Biphasic Pulses Research Articles

Electrically evoked auditory cortical responses elicited from individually fitted stimulation parameters in cochlear implant users

Objective To investigate electrically evoked auditory cortical responses (eACR) elicited from the stimulation of intracochlear electrodes based on individually fitted stimulation parameters in cochlear implant (CI) users. Design An eACR setup based on individual fitting parameters is proposed. A 50-ms alternating biphasic pulse train was used to stimulate apical, medial, and basal electrodes and to evoke auditory cortical potentials (N1-P2 complex). Study sample The eACR setup proposed was validated with 14 adult CI users. Results Individual and grand-average eACR waveforms were obtained. The eACR amplitudes were lower in the basal than in the apical and medial regions. Earlier N1 latencies were found in CI users with lower maximum comfortable loudness levels and shorter phase duration in response to apical stimulation, while medial and basal stimulation resulted in earlier N1 latencies and larger N1-P2 amplitudes in users with longer CI experience. Conclusions eACR could be elicited by direct intracochlear stimulation using individual fitting parameters with a success rate of 71%. The highest cortical peak-to-peak amplitudes were obtained in response to apical stimulation. Unlike the P2, the N1 component appeared to be a consistent cortical potential to determine eACR and gain knowledge of the auditory processing beyond the cochlea in CI users. Highlights eACR can be elicited through direct stimulation of intracochlear electrodes. Stimulation of apical and medial regions yielded the highest N1-P2 amplitudes. CI users with lower maximum comfortable loudness levels had shorter N1 latencies during apical stimulation. The present dataset of mainly well-performing CI users suggests better cortical processing, that is, higher amplitudes and shorter latencies of N1. The N1 potential appears a more consistent and reliable potential than the P2 to determine eACR responses in CI users.

Hexagonal Stimulation Digital Controller Design and Verification for Wireless Subretinal Implant Device.

Significant progress has been made in the field of micro/nano-retinal implant technologies. However, the high pixel range, power leakage, reliability, and lifespan of retinal implants are still questionable. Active implantable devices are safe, cost-effective, and reliable. Although a device that can meet basic safety requirements set by the Food and Drug Administration and the European Union is reliable for long-term use and provides control on current and voltage parameters, it will be expensive and cannot be commercially successful. This study proposes an economical, fully controllable, and configurable wireless communication system based on field-programmable gated arrays (FPGAs) that were designed with the ability to cope with the issues that arise in retinal implantation. This system incorporates hexagonal biphasic stimulation pulses generated by a digital controller that can be fully controlled using an external transmitter. The integration of two separate domain analog systems and a digital controller based on FPGAs is proposed in this study. The system was also implemented on a microchip and verified using in vitro results.

Vestibular Co-stimulation in Adults with a Cochlear Implant.

Background : Vestibular co-stimulation is a side effect of cochlear implant stimulation. The electrical currents delivered by the cochlear implant can spread toward the vestibular system and thus stimulate it. The aim of the study is to evaluate whether it is feasible to functionally restore the balance by modifying the vestibular co-stimulation.Methods: Four adult patients, who had received a commercially available cochlear implant previously, were enrolled. Counterbalanced biphasic pulses were presented as bursts or as an amplitude-modulated biphasic pulse train (modulation frequencies ranging from 1 to 500 Hz) at the participant’s upper comfortable level for electrical stimulation. Subjective sensations and vestibular-mediated eye movements were used for evaluating the possible effects of vestibular co-stimulation.Results: One participant experienced a cyclic tilting of his head in response to an amplitude-modulated biphasic pulse train with a modulation frequency of 2 and 400 Hz. However, during a follow-up visit, the sensation could not be replicated.Conclusion: Subjective vestibular sensations or vestibular-mediated eye movements could not be electrically evoked with a commercially available cochlear implant in 4 adult patients with almost normal vestibular function. Therefore, customized design of the hard-, firm-, and/or software of the commercially available cochlear implant might be necessary in order to electrically restore vestibular performance.

