Biphasic Electrical Stimulation Research Articles

Locomotion Control of Cyborg Insects by Charge-Balanced Biphasic Electrical Stimulation.

The integration of electronic stimulation devices with insects in the context of cyborg insect systems has great application potential, particularly in the fields of environmental monitoring, urban surveillance, and rescue missions. Despite considerable advantages compared to the current robot technology, including flexibility, durability, and low energy consumption, this integration faces certain challenges related to the potential risk of charge accumulation caused by prolonged and repetitive electrical stimulations. To address these challenges, this study proposes a universal system for remote signal output control using infrared signals. The proposed system integrates high-precision digital-to-analog converters capable of generating customized waveform electrical stimulation signals within defined ranges. This enhances the accuracy of locomotion control in cyborg insects while maintaining real-time control and dynamic parameter adjustment. The proposed system is verified by experiments. The experimental results show that the signals generated by the proposed system have a success rate of over 76.25% in controlling the turning locomotion of cyborg insects, which is higher than previously reported results. In addition, the charge-balanced characteristics of these signals can minimize muscle tissue damage, thus substantially enhancing control repeatability. This study provides a comprehensive solution for the remote control and monitoring of cyborg insects, whose flexibility and adaptability can meet various application and experimental requirements. The results presented in this study lay a robust foundation for further advancement of various technologies, particularly those related to cyborg insect locomotion control systems and wireless control mechanisms for cyborg insects.

Versatile electrical stimulator for cardiac tissue engineering-Investigation of charge-balanced monophasic and biphasic electrical stimulations.

The application of biomimetic physical stimuli replicating the in vivo dynamic microenvironment is crucial for the in vitro development of functional cardiac tissues. In particular, pulsed electrical stimulation (ES) has been shown to improve the functional properties of in vitro cultured cardiomyocytes. However, commercially available electrical stimulators are expensive and cumbersome devices while customized solutions often allow limited parameter tunability, constraining the investigation of different ES protocols. The goal of this study was to develop a versatile compact electrical stimulator (ELETTRA) for biomimetic cardiac tissue engineering approaches, designed for delivering controlled parallelizable ES at a competitive cost. ELETTRA is based on an open-source micro-controller running custom software and is combinable with different cell/tissue culture set-ups, allowing simultaneously testing different ES patterns on multiple samples. In particular, customized culture chambers were appositely designed and manufactured for investigating the influence of monophasic and biphasic pulsed ES on cardiac cell monolayers. Finite element analysis was performed for characterizing the spatial distributions of the electrical field and the current density within the culture chamber. Performance tests confirmed the accuracy, compliance, and reliability of the ES parameters delivered by ELETTRA. Biological tests were performed on neonatal rat cardiac cells, electrically stimulated for 4days, by comparing, for the first time, the monophasic waveform (electric field = 5V/cm) to biphasic waveforms by matching either the absolute value of the electric field variation (biphasic ES at ±2.5V/cm) or the total delivered charge (biphasic ES at ±5V/cm). Findings suggested that monophasic ES at 5V/cm and, particularly, charge-balanced biphasic ES at ±5V/cm were effective in enhancing electrical functionality of stimulated cardiac cells and in promoting synchronous contraction.

Abstract 11957: Physical Training Augmented With Whole Body Electronic Muscle Stimulation is Superior to Conventional Training Alone in Healthy Subjects, a Pilot Randomized Controlled Trial

