, but there is a need for improvements in technology to address key needs for surgical approaches., Summary: Electrical neuromodulation approaches in the treatment of migraine is undergoing a transformation towards improved outcomes with better technologies that may suit various patient needs on a more individualized basis., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Abstract: Current practice lacks effective periprocedural pain management during common gynecological procedures such as intrauterine device insertion, increasing the possibility of significant pain and adverse reaction to such procedures. Because of this, pain can often be a barrier for a patient in choosing a form of contraception that best serves them. Transcutaneous electrical nerve stimulation offers an option for effective pain control during intrauterine device insertion. This case review characterizes five cases where patients were offered transcutaneous electrical nerve stimulation for pain control during intrauterine device insertion. The patients reported a range of no pain to moderate pain during intrauterine device insertion and rated their pain experience as better compared with prior insertions. Although limited to a case review, our findings suggest a promising clinical indication for transcutaneous electrical nerve stimulation as a pain management strategy for intrauterine device insertion., Competing Interests: Competing interests: The authors report no conflicts of interest., (Copyright © 2024 American Association of Nurse Practitioners.)

Aims: Transcutaneous auricular vagus nerve stimulation (taVNS) is widely used to treat a variety of disorders because it is noninvasive, safe, and well tolerated by awake patients. However, long-term and repetitive taVNS is difficult to achieve in awake mice. Therefore, developing a new taVNS method that fully mimics the method used in clinical settings and is well-tolerated by awake mice is greatly important for generalizing research findings related to the effects of taVNS. The study aimed to develop a new taVNS device for use in awake mice and to test its reliability and effectiveness., Methods: We demonstrated the reliability of this taVNS device through retrograde neurotropic pseudorabies virus (PRV) tracing and evaluated its effectiveness through morphological analysis. After 3 weeks of taVNS application, the open field test (OFT) and elevated plus maze (EPM) were used to evaluate anxiety-like behaviors, and the Y-maze test and novel object recognition test (NORT) were used to evaluate recognition memory behaviors, respectively., Results: We found that repetitive taVNS was well tolerated by awake mice, had no effect on anxiety-like behaviors, and significantly improved memory., Conclusion: Our findings suggest that this new taVNS device for repetitive stimulation of awake mice is safe, tolerable, and effective., (© 2024 The Author(s). CNS Neuroscience & Therapeutics published by John Wiley & Sons Ltd.)

The tibial nerve is an established target for neuromodulation in the management of overactive bladder (OAB) and its associated symptoms, including urge urinary incontinence (UUI). Technologies are currently available to deliver tibial nerve stimulation (TNS) through percutaneous devices or through implantable devices. The benefits and safety of percutaneous TNS have led to it as a guideline-recommended therapy. However, patient compliance is limited by the burden of weekly office visits and the need for maintenance treatments. Further, insurance often only covers a limited number of lifetime visits for percutaneous TNS. These factors and others have led to the development, study, and utilization of implantable TNS devices. Implantable TNS devices deliver the same therapeutic mechanism of action for nerve stimulation with a permanent implanted device that provides at-home stimulation rather than in-office therapy delivery. Additionally, there is an added potential for dynamic and patient-centered stimulation. There is a large body of high-quality evidence published for TNS, including numerous randomized controlled trials published on percutaneous TNS which have consistently demonstrated superior efficacy to sham and similar efficacy to that of anticholinergic medications. Percutaneous TNS also performs better than conservative therapy including pelvic floor muscle training. The percutaneous and implantable approaches deliver nerve stimulation to the same target nerve, using the same mechanism of action. Therefore, data from randomized trials of percutaneous TNS are informative for implantable TNS devices. At the time of this article's publication, at least two implantable TNS devices have received marketing authorization from the Food and Drug Administration (FDA). The objective of this review is to discuss the mechanism of action for TNS and summarize the published literature from clinical trials of percutaneous TNS as a foundation of high-quality evidence for implantable devices targeting the tibial nerve., (© 2024. The Author(s), under exclusive licence to Springer Healthcare Ltd., part of Springer Nature.)

Objectives: Transcutaneous vagus nerve stimulation has shown promising results in improving cognitive and motor function after stroke. However, to our knowledge, there have been no studies in the modulation of the cervical vagus nerve using repetitive transcranial magnetic stimulation (rTMS) in patients with traumatic brain injury (TBI) with cognitive dysfunction. Thus, we conducted a single-arm feasibility trial to assess the safety and effectiveness of rTMS of the vagus nerve in patients with TBI., Materials and Methods: We enrolled ten patients with TBI and administered half-hour vagus nerve magnetic stimulation (VNMS) sessions for ten days to evaluate the feasibility of the treatment. The Montreal cognitive assessment-Beijing (MoCA-B), the Digit Span Test, and the Auditory Verbal Learning Test (AVLT) were used to measure cognitive function before and after the VNMS treatment. Physiological parameters of all subjects were assessed by electrocardiogram., Results: The findings showed that daily half-hour VNMS for ten days was feasible in patients with TBI, with minimal side effects and no clinically significant effects on physiological parameters. Eight patients showed improvement in MoCA-B, and five patients showed improvement in immediate memory as measured by AVLT., Conclusions: We conclude that VNMS is a safe and feasible treatment option for patients with TBI with cognitive dysfunction. However, further controlled studies are necessary to establish the efficacy of VNMS in promoting cognitive recovery after TBI., Significance: This study is, to our knowledge, the first study to investigate the feasibility of VNMS for cognitive dysfunction in patients with TBI. Our findings offer the possibility of rTMS applied to the vagus nerve in clinical practice., Competing Interests: Conflict of interest The authors reported no conflict of interest., (Copyright © 2023 International Neuromodulation Society. Published by Elsevier Inc. All rights reserved.)

Objective: To evaluate the efficacy and safety of a wearable, smartphone-controlled, rechargeable transcutaneous tibial nerve stimulation (TTNS) device in patients with overactive bladder (OAB)., Patients and Methods: This multicentre, prospective, single-blind, randomised clinical trial included eligible patients with OAB symptoms who were randomly assigned to the stimulation group or sham group. The primary efficacy outcome was change from baseline in voiding frequency/24 h after 4 weeks of treatment. The secondary efficacy outcomes included changes in bladder diary outcomes (urgency score/void, nocturia episodes/day, micturition volume/void, and incontinence episodes/day), questionnaires on Overactive Bladder Symptom Score (OABSS), Patient Perception of Bladder Condition (PPBC), and American Urological Association Symptom Index Quality of Life Score (AUA-SI-QoL) at baseline and after 4 weeks of treatment. Device-related adverse events (AEs) were also evaluated., Results: In the full analysis set (FAS), the mean (sd) change of voiding frequency/24 h in the stimulation group and sham group at 4 weeks were -3.5 (2.9) and -0.6 (2.4), respectively (P < 0.01). Similar results were obtained in the per-protocol set (PPS): -3.5 (2.9) vs -0.4 (2.3) (P < 0.01). In the FAS and PPS, micturition volume/void significantly improved at 4 weeks (P = 0.01 and P = 0.02). PPBC improvement almost reached significance in the FAS (P = 0.05), while it was significant in the PPS (P = 0.02). In the FAS and PPS, AUA-SI-QoL significantly improved at 4 weeks in the two groups (P < 0.01 and P < 0.01), whereas there were no significant differences in urgency score/void, nocturia episodes/day or OABSS between the groups. Also, no device-related serious AEs were reported., Conclusions: The non-invasive neuromodulation technique using the novel ambulatory TTNS device is effective and safe for treating OAB. Its convenience and easy maintenance make it a new potential home-based treatment modality. Future studies are warranted to confirm its longer-term efficacy., (© 2024 BJU International.)

