Electrical Stimulation Of Peripheral Nerves Research Articles

Highly efficient modeling and optimization of neural fiber responses to electrical stimulation

Peripheral neuromodulation has emerged as a powerful modality for controlling physiological functions and treating a variety of medical conditions including chronic pain and organ dysfunction. The underlying complexity of the nonlinear responses to electrical stimulation make it challenging to design precise and effective neuromodulation protocols. Computational models have thus become indispensable in advancing our understanding and control of neural responses to electrical stimulation. However, existing approaches suffer from computational bottlenecks, rendering them unsuitable for real-time applications, large-scale parameter sweeps, or sophisticated optimization. In this work, we introduce an approach for massively parallel estimation and optimization of neural fiber responses to electrical stimulation using machine learning techniques. By leveraging advances in high-performance computing and parallel programming, we present a surrogate fiber model that generates spatiotemporal responses to a wide variety of cuff-based electrical peripheral nerve stimulation protocols. We used our surrogate fiber model to design stimulation parameters for selective stimulation of pig and human vagus nerves. Our approach yields a several-orders-of-magnitude improvement in computational efficiency while retaining generality and high predictive accuracy, demonstrating its robustness and potential to enhance the design and optimization of peripheral neuromodulation therapies.

Magnetically coupled percutaneous connector for chronic electrical peripheral nerve stimulation and recording in awake rats.

Here we aimed to develop and validate a chronic magnetic percutaneous connector designed for placement on the dorsal-lumbar aspect of the spine of awake, freely moving rats. A pedestal and external connector was developed, bench tested to assess for continuity, durability and disconnection forces, and validated in awake rats chronically implanted with an abdominal vagus nerve electrode array. The implanted pedestal and external connector were designed with custom PCBs, spring-loaded pins, magnets and biocompatible 3D printed housing. The magnetic coupling mechanism allowed disconnection with minimal force, was highly reliable in maintaining electrical connection in awake rats and allowed recording of electrically evoked compound action potentials after chronic implantation. In conclusion, this percutaneous connector is a useful research tool for peripheral nerve stimulation studies. The connector described will allow investigation into the safety and efficacy of emerging neuromodulation therapies for the treatment of disease.

Blocking Aδ- and C-fiber neural transmission by sub-kilohertz peripheral nerve stimulation.

We recently showed that sub-kilohertz electrical stimulation of the afferent somata in the dorsal root ganglia (DRG) reversibly blocks afferent transmission. Here, we further investigated whether similar conduction block can be achieved by stimulating the nerve trunk with electrical peripheral nerve stimulation (ePNS). We explored the mechanisms and parameters of conduction block by ePNS via ex vivo single-fiber recordings from two somatic (sciatic and saphenous) and one autonomic (vagal) nerves harvested from mice. Action potentials were evoked on one end of the nerve and recorded on the other end from teased nerve filaments, i.e., single-fiber recordings. ePNS was delivered in the middle of the nerve trunk using a glass suction electrode at frequencies of 5, 10, 50, 100, 500, and 1000 Hz. Suprathreshold ePNS reversibly blocks axonal neural transmission of both thinly myelinated Aδ-fiber axons and unmyelinated C-fiber axons. ePNS leads to a progressive decrease in conduction velocity (CV) until transmission blockage, suggesting activity-dependent conduction slowing. The blocking efficiency is dependent on the axonal conduction velocity, with Aδ-fibers efficiently blocked by 50-1000 Hz stimulation and C-fibers blocked by 10-50 Hz. The corresponding NEURON simulation of action potential transmission indicates that the disrupted transmembrane sodium and potassium concentration gradients underly the transmission block by the ePNS. The current study provides direct evidence of reversible Aδ- and C-fiber transmission blockage by low-frequency (<100 Hz) electrical stimulation of the nerve trunk, a previously overlooked mechanism that can be harnessed to enhance the therapeutic effect of ePNS in treating neurological disorders.

NRV: An open framework for in silico evaluation of peripheral nerve electrical stimulation strategies.