Introduction: Physical activity is protective against cardiovascular (CV) disease and mortality, yet more than 25% of adults do not perform any regular exercise. Whole body electronic muscle stimulation (WB-EMS) is a novel FDA-approved device used for physical training that simultaneously stimulates all major muscle groups using percutaneous electrical impulse transmission during exercise. Preliminary studies demonstrated increased muscle mass, reduced fat mass, and improved functional capacity in elderly individuals who trained with WB-EMS. We evaluated the effects of training with WB-EMS on measures of CV health. Methods: Healthy adults were randomized to physical training with versus without WB-EMS for one 20-minute session each week for 16 weeks. Participants wore a specifically designed vest and arm and leg straps connected to the WB-EMS device (Miha Bodytec, Germany). Biphasic electrical stimulation was delivered through the vest and straps (4 sec on, 4 sec off) at a frequency that elicited a score of 5-6 on the Borg perceived exertion scale when each major muscle group was stimulated. Individuals randomized to no WB-EMS wore the same equipment but received no stimulation. Sessions were provided by trainers certified in WB-EMS training and consisted of a fixed protocol of simple exercises such as squats and lunges. Temporal changes in measures of CV health were compared between groups. Results: Forty-one individuals were recruited between 02/2021 and 02/2022 (n=24 WB-EMS, n=17 no WB-EMS; mean age 35.9±11.2 yrs; 61.3% females; median BMI 24.3 (21.8, 28.1) kg/m 2 . After 16 weeks there were significant and favorable differences in the intervention group compared to controls in waist: hip ratio (-1.2 cm vs. 0.9, p=0.05); total cholesterol (-1.1 mg/kg vs. 14.2 mg/kg, p=0.02); anaerobic threshold (68.2% vs. 30.8%, p=0.03); breathing efficiency (VE/VCO2: -10.36 vs -7.38, p=0.01); and peripheral endothelial function, measured with reactive hyperemia peripheral arterial tonometry (-0.009 vs. -0.29, p=0.06). Conclusions: Once weekly training with WB-EMS yielded more favorable changes in CV biomarkers compared to conventional training alone in healthy adults, and thus may offer an effective and time-efficient method of physical training.

Wireless Multimodality Sensing System-on-a-Chip With Time-Based Resolution Scaling Technique and Analog Waveform Generator in 0.18 μm CMOS for Chronic Wound Care.

Multimodal sensing can provide a comprehensive and accurate diagnosis of biological information. This paper presents a fully integrated wireless multimodal sensing chip with voltammetric electrochemical sensing at a scanning rate range of 0.08-400 V/s, temperature monitoring, and bi-phasic electrical stimulation for wound healing progress monitoring. The time-based readout circuitry can achieve a 1-20X scalable resolution through dynamic threshold voltage adjustment. A low-noise analog waveform generator is designed using current reducer techniques to eliminate the large passive components. The chip is fabricated via a 0.18 μm CMOS process. The design achieves R2 linearity of 0.995 over a wide current detection range (2 pA-12 μA) while consuming 49 μW at 1.2 V supply. The temperature sensing circuit achieves a 43 mK resolution from 20 to 80 degrees. The current stimulator provides an output current ranging from 8 μA to 1 mA in an impedance range of up to 3 kΩ. A wakeup receiver with data correlators is used to control the operation modes. The sensing data are wirelessly transmitted to the external readers. The proposed sensing IC is verified for measuring critical biomarkers, including C-reactive protein, uric acid, and temperature.

Residual voltage as an ad-hoc indicator of electrode damage in biphasic electrical stimulation

Objective. We derive and demonstrate how residual voltage (RV) from a biphasic electrical stimulation pulse can be used to recognize degradation at the electrode-tissue interface. Approach. Using a first order model of the electrode-tissue interface and a rectangular biphasic stimulation current waveform, we derive the equations for RV as well as RV growth over several stimulation pulses. To demonstrate the use of RV for damage detection, we simulate accelerated damage on sputtered iridium oxide film (SIROF) electrodes using potential cycling. RV measurements of the degraded electrodes are compared against standard characterization methods of cyclic voltammetry and electrochemical impedance spectroscopy. Main results. Our theoretical discussion illustrates how an intrinsic RV arises even from perfectly balanced biphasic pulses due to leakage via the charge-transfer resistance. Preliminary data in in-vivo rat experiments follow the derived model of RV growth, thereby validating our hypothesis that RV is a characteristic of the electrode-tissue interface. RV can therefore be utilized for detecting damage at the electrode. Our experimental results for damage detection show that delamination of SIROF electrodes causes a reduction in charge storage capacity, which in turn reflects a measurable increase in RV. Significance. Chronically implanted electrical stimulation systems with multi-electrode arrays have been the focus of physiological engineering research for the last decade. Changes in RV over time can be a quick and effective method to identify and disconnect faulty electrodes in large arrays. Timely diagnoses of electrode status can ensure optimal long term operation, and prevent further damage to the tissue near these electrodes.