Chemotherapy-induced peripheral neuropathy (CIPN) affects approximately 30 to 60% of people who receive neurotoxic chemotherapy. CIPN is associated with impaired quality of life and function and has few effective treatments. This 6-site, subject and assessor-blinded randomized clinical trial (RCT) was designed to assess 1) preliminary efficacy (ie, alpha pre-specified at .2) of a wearable, app-controlled, transcutaneous electrical nerve stimulation (TENS) device for chronic CIPN and 2) feasibility of conducting a confirmatory trial within the National Cancer Institute Community Oncology Research Program (NCORP) (NCT04367480). The primary outcome was the EORTC-CIPN20. The main secondary outcomes were individual symptoms assessed daily (via 0-10 numeric rating scales). The primary analysis was an analysis of covariance (outcome: EORTC-CIPN20, fixed effect: arm, covariates: baseline EORTC-CIPN20 and site). Secondary analyses used a similar analysis of covariance models (excluding site) for each symptom on subgroups of subjects with ≥4 out of 10 for that symptom at baseline. 142 eligible subjects were randomized and received a device; 130 (91%) completed the study. The difference between groups in the EORCT-CIPN20 at the endpoint (placebo-active) was 1.05 (95% Confidence Interval: -.56, 2.67; P = .199). The difference between groups for the individual symptoms was as follows: hot/burning pain: 1.37 (-.33, 3.08; P = .112), sharp/shooting pain: 1.21 (-.37, 2.79; P = .128), cramping: 1.35 (-.32, 3.02; P = .110), tingling: .23 (-.61, 1.08; P = .587), numbness: .27 (-.51, 1.05; P = .492). An RCT of an app-controlled TENS device for chronic CIPN with excellent retention is feasible in the NCORP. Preliminary efficacy evidence suggests that TENS is promising for pain and cramping from CIPN. A confirmatory RCT of TENS for painful CIPN is highly warranted. PERSPECTIVE: Daily, home-based TENS therapy demonstrates promising efficacy for painful CIPN symptoms in this proof-of-concept randomized clinical trial. Future confirmatory trial is warranted., (Copyright © 2024 United States Association for the Study of Pain, Inc. Published by Elsevier Inc. All rights reserved.)

Transcutaneous spinal stimulation (TSS) is a promising rehabilitative intervention to restore motor function and coordination for individuals with spinal cord injury (SCI). The effects of TSS are most commonly assessed by evaluating muscle response to stimulation using surface electromyography (sEMG). Given the increasing use of robotic devices to deliver therapy and the emerging potential of hybrid rehabilitation interventions that combine neuromodulation with robotic devices, there is an opportunity to leverage the on-board sensors of the robots to measure kinematic and torque changes of joints in the presence of stimulation. This paper explores the potential for robotic assessment of the effects of TSS delivered to the cervical spinal cord. We used a four degree-of-freedom exoskeleton to measure the torque response of upper limb (UL) joints during stimulation, while simultaneously recording sEMG. We analyzed joint torque and electromyography data generated during TSS delivered over individual sites of the cervical spinal cord in neurologically intact participants. We show that site-specific effects of TSS are manifested not only by modulation of the amplitude of spinally evoked motor potentials in UL muscles, but also by changes in torque generated by individual UL joints. We observed preferential resultant action of proximal muscles and joints with stimulation at the rostral site, and of proximal joints with rostral-lateral stimulation. Robotic assessment can be used to measure the effects of TSS, and could be integrated into complex control algorithms that govern the behavior of hybrid neuromodulation-robotic systems.

Introduction: Both physical therapists and police officers use electrical muscle stimulation. The typical physical therapist unit is attached with adhesive patches while the police models use needle-based electrodes to penetrate clothing. There have been very few papers describing the outputs of these physical therapy EMS (electrical muscle stimulator) units., Methods: We purchased 6 TENS/EMS units at retail and tested them with loads of 500 Ω, 2 kΩ, and 10 kΩ., Results: For the typical impedance of 500 Ω, the EMS units delivered the most current followed by the electrical weapons; TENS units delivered the least current. At higher im-pedances (> 2 kΩ) the electrical weapons delivered more current than the EMS units, which is explained by the higher voltage-compliance of their circuits. Some multi channel EMS units deliver more calculated muscle stimula tion than the multi-channel weapons., Conclusion: Present therapeutic electrical muscle stimula-tors can deliver more current than present law-enforcement muscle stimulators.

Objective: The purpose of this study is to determine if different facial muscle groups demonstrate different responses to facial nerve stimulation, the results of which could potentially improve intraoperative facial nerve monitoring (IOFNM)., Methods: IOFNM data were prospectively collected from patients undergoing cochlear implantation. At different stages of nerve exposure, three sites were stimulated using a monopolar pulse. Peak electromyography (EMG) amplitude (μV) in four muscle groups innervated by four different branches of the facial nerve (frontalis-temporal, inferior orbicularis oculi-zygomatic, superior oribularis oris-buccal, and mentalis-marginal mandibular) were recorded., Results: A total of 279 peak EMG amplitudes were recorded in 93 patients. At all three stimulating sites, the zygomatic branch mean peak EMG amplitudes were statistically greater than those of the temporal, buccal, and marginal mandibular branches (P < .05). At stimulating Site C, the marginal mandibular branch mean peak EMG was stronger than the temporal or buccal branches (P < .05). Of the 279 stimulations, the zygomatic branch demonstrated the highest amplitude in 128 (45.9%) trials, followed by the marginal mandibular branch (22.2%)., Conclusions: When utilized, IOFNM should be performed with at least two electrodes, one of which is placed in the orbicularis oculi muscles and the other in the mentalis muscle. However, there is wide variability between patients. As such, in cases of suspected variant nerve anatomy or increased risk of injury (intradural procedures), surgeons should consider using more than two recording electrodes, with at least one in the orbicularis oculi muscle., Level of Evidence: 3 Laryngoscope, 131:E2329-E2334, 2021., (© 2021 The American Laryngological, Rhinological and Otological Society, Inc.)