Electrical stimulation of peripheral nerves has been used in various pathological contexts for rehabilitation purposes or to alleviate the symptoms of neuropathologies, thus improving the overall quality of life of patients. However, the development of novel therapeutic strategies is still a challenging issue requiring extensive in vivo experimental campaigns and technical development. To facilitate the design of new stimulation strategies, we provide a fully open source and self-contained software framework for the in silico evaluation of peripheral nerve electrical stimulation. Our modeling approach, developed in the popular and well-established Python language, uses an object-oriented paradigm to map the physiological and electrical context. The framework is designed to facilitate multi-scale analysis, from single fiber stimulation to whole multifascicular nerves. It also allows the simulation of complex strategies such as multiple electrode combinations and waveforms ranging from conventional biphasic pulses to more complex modulated kHz stimuli. In addition, we provide automated support for stimulation strategy optimization and handle the computational backend transparently to the user. Our framework has been extensively tested and validated with several existing results in the literature.

Feasibility of endovascular stimulation of the femoral nerve using a stent-mounted electrode array

Objective. Electrical stimulation of peripheral nerves has long been a treatment option to restore impaired neural functions that cannot be restored by conventional pharmacological therapies. Endovascular neurostimulation with stent-mounted electrode arrays is a promising and less invasive alternative to traditional implanted electrodes, which typically require invasive implantation surgery. In this study, we investigated the feasibility of endovascular stimulation of the femoral nerve using a stent-mounted electrode array and compared its performance to that of a commercially available pacing catheter. Approach. In acute animal experiments, a pacing catheter was implanted unilaterally in the femoral artery to stimulate the femoral nerve in a bipolar configuration. Electromyogram of the quadriceps and electroneurogram of a distal branch of the femoral nerve were recorded. After retrieval of the pacing catheter, a bipolar stent-mounted electrode array was implanted in the same artery and the recording sessions were repeated. Main Results. Stimulation of the femoral nerve was feasible with the stent-electrode array. Although the threshold stimulus intensities required with the stent-mounted electrode array (at 100–500 µs increasing pulse width, 2.17 ± 0.87 mA–1.00 ± 0.11 mA) were more than two times higher than the pacing catheter electrodes (1.05 ± 0.48 mA–0.57 ± 0.28 mA), we demonstrated that, by reducing the stimulus pulse width to 100 µs, the threshold charge per phase and charge density can be reduced to 0.22 ± 0.09 µC and 24.62 ± 9.81 µC cm−2, which were below the tissue-damaging limit, as defined by the Shannon criteria. Significance. The present study is the first to report in vivo feasibility and efficiency of peripheral nerve stimulation using an endovascular stent-mounted electrode array.

Unraveling the Potential of Electroanalgesia: A Literature Review of Current Therapeutics.

Neuropathic pain (NP), arising from dysfunction in the neurological system, poses a significant challenge in pain management due to its intricate origin and unpredictable response to conventional treatments. Electroanalgesia, a collection of techniques such as transcutaneous electric nerve stimulation (TENS), peripheral electrical nerve stimulation (PENS), spinal cord stimulation (SCS), deep brain stimulation (DBS), and electroacupuncture (EA), presents a potential alternative or complementary approach. This review brings together evidence from 56 studies to evaluate the effectiveness and safety of electroanalgesia in chronic NP. It discusses the mechanisms underlying NP, the indications for electroanalgesia, and the techniques utilized, emphasizing the diverse applications and potential benefits. However, despite its potential uses, electroanalgesia has its limitations, including variable effectiveness and potential adverse effects. Furthermore, the review recognizes the limitations of the methodology and the need for further research to refine treatment protocols and enhance the understanding of electroanalgesia's role in comprehensive pain management strategies.