IDF21-0192 Preliminary findings of plantar stimulation combined with balance training on postural stability in diabetic neuropathy

Background: Diabetic peripheral neuropathy (DPN) is most common complication seen in the patients with type 2 diabetes mellitus. It is usually reduced sensation of plantar surface of foot. There are evidences demonstrate that patients with type 2 diabetes mellitus with DPN are associated with decline in postural stability in standing and increase risk of falls. Previous studies found that plantar electrical stimulation can improve plantar sensation. Recently, exercise is possibly an alternative intervention to improve balance in the adults. However, balance exercise is inappropriate for patients with type 2 diabetes mellitus with DPN who are impaired plantar sensation and concern about the potential risk of falls. However, no studies have explored whether plantar electrical stimulation combined with standing balance training has positive effects in patients with type 2 diabetes mellitus with DPN. Aim: The purpose of this pilot study was to determine the immediate and long-term effects of 4-week of plantar electrical stimulation combined with standing balance training on postural stability and walking ability in patients with type 2 diabetes mellitus with DP. Method: Four patients with type 2 diabetes mellitus with DPN were participated in this study. Each patient was completed plantar electrical stimulation combined with standing balance training 3 days per week for 4 weeks. Electrical stimulation (biphasic pulse current with a pulse duration of 0.1 ms, 100 Hz) was delivered via two self-adhesive surface electrodes for plantar of feet. The proximal electrode was placed over plantar forefoot area and the distal electrode was placed over plantar heel area. The current intensity was adjusted to produce tingling sensation without any discomfort. During plantar electrical therapy, each patient was performed simultaneously with standing balance training with both feet apart, feet together, tandem standing under eyes open and eyes closed conditions. Postural sway was assessed by total sway area using Lord’s sway meter during standing on 4 sensory conditions (eyes open and closed on a firm surface, eyes open and closed on a foam rubber mat) for 30 seconds of each condition. The walking ability was assessed by 10-meter walk test (10MWT) at preferred speed and maximum speed. All outcome measures were assessed before training, after 4-week training and 2-week follow-up. Results: Four weeks after training, all patients showed decreased total sway area during standing on 4 sensory conditions and increased walking speed on preferred and maximum conditions. Moreover, the results showed a trend toward decreased total sway area during standing on 4 sensory conditions and increased walking speed at 2-week follow-up period. Discussion: The findings from this pilot study showed that the immediate and long-term effects of 4-week of plantar electrical stimulation combined with standing balance training could help to improve postural stability and walking speed in patients with type 2 diabetes mellitus with DPN. This present method might be use as method for improving postural stability and reducing risk of falls in patients with type 2 diabetes mellitus with DPN. However, large sample sizes are still needed to confirm the finding in further study.

Preclinical Study of Biphasic Asymmetric Pulsed Field Ablation.

Pulsed field ablation (PFA) is a novel method of pulmonary venous isolation in atrial fibrillation ablation and is featured by tissue-selective ablation. Isolation is achieved via the application of high-voltage microsecond pulses that create irreversible perforations in cell membranes (i.e., electroporation). We proposed a new biphasic asymmetric pulse mode and verified the lesion persistence and safety of this mode for pulmonary vein ostia ablation in preclinical studies. We found that biphasic asymmetric pulses can effectively reduce muscle contractions and drop ablation threshold. In the electroanatomic mapping, the ablation site showed a continuous low potential area, and the atrium was not captured after 30 days of pacing. Pathological staining showed that cardiomyocytes in the ablation area were replaced by fibroblasts and there was no damage outside the ablation zone. Our results show that pulmonary venous isolation using the biphasic asymmetric discharge mode is safe, durable, effective, and causes no damage to other tissues.

An Anodic Phase Can Facilitate Rather Than Weaken a Cathodic Phase to Activate Neurons in Biphasic-Pulse Axonal Stimulations.