Background: Percutaneous peripheral nerve stimulation is an analgesic technique involving the percutaneous implantation of a lead followed by the delivery of electric current using an external pulse generator. Percutaneous peripheral nerve stimulation has been used extensively for chronic pain, but only uncontrolled series have been published for acute postoperative pain. The current multicenter study was undertaken to (1) determine the feasibility and optimize the protocol for a subsequent clinical trial and (2) estimate the treatment effect of percutaneous peripheral nerve stimulation on postoperative pain and opioid consumption., Methods: Preoperatively, an electrical lead was percutaneously implanted to target the sciatic nerve for major foot/ankle surgery (e.g., hallux valgus correction), the femoral nerve for anterior cruciate ligament reconstruction, or the brachial plexus for rotator cuff repair, followed by a single injection of long-acting local anesthetic along the same nerve/plexus. Postoperatively, participants were randomized to 14 days of either electrical stimulation (n = 32) or sham stimulation (n = 34) using an external pulse generator in a double-masked fashion. The dual primary treatment effect outcome measures were (1) cumulative opioid consumption (in oral morphine equivalents) and (2) mean values of the "average" daily pain scores measured on the 0 to 10 Numeric Rating Scale within the first 7 postoperative days., Results: During the first 7 postoperative days, opioid consumption in participants given active stimulation was a median (interquartile range) of 5 mg (0 to 30) versus 48 mg (25 to 90) in patients given sham treatment (ratio of geometric means, 0.20 [97.5% CI, 0.07 to 0.57]; P < 0.001). During this same period, the average pain intensity in patients given active stimulation was a mean ± SD of 1.1 ± 1.1 versus 3.1 ± 1.7 in those given sham (difference, -1.8 [97.5% CI, -2.6 to -0.9]; P < 0.001)., Conclusions: Percutaneous peripheral nerve stimulation reduced pain scores and opioid requirements free of systemic side effects during at least the initial week after ambulatory orthopedic surgery., (Copyright © 2021, the American Society of Anesthesiologists. All Rights Reserved.)

Objective: To determine predictors of success for sacral neuromodulation in women with overactive bladder, urinary retention, and fecal incontinence., Methods: A retrospective chart review was performed on women who underwent a staged sacral neuromodulation implantation between 2007 and 2018. Clinical and procedural characteristics were recorded. Presence of intraoperative motor responses in either all 4 or <4 electrodes were used to group women. Endpoints included completion of stage II implant, tined lead revision, and patient-reported success., Results: In 198 women with a mean age of 62.9 years (SD+/- 14.7), completion of stage II implant occurred in 92.4% of women, and 83.3% of these women reported success at the first postoperative visit. Continued success at 6 months was reported in 70.3%. Lead revision was noted in 23.0%. Age >65 years (odds ratio [OR] = 0.2, 95% confidence interval [CI] = 0.06-0.8) and prior onabotulinumtoxinA (onaBoNT-A) (OR = 0.2, 95% CI = 0.06-0.9) were negative predictors for completion of stage II implant on multivariable analysis. Also, prior pelvic floor physical therapy was a significant negative predictor of postoperative patient-reported success on multivariable analysis (OR = 0.25, 95% CI = 0.1-0.6). There were no differences seen in women who had motor responses with either all 4 electrodes or <4 electrodes in any endpoint (P > .05)., Conclusion: Patient age >65 and history of prior onaBoNT-A were associated with failure to complete stage II implant. Women with prior pelvic floor physical therapy were less likely to report success after sacral neuromodulation. Motor responses in <4 electrodes during lead testing did not impact patient-reported success., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Introduction : Many patients with migraine are non-responsive or intolerant to pharmaceutical or surgical interventions. Peripheral nerve stimulation (PNS) offers a potential solution for these patients. This review discusses the external combined occipital and trigeminal neurostimulation (eCOT-NS) provided by the Relivion®, a multi-channel head-mounted device for self-administered PNS. Areas covered : Challenges and advantages of PNS systems for the treatment of migraine and depression are introduced, followed by an overall review of clinical evidence of the efficacy of the Relivion® system in treating migraine. The supporting smartphone app and cloud-based analytics which enable remote treatment management by the health care provider are also discussed. Recent empirical indications for the potency of this PNS combination for the treatment of depression are also summarized. Expert opinion : Relivion® is an eCOT-NS system, featuring Food and Drug Administration-approved, noninvasive, self-administered, customizable, multi-focal PNS for the treatment of migraine. In accordance with current telehealth trends, the Relivion® also enhances remote disease management and personalization using digital-monitoring, cloud-based technology, and artificial intelligence. As research on this system progresses, it may become the preferred treatment for the management of a number of neurological and psychiatric diseases, with migraine and major depressive disorders as precedents.

Spinal cord injury (SCI) leads to severe impairment in cardiovascular control, commonly manifested as a rapid, uncontrolled rise in blood pressure triggered by peripheral stimuli-a condition called autonomic dysreflexia. The objective was to demonstrate the translational potential of noninvasive transcutaneous stimulation (TCS) in mitigating autonomic dysreflexia following SCI, using pre-clinical evidence and a clinical case report. In rats with SCI, we show that TCS not only prevents the instigation of autonomic dysreflexia, but also mitigates its severity when delivered during an already-triggered episode. Furthermore, when TCS was delivered as a multisession therapy for 6 weeks post-SCI, the severity of autonomic dysreflexia was significantly reduced when tested in the absence of concurrent TCS. This treatment effect persisted for at least 1 week after the end of therapy. More importantly, we demonstrate the clinical applicability of TCS in treatment of autonomic dysreflexia in an individual with cervical, motor-complete, chronic SCI. We anticipate that TCS will offer significant therapeutic advantages, such as obviating the need for surgery resulting in reduced risk and medical expenses. Furthermore, this study provides a framework for testing the potential of TCS in improving recovery of other autonomic functions such lower urinary tract, bowel, and sexual dysfunction following SCI., (© 2021. The Author(s).)

There is a critical need to transition research level flexible polymer bioelectronics toward the clinic by demonstrating both reliability in fabrication and stable device performance. Conductive elastomers (CEs) are composites of conductive polymers in elastomeric matrices that provide both flexibility and enhanced electrochemical properties compared to conventional metallic electrodes. This work focuses on the development of nerve cuff devices and the assessment of the device functionality at each development stage, from CE material to fully polymeric electrode arrays. Two device types are fabricated by laser machining of a thick and thin CE sheet variant on an insulative polydimethylsiloxane substrate and lamination into tubing to produce pre-curled cuffs. Device performance and stability following sterilization and mechanical loading are compared to a state-of-the-art stretchable metallic nerve cuff. The CE cuffs are found to be electrically and mechanically stable with improved charge transfer properties compared to the commercial cuff. All devices are applied to an ex vivo whole sciatic nerve and shown to be functional, with the CE cuffs demonstrating superior charge transfer and electrochemical safety in the biological environment., Competing Interests: The authors declare no conflict of interest., (© 2021 The Authors. Advanced Science published by Wiley‐VCH GmbH.)