Continuous peripheral electrical nerve stimulation improves cardiac function via autonomic nerve regulation in MI rats

BackgroundPeripheral electrical nerve stimulation (PENS) reportedly improves cardiac function after myocardial ischemia (MI) by rebalancing the cardiac autonomic nervous system. The dynamic and continuous influence of PENS on autonomic and cardiac function based on cardiac self-repair is not well understood. ObjectivesThis study aimed to explore the relationship between autonomic nervous balance and functional cardiac repair after MI and to clarify the optimal acupoint selection and time course for PENS. MethodsThe activities of the superior cervical cardiac sympathetic nerve and vagus nerve were recorded to evaluate the autonomic tone directly. The pressure-volume loop system was used for left ventricular diastolic and systolic function. Noninvasive continuous electrocardiography and echocardiography were performed to analyze heart rate, heart rate variability, and left ventricular function. The effect of continuous PENS (cPENS) or instant PENS (iPENS) on autonomic and cardiac indications was tested. ResultsSympathetic nerve activity and vagus nerve activity increased as compensatory self-regulation on days 7 and 14 post-MI, followed by an imbalance of autonomic tone and cardiac dysfunction on day 28. cPENS at acupoint PC6 maintained autonomic hyperexcitability, improved myocardial systolic and diastolic abilities, and reduced myocardial fibrosis on day 28 post-MI, whereas cPENS at acupoint ST36 had a limited effect. Both iPENS at PC6 and ST36 improved the autonomic and cardiac function of rats in the cPENS groups. ConclusionRats showed autonomic fluctuations and cardiac dysfunction 28 days post-MI. cPENS produced sympathomimetic action to sustain cardiac self-compensation, but with acupoint specificity. On the basis of cPENS, iPENS evoked autonomic regulation and cardiac benefits without acupoint differentiation.

Attentional state-synchronous peripheral electrical stimulation during action observation induced distinct modulation of corticospinal plasticity after stroke.

Brain computer interface-based action observation (BCI-AO) is a promising technique in detecting the user's cortical state of visual attention and providing feedback to assist rehabilitation. Peripheral nerve electrical stimulation (PES) is a conventional method used to enhance outcomes in upper extremity function by increasing activation in the motor cortex. In this study, we examined the effects of different pairings of peripheral nerve electrical stimulation (PES) during BCI-AO tasks and their impact on corticospinal plasticity. Our innovative BCI-AO interventions decoded user's attentive watching during task completion. This process involved providing rewarding visual cues while simultaneously activating afferent pathways through PES. Fifteen stroke patients were included in the analysis. All patients underwent a 15 min BCI-AO program under four different experimental conditions: BCI-AO without PES, BCI-AO with continuous PES, BCI-AO with triggered PES, and BCI-AO with reverse PES application. PES was applied at the ulnar nerve of the wrist at an intensity equivalent to 120% of the sensory threshold and a frequency of 50 Hz. The experiment was conducted randomly at least 3 days apart. To assess corticospinal and peripheral nerve excitability, we compared pre and post-task (post 0, post 20 min) parameters of motor evoked potential and F waves under the four conditions in the muscle of the affected hand. The findings indicated that corticospinal excitability in the affected hemisphere was higher when PES was synchronously applied with AO training, using BCI during a state of attentive watching. In contrast, there was no effect on corticospinal activation when PES was applied continuously or in the reverse manner. This paradigm promoted corticospinal plasticity for up to 20 min after task completion. Importantly, the effect was more evident in patients over 65 years of age. The results showed that task-driven corticospinal plasticity was higher when PES was applied synchronously with a highly attentive brain state during the action observation task, compared to continuous or asynchronous application. This study provides insight into how optimized BCI technologies dependent on brain state used in conjunction with other rehabilitation training could enhance treatment-induced neural plasticity.

A commentary on 'Efficacy of peripheral electrical nerve stimulation on improvements of urodynamics and voiding diary in patients with neurogenic lower urinary tract dysfunction: a systematic review and meta-analysis'.

A commentary on 'Efficacy of peripheral electrical nerve stimulation on improvements of urodynamics and voiding diary in patients with neurogenic lower urinary tract dysfunction: a systematic review and meta-analysis'.