Electrical pulses have been promisingly utilized in neural stimulations to treat various diseases. Usually, charge-balanced biphasic pulses are applied in the clinic to eliminate the possible side effects caused by charge accumulations. Because of its reversal action to the preceding cathodic phase, the subsequent anodic phase has been commonly considered to lower the activation efficiency of biphasic pulses. However, an anodic pulse itself can also activate axons with its “virtual cathode” effect. Therefore, we hypothesized that the anodic phase of a biphasic pulse could facilitate neuronal activation in some circumstances. To verify the hypothesis, we compared the activation efficiencies of cathodic pulse, biphasic pulse, and anodic pulse applied in both monopolar and bipolar modes in the axonal stimulation of alveus in rat hippocampal CA1 region in vivo. The antidromically evoked population spikes (APS) were recorded and used to evaluate the amount of integrated firing of pyramidal neurons induced by pulse stimulations. We also used a computational model to investigate the pulse effects on axons at various distances from the stimulation electrode. The experimental results showed that, with a small pulse intensity, a cathodic pulse recruited more neurons to fire than a biphasic pulse. However, the situation was reversed with an increased pulse intensity. In addition, setting an inter-phase gap of 100 μs was able to increase the activation efficiency of a biphasic pulse to exceed a cathodic pulse even with a relatively small pulse intensity. Furthermore, the latency of APS evoked by a cathodic pulse was always longer than that of APS evoked by a biphasic pulse, indicating different initial sites of the neuronal firing evoked by the different types of pulses. The computational results of axon modeling showed that the subsequent anodic phase was able to relieve the hyperpolarization block in the flanking regions generated by the preceding cathodic phase, thereby increasing rather than decreasing the activation efficiency of a biphasic pulse with a relatively great intensity. These results of both rat experiments and computational modeling firstly reveal a facilitation rather than an attenuation effect of the anodic phase on biphasic-pulse stimulations, which provides important information for designing electrical stimulations for neural therapies.

Modular multilevel TMS device with wide output range and ultrabrief pulse capability for sound reduction

Objective. This article presents a novel transcranial magnetic stimulation (TMS) pulse generator with a wide range of pulse shape, amplitude, and width. Approach. Based on a modular multilevel TMS (MM-TMS) topology we had proposed previously, we realized the first such device operating at full TMS energy levels. It consists of ten cascaded H-bridge modules, each implemented with insulated-gate bipolar transistors, enabling both novel high-amplitude ultrabrief pulses as well as pulses with conventional amplitude and duration. The MM-TMS device can output pulses including up to 21 voltage levels with a step size of up to 1100 V, allowing relatively flexible generation of various pulse waveforms and sequences. The circuit further allows charging the energy storage capacitor on each of the ten cascaded modules with a conventional TMS power supply. Main results. The MM-TMS device can output peak coil voltages and currents of 11 kV and 10 kA, respectively, enabling suprathreshold ultrabrief pulses (>8.25 μs active electric field phase). Further, the MM-TMS device can generate a wide range of near-rectangular monophasic and biphasic pulses, as well as more complex staircase-approximated sinusoidal, polyphasic, and amplitude-modulated pulses. At matched estimated stimulation strength, briefer pulses emit less sound, which could enable quieter TMS. Finally, the MM-TMS device can instantaneously increase or decrease the amplitude from one pulse to the next in discrete steps by adding or removing modules in series, which enables rapid pulse sequences and paired-pulse protocols with variable pulse shapes and amplitudes. Significance. The MM-TMS device allows unprecedented control of the pulse characteristics which could enable novel protocols and quieter pulses.

Contact Separation Triboelectric Nanogenerator Based Neural Interfacing for Effective Sciatic Nerve Restoration

AbstractPeripheral nerve injuries represent one of the most common causes of permanent disabilities. Therapeutic electrical stimulation has been widely used in neural regeneration for decades. Combined with the implantation of a nerve cuff, several outcomes have proven effectiveness and feasibility in neuroprosthetic applications. However, the current electrical stimulation strategy fails to complete nerve repair. There is a lack of research on long‐term implantable nanogenerators in the neurostimulation scenario. Especially considering many disease models, those devices may not reach the in vitro simulative working setting. Thus, an implanted sciatic nerve stimulation system that spontaneously generates biphasic electric pulses in response to rats’ movement is developed. The electric signals generated by this device could stimulate injured sciatic nerve by cuff electrode. This work introduces an implantable self‐regulated neural electrical stimulation system generated by a contact separation triboelectric nanogenerator with a nerve cuff electrode and compares it with chronic therapeutic electrical stimulation for sciatic nerve restoration effect. Neural function restoration is observed in gait and histological analysis. Moreover, the upregulation of growth associated protein 43 can be a protentional target. This could have potential clinical application in facilitating closed‐loop energy harvesting for long‐term electrical stimulation.