Introduction: Ultrasound-guided percutaneous peripheral nerve stimulation (PNS) may be used to treat acute postoperative pain for various types of surgeries. This modality avoids several limitations of traditional local anesthetic-based peripheral nerve blocks including avoidance of motor blockade and sensory deficits., Areas Covered: In this review, we discuss the use of SPRINT (SPR Therapeutics, Cleveland, OH) neuromodulation system in the setting of acute postoperative pain management., Expert Opinion: PNS is a novel modality in regional anesthesia that has much promise in reducing overall opioid use after surgery. Placement of PNS is very similar to that of catheter-based regional anesthesia techniques. Ultrasound is used to guide the percutaneously placed introducer needle in proximity to the target nerve. There are several benefits of PNS over catheter-based approaches, including: 1) avoidance of motor or sensory blockade; 2) no medication bag required to be carried; and 3) electric leads may be kept in situ safely for up to 60 days. While several proof-of-concept studies have been published highlighting its use in various types of surgeries, large high-quality randomized controlled trials are still needed.

Objectives: Migraine is a common disabling neurological disorder. Current acute treatments for migraine in adolescents are mostly pharmacological and may have limited effectiveness, can cause side effects, and may lead to medication overuse. There is an unmet need for effective and well-tolerated treatments. Remote electrical neuromodulation (REN) is a novel acute treatment of migraine that stimulates upper arm peripheral nerves to induce conditioned pain modulation (CPM)-an endogenous analgesic mechanism. The REN device (Nerivio ® , Theranica Bio-Electronics Ltd., Israel) is a FDA-authorized device for acute treatment of migraine in adults. This study assessed the efficacy and safety of REN in adolescents with migraine., Design and Methods: This was an open-label, single-arm, multicenter study in adolescents (ages 12-17 years) with migraine. Participants underwent a 4-week run-in phase. Eligible participants continued to an 8-week treatment phase with the device. Pain severity, associated symptoms, and functional disability were recorded at treatment initiation, and 2 and 24 hours post-treatment. The primary endpoints of this study were related to the safety and tolerability of REN. The secondary endpoints were related to device efficacy and included the proportion of participants who achieved pain relief at 2 hours post-treatment and the proportion of participants who achieved pain freedom at 2 hours. The presented results reflect an interim analysis with subsequent stopping of the rest of the study., Results: Sixty participants were enrolled for the study; of these, 14 failed to meet the run-in criteria and 1 was lost to follow-up. Forty-five participants performed at least one treatment, of which 39 participants completed a test treatment with REN. One device-related adverse event (2%) was reported in which a temporary feeling of pain in the arm was felt. Pain relief and pain-free at 2 hours were achieved by 71% (28/39) and 35% (14/39) participants, respectively. At 2 hours, 69% (23/33) participants experienced improvement in functional ability., Conclusions: REN may offer a safe and effective non-pharmacological alternative for acute treatment in adolescents., (© 2020 American Headache Society.)

In recent years, electroceuticals have been spotlighted as an emerging treatment for various severe chronic brain diseases, owing to their intrinsic advantage of electrical interaction with the brain, which is the most electrically active organ. However, the majority of research has verified only the short-term efficacy through acute studies in laboratory tests owing to the lack of a reliable miniaturized platform for long-term animal studies. The construction of a sufficient integrated system for such a platform is extremely difficult because it requires multi-disciplinary work using state-of-the-art technologies in a wide range of fields. In this study, we propose a complete system of an implantable platform for long-term preclinical brain studies. Our proposed system, the extra-cranial brain activator (ECBA), consists of a titanium-packaged implantable module and a helmet-type base station that powers the module wirelessly. The ECBA can also be controlled by a remote handheld device. Using the ECBA, we performed a long-term non-anesthetic study with multiple canine subjects, and the resulting PET-CT scans demonstrated remarkable enhancement in brain activity relating to memory and sensory skills. Furthermore, the histological analysis and high-temperature aging test confirmed the reliability of the system for up to 31 months. Hence, the proposed ECBA system is expected to lead a new paradigm of human neuromodulation studies in the near future.

A flexible, multifunctional, and intelligent analgesic bracelet was proposed in this article to alleviate symptoms of pain. Based on the theory of wrist-ankle acupuncture in traditional Chinese medicine, transcutaneous electrical nerve stimulation is the technical basis of the method. A set of targeted circuit system capable of generating adjustable electrical stimulation signals to simulate filamentary acupuncture was designed. The system architecture includes a wireless communication module, a signal control module, a stimulus signal generation module, and a wearable, flexible bracelet. In addition, a pain assessment interface with a visual analog scale was designed to assess pain levels. Two comparative experiments were designed, involving a custom pain assessment scale and hand-held dolorimeter that were performed before and after wearing the bracelet to verify the analgesic effect of the bracelet. The results showed that the wrist-worn analgesic bracelet is significantly effective in alleviating pain in various parts of the human body.

Background: Reading is a critical skill in modern society but is significantly more difficult to acquire during adulthood. Many adults are required to learn a new orthography after this window closes for personal or vocational reasons and while many programs and training methods exist for learning to read in adulthood, none result in native-like fluency. Implantable cervical vagus nerve stimulation is capable of driving neural plasticity but is invasive and not practical as a reading intervention., Objective: The goal of the current study was to evaluate whether non-invasive transcutaneous auricular vagus nerve stimulation (taVNS) is effective at enhancing novel orthography acquisition in young adults., Methods: We enrolled 37 typically developing participants and randomly assigned them to a computer control, device sham control, earlobe stimulation control, or experimental transcutaneous auricular stimulation (taVNS) group. Participants then learned novel letter-sound correspondences in Hebrew over five training lessons. Performance was assessed using three measures to evaluate various aspects of reading: Letter ID, Automaticity, and Decoding., Results: The taVNS group significantly outperformed the three control groups on both the Automaticity and Decoding tasks. There was no difference on the Letter ID task., Conclusions: These results demonstrate, for the first time, that taVNS is capable of improving aspects of reading acquisition in adults. These findings have potential implications for a wide range of cognitive tasks., Competing Interests: Declaration of competing interest The authors have no conflicts of interest to declare., (Copyright © 2020 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Spasticity after lesions of central motor pathways may be disabling and there is a need for new, cost-effective treatment methods. One novel approach is offered by the electro-dress Mollii®, primarily designed to enhance reciprocal inhibition of spastic muscles by multifocal, transcutaneous antagonist stimulation., Methods: The Mollii® suit was set individually for 20 participants living with spasticity and hemiplegia after stroke and used in the home setting for 6 weeks. Usability and perceived effects were monitored by weekly telephone interviews. Outcome was assessed by use of the NeuroFlexor™ method for quantification of the neural component (NC) of resistance to passive stretch (spasticity), and the modified Ashworth scale (MAS) for total resistance, Fugl-Meyer Assessment of motor recovery for sensorimotor function in upper (FM-UE) and lower extremities (FM-LE), activity performance with the Action Research Arm Test (ARAT), Berg balance scale, 10 m and 6 min walk tests, and perceived functioning with the Stroke Impact Scale., Results: Compliance was high (mean 19.25 of 21 sessions). Perceived positive effects were reported by 60% and most commonly related to decreased muscle tone (n = 9), improved gait pattern function (n = 7) and voluntary movement in the upper extremity (n = 6). On a group level, the NC decreased significantly in the wrist flexors of the affected hand (p = 0.023) and significant improvements according to FM-UE (p = 0.000) and FM-LE (p = 0.003) were seen after the intervention. No significant difference was detected with MAS or assessed activity performance, except for the ARAT (p = 0.000). FM-UE score change correlated significantly and fairly with the perceived effect in the upper extremity (r 0.498 p = 0.025) and in the corresponding analysis for the FM-LE and perceived effect in the lower extremity (r = 0.469 p = 0.037)., Conclusion: This study indicates that the Mollii® method is feasible when used in the home setting to decrease spasticity and improve sensorimotor function. The results may guide a larger controlled study combined with rehabilitation interventions to enhance effects on activity and participation domains., Trial Registration: NCT04076878 . Registered 2 September 2019 - Retrospectively registered.