Cellular Interactions with Lubricin and Hyaluronic Acid-Lubricin Composite Coatings on Gold Electrodes in Passive and Electrically Stimulated Environments.

In the field of bionics, the long-term effectiveness of implantable bionic interfaces depends upon maintaining a "clean" and unfouled electrical interface with biological tissues. Lubricin (LUB) is an innately biocompatible glycoprotein with impressive antifouling properties. Unlike traditional antiadhesive coatings, LUB coatings do not passivate electrode surfaces, giving LUB coatings great potential for controlling surface fouling of implantable electrode interfaces. This study characterizes the antifouling properties of bovine native LUB (N-LUB), recombinant human LUB (R-LUB), hyaluronic acid (HA), and composite coatings of HA and R-LUB (HA/R-LUB) on gold electrodes against human primary fibroblasts and chondrocytes in passive and electrically stimulated environments for up to 96 h. R-LUB coatings demonstrated highly effective antifouling properties, preventing nearly all adhesion and proliferation of fibroblasts and chondrocytes even under biphasic electrical stimulation. N-LUB coatings, while showing efficacy in the short term, failed to produce sustained antifouling properties against fibroblasts or chondrocytes over longer periods of time. HA/R-LUB composite films also demonstrated highly effective antifouling performance equal to the R-LUB coatings in both passive and electrically stimulated environments. The high electrochemical stability and long-lasting antifouling properties of R-LUB and HA/R-LUB coatings in electrically stimulating environments reveal the potential of these coatings for controlling unwanted cell adhesion in implantable bionic applications.

The Influence of Cochlear Implant-Based Electric Stimulation on the Electrophysiological Characteristics of Cultured Spiral Ganglion Neurons.

Background Cochlear implant-based electrical stimulation may be an important reason to induce the residual hearing loss after cochlear implantation. In our previous study, we found that charge-balanced biphasic electrical stimulation inhibited the neurite growth of spiral ganglion neurons (SGNs) and decreased Schwann cell density in vitro. In this study, we want to know whether cochlear implant-based electrical stimulation can induce the change of electrical activity in cultured SGNs. Methods Spiral ganglion neuron electrical stimulation in vitro model is established using the devices delivering cochlear implant-based electrical stimulation. After 48 h treatment by 50 μA or 100 μA electrical stimulation, the action potential (AP) and voltage depended calcium current (ICa) of SGNs are recorded using whole-cell electrophysiological method. Results The results show that the ICa of SGNs is decreased significantly in 50 μA and 100 μA electrical stimulation groups. The reversal potential of ICa is nearly +80 mV in control SGN, but the reversal potential decreases to +50 mV in 50 μA and 100 μA electrical stimulation groups. Interestingly, the AP amplitude, the AP latency, and the AP duration of SGNs have no statistically significant differences in all three groups. Conclusion Our study suggests cochlear implant-based electrical stimulation only significantly inhibit the ICa of cultured SGNs but has no effect on the firing of AP, and the relation of ICa inhibition and SGN damage induced by electrical stimulation and its mechanism needs to be further studied.

Electric Field Application In Vivo Regulates Neural Precursor Cell Behavior in the Adult Mammalian Forebrain.

Deep brain stimulation (DBS), which uses electrical stimulation, is a well-established neurosurgical technique used to treat neurologic disorders. Despite its broad therapeutic use, the effects of electrical stimulation on brain cells is not fully understood. Here, we examine the effects of electrical stimulation on neural stem and progenitor cells (collectively neural precursor cells; NPCs) from the subventricular zone in the adult forebrain of C57BL/6J mice. Previous work has demonstrated that adult-derived NPCs are electro sensitive and undergo rapid and directed migration in response to application of clinically relevant electric fields (EFs). We examine NPC proliferation kinetics and their differentiation profile following EF application using in vitro and in vivo assays. In vitro direct current electrical stimulation of 250 mV/mm is sufficient to elicit a 2-fold increase in the neural stem cell pool and increases neurogenesis and oligogenesis. In vivo, asymmetric biphasic electrical stimulation similarly increases the size of the NPC pool and alters neurogenesis. These findings provide insight into the effects of electrical stimulation on NPCs and suggest its potential use as a regenerative approach to neural repair.

A mm-Sized Free-Floating Wireless Implantable Opto-Electro Stimulation Device.