Primary Perianal Malignant Melanoma in a Dog - Combination Therapy

Background: Melanocytic neoplasm can arise from melanocytes in any location of the body. Malignant melanoma (MM) has a poor prognosis in dogs and presence of lymphvascular invasion, distant metastasis, or mitotic activity present prognostic value. Primary melanoma affecting the gastrointestinal tract has been rarely reported in veterinary literature, thus the prognosis affecting gastrointestinal tract is unknown. Electrochemotherapy (ECT) is an effective local treatment which combines chemotherapeutic drugs mainly bleomycin or cisplatin followed by the delivery of permeabilizing electrical pulses However, other hydrophilic drugs seem to present an increase cytotoxic effect such as carboplatin.Case: A 9-year-old mixed-breed neutered dog was referred to a private clinic with a mass in the perianal region diagnosed as perianal melanoma. No metastasis was observed on abdominal ultrasound nor chest x-ray (3 views). Clinical signs noted were tenesmus, hemorrhagic discharge, weight loss and hyporexia. Considering the tumor volume (16.0 x 10.0 cm), a neoadjuvant ECT session was proposed. The authors opted for carboplatin (300 mg/m², intravenously), administered over 20 min and cisplatin intratumorally (1 mg/cm³, equivalent to 1 mL/1cm³; total volume 20 mL) administered in the upper parts of the mass that could be reached while avoiding drug leakage. After administration, sequences of eight biphasic pulses, (100 microseconds), with a voltage ranging from 650-1,000V/cm (pulse generator Onkodisruptor®) using a hexagonal/single pair and plate electrode were delivered. At day 30th, a partial response was observed accordingly to RECIST system, with tumor size of 5.0 x 5.0 cm (65.4 cm³). A second ECT session was performed with the same previous protocol, but with a decreased dosage of carboplatin (240 mg/m² consistent with 20% reduction) due to adverse effects in the first session, resulting in stable disease at day 60th (30 days after second ECT). Then, we proposed a surgical excision of the mass including partial resection of ventral rectum with intraoperative ECT. Afterwards, it was observed fecal incontinence that did not resolved after time but did not significant cause a morbidity in the patient. Patient achieved a disease-free interval (DFI) of 700 days and survival time of 730 days. Unfortunately, patient died due to distant metastasis.Discussion: Surgery is still the cornerstone treatment for MM in dogs, regardless anatomic site. However, in perianal region, wide or radical local surgical excision is a challenge due to anatomic region which precluded most of the time to achieve complete margins. In this report, the origin of the tumors was not defined since no normal tissue was found surrounding tumors cells probably due to tumor invasion and destruction of surrounding tissue. Thus, based on the previous literature, this tumor could have been arisen from rectum wall or anal sac. The longer DFI and survival time from this patient is superior from the most veterinary cases in literature which combined different types of treatment such as surgery, chemotherapy, immunotherapy, palliative care or ECT. Neoadjuvant ECT leaded to a reliable approach for partial remission in order to perform a better surgical approach in this case report. To conclude, ECT may be an option for partial remission and local control in regions which anatomic limitation is a challenge for wide excision.Keywords: bleomycin, carboplatin, cisplatin, electroporation, melanocytic tumor.

Anodic and symmetric biphasic pulses enlarge the therapeutic window in deep brain stimulation for essential tremor

BackgroundSince the inception of DBS, cathodic pulses have been used. ObjectiveTo investigate the effect of anodic and symmetric biphasic pulses on the therapeutic window (TW) in essential tremor (ET) patients. MethodsA randomized, doubled-blinded, cross-over design was used to test the effect of cathodic, anodic and symmetric biphasic pulses (cathode-first and anode-first) on the TW in an acute clinical setting. TW was defined as the difference between the minimal stimulation amplitude provoking side effects and minimal stimulation amplitude inducing tremor arrest. Results9 ET patients (10 hemispheres) were included. Anodic stimulation induced a significantly larger TW compared to cathodic stimulation (p = 0.008). Symmetric biphasic stimulation also widened the TW compared to cathodic stimulation for both cathode- (p = 0.047) and anode-first (p = 0.008) biphasic pulses. For both anodic and biphasic pulses, the effect on TW was mainly driven by the change in side effect threshold. The order of the phases in the biphasic pulse had a significant effect on the side effect threshold (p = 0.039), with biphasic-anode first having the highest value. All pulse shapes were safe in the acute setting. ConclusionAnodic and symmetric biphasic pulses increase TW in ET patients.