Research advances in neuromodulation techniques for blood glucose regulation and diabetes intervention

Diabetes and its complications that seriously threaten the health and life of human, has become a public health problem of global concern. Glycemic control remains a major focus in the treatment and management of patients with diabetes. The traditional lifestyle interventions, drug therapies, and surgeries have benefited many patients with diabetes. However, due to problems such as poor patient compliance, drug side effects, and limited surgical indications, there are still patients who fail to effectively control their blood glucose levels. With the development of bioelectronic medicine, neuromodulation techniques have shown great potential in the field of glycemic control and diabetes intervention with its unique advantages. This paper mainly reviewed the research advances and latest achievements of neuromodulation technologies such as peripheral nerve electrical stimulation, ultrasound neuromodulation, and optogenetics in blood glucose regulation and diabetes intervention, analyzed the existing problems and presented prospects for the future development trend to promote clinical research and application of neuromodulation technologies in the treatment of diabetes.

Mapping the hotspots and future trends of electrical stimulation for peripheral nerve injury: A bibliometric analysis from 2002 to 2023.

Peripheral nerve injuries often result in severe personal and social burden, and even with surgical treatment, patients continue to have poor clinical outcomes. Over the past two decades, electrical stimulation has been shown to promote axonal regeneration and alleviate refractory neuropathic pain. The aim of this study was to analyse this field using a bibliometric approach. Literature was searched through Web of Science Core Collection (WOSCC) for the years 2002-2023. Literature analysis included: (1) Describing publication trends in the field. (2) Exploring collaborative network relationships. (3) Finding research advances and research hotspots in the field. (4) Summarizing research trends in the field. With the number of studies in this field still increasing, a total of 693 publications were included in the analysis. This field of research is interdisciplinary in nature. Research hotspots include peripheral nerve regeneration, the treatment of neuropathic pain, materials for nerve injury repair, and the restoration of sensory function in patients with peripheral nerve injury. Correspondingly, the development of nerve conduits and systems for peripheral nerve electrical stimulation, clinical trials of peripheral nerve electrical stimulation, and tactile recovery and movement for amputees have shown significant promise as future research trends in this field.

Mechanism of Action of Temporary Peripheral Nerve Stimulation.

Peripheral nerve stimulation (PNS) refers to the technique of utilizing electrical stimulation of peripheral nerves to inhibit the transmission of pain signals. PNS is used to treat chronic intractable pain and post-surgical or post-traumatic pain alongside a variety of other pain conditions, including headaches, facial pain, pelvic and urogenital pain, chest wall pain, residual limb or phantom limb pain, and back pain. More recently, PNS has been used temporarily for periods of time less than 60days to treat acute post-surgical pain. Peripheral nerve stimulation is believed to be effective due to its effects on both central and peripheral pathways. Centrally, it is proposed that the electrical pulses of PNS inhibit alpha-delta and C fibers, which decreases pain signaling in the higher centers of the central nervous system. Peripherally, gate theory is applied as it is theorized that PNS downregulates inflammatory mediators, endorphins, and neurotransmitters associated with pain signaling to decrease the transmission of efferent nociception and reduce pain sensations.

Stabilizing leaning postures with feedback controlled functional neuromuscular stimulation after trunk paralysis.

Spinal cord injury (SCI) can cause paralysis of trunk and hip musculature that negatively impacts seated balance and ability to lean away from an upright posture and interact fully with the environment. Constant levels of electrical stimulation of peripheral nerves can activate typically paralyzed muscles and aid in maintaining a single upright seated posture. However, in the absence of a feedback controller, such seated postures and leaning motions are inherently unstable and unable to respond to perturbations. Three individuals with motor complete SCI who had previously received a neuroprosthesis capable of activating the hip and trunk musculature volunteered for this study. Subject-specific muscle synergies were identified through system identification of the lumbar moments produced via neural stimulation. Synergy-based calculations determined the real-time stimulation parameters required to assume leaning postures. When combined with a proportional, integral, derivative (PID) feedback controller and an accelerometer to infer trunk orientation, all individuals were able to assume non-erect postures of 30-40° flexion and 15° lateral bending. Leaning postures increased forward reaching capabilities by 10.2, 46.7, and 16 cm respectively for each subject when compared with no stimulation. Additionally, the leaning controllers were able to resist perturbations of up to 90 N, and all subjects perceived the leaning postures as moderately to very stable. Implementation of leaning controllers for neuroprostheses have the potential of expanding workspaces, increasing independence, and facilitating activities of daily living for individuals with paralysis.