Towards a distributed neural interface, consisting of multiple miniaturized implants, for interfacing with large-scale neuronal ensembles over large brain areas, this paper presents a mm-sized free-floating wirelessly-powered implantable opto-electro stimulation (FF-WIOS2) device equipped with 16-ch optical and 4-ch electrical stimulation for reconfigurable neuromodulation. The FF-WIOS2 is wirelessly powered and controlled through a 3-coil inductive link at 60 MHz. The FF-WIOS2 receives stimulation parameters via on-off keying (OOK) while sending its rectified voltage information to an external headstage for closed-loop power control (CLPC) via load-shift-keying (LSK). The FF-WIOS2 system-on-chip (SoC), fabricated in a 0.35-µm standard CMOS process, employs switched-capacitor-based stimulation (SCS) architecture to provide large instantaneous current needed for surpassing the optical stimulation threshold. The SCS charger charges an off-chip capacitor up to 5 V at 37% efficiency. At the onset of stimulation, the capacitor delivers charge with peak current in 1.7–12 mA range to a micro-LED (µLED) array for optical stimulation or 100–700 μA range to a micro-electrode array (MEA) for biphasic electrical stimulation. Active and passive charge balancing circuits are activated in electrical stimulation mode to ensure stimulation safety. In vivo experiments conducted on three anesthetized rats verified the efficacy of the two stimulation mechanisms. The proposed FF-WIOS2 is potentially a reconfigurable tool for performing untethered neuromodulation.

Differential Effects of Low- and High-Dose Dexamethasone on Electrically Induced Damage of the Cultured Organ of Corti

An increased number of patients with residual hearing are undergoing cochlear implantation. A subset of these experience delayed hearing loss post-implantation, and the aetiology of this loss is not well understood. Our previous studies suggest that electrical stimulation can induce damage to hair cells in organ of Corti (OC) organotypic cultures. Dexamethasone has the potential to protect residual hearing due to its multiple effects on cells and tissue (e.g., anti-inflammatory, free radical scavenger). We therefore hypothesized that dexamethasone treatment could prevent electrical stimulation induced changes in the OC. Organ of Corti explants from neonatal rats (P2–4) were cultured for 24 h with two different concentrations of dexamethasone. Thereafter, OC were subjected to a charge-balanced biphasic pulsed electrical stimulation (0.44–2 mA) for a further 24 h. Unstimulated dexamethasone-treated OC served as controls. Outcome analysis included immunohistochemical labelling of ribbon synapses, histochemical analysis of free reactive oxygen species and morphological analysis of stereocilia bundles. Overall, the protective effects of dexamethasone on electrically induced damage in cochlear explants were moderate. High-dose dexamethasone protected bundle integrity at higher current levels. Low-dose dexamethasone tended to increase ribbon density in the apical region.

Movement Caused by Electrical Stimulation of the Lumbosacral Region in Standing Horses

Electrical stimulation is commonly used as a modality for physical therapy in human and veterinary medicine. However, studies measuring the movement generated by electrical stimulation in horses are rare. The present study therefore evaluates the range of movement provoked by a commercially available physical therapy unit (FES310) and contrasts it with the movement generated by manually induced pelvic inclination (back rounding). Ten horses were tested on three measurement days over one week. Electrical stimulation was applied via a back treatment pad (belonging to the FES310 system) containing six electrodes (three on either side of the spine) placed over the lumbosacral region. This system produced a pulsed, biphasic electrical stimulation in a rectangular waveform which was gradually increased to a maximum of 10 volts. Before and after electrical stimulation testing, manual pelvic inclination was achieved by pressure on two points lateral to the root of the tail. Muscle tone and lameness were evaluated before and after treatments. Skinfold thickness, body condition score, and body mass were measured to detect possible confounding factors. Using kinematics, the angle ranges during movement of ten three-dimensional angles of the trunk, the pelvis, and the hind limbs were further analyzed. Movement was produced with manual stimulation in every tested individual on all measurement days and with electrical stimulation on at least one measurement day. The electrical stimulation led to significantly (P < .05) smaller angle ranges which were 15 %–57 % of the median of the manually stimulated movement. Strong positive correlations between angle ranges of the electrically generated movement were found for the hind limbs implicating their involvement in the movement created. Correlations between skinfold thickness, body condition score, and body mass with the angle ranges were weak and not significant. Before and after electrical and manual stimulation, muscle tone and lameness were similar. In the present study, both electrical and manual stimulation were proven to produce significant trunk and hind limb movement. Within this study’s electrical stimulation treatment protocol, the movement generated by electrical stimulation was significantly less than the movement caused by manual pelvic inclination. However, electrical stimulation could easily be applied over a longer period and in a higher frequency than it would be possible for manual pelvic inclination. This treatment shows potential for stabilization and or mobilization of the lumbosacral region, although its efficiency as a therapeutic tool and its effect on specific orthopedic problems and is to be evaluated in further research.