Management of Severe Facial Nerve Cross Stimulation by Cochlear Implant Replacement to Change Pulse Shape and Grounding Configuration: A Case-series.

Objectives:To investigate the combined effect of changing pulse shape and grounding configuration to manage facial nerve stimulation (FNS) in cochlear implant (CI) recipients.Patients:Three adult CI recipients with severe FNS were offered a replacement implant when standard stimulation strategies and programming adjustments did not resolve symptoms. Our hypothesis was that the facial nerve was less likely to be activated when using anodic pulses with “mixed-mode” intra-cochlear and extra-cochlear current return.Intervention:All patients were reimplanted with an implant that uses a pseudo-monophasic anodic pulse shape, with mixed-mode grounding (stimulus mixed-mode anodic)—the Neuro Zti CI (Oticon Medical). This device also allows measurements of neural function and loudness with monopolar, symmetric biphasic pulses (stimulus MB), the clinical standard used by most CIs as a comparison.Main Outcome Measures:The combined effect of pulse shape and grounding configuration on FNS was monitored during surgery. Following CI activation, FNS symptoms and performance with the Neuro Zti implant were compared with outcomes before reimplantation.Results:FNS could only be recorded using stimulus MB for all patients. In clinical use, all patients reported reduced FNS and showed an improvement in Bamford-Kowal-Bench sentences recognition compared with immediately before reimplantation. Bamford-Kowal-Bench scores with a male speaker were lower compared with measurements taken before the onset of severe FNS for patients 1 and 2.Conclusions:In patients where CI auditory performance was severely limited by FNS, charge-balanced pseudo-monophasic stimulation mode with a mixed-mode grounding configuration limited FNS and improved loudness percept compared with standard biphasic stimulation with monopolar grounding.

Morphology-dependent electrochemical stability of electrodeposited polypyrrole/nano-ZnO composite coatings

To elevate the electrochemical stability of polypyrrole–zinc oxide (PPy–ZnO) coatings, five different electrodeposition protocols were attempted to fabricate PPy–ZnO nanocomposites on tungsten substrates. The effects of the electrodeposition schemes on the morphology, microstructure and electrochemical properties of coatings were systematically analyzed, and the long-term electrochemical stability was examined via biphasic current pulse measurement in 0.01 M phosphate-buffered saline (PBS). Results indicated that our newly coated samples displayed safer capacitive charge transform behaviors. In particular, the cathodic charge storage capacity (CCSC) and safe charge injection capacity (Qinj) of the coated sample prepared by cyclic voltammetry (CV) electrodeposition were 15.3 and 0.26 mC/cm2, respectively, which were approximately 7 times and 30% greater than those of pure substrate. Moreover, the coated sample also showed perfect long-term electrochemical stability with no delamination, cracks, or ridges on the coating surface. This improvement is mainly attributed to CV electrodeposition, which smoothed the polymer morphology, compacted the structure, enhanced the interface adhesion, and diminished the internal micropores, leading to minimized volumetric expansion and shrinking of coatings in the long-term charge/discharge process.

A Flexible Pulse Generator Based on a Field Programmable Gate Array Architecture for Functional Electrical Stimulation.

Non-invasive Functional Electrical Stimulation (FES) is a technique applied for motor rehabilitation of patients with central nervous system injury. This technique requires programmable multichannel systems to configure the stimulation parameters (amplitude, frequency, and pulse width). Most FES systems are based on microcontrollers with fixed architecture; this limits the control of the parameters and the scaling to multiple channels. Although field programmable gate arrays (FPGA) have been used in FES systems as alternative to microcontrollers, most of them focus on signal acquisition, processing, or communication functions, or are for invasive stimulation. A few FES systems report using FPGAs for parameter configuration and pulse generation in non-invasive FES. However, generally they limit the value of the frequency or amplitude parameters to enable multichannel operation. This restricts free selection of parameters and implementation of modulation patterns, previously reported to delay FES-induced muscle fatigue. To overcome those limitations, this paper presents a proof-of-concept (technology readiness level three-TRL 3) regarding the technical feasibility and potential use of an FPGA-based pulse generator for non-invasive FES applications (PG-nFES). The main aims were: (1) the development of a flexible pulse generator for FES applications and (2) to perform a proof-of-concept of the system, comprising: electrical characterization of the stimulation parameters, and verification of its potential for upper limb FES applications. Biphasic stimulation pulses with high linearity (r2 > 0.9998) and repeatability (>0.81) were achieved by combining the PG-nFES with a current-controlled output stage. Average percentage error in the characterizations was under 3% for amplitude (1–48 mA) and pulse width (20–400 μs), and 0% for frequency (10–150 Hz). A six-channel version of the PG-nFES was implemented to demonstrate the scalability feature. The independence of parameters was tested with three patterns of co-modulation of two parameters. Moreover, two complete FES channels were implemented and the claimed features of the PG-nFES were verified by performing upper limb functional movements involving the hand and the arm. Finally, the system enabled implementation of a stimulation pattern with co-modulation of frequency and pulse width, applied successfully for efficient elbow during repetitions of a functional movement.