Long-term invasive electrical stimulation of peripheral nerve in the functional recovery of neuromuscular complex in experiment

Background. Limb damage dominates in the structure of combat trauma, making up to 75 % in modern wars and the number of wounded with peripheral nerve injuries of the limbs can be up to 25 %. The degree of disability of patients is 65–70 %, which makes the problem of restoring peripheral nerves extremely actual. The purpose of the study was to determine the effect of long-term invasive electrical stimulation on the functional restoration of the neuromuscular complex in experiment. Materials and methods. The study was performed on 29 white outbred rabbits (2500 ± 250 g, 5–6 months) according to all norms of bio­ethics. Animals were divided into the following experimental groups: group 1 (n = 8, controls) — epineural suture of the sciatic nerve and implantation of a non-working antenna of the electrical stimulation device; group 2 (n = 7): similar operation of epineural suture of the sciatic nerve with implantation of the electric stimulator antenna and stimulation on beginning at the 2nd day after the operation; group 3 (n = 7): a similar operation of the sciatic nerve epineural suture with implantation of an electric stimulator antenna and the start of stimulation after 2 weeks, when the initial signs of nerve regeneration were observed; group 4 (n = 7): autografting of the sciatic nerve and implantation of an electrical stimulator and the beginning of stimulation at a time point that will coincide with the signs of nerve regeneration. Results. Therefore, in group 2, where electrical stimulation was started the day after the operation, the indicators of functional recovery of the neuromuscular complex were better than in its absence, as well as under the conditions of starting the stimulation in the period when the initial signs of regeneration were observed. Therefore, it can be assumed that the invasive electrical stimulation of the peripheral nerve, started in the acute period after the injury, has a positive effect on the regeneration of the peripheral nerves, as well as on the results of the functional restoration of the neuromuscular complex. The positive effect of electrical stimulation on the functional state of muscles is indirectly evidenced by the larger amplitude of the compound muscle action potential (CMAP) in the group where the stimulation was started faster. A larger amplitude of the CMAP during the observation indicates a greater number of axons that reached the muscle during 8 weeks. Given that the growth cone of the regenerating nerve contains a certain number of axons that first grow to the effector organ, in this case the muscle, with a relatively unchanged action potential latency, it can be assumed that direct electrical stimulation of the peripheral nerve leads to an increase speed of axons sprouting, with their relatively unchanged number. The absence of a significant difference in the action potential latency in the groups where autografting and suture were performed under the same conditions of stimulation indicates a positive effect of stimulation on the myelination of nerve fibers. A better CMAP indirectly indicates a satisfactory functional state of the muscle, which in conditions of denervation allows to preserve its potential for recovery and prevent atrophy. Conclusions. Summarizing all of the above, according to the data of electrophysiological research, we can indirectly conclude that: 1) the impact of invasive electrical stimulation on the regeneration of the neuromuscular complex is positive, and is accompanied by a better effect if it is performed early after the injury; 2) invasive electrical stimulation of the peripheral nerve is a procedure that allows to accelerate the growth of nerve fibers, improve their myelination and prevent the loss of functional capacity of the denervated muscle.

Magnetic Peripheral Nerve Stimulation (mPNS) for Chronic Pain.

To assess magnetic peripheral nerve stimulation (mPNS) for the treatment of chronic or chronic and intractable neuropathic pain with a retrospective review case series. Twenty-four patients with predominantly neuropathic post-traumatic or postoperative pain were treated as per protocol and followed for 3 months. Data were analyzed as an observational, one-armed, convenience sample. Graphical evidence backed up by a mixed model for repeated measures statistical analysis showed a highly significant reduction of pain at one month out from initial treatment with mPNS. At one month, there was a 3.8 average reduction in pre-pain scores using a visual analogue scale (VAS), and that relief was generally durable measured out to three months. Two-thirds of patients, deemed responders, showed an 87% reduction in pain. Opioid reduction was seen in 58.3% of responders as well. mPNS appears promising for the treatment of chronic or chronic and intractable neuropathic pain for many of the same indications as traditional electrical peripheral nerve stimulation (PNS). No invasive techniques or implants are needed for mPNS.

