Biphasic Pulses Research Articles

The Variation of Electrical Pulse Duration Elicits Reliable Network-Mediated Responses of Retinal Ganglion Cells in Normal, Not in Degenerate Primate Retinas.

This study aims to investigate the efficacy of electrical stimulation by comparing network-mediated RGC responses in normal and degenerate retinas using a N-methyl-N-nitrosourea (MNU)-induced non-human primate (NHPs) retinitis pigmentosa (RP) model. Adult cynomolgus monkeys were used for normal and outer retinal degeneration (RD) induced by MNU. The network-mediated RGC responses were recorded from the peripheral retina mounted on an 8 × 8 multielectrode array (MEA). The amplitude and duration of biphasic current pulses were modulated from 1 to 50 μA and 500 to 4000 μs, respectively. The threshold charge density for eliciting a network-mediated RGC response was higher in the RD monkeys than in the normal monkeys (1.47 ± 0.13 mC/cm2 vs. 1.06 ± 0.09 mC/cm2, p < 0.05) at a 500 μs pulse duration. The monkeys required a higher charge density than rodents among the RD models (monkeys; 1.47 ± 0.13 mC/cm2, mouse; 1.04 ± 0.09 mC/cm2, and rat; 1.16 ± 0.16 mC/cm2, p < 0.01). Increasing the pulse amplitude and pulse duration elicited more RGC spikes in the normal primate retinas. However, only pulse amplitude variation elicited more RGC spikes in degenerate primate retinas. Therefore, the pulse strategy for primate RD retinas should be optimized, eventually contributing to retinal prosthetics. Given that RD NHP RGCs are not sensitive to pulse duration, using shorter pulses may potentially be a more charge-effective approach for retinal prosthetics.

Interactions between cathodic- and anodic-pulses during high-frequency stimulations with the monophasic-pulses alternating in polarity at axons—experiment and simulation studies

Background. Electrical neuromodulation therapies commonly utilize high-frequency stimulations (HFS) of biphasic-pulses to treat neurological disorders. The biphasic pulse consists of a leading cathodic-phase to activate neurons and a lagging anodic-phase to balance electrical charges. Because both monophasic cathodic- and anodic-pulses can depolarize neuronal membranes, splitting biphasic-pulses into alternate cathodic- and anodic-pulses could be a feasible strategy to improve stimulation efficiency. Objective. We speculated that neurons in the volume initially activated by both polarity pulses could change to be activated only by anodic-pulses during sustained HFS of alternate monophasic-pulses. To verify the hypothesis, we investigated the interactions of the monophasic pulses during HFS and revealed possible underlying mechanisms. Approach. Different types of pulse stimulations were applied at the alvear fibers (i.e. the axons of CA1 pyramidal neurons) to antidromically activate the neuronal cell bodies in the hippocampal CA1 region of anesthetized rats in-vivo. Sequences of antidromic HFS (A-HFS) were applied with alternate monophasic-pulses or biphasic-pulses. The pulse frequency in the A-HFS sequences was 50 or 100 Hz. The A-HFS duration was 120 s. The amplitude of antidromically-evoked population spike was measured to evaluate the neuronal firing induced by each pulse. A computational model of axon was used to explore the possible mechanisms of neuronal modulations. The changes of model variables during sustained A-HFS were analyzed. Main results. In rat experiments, with a same pulse intensity, the activation volume of a cathodic-pulse was greater than that of an anodic-pulse. In paired-pulse tests, a preceding cathodic-pulse was able to prevent a following anodic-pulse from activating neurons due to refractory period. This indicated that the activation volume of a cathodic-pulse covered that of an anodic-pulse. However, during sustained A-HFS of alternate monophasic-pulses, the anodic-pulses were able to prevail over the cathodic-pulses in activating neurons in the overlapped activation volume. Model simulation results show the mechanisms of the activation failures of cathodic-pulses. They include the excessive membrane depolarization caused by an accumulation of potassium ions, the obstacle of hyperpolarization in the conduction pathway and the interactions from anodic-pulses. Significance. The study firstly showed the domination of anodic-pulses over cathodic-pulses in their competitions to activate neurons during sustained HFS. The finding provides new clues for designing HFS paradigms to improve the efficiency of neuromodulation therapies.