Parametric Assessment of Spinal Cord Stimulation on Bladder Pain—Like Responses in Rats

ObjectivesSpinal cord stimulation (SCS) for the treatment of pelvic visceral pains has been understudied and underused. The goal of the current study was to examine multiple stimulation parameters of SCS to determine optimal settings for the inhibition of responses to urinary bladder distension (UBD) in animal models of bladder pain as a guide for human studies. Materials and MethodsAdult, female isoflurane/urethane-anesthetized rats underwent a T13/L1 mini-laminectomy sufficient to implant an SCS paddle lead for neuromodulation. Silver wire electrodes were inserted into the external oblique musculature. A 22-gauge angiocatheter was placed transurethrally into the bladder and used to deliver phasic, air UBDs at pressures of 10 to 60 mm Hg and visceromotor (abdominal contractile) electromyographic responses to UBD measured in the presence and absence of SCS. Electromyographic activity was quantified using standard differential amplification and rectification. Parameter settings for SCS included both conventional (10, 50, 100 Hz) and high frequency (1,000, 5,000, and 10,000 Hz) biphasic square wave pulses with 50 to 200 μs durations. To create states of hypersensitivity, pretreatment of adult rats included an intravesical zymosan infusion 24 hours before testing with and without a preceding episode of neonatal bladder inflammation. ResultsLow frequency (10, 50, and 100 Hz) 200 μs biphasic pulses at submotor thresholds demonstrated inhibition of visceromotor responses (VMRs) to UBD in rats made hypersensitive to UBD by a protocol that included neonatal cystitis. Onset of inhibitory effects occurred within 20 minutes of beginning SCS. Otherwise, SCS at all other parameters studied and in other tested rat models produced either no significant effect or augmentation of VMRs. ConclusionsDemonstration of inhibitory effects of SCS in a clinically relevant model of bladder pain suggests the potential utility of this therapy in patients with painful bladder disorders.

Emergence of stochastic resonance in a two-compartment hippocampal pyramidal neuron model.

In vitro studies have shown that hippocampal pyramidal neurons employ a mechanism similar to stochastic resonance (SR) to enhance the detection and transmission of weak stimuli generated at distal synapses. To support the experimental findings from the perspective of multicompartment model analysis, this paper aimed to elucidate the phenomenon of SR in a noisy two-compartment hippocampal pyramidal neuron model, which was a variant of the Pinsky-Rinzel neuron model with smooth activation functions and a hyperpolarization-activated cation current. With a bifurcation analysis of the model, we demonstrated the underlying dynamical structure responsible for the occurrence of SR. Furthermore, using a stochastically generated biphasic pulse train and broadband noise generated by the Orenstein-Uhlenbeck process as noise perturbation, both SR and suprathreshold SR were observed and quantified. Spectral analysis revealed that the distribution of spectral power under noise perturbations, in addition to inherent neurodynamics, is the main factor affecting SR behavior. The research results suggested that noise enhances the transmission of weak stimuli associated with elongated dendritic structures of hippocampal pyramidal neurons, thereby providing support for related laboratory findings.

Development of a High-Power Capacity Open Source Electrical Stimulation System to Enhance Research into FES-Assisted Devices: Validation of FES Cycling.