Medications used to treat bladder disorders may alter effects of neuromodulation.

Neuromodulation (nerve stimulation) can produce analgesia. One form, bilateral pudendal nerve stimulation (bPNS), suppresses responses to urinary bladder distension (UBD) in hypersensitive rats. Drugs can modify this effect (eg, benzodiazepines, but not opioids, suppress bPNS effects). Prior to a clinical trial of bPNS effects on bladder pain, we felt it was prudent to survey the effects of medications commonly used in patients with bladder disorders. Bladder hypersensitivity was produced by neonatal bladder inflammation in rat pups coupled with a second inflammatory insult as an adult. Antimuscarinic (oxybutynin), β3 -adrenoceptor agonist (mirabegron, CL316243), α1 -adrenoceptor antagonist (tamsulosin), antidepressant (amitriptyline), muscle relaxing (baclofen), and sedative (propofol) agents were administered and effects of bPNS on responses to UBD assessed. bPNS consisted of bilateral biphasic electrical stimulation of the mixed motor/sensory component of the pudendal nerves. Visceromotor responses (VMRs; abdominal muscle contractile responses) were used as nociceptive endpoints. Many of these drugs directly inhibited the VMRs to UBD, but only mirabegron, at the doses employed, significantly reduced inhibitory effects of bPNS. In the presence of the other drugs, bPNS continued to produce statistically significant inhibition of VMRs to UBD. This study suggests that concurrent therapy with drugs used to treat bladder disorders could affect assessment of the effects of bPNS on bladder hypersensitivity. This study gives guidance to clinical trials using bPNS for the treatment of painful bladder syndromes and suggests potential clinical use of some of these medications in the treatment of these same disorders.

Benzodiazepines Suppress Neuromodulatory Effects of Pudendal Nerve Stimulation on Rat Bladder Nociception.

Neuromodulation, as a therapeutic modality for pain treatment, is an alternative to opioid therapies and therefore receiving increased interest and use. Neuromodulation at a peripheral nerve target, in the form of bilateral electrical pudendal nerve stimulation (bPNS), has been shown to reduce bladder hypersensitivity in rats and anecdotally reduces pain in humans with pelvic pain of urological origin. Recent studies have identified a role for spinal γ-aminobutyric acid (GABA) receptors in this effect. Concomitant medication use, such as benzodiazepines, could alter responses to neuromodulation, and so before the development of a clinical trial to confirm translation of this potential therapy, the potential interactions between acute and chronic use of benzodiazepines and bPNS were examined in a preclinical model. Bladder hypersensitivity was produced by neonatal bladder inflammation in rat pups coupled with a second inflammatory insult as an adult. Diazepam (1-5 mg/kg intraperitoneal [i.p.]) or vehicle was administered acutely (with or without bPNS) and chronically (5 mg/kg subcutaneous [s.c.] daily for 2 weeks before the final experiment). bPNS was delivered as bilateral biphasic electrical stimulation of the mixed motor/sensory component of the pudendal nerves. Visceromotor responses (VMRs; abdominal muscle contractile responses to urinary bladder distension [UBD]) were used as nociceptive end points. Due to the profound effects of diazepam, the effect of midazolam (0.5-1.0 mg/kg i.p.) on VMRs and bPNS effects was also studied. Diazepam and midazolam both produced a dose-dependent, flumazenil-reversible inhibition of VMRs to UBD. bPNS resulted in statistically significant inhibition of VMRs to UBD in hypersensitive rats that had received vehicle injections. Select doses of diazepam and midazolam suppressed the inhibitory effect of bPNS on VMRs. This study suggests that inhibitory effects of bPNS on bladder pain could be suppressed in subjects receiving benzodiazepine therapy, suggesting that potential clinical testing of pudendal nerve stimulation for the treatment of painful bladder syndromes may be confounded by the use of benzodiazepines. Clinical assessment of other forms of neuromodulation should also be screened for impacts of benzodiazepines.