Purpose: The aim of this study was to evaluate the effects of transcutaneous electrical nerve stimulation at acupuncture points versus trigger points on myofascial pain, moods, and sleep quality., Design: A randomized controlled study recruited 64 patients with spinal cord injury with myofascial pain., Methods: Outcomes of pain, moods, and sleep quality were measured and analyzed by the generalized estimation equation, analysis of covariance, and paired t test. Transcutaneous electrical nerve stimulation was applied for seven consecutive days at Hegu (LI4) and Daling (PC7) acupuncture points or myofascial trigger points., Finding: Significant differences were found in pain intensity from Day 3 forward, after controlling for confounders. Significant within-group differences were found in pain, moods, and sleep quality., Conclusions: Transcutaneous electrical nerve stimulation at acupuncture and trigger points effectively improved pain, moods, and sleep quality in patients with spinal cord injury with myofascial pain. Acupuncture points had superior improvement in pain intensity and slight improvement in sleep quality than did trigger points., Clinical Relevance: Transcutaneous electrical nerve stimulation at acupuncture points could be applied for improving myofascial pain.

A high-performance, wide dynamic range, fully-integrated neural interface is one key component for many advanced bidirectional neuromodulation technologies. In this paper, to complement the previously proposed frequency-shaping amplifier (FSA) and high-precision electrical microstimulator, we will present a proof-of-concept design of a neural data acquisition (DAQ) system that includes a 15-bit, low-power Delta-Sigma analog-to-digital converter (ADC) and a real-time spike processor based on one exponential component-polynomial component (EC-PC) algorithm. High-precision data conversion with low power consumption and small chip area is achieved by employing several techniques, such as opamp-sharing, multi-bit successive approximation (SAR) quantizer, two-step summation, and ultra-low distortion data weighted averaging (DWA). The on-chip EC-PC engine enables low latency, automatic detection, and extraction of spiking activities, thus supporting closed-loop control, real-time data compression and /or neural information decoding. The prototype chip was fabricated in a 0.13  μm CMOS process and verified in both bench-top and In-Vivo experiments. Bench-top measurement results indicate the designed ADC achieves a peak signal-to-noise and distortion ratio (SNDR) of 91.8 dB and a dynamic range of 93.0 dB over a 10 kHz bandwidth, where the total power consumption of the modulator is only 20  μW at 1.0 V supply, corresponding to a figure-of-merit (FOM) of 31.4fJ /conversion-step. In In-Vivo experiments, the proposed DAQ system has been demonstrated to obtain high-quality neural activities from a rat's motor cortex and also greatly reduce recovery time from system saturation due to electrical microstimulation.

Purpose: One risk of removal of a tined sacral neuromodulation lead is breakage, resulting in a retained lead fragment. We report lead breakage rates, risk factors and outcomes of retained fragments., Materials and Methods: We report on 464 tined lead removals from 2002 to 2018. Clinical and surgical factors were reviewed and appropriate statistical analysis performed. Retained fragments were reviewed for fragment description and long-term complications., Results: A total of 464 tined lead removals were included, with 35 lead breaks identified, for a rate of 7.5% (35). Factors associated with breakage included male gender (OR 6.58, 95% CI 2.54-17.01, p=0.001) and diabetes (OR 2.42, 95% CI 1.05-5.58, p=0.019). A shorter time since implantation was protective (OR 0.86, 95% CI 0.76-0.98, p=0.002). There was no difference in breakage rate based on age, weight, history of prior revision, bilateral leads, reason for lead removal, surgical technique or surgeon. Of the 35 breaks 27 had imaging available. Of these 66% (18) broke in the tined region and 81% (22) were ghost leads. Most patients (80%, 28 of 35) with retained lead fragments received another implant. Only 1 patient had a related complication of additional surgery for pain related to the fragment., Conclusions: There is a low rate of tined lead breakage during lead removal. However, it is higher than the manufacturer estimate. Protective factors include a shorter time between implant and lead revision. The most common location for lead breakage is in the region of the tines, most are ghost fragments and long-term complications are uncommon.

Background and Objectives: Needle insertion pain during spinal anesthesia is an unpleasant experience for patients. This study aimed to investigate the effects of Transcutaneous Electrical Nerve Stimulation (TENS) on the pain intensity during the insertion of spinal needles in patients undergoing spinal anesthesia., Materials and Methods: In a double-blind clinical trial, 60 candidates for elective Trans Ureteral Lithotripsy surgery under spinal anesthesia were randomly divided into intervention and control groups. The electrodes of the TENS device were placed in the space between L3-L4 and L5-S1 vertebrae. The intensity of pain during insertion of the spinal needle by Visual Analog Scale and the frequency of attempts were recorded., Results: The mean age of the study samples was 34.26 ± 5.07 and 32.8 ± 5.28 in the control and intervention group, respectively. The pain intensity during insertion of spinal needles was less significant in the intervention group compared to the control group (p = 0.001). The number of attempts to insert the spinal needle between the two groups was not statistically significant (p = 0.51). The duration of spinal anesthesia implementation procedure by physician in the intervention group was significantly shorter than that of the control group (p = 0.001)., Conclusion: The use of TENS effectively reduced the pain of spinal needle insertion. Considering these beneficial effects, it is suggested that this procedure be used to relive pain in patients with spinal anesthesia., Competing Interests: Declaration of Competing Interest All authors had an equal role in design, work, statistical analysis and manuscript writing. The authors declare no conflict of interest., (Copyright © 2020. Published by Elsevier B.V.)