Cochlear Implant Stimulation Parameters Play a Key Role in Reducing Facial Nerve Stimulation.

A percentage (i.e., 5.6%) of Cochlear Implant (CI) users reportedly experience unwanted facial nerve stimulation (FNS). For some, the effort to control this problem results in changing stimulation parameters, thereby reducing their hearing performance. For others, the only viable solution is to deactivate the CI completely. A growing body of evidence in the form of case reports suggests that undesired FNS can be effectively addressed through re-implantation with an Oticon Medical (OM) Neuro-Zti implant. However, the root of this benefit is still unknown: is it due to surgical adjustments, such as varied array geometries and/or positioning, or does it stem from differences in stimulation parameters and/or grounding? The OM device exhibits two distinct features: (1) unique stimulation parameters, including anodic leading pulses and loudness controlled by pulse duration-not current-resulting in lower overall current amplitudes; and (2) unconventional grounding, including both passive (capacitive) discharge, which creates a pseudo-monophasic pulse shape, and a 'distributed-all-polar' (DAP) grounding scheme, which is thought to reduce current spread. Unfortunately, case reports alone cannot distinguish between surgical factors and these implant-related ones. In this paper, we present a novel follow-up study of two CI subjects who previously experienced FNS before re-implantation with Neuro-Zti implants. We used the Oticon Medical Research Platform (OMRP) to stimulate a single electrode in each subject in two ways: (1) with traditional monopolar biphasic cathodic-first pulses, and (2) with distinct OM clinical stimulation. We progressively increased the stimulation intensity until FNS occurred or the sound became excessively loud. Non-auditory/FNS sensations were observed with the traditional stimulation but not with the OM clinical one. This provides the first direct evidence demonstrating that stimulation parameters and/or grounding-not surgical factors-play a key role in mitigating FNS.

An extraocular electrical stimulation approach to slow down the progression of retinal degeneration in an animal model

Retinal diseases such as retinitis pigmentosa (RP) and age-related macular degeneration (AMD) are characterized by unrelenting neuronal death. However, electrical stimulation has been shown to induce neuroprotective changes in the retina capable of slowing down the progression of retinal blindness. In this work, a multi-scale computational model and modeling platform were used to design electrical stimulation strategies to better target the bipolar cells (BCs), that along with photoreceptors are affected at the early stage of retinal degenerative diseases. Our computational findings revealed that biphasic stimulus pulses of long pulse duration could decrease the activation threshold of BCs, and the differential stimulus threshold between ganglion cells (RGCs) and BCs, offering the potential of targeting the BCs during the early phase of degeneration. In vivo experiments were performed to evaluate the electrode placement and parameters found to target bipolar cells and evaluate the safety and efficacy of the treatment. Results indicate that the proposed transcorneal Electrical Stimulation (TES) strategy can attenuate retinal degeneration in a Royal College of Surgeon (RCS) rodent model, offering the potential to translate this work to clinical practice.

A Fine-Scale and Minimally Invasive Marking Method for Use with Conventional Tungsten Microelectrodes.

In neurophysiology, achieving precise correlation between physiological responses and anatomic structures is a significant challenge. Therefore, the accuracy of the electrode marking method is crucial. In this study, we describe a tungsten-deposition method, in which tungsten oxide is generated by applying biphasic current pulses to conventional tungsten electrodes. The electrical current used was 40-50 μA, which is similar to that used in electrical microstimulation experiments. The size of the markings ranged from 10 to 100 μm, corresponding to the size of the electrode tip, which is smaller than that of existing marking methods. Despite the small size of the markings, detection is easy as the marking appears in bright red under dark-field observation after Nissl staining. This marking technique resulted in low tissue damage and was maintained in vivo for at least two years. The feasibility of this method was tested in mouse and macaque brains.

Effects of transcranial magnetic stimulation (TMS) current direction and pulse waveform on cortico-cortical connectivity: A registered report TMS-EEG study.