Implantable electrical stimulation bioreactor with liquid crystal polymer-based electrodes for enhanced bone regeneration at mandibular large defects in rabbit.

The osseous regeneration of large bone defects is still a major clinical challenge in maxillofacial and orthopedic surgery. Previous studies demonstrated that biphasic electrical stimulation (ES) stimulates bone formation; however, polyimide electrode should be removed after regeneration. This study presents an implantable electrical stimulation bioreactor with electrodes based on liquid crystal polymer (LCP), which can be permanently implanted due to excellent biocompatibility to bone tissue. The bioreactor was implanted into a critical-sized bone defect and subjected to ES for one week, where bone regeneration was evaluated four weeks after surgery using micro-CT. The effect of ES via the bioreactor was compared with a sham control group and a positive control group that received recombinant human bone morphogenetic protein (rhBMP)-2 (20μg). New bone volume per tissue volume (BV/TV) in the ES and rhBMP-2 groups increased to 132% (p < 0.05) and 174% (p < 0.01), respectively, compared to that in the sham control group. In the histological evaluation, there was no inflammation within the bone defects and adjacent to LCP in all the groups. This study showed that the ES bioreactor with LCP electrodes could enhance bone regeneration at large bone defects, where LCP can act as a mechanically resistant outer box without inflammation. Graphical abstract To enhance bone regeneration, a bioreactor comprising collagen sponge and liquid crystal polymer-based electrode was implanted in the bone defect. Within the defect, electrical current pulses having biphasic waveform were applied from the implanted bioreactor.

Electrical Stimulation Degenerated Cochlear Synapses Through Oxidative Stress in Neonatal Cochlear Explants.

Neurostimulation devices use electrical stimulation (ES) to substitute, supplement or modulate neural function. However, the impact of ES on their modulating structures is largely unknown. For example, recipients of cochlear implants using electroacoustic stimulation experienced delayed loss of residual hearing over time after ES, even though ES had no impact on the morphology of hair cells. In this study, using a novel model of cochlear explant culture with charge-balanced biphasic ES, we found that ES did not change the quantity and morphology of hair cells but decreased the number of inner hair cell (IHC) synapses and the density of spiral ganglion neuron (SGN) peripheral fibers. Inhibiting calcium influx with voltage-dependent calcium channel (VDCC) blockers attenuated the loss of SGN peripheral fibers and IHC synapses induced by ES. ES increased ROS/RNS in cochlear explants, but the inhibition of calcium influx abolished this effect. Glutathione peroxidase 1 (GPx1) and GPx2 in cochlear explants decreased under ES and ebselen abolished this effect and attenuated the loss of SGN peripheral fibers. This finding demonstrated that ES induced the degeneration of SGN peripheral fibers and IHC synapses in a current intensity- and duration-dependent manner in vitro. Calcium influx resulting in oxidative stress played an important role in this process. Additionally, ebselen might be a potential protector of ES-induced cochlear synaptic degeneration.

Neuromodulatory effects of pudendal nerve stimulation on bladder hypersensitivity are present in opioid-pretreated rats

Background and objectivesBilateral electrical pudendal nerve stimulation (bPNS) reduces bladder hypersensitivity in rat models and anecdotally reduces pain in humans with pelvic pain of urologic origin. Concomitant opioids are known...