The paper presents the design and validation of body-conformal active ultrasound patches with integrated imaging and modulation modalities for image-guided neural therapy. A mechanically-flexible linear 64-element array of piezoelectric transducers with a resonance frequency of 5 MHz was designed for nerve localization. A second 8-element array using larger elements was integrated on the wearable probe for low intensity focused ultrasound neuromodulation at a resonance frequency of 1.3 MHz. Full-wave simulations were used to model the flexible arrays and estimate their generated pressure profiles. A focal depth of 10-20 mm was assumed for beamforming and focusing to support modulation of the vagus, tibial, and other nerves. A strain sensor integrated on the probe provides patient-specific feedback information on array curvature for real-time optimization of focusing and image processing. Each patch also includes high voltage (HV) multiplexers, transmit/receive switches, and pre-amplifiers that simplify connectivity and also improve the signal-to-noise ratio (SNR) of the received echo signals by  ∼ 5 dB. Experimental results from a flexible prototype show a sensitivity of 80 kPa/V with  ∼ 3 MHz bandwidth for the modulation and 20 kPa/V with  ∼ 6 MHz bandwidth for the imaging array. An algorithm for accurate and automatic localization of targeted nerves based on using nearby blood vessels (e.g., the carotid artery) as image markers is also presented.

Introduction: Powered muscle stimulators have been popularized in recent years due to their muscle toning effects. This study aims to describe marketing trends and reporting of adverse effects of powered muscle stimulators. Methods: We performed a cross-sectional retrospective analysis of records from the United States FDA database for 510(k) premarket approval of powered muscle stimulators between January 1, 2000 and December 31, 2018. The FDA MAUDE database was reviewed for adverse events reported with device usage. Results: One hundred and seventeen devices received 510(k) premarket approval between 2000 and 2018, with the first approval occurring in 2001. Initially, devices were marketed to assist with muscle toning and strengthening, but more recent indications include the treatment of pain, increased local muscle blood circulation, and prevention of post-surgical venous thrombosis. Thirty-six adverse event reports have been submitted and published in the MAUDE database over the past 10 years by 11% of manufacturers. Discussion: Powered muscle stimulators are growing increasingly popular amongst consumers and healthcare providers due to their ease of use and perceived esthetic, muscle strength, and pain relief benefits. Additional investigation to determine optimal treatment parameters and potential adverse effects is necessary due to the growing popularity of these devices.

Background: Knee osteoarthritis (KOA) is a common degenerative joint disorder that affects 250 million people globally. KOA can lead to disability and is often associated with cardiovascular disease, poor quality of life, and mortality. The most common treatment for KOA is non-steroidal anti-inflammatory drug administration. However, the analgesic effect is limited and often accompanied by multiple side effects. Hence, many KOA patients opt for complementary and alternative medicine. Acupuncture is one of the most popular complementary treatments with great analgesic effect and minimal side effect. Electroacupuncture (EA) and laser acupuncture (LA) have been known to reduce pain in KOA patients. However, to date, no study has assessed the benefits of combining these two therapies., Methods: Fifty participants diagnosed with KOA, aged 50 years or older, and with consistent knee pain for more than 3 months were recruited and randomly assigned to the treatment group (EA plus LA) or control group (EA plus sham LA without laser output). All subjects in the treatment group will undergo a combined EA and LA treatment thrice a week for 4 weeks. The acupuncture will be performed on GB33, GB34, SP9, SP10, and ST36 sites. The treatment group will receive acupuncture with a transcutaneous electrical nerve stimulator at GB33, GB34, SP9, and SP10 sites and with LA at EX-LE5, ST35, and BL40 sites. The subjects in the control group will undergo the same treatment modality as the treatment group, except these subjects will not be exposed to laser output. Outcome measurements will include visual analog scale, Western Ontario McMaster Universities Osteoarthritis Index, Knee injury and osteoarthritis outcome, body composition analysis, knee range of motion, quadriceps muscle stiffness, one-leg standing with eyes open test, and the 30-s chair stand test before and after 4 weeks of intervention., Objectives: This protocol aims to investigate the combined effect of EA and LA in KOA patients.

Background: Urgency is a complaint of sudden, compelling desire to pass urine, which is difficult to defer, caused by involuntary contraction of the detrusor muscle during the bladder-filling stage. To enable detrusor inhibition, electrotherapy resources such as transcutaneous tibial nerve stimulation (TTNS) and parasacral transcutaneous electrical stimulation (PTES) have been used. The objective this study is to publish the study protocol that aims to investigate whether urgency decreases after treatment with both of the techniques., Methods: This randomized controlled clinical trial will include 99 women, aged more than 18 years old, with urgency (score ≥ 8 in the Overactive Bladder-Validated 8-Question Awareness Tool [OAB-V8]). Women will be randomly allocated into three groups: TTNS, PTES, and placebo. The following questionnaires will be applied: the Anamnesis Record, the Incontinence Questionnaire Overactive Bladder, the King's Health Questionnaire, the 24-Hour Voiding Diary, and the OAB-V8, at four different time points: at baseline prior to the first session, at the 6th session, the 12th session and at follow-up. The current used for the transcutaneous electrical stimulation will be a symmetrical balanced biphasic pulsed current, for 12 sessions, twice a week, for 20 minutes. Qualitative variables will be displayed as frequency and percentage, quantitative variables as mean and standard deviation. Comparison of urgency severity among groups will be performed with a repeated measures ANOVA, considering the effect of the three groups and the four evaluations, and interactions among them., Discussion: The present study aims to contribute evidence for a more in-depth discussion on electrode positioning for electrostimulation used in urgency treatment. It should be emphasized that, based on the possibility of confirming the hypothesis that urgency will decrease in a similar way after both treatments (TTNS and PTES), the PTES will be used as an option for positioning the electrodes alternatively to the tibial nerve region in special populations, such as amputees or people with severe lower limb sensory impairment., Trial Registration: Brazilian Registry of Clinical Trials (ReBEC) ID: RBR-9rf33n, date of registration: 17 May 2018.

Recently rechargeable devices have been introduced for sacral neuromodulation (SNM) with conditional safety for full-body magnetic resonance imaging (MRI). Currently a recharge-free SNM device represents the standard implant; however, it is only approved for MRI head scans. As further new technologies with broader MRI capabilities are emerging, the advantages as well as disadvantages of both rechargeable versus recharge-free devices will be briefly discussed in this commentary from the perspective of patients, healthcare professionals, and providers.