Transcranial magnetic stimulation (TMS)-evoked potentials (TEPs) are a promising proxy for measuring effective connectivity, that is, the directed transmission of physiological signals along cortico-cortical tracts, and for developing connectivity-based biomarkers. A crucial point is how stimulation parameters may affect TEPs, as they may contribute to the general variability of findings across studies. Here, we manipulated two TMS parameters (i.e. current direction and pulse waveform) while measuring (a) an early TEP component reflecting contralateral inhibition of motor areas, namely, M1-P15, as an operative model of interhemispheric cortico-cortical connectivity, and (b) motor-evoked potentials (MEP) for the corticospinal pathway. Our results showed that these two TMS parameters are crucial to evoke the M1-P15, influencing its amplitude, latency, and replicability. Specifically, (a) M1-P15 amplitude was strongly affected by current direction in monophasic stimulation; (b) M1-P15 latency was significantly modulated by current direction for monophasic and biphasic pulses. The replicability of M1-P15 was substantial for the same stimulation condition. At the same time, it was poor when stimulation parameters were changed, suggesting that these factors must be controlled to obtain stable single-subject measures. Finally, MEP latency was modulated by current direction, whereas non-statistically significant changes were evident for amplitude. Overall, our study highlights the importance of TMS parameters for early TEP responses recording and suggests controlling their impact in developing connectivity biomarkers from TEPs. Moreover, these results point out that the excitability of the corticospinal tract, which is commonly used as a reference to set TMS intensity, may not correspond to the excitability of cortico-cortical pathways.

Functional Enhancement and Characterization of an Electrophysiological Mapping Electrode Probe with Carbonic, Directional Macrocontacts.

Electrophysiological mapping (EM) using acute electrode probes is a common procedure performed during functional neurosurgery. Due to their constructive specificities, the EM probes are lagging in innovative enhancements. This work addressed complementing a clinically employed EM probe with carbonic and circumferentially segmented macrocontacts that are operable both for neurophysiological sensing ("recording") of local field potentials (LFP) and for test stimulation. This paper illustrates in-depth the development that is based on the direct writing of functional materials. The unconventional fabrication processes were optimized on planar geometry and then transferred to the cylindrically thin probe body. We report and discuss the constructive concept and architecture of the probe, characteristics of the electrochemical interface deduced from voltammetry and chronopotentiometry, and the results of in vitro and in vivo recording and pulse stimulation tests. Two- and three-directional macrocontacts were added on probes having shanks of 550 and 770 μm diameters and 10-23 cm lengths. The graphitic material presents a ~2.7 V wide, almost symmetric water electrolysis window, and an ultra-capacitive charge transfer. When tested with clinically relevant 150 μs biphasic current pulses, the interfacial polarization stayed safely away from the water window for pulse amplitudes up to 9 mA (135 μC/cm2). The in vivo experiments on adult rat models confirmed the high-quality sensing of LFPs. Additionally, the in vivo-prevailing increase in the electrode impedance and overpotential are discussed and modeled by an ionic mobility-reducing spongiform structure; this restricted diffusion model gives new applicative insight into the in vivo-uprisen stimulation overpotential.

Monitoring pressure changes in the inner ear induced by middle ear pressure therapy with an EFET01 device in guinea pigs

Background As a low-cost, portable, handheld air pressure generation tool not requiring a ventilation tube, the EFET01 device has shown clinical effectiveness for intractable Ménière’s disease (MD) patients in Japan. However, no animal studies have investigated changes in inner ear pressure (PI) when applying this device. Objective To determine the PI properties in response to middle ear pressure therapy (MEPT) induced by the EFET01 in guinea pigs. Material and Methods In seven healthy guinea pigs, bi-phasic pressure pulses from −5 to 12 cm H2O were delivered to the external ear canal and transmitted to the middle and inner ear cavities with an intact tympanic membrane. Hydrostatic pressure change in the inner ear perilymphatic compartment was measured by a servo-controlled micropipette system. Results From eight successful ears, pressure changes in the middle ear slightly decreased and were instantly transferred to the inner ear. The EFET01 produces a bi-phasic positive/negative pressure pulse, which is approximately twice as large as the monophasic pressure pulse. Conclusion Our study clarified the EFET01’s ability to transmit pressure and verified its effectiveness in MD patients as observed in clinical studies. Significance The PI properties in guinea pig response to MEPT with the EFET01 device were investigated.

Enhanced selectivity of transcutaneous spinal cord stimulation by multielectrode configuration.