Since the first Cybathlon 2016, when twelve teams competed in the FES bike race, we have witnessed a global effort towards the development of stimulation and control strategies to improve FES-assisted devices, particularly for cycling, as a means to practice a recreational physical activity. As a result, a set of technical notes and research paved the way for many other studies and the potential behind FES-assisted cycling has been consolidated. However, engineering research needs instrumented devices to support novel developments and enable precise assessment. Therefore, some researchers struggle to develop their own FES-assisted devices or find it challenging to implement their instrumentation using commercial devices, which often limits the implementation of advanced control strategies and the possibility to connect different types of sensor. In this regard, we hypothesize that it would be advantageous for some researchers in our community to enjoy access to an entire open-source FES platform that allows different control strategies to be implemented, offers greater adaptability and power capacity than commercial devices, and can be used to assist different functional activities in addition to cycling. Hence, it appears to be of interest to make our proprietary electrical stimulation system an open-source device and to prove its capabilities by addressing all the aspects necessary to implement a FES cycling system. The high-power capacity stimulation device is based on a constant current topology that allows the creation of biphasic electrical pulses with amplitude, width, and frequency up to 150 mA, 1000 µs, and 100 Hz, respectively. A mobile application (Android) was developed to set and modify the stimulation parameters of up to eight stimulation channels. A proportional-integral controller was implemented for cadence tracking with the aim to improve the overall cycling performance. A volunteer with complete paraplegia participated in the functional testing of the system. He was able to cycle indoors for 45 min, accomplish distances of more than 5 km using a passive cycling trainer, and pedal 2400 m overground in 32 min. The results evidenced the capacity of our FES cycling system to be employed as a cycling tool for individuals with spinal cord injury. The methodological strategies used to improve FES efficiency suggest the possibility of maximizing pedaling duration through more advanced control techniques.

Characterizing Polarity Sensitivity in Cochlear Implant Recipients: Demographic Effects and Potential Implications for Estimating Neural Health.

Stimulus polarity can affect both physiological and perceptual measures in cochlear-implant recipients. Large differences between polarities for various outcome measures (e.g., eCAP threshold, amplitude, or slope) theoretically reflect poorer neural health, whereas smaller differences reflect better neural health. Therefore, we expect large polarity effects to be correlated with other measures shown to contribute to poor neural health, such as advanced age or prolonged deafness. Our earlier studies using the electrically evoked compound action potential (eCAP) demonstrated differences in polarity effects between users of Cochlear and Advanced Bionics devices when device-specific clinical pulse designs were used. Since the stimuli differed slightly between devices, the first goal of this study was to determine whether small, clinically relevant differences in pulse phase duration (PD) have a significant impact on eCAP polarity effects to potentially explain the device differences observed previously. Polarity effects were quantified as the difference in eCAP thresholds, mean normalized amplitudes, and slope of the amplitude growth function obtained for anodic-first versus cathodic-first biphasic pulses. The results showed that small variations in PD did not explain the observed differences in eCAP polarity effects between devices. Therefore, eCAP polarity sensitivity measures are relatively robust to small differences in pulse parameters. However, it remains unclear what underlies the observed manufacturer differences, which may limit the utility of eCAP polarity sensitivity measures. The second goal was to characterize polarity sensitivity in a large group of CI recipients (65 ears) to relate polarity sensitivity to age and duration of deafness as a proxy for neural health. The same pulse parameters were used for both device groups. The only significant predictors of eCAP polarity effects were age for threshold and amplitude polarity effects for Cochlear recipients and age and duration of deafness for slope for AB recipients. However, three of these four correlations were in the opposite direction of what was expected. These results suggest that eCAP polarity sensitivity measures likely reflect different mechanisms than the effects that age and duration of deafness induce on the peripheral auditory system.

Transcorneal electrical stimulation reduces the annual rate of visual field decline in retinitis pigmentosa