Vagus nerve stimulation: mechanisms and factors involved in memory enhancement.

Vagus nerve stimulation (VNS) has been recognized as a useful neuromodulation tool to target the central nervous system by electrical stimulation of peripheral nerves. Activation of the nucleus of the solitary tract (NTS) in the brainstem by vagal afferent nerve fibers allows for modulation of various higher order brain regions, including limbic and cerebral cortex structures. Along with neurological and psychiatric indications, clinical and preclinical studies suggest that VNS can improve memory. While the underlying mechanisms to improve memory with VNS involve brain areas, such as the prefrontal cortex and processes including alertness and arousal, here we focus on VNS-induced memory improvements related to the hippocampus, the main area implicated in memory acquisition. In addition, we detail research demonstrating that a targeted approach to VNS can modify memory outcomes and delve into the molecular mechanisms associated with these changes. These findings indicate that a greater understanding of VNS mechanisms while also considering stimulation parameters, administration site, timing in relation to training, and sex-specific factors, may allow for optimal VNS application to enhance memory.

Transcutaneous electrical stimulation for gastrointestinal motility disorders.

Gastrointestinal (GI) dysmotility is categorized by muscle or nerve dysfunctions in any portion of the GI tract, which leads to abnormalities in GI motor and sensory function. Symptoms may vary depending on the organ affected and can be debilitating. Treatment usually involves diet and lifestyle changes. Pharmacotherapy is limited in effectiveness with various side effects. Transcutaneous electrical stimulation (TES), a noninvasive, needleless technique that provides electrical stimulation using cutaneous non-needle electrodes, has become increasingly popular. It has been shown to be beneficial in treating GI motility disorders. This review paper navigates through the different TES techniques, including transcutaneous peripheral nerve (vagal/sacral/tibial nerves) electrical stimulation, transcutaneous electrical acustimulation (stimulation via acupuncture point), transcutaneous interferential current therapy, and transcutaneous electrical nerve stimulation. As we delve deeper, we explore the promising effects of TES on dysphagia, gastroesophageal reflux disease, functional dyspepsia, gastroparesis, postoperative ileus, constipation, and irritable bowel syndrome. The literature at hand speaks volumes about the therapeutic prowess of this noninvasive technique. The time is ripe to evaluate further the full therapeutic potential of TES, a noninvasive, nonpharmaceutical, nonsurgical, and home-based self-administrative technique in managing GI motility disorders.

Efficacy of peripheral electrical nerve stimulation on improvements of urodynamics and voiding diary in patients with neurogenic lower urinary tract dysfunction: a systematic review and meta-analysis.

Peripheral electrical nerve stimulation is a routinely recommended treatment for non-neurogenic overactive bladder but has not been approved for patients with neurogenic lower urinary tract dysfunction (NLUTD). This systematic review and meta-analysis was to elucidate the efficacy and safety of electrostimulation and thus provide firm evidence for treating NLUTD. We systematically performed the literature search through PubMed, Web of Science, and Cochrane Library databases in March 2022. The eligible studies were identified across the inclusion criteria and the data on urodynamic outcomes, voiding diary parameters, and safety was collected to quantitatively synthesize the pooled mean differences (MDs) with 95% CIs. Subgroup analyses and sensitivity analyses were subsequently used to investigate the possible heterogeneity. This report was achieved in accordance with the preferred reporting items for systematic reviews and meta-analyses statement. A total of 10 studies involving 464 subjects and 8 studies with 400 patients were included for systematic review and meta-analysis, respectively. The pooled effect estimates indicated that electrostimulation could significantly improve urodynamic outcomes, including maximum cystometric capacity (MD=55.72, 95% CI 15.73, 95.72), maximum flow rate (MD=4.71, 95% CI 1.78, 7.65), maximal detrusor pressure (MD=-10.59, 95% CI -11.45, -9.73), voided volume (MD=58.14, 95% CI 42.97, 73.31), and post-void residual (MD=-32.46, 95% CI -46.63, -18.29); for voiding diary parameters, patients undergoing electrostimulation showed lower MDs of incontinence episodes per 24h (MD=-2.45, 95% CI -4.69, -0.20) and overactive bladder symptom score (MD=-4.46, 95% CI -6.00, -2.91). In addition to surface redness and swelling, no stimulation-related severe adverse events were reported else. The current evidence demonstrated that peripheral electrical nerve stimulation might be effective and safe for managing NLUTD, whereas more reliable data from large-scale randomized controlled trials are necessary to strengthen this concept.