Miniature electroparticle-cuff for wireless peripheral neuromodulation

Objective. Recent developments in peripheral nerve electrodes allow the efficient and selective neuromodulation of somatic and autonomic nerves, which has proven beneficial in specific bioelectronic medical applications. However, current most clinical devices are wired and powered by implantable batteries which suffer from several limitations. We recently developed a sub-millimeter inductively powered neural stimulator (electroparticle; EP), and in this study, we report the integration of the EP onto commercial cuff electrodes (EP-C) allowing the wireless activation of peripheral nerves. Approach. The current output of this device was defined at different magnetic field strenghts, and with respect to external antenna distance and activation angles. In acute in vivo testing, stimulation of the rat sciatic nerve (ScN) with the EP-C was able to evoke motor responses quantified by 3D tracking of the hind limb movement. Motor recruitment curves were obtained in response to variations in magnetic field strength (0–92.91 A m−1), stimulation frequencies (2–7 Hz), and pulse widths (50–200 µs). Main results. The results show constant output voltage throughout 50 400 stimulating cycles on a benchtop setting, and successful ScN motor activation with a 4 cm distance between external antenna and receiver. We achieved optimal motor recruitment indicated by maximizing range of hindlimb movement (6.01 ± 2.92 mm) with a magnetic field of 40.02 ± 2.85 A m−1 and 150 µs pulse width. Stimulating pulse width or frequency did not significantly influence motor recruitment. Significance. We confirmed that continuous stimulation for 14 min using monophasic pulses did not deleteriously affect the evoked motor responses when compared to wired charge-balanced biphasic electrical stimulation. We observed, however, a 36%–44% decrease in the evoked limb movement in both groups over time due to muscle fatigue. This study shows that the EP-C device can be used effectively for peripheral nerve neuromodulation.

The effect of anodal/cathodal biphasic electrical stimulation on insulin release.

We studied the effects of electrical stimulation on insulin release from rat insulinoma (INS-1) cells. The anodal/cathodal biphasic stimulation (ACBPS) electrical waveform resulted in a voltage- and stimulation duration-dependent increase in insulin release. ACBPS elicited insulin release both in the presence and absence of glucose. Basal and ACBPS-induced insulin secretion could be inhibited by mitochondrial poisons and calcium channel blockers, indicating that insulin release was dependent on adenosine triphosphate (ATP) and the influx of calcium. ACBPS parameters that released insulin caused no detectable plasma membrane damage or cytotoxicity, although temporary morphological changes could be observed immediately after ACBPS. ACBPS did not alter the plasma membrane transmembrane potential but did cause pronounced uptake of MitoTracker Red into the mitochondrial membrane, indicating an increased mitochondrial membrane potential. While the ATP:ADP ratio after ACBPS did not change, the guanosine triphosphate (GTP) levels increased and increased GTP levels have previously been associated with insulin release in INS-1 cells. These results provide evidence that ACBPS can have significant biological effects on cells. In the case of INS-1 cells, ACBPS promotes insulin release without causing cytotoxicity.

Arrested Progression of Symptoms of a Patient Diagnosed with Multiple System Atrophy for a Period Over 6 Months

Arrested Progression of Symptoms of a Patient Diagnosed with Multiple System Atrophy for a Period Over 6 Months

Spinal mechanisms of pudendal nerve stimulation-induced inhibition of bladder hypersensitivity in rats

Bilateral electrical pudendal nerve stimulation (bPNS) reduces bladder hypersensitivity in rat models of bladder pain and anecdotally reduces pain in humans with pelvic pain of urologic origin. The spinal neurochemical mechanisms of this antinociception are unknown. In the present study, bladder hypersensitivity was produced by neonatal bladder inflammation in rat pups coupled with a second inflammatory insult as an adult. Visceromotor responses (VMRs; abdominal muscle contractions) to urinary bladder distension (UBD) were used as a nociceptive endpoint under urethane-isoflurane anesthesia. bPNS consisted of bilateral biphasic electrical stimulation of the mixed motor/sensory component of the pudendal nerves. Following determination of the inhibitory effect of bPNS on VMRs, pharmacological antagonists were administered via an intrathecal catheter onto the lumbosacral spinal cord and bPNS effects on VMRs redetermined. bPNS resulted in statistically significant inhibition of VMRs to UBD in hypersensitive rats that was statistically reduced by the intrathecal administration of methysergide, WAY100636, CGP35348 and strychnine but was unaffected by naloxone, bicuculline, phentolamine, ondansetron and normal saline. This study suggests that inhibitory effects of bPNS may include serotonergic, GABA-B-ergic and glycinergic mechanisms suggesting the potential for interaction of the neuromodulatory effect with concommitant drug therapies.