AbstractPurposeIn retinitis pigmentosa (RP) the visual field area (VFA) declines exponentially. We investigated whether the annual decline rate (ADR) can be slowed by transcorneal electrical stimulation (TcES).MethodsWe conducted an a posteriori analysis of data from 51 adult patients with RP who participated in an interventional, randomized, single‐masked study (clinicaltrials.gov: NCT01837901; Schatz et al., 2017, IOVS 58(1)). Patients were randomized into 3 groups stimulated with 0 mA (sham stimulation), 150% or 200% of their phosphene threshold, respectively. Over one year, TcES was applied monocularly, 30 min per week with biphasic current pulses (OkuStim, 5 ms each phase, 20 Hz, 0.2 to 1.0 mA). VFA were repeatedly assessed in both eyes (Octopus 900, target V4e). VFA values were normalized to percentage of baseline value, transformed into the natural logarithm, averaged within groups, and subjected to a weighted linear regression analysis. ADR was calculated from the slope of best fit line for both eyes in the sham group (n = 20) and in the treated group (n = 31, 150% and 200% groups pooled).ResultsIn the sham group, for the stimulated eyes the ADR was 8.0% (F‐test for slope: p = 0.011) while for the non‐stimulated eyes it was 9.6% (p = 0.005). In the treated group, for the stimulated eyes the ADR was 3.4% (p = 0.276), and for the non‐stimulated eyes it was 7.0% (p = 0.035). The difference between the ADR in the stimulated and non‐stimulated eyes was evident when only eyes stimulated with >0.8 mA (n = 9) were included. The progression in the stimulated eyes had almost stopped, the ADR was 2.7% (p = 0.397) compared to 9.2% (p = 0.022) in the non‐stimulated eyes. The analysis is limited by data variability, sample size and observation period.ConclusionThe analysis showed that the ADR can be markedly slowed by TcES in a dose‐dependent manner. Thus, regular use of TcES is an effective therapeutic method for slowing or arresting disease progression in RP.

Design and application of neural electrical stimulation system with time-varying parameters

Currently, commercial devices for electrical neural stimulations can only provide fixed stimulation paradigms with preset constant parameters, while the development of new stimulation paradigms with time-varying parameters has emerged as one of the important research directions for expanding clinical applications. To facilitate the performance of electrical stimulation paradigms with time-varying parameters in animal experiments, the present study developed a well-integrated stimulation system to output various pulse sequences by designing a LabVIEW software to control a general data acquisition card and an electrical stimulus isolator. The system was able to generate pulse sequences with inter-pulse-intervals (IPI) randomly varying in real time with specific distributions such as uniform distribution, normal distribution, gamma distribution and Poisson distribution. It was also able to generate pulse sequences with arbitrary time-varying IPIs. In addition, the pulse parameters, including pulse amplitude, pulse width, interphase delay of biphasic pulse and duration of pulse sequence, were adjustable. The results of performance tests of the stimulation system showed that the errors of the parameters of pulse sequences output by the system were all less than 1%. By utilizing the stimulation system, pulse sequences with IPI randomly varying in the range of 5~10 ms were generated and applied in rat hippocampal regions for animal experiments. The experimental results showed that, even with a same mean pulse frequency of ~130 Hz, for neuronal populations, the excitatory effect of stimulations with randomly varying IPIs was significantly greater than the effect of stimulations with fixed IPIs. In conclusion, the stimulation system designed here may provide a useful tool for the researches and the development of new paradigms of neural electrical stimulations.

Imaging the effective networks associated with cortical function through intracranial high-frequency stimulation.

Direct electrical stimulation (DES) is considered to be the gold standard for mapping cortical function. A careful mapping of the eloquent cortex is key to successful resective or ablative surgeries, with a minimal postoperative deficit, for treatment of drug‐resistant epilepsy. There is accumulating evidence suggesting that not only local, but also remote activations play an equally important role in evoking clinical effects. By introducing a new intracranial stimulation paradigm and signal analysis methodology allowing to disambiguate EEG responses from stimulation artifacts we highlight the spatial extent of the networks associated with clinical effects. Our study includes 26 patients that underwent stereoelectroencephalographic investigations for drug‐resistant epilepsy, having 337 depth electrodes with 4,351 contacts sampling most brain structures. The routine high‐frequency electrical stimulation protocol for eloquent cortex mapping was altered in a subtle way, by alternating the polarity of the biphasic pulses in a train, causing the splitting the spectral lines of the artifactual components, exposing the underlying tissue response. By performing a frequency‐domain analysis of the EEG responses during DES we were able to capture remote activations and highlight the effect's network. By using standard intersubject averaging and a fine granularity HCP‐MMP parcellation, we were able to create local and distant connectivity maps for 614 stimulations evoking specific clinical effects. The clinical value of such maps is not only for a better understanding of the extent of the effects' networks guiding the invasive exploration, but also for understanding the spatial patterns of seizure propagation given the timeline of the seizure semiology.