Objective: We present a PNS oracle, which solves these computation time and linearity problems and is, therefore, well-suited for fast optimization of voltage distributions in contact electrode arrays and current drive patterns in non-contact magnetic coil arrays., Approach: The PNS oracle metric for a nerve fiber is computed from an electric field map using only linear operations (projection, differentiation, convolution, scaling). Due to its linearity, this PNS metric can be precomputed for a set of coil or electrode segments, allowing rapid PNS prediction and comparison of any possible coil or electrode stimulation configuration constructed from this set. The PNS oracle is closely related to the classical activating function and modified driving functions but is adjusted to better correlate with full neurodynamic modeling of myelinated mammalian nerves., Main Results: We validated the PNS oracle in three MRI gradient coils and two body models and found good correlation between the PNS oracle and the full neurodynamic modeling approach (R 2   >  0.995). Finally, we demonstrated its potential utility by optimizing the driving currents and voltages of arrays of 108 magnetic coils or 108 contact electrodes to selectively stimulate target nerves in the lower leg., Significance: Peripheral nerve stimulation (PNS) by electromagnetic fields can be accurately simulated using coupled electromagnetic and neurodynamic modeling. Such simulations are slow and non-linear in the electric field, which makes it difficult to iteratively optimize coil and electrode configurations or drive patterns aiming to avoid PNS or to initiate it for therapeutic purposes.

Noninvasive neurostimulation methods are particularly suited for migraine treatment thanks to their most favorable adverse event profile. Among them, noninvasive vagus nerve stimulation (nVNS) has raised great hope because of the role the vagus nerve is known to play in pain modulation, inflammation and brain excitability. We will critically review the clinical studies performed for migraine attack treatment and migraine prevention with the GammaCore® device, which allows cervical vagus nerve stimulation. nVNS is effective for the abortive treatment of migraine attacks, although the effect size is modest and numbers-to-treat appear not superior to those of other noninvasive neurostimulation methods, and inferior to those of oral triptans. The effect of nVNS with the GammaCore® in migraine prevention is not superior to sham stimulation, except possibly in patients with high adherence to the treatment. Both in acute and preventive trials, nVNS was characterized by an outstanding tolerance and safety profile, like the other noninvasive neurostimulation techniques. In physiological animal and human studies, cervical nVNS was shown to generate somatosensory evoked responses, to modulate pain perception and several areas of the cerebral pain network, and to inhibit experimental cortical spreading depression, which are relevant effects for migraine therapy., (© 2020 Elsevier B.V. All rights reserved.)

The United States Food and Drug Administration (FDA) ensures that patients in the United States have access to safe and effective medical devices. The division of neurological and physical medicine devices reviews medical technologies that interface with the nervous system, including many neuromodulation devices. This article focuses on neuromodulation devices and addresses how to navigate the FDA's regulatory landscape to successfully bring devices to patients., (Published 2020. This article is a U.S. Government work and is in the public domain in the USA.)

Objective: Conventional treatment methods for migraine often have side effects. One treatment involves a wearable neuromodulator targeting frontal nerves. Studies based on this technique have shown limited efficacy and the existing setting can cause pain. These may be associated with neuroanatomical variations which lead to high levels of required stimulus current. The aim of this paper is to study the effect of such variations on the activation currents of the Cefaly neuromodulator. Also, using a different electrode orientation, the possibility of reducing activation current levels to avoid painful side-effects and improve efficacy, is explored., Approach: This paper investigates the effect of neuroanatomical variations and electrode orientation on the stimulus current thresholds using a computational hybrid model involving a volume conductor and an advanced nerve model. Ten human head models are developed considering statistical variations of key neuroanatomical features, to model a representative population., Main Results: By simulating the required stimulus current level in the head models, it is shown that neuroanatomical variations have a significant impact on the outcome, which is not solely a function of one specific neuroanatomical feature. The stimulus current thresholds based on the conventional Cefaly system vary from 4.4 mA to 25.1 mA across all head models. By altering the electrode orientation to align with the nerve branches, the stimulus current thresholds are substantially reduced to between 0.28 mA and 15 mA, reducing current density near pain-sensitive structures which may lead to a higher level of patient acceptance, further improving the efficacy., Significance: Computational modeling based on statistically valid neuroanatomical parameters, covering a representative adult population, offers a powerful tool for quantitative comparison of the effect of the position of stimulating electrodes which is otherwise not possible in clinical studies.

Objective: Electrical stimulation is a blunt tool for evoking neural activity. Neurons are naturally activated asynchronously and non-uniformly, whereas stimulation drives simultaneous activity within a population of cells. These differences in activation pattern can result in unintended side effects, including muddled sensory percepts and undesirable muscle contractions. These effects can be mitigated by the placement of electrodes in close approximation to nerve fibers and careful selection of the neural interface's location. This work describes the benefits of placing electrodes within specific fascicles of peripheral nerve to form selective neural interfaces for bidirectional neuroprosthetic devices., Approach: Chronic electrodes were targeted to individual fascicles of the ulnar and median nerves in the forearm of four human subjects. During the surgical implant procedure, fascicles were dissected from each nerve, and functional testing was used to identify the relative composition of sensory and motor fibers within each. FAST-LIFE arrays, composed of longitudinal intrafascicular arrays and fascicular cuff electrodes, were implanted in each fascicle. The location, quality, and stimulation parameters associated with sensations evoked by electrical stimulation on these electrodes were characterized throughout the 90-180 d implant period., Main Results: FAST-LIFE arrays enable selective and chronic electrical stimulation of individual peripheral nerve fascicles. The quality of sensations evoked by stimulation in each fascicle is predictable and distinct; subjects reported tactile and cutaneous sensations during stimulation of sensory fascicles and deeper proprioceptive sensations during stimulation of motor fascicles. Stimulation thresholds and strength-duration time constants were typically higher within sensory fascicles., Significance: Highly selective, stable neural interfaces can be created by placing electrodes within and around single fascicles of peripheral nerves. This method enables targeting electrodes to nerve fibers that innervate a specific body region or have specific functions. Fascicle-specific interfacing techniques have broad potential to maximize the therapeutic effects of electrical stimulation in many neuromodulation applications. (Clinical Trial ID NCT02994160.).