Diagnostic Accuracy of Manual Muscle Testing to Identify Nerve Transfer Candidates in Children with Acute Flaccid Myelitis.

Manual muscle testing is a mainstay of strength assessment despite not having been compared with intraoperative electrical stimulation of peripheral nerves. Intraoperative electrical stimulation served as the reference standard in evaluating predictive accuracy of the Active Movement Scale (AMS) and the Medical Research Council (MRC) scale. Retrospective consecutive sampling of all patients with AFM who underwent exploration or nerve transfer at a pediatric multidisciplinary brachial plexus and peripheral nerve center from March of 2016 to July of 2020 were included. The nonparametric area under the curve (AUC) was calculated. Optimal cutoff score (Youden J ) and diagnostic accuracy values were reported. The AMS and MRC scale were directly compared for predictive superiority. A total of 181 upper extremity nerves (73 donor nerve candidates and 108 recipient nerve candidates) were tested intraoperatively from 40 children (mean age ± SD, 7.9 ± 4.9 years). The scales performed similarly ( P = 0.953) in classifying suitable donor nerves with satisfactory accuracy (AUC AMS , 71.5%; AUC MRC , 70.7%; optimal cutoff, AMS >5 and MRC >2). The scales performed similarly ( P = 0.688) in classifying suitable recipient nerves with good accuracy (AUC AMS , 92.1%; AUC MRC :, 94.9%; optimal cutoff, AMS ≤3 and MRC ≤1). Manual muscle testing is an accurate, noninvasive means of identifying donor and recipient nerves for transfer in children with acute flaccid myelitis. The utility of these results is in minimizing unexpected findings in the operating room and aiding in the development of contingency plans. Further research may extend these findings to test the validity of manual muscle testing as an outcome measure of the success of nerve transfer. Diagnostic, I.

Asynchronous axonal firing patterns evoked via continuous subthreshold kilohertz stimulation

Objective. Transcutaneous electrical stimulation of peripheral nerves is a common technique to assist or rehabilitate impaired muscle activation. However, conventional stimulation paradigms activate nerve fibers synchronously with action potentials time-locked with stimulation pulses. Such synchronous activation limits fine control of muscle force due to synchronized force twitches. Accordingly, we developed a subthreshold high-frequency stimulation waveform with the goal of activating axons asynchronously. Approach. We evaluated our waveform experimentally and through model simulations. During the experiment, we delivered continuous subthreshold pulses at frequencies of 16.67, 12.5, or 10 kHz transcutaneously to the median and ulnar nerves. We obtained high-density electromyographic (EMG) signals and fingertip forces to quantify the axonal activation patterns. We used a conventional 30 Hz stimulation waveform and the associated voluntary muscle activation for comparison. We modeled stimulation of biophysically realistic myelinated mammalian axons using a simplified volume conductor model to solve for extracellular electric potentials. We compared the firing properties under kHz and conventional 30 Hz stimulation. Main results. EMG activity evoked by kHz stimulation showed high entropy values similar to voluntary EMG activity, indicating asynchronous axon firing activity. In contrast, we observed low entropy values in EMG evoked by conventional 30 Hz stimulation. The muscle forces evoked by kHz stimulation also showed more stable force profiles across repeated trials compared with 30 Hz stimulation. Our simulation results provide direct evidence of asynchronous firing patterns across a population of axons in response to kHz frequency stimulation, while 30 Hz stimulation elicited synchronized time-locked responses across the population. Significance. We demonstrate that the continuous subthreshold high-frequency stimulation waveform can elicit asynchronous axon firing patterns, which can lead to finer control of muscle forces.