Recently, electrical stimulation in vocal rehabilitation has been the subject of studies. This treatment has shown promising results regarding the decrease of vocal/laryngeal symptoms, pain and the improvement of vocal tension. In addition to decreasing pain symptoms, TENS treatments may lead to muscle relaxation. There is no data on the effects of this resource as a vocal therapy in women with behavioral dysphonia. Research in this area may provide evidence to assist the clinical decision related to the treatment of women with complaints of behavioral dysphonia and musculoskeletal pain., Objective: To verify the effects of low-frequency TENS in association with vocal therapy on musculoskeletal pain in women with behavioral dysphonia., Methods: Participants included 27 women with vocal nodules randomized into two groups. The experimental group (EG) - 13 women received 12 sessions of TENS (pulse of 200 μs, frequency at 10 Hz, in motor threshold) with electrodes placed bilaterally on the trapezius muscle and submandibular area for 20 min followed by 30 min of vocal therapy, and the control group (CG) - 14 women received 12 sessions of 20 min of a placebo TENS followed by 30 min of vocal therapy. We investigated the frequency and intensity of the musculoskeletal pain in several body regions, as well as the intensity of pain at rest and in the application of pressure with an algometer applied to the descending fibers of the trapezius muscle. The pressure-pain threshold (PPT) was also investigated. All evaluations occurred before, immediately after, and at one and three months after treatment in both groups., Results: We observed a reduction in the frequency of pain in the larynx after treatment of both groups, but only the EG showed a decrease in pain intensity in this region. It was verified with an algometer to the trapezius muscle that the electrical stimulation associated with the vocal therapy decreased the intensity of pain during the application of pressure and increased the PPT. There were no significant differences with regard to variables investigated in the comparison between the interventions. On the other hand, there was decreased pain in the trapezius muscle for the EG in comparison to the pre- and post-intervention., Conclusion: The vocal therapyprogram reduced the frequency and intensity of the musculoskeletal pain in the regions proximal to the larynx of women with behavioral dysphonia. In addition, TENS followed by vocal therapy increased the threshold of sensitivity to muscular pain in the trapezius, demonstrating that it is a good resource to use in conjunction with traditional vocal therapy in cases of behavioral dysphonia associated with pain and muscle tension., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Objective: The development of non-invasive, quickly reversible techniques for controlling undesired muscle force production (e.g. spasticity) could expand rehabilitation approaches in those with pathology by increasing the type and intensity of exercises that can be performed. High-frequency alternating current (HFAC) has been previously established as a viable method for blocking neural conduction in peripheral nerves. However, clinical application of HFAC for nerve conduction block is limited due to the invasiveness of surgical procedures and the painful onset response. This study aimed to examine the use of transcutaneous HFAC (tHFAC) at various stimulation frequencies to address these shortfalls., Approach: Ten individuals participated in the study. Surface electrodes were utilized to apply tHFAC (0.5-12 kHz) to the median and ulnar nerves. Individual pain threshold was determined by gradual increase of stimulation amplitude. Subjects then performed a force-matching task by producing grip forces up to the maximal voluntary contraction level with and without application of tHFAC below the pain threshold., Main Results: Pain threshold current amplitude increased linearly with stimulation frequency. Statistical analysis showed that both stimulation frequency and charge injected per phase had significant effects (p   <  0.05) on grip force reduction. At the group level, application of tHFAC below pain threshold reduced grip force by a maximum of 40.7%  ±  8.1%. Baseline grip force trials interspersed between tHFAC trials showed consistent grip force, indicating that fatigue was not a factor in force reduction., Significance: Our results demonstrate the effectiveness of tHFAC at reducing muscle force when applied below the pain threshold, suggesting its potential clinical viability. Future studies are necessary to further elucidate the mechanism of force reduction before clinical application.

Electrical stimulation is widely used in pain research and profiling, but current technologies lack selectivity toward small sensory fibers. Pin electrodes deliver high current density in upper skin layers, and it has been proposed that slowly rising exponential pulses can elevate large-fiber activation threshold and thereby increase preferential small-fiber activation. Optimal stimulation parameters for the combined pin electrode and exponential pulse stimulation have so far not been established, which is the aim of this study. Perception thresholds were compared between pin and patch electrodes using single 1- to 100-ms exponential and rectangular pulses. Stimulus-response functions were evaluated for both pulse shapes delivered as single pulses and pulse trains of 10 Hz using intensities from 0.1 to 20 times perception threshold. Perception thresholds (mA) decreased when duration was increased for both electrodes with rectangular pulses and the pin electrode with exponential pulses. For the patch electrode, perception thresholds for exponential pulses decreased for durations ≤10 ms but increased for durations ≥15 ms, indicating accommodation of large fibers. Stimulus-response curves for single pulses were similar for the two pulse shapes. For pulse trains, the slope of the curve was higher for rectangular pulses. Maximal large-fiber accommodation to exponential pulses was observed for 100-ms pulses, indicating that 100-ms exponential pulses should be applied for preferential small-fiber activation. Intensity of 10 times perception threshold was sufficient to cause maximal pain ratings. The developed methodology may open new opportunities for using electrical stimulation paradigms for small-fiber stimulation and diagnostics. NEW & NOTEWORTHY Selective activation of small cutaneous nerve fibers is pivotal for investigations of the pain system. The present study demonstrated that patch electrode perception thresholds increase with increased duration of exponential currents from 20 to 100 ms. This is likely caused by large-fiber accommodation, which can be utilized to activate small fibers preferentially through small-diameter pin electrodes. This finding may be utilized in studies of fundamental pain mechanisms and, for example, in small-fiber neuropathy.

Objective: To assess the efficacy and safety of a remote electrical neuromodulation (REN) device for the acute treatment of migraine., Background: There is a significant unmet need for novel effective well-tolerated acute migraine treatments. REN is a novel acute migraine treatment that stimulates upper arm peripheral nerves to induce conditioned pain modulation - an endogenous analgesic mechanism in which conditioning stimulation inhibits pain in remote body regions. A recent pilot study showed that REN can significantly reduce headache. We have conducted a randomized, double-blind, sham-controlled study to further evaluate the efficacy and safety of REN for the acute treatment of migraine., Methods: This was a randomized, double-blind, sham-controlled, multicenter study conducted at 7 sites in the United States and 5 sites in Israel. Two hundred and fifty-two adults meeting the International Classification of Headache Disorders criteria for migraine with 2-8 migraine headaches per month were randomized in a 1:1 ratio to active or sham stimulation. A smartphone-controlled wireless device was applied for 30-45 minutes on the upper arm within 1 hour of attack onset; electrical stimulation was at a perceptible but non-painful intensity level. Migraine pain levels were recorded at baseline, 2, and 48 hours post-treatment. Most bothersome symptoms (MBS) were also recorded. The primary efficacy endpoint was the proportion of participants achieving pain relief at 2 hours post-treatment (improvement from severe or moderate pain to mild or none, or from mild pain to none). Relief of MBS and pain-free at 2 hours were key secondary endpoints., Results: Active stimulation was more effective than sham stimulation in achieving pain relief (66.7% [66/99] vs 38.8% [40/103]; therapeutic gain of 27.9% [CI 95% , 15.6-40.2]; P < .0001), pain-free (37.4% vs 18.4%, P = .003), and MBS relief (46.3% vs 22.2%, P = .0008) at 2 hours post-treatment. The pain relief and pain-free superiority of the active treatment was sustained 48 hours post-treatment. The incidence of device-related adverse events was low and similar between treatment groups (4.8% [6/126] vs 2.4% [3/126], P = .499)., Conclusions: REN provides superior clinically meaningful relief of migraine pain and MBS compared to placebo, offering a safe and effective non-pharmacological alternative for acute migraine treatment., (© 2019 The Authors. Headache: The Journal of Head and Face Pain published by Wiley Periodicals, Inc. on behalf of American Headache Society.)