Transcutaneous spinal cord stimulation (tSCS) has been gaining momentum as a non-invasive rehabilitation approach to restore movement to paralyzed muscles after spinal cord injury (SCI). However, its low selectivity limits the types of movements that can be enabled and, thus, its potential applications in rehabilitation. In this cross-over study design, we investigated whether muscle recruitment selectivity of individual muscles could be enhanced by multielectrode configurations of tSCS in 16 neurologically intact individuals. We hypothesized that due to the segmental innervation of lower limb muscles, we could identify muscle-specific optimal stimulation locations that would enable improved recruitment selectivity over conventional tSCS. We elicited leg muscle responses by delivering biphasic pulses of electrical stimulation to the lumbosacral enlargement using conventional and multielectrode tSCS. Analysis of recruitment curve responses confirmed that multielectrode configurations could improve the rostrocaudal and lateral selectivity of tSCS. To investigate whether motor responses elicited by spatially selective tSCS were mediated by posterior root-muscle reflexes, each stimulation event was a paired pulse with a conditioning-test interval of 33.3 ms. Muscle responses to the second stimulation pulse were significantly suppressed, a characteristic of post-activation depression suggesting that spatially selective tSCS recruits proprioceptive fibers that reflexively activate muscle specific-motor neurons in the spinal cord. Moreover, the combination of leg muscle recruitment probability and segmental innervation maps revealed a stereotypical spinal activation map in congruence with each electrode's position. Improvements in muscle recruitment selectivity could be essential for the effective translation into stimulation protocols that selectively enhance single-joint movements in neurorehabilitation.&#xD.

Evaluation of electric phrenic nerve stimulation patterns for mechanical ventilation: a pilot study

Diaphragm atrophy is a common side effect of mechanical ventilation and results in prolonged weaning. Electric phrenic nerve stimulation presents a possibility to avoid diaphragm atrophy by keeping the diaphragm conditioned in sedated patients. There is a need of further investigation on how to set stimulation parameters to achieve sufficient ventilation. A prototype system is presented with a systematic evaluation for stimulation pattern adjustments. The main indicator for efficient stimulation was the tidal volume. The evaluation was performed in two pig models. As a major finding, the results for biphasic pulses were more consistent than for alternating pulses. The tidal volume increased for a range of pulse frequency and pulse width until reaching a plateau at 80–120 Hz and 0.15 ms. Furthermore, the generated tidal volume and the stimulation pulse frequency were significantly correlated (0.42–0.84, p<0.001). The results show which stimulation parameter combinations generate the highest tidal volume. We established a guideline on how to set stimulation parameters. The guideline is helpful for future clinical applications of phrenic nerve stimulation.

How far does electrical stimulation activate white matter tracts? A computational modeling study

ObjectiveThe aim of this study was to model how the different parameters of electrical stimulation (intensity, pulse shape, probe geometry) influence the extent of white matter activation. MethodsThe electrical potentials generated by the stimulating electrodes were determined by solving Laplace equation. The temporal evolution of membrane potentials at each nodes of Ranvier of an axon was then computed by solving the coupled system of differential equations describing membrane dynamics and cable propagation. ResultsRegions of unilateral propagation were observed for monophasic pulses delivered with a bipolar probe aligned along the tract. For biphasic pulses, the largest activation areas and depths were found with a high inter-electrode-distance (IED) bipolar probe, oriented orthogonally to the tract. The smallest activation areas and depths were found for bipolar stimulations with the probe aligned parallel to the tract and low IED. For isotropic white matter regions, the activation area and depth were three times larger than for anisotropic white matter tracts. ConclusionsBipolar probes with biphasic pulses offer the greatest versatility: an orthogonal orientation acts as two monopolars (increased sensitivity when searching for a tract), whereas a parallel orientation corresponds to a single monopolar (increased specificity). Activation is more superficial when stimulating highly anisotropic tracts. SignificanceThis knowledge is essential for interpreting the behavorial effects of stimulation and the recordings of axono-cortical evoked potentials.

The effect of pulse shape in theta-burst stimulation: Monophasic vs biphasic TMS

BackgroundIntermittent theta-burst stimulation (i) (TBS) is a transcranial magnetic stimulation (TMS) plasticity protocol. Conventionally, TBS is applied using biphasic pulses due to hardware limitations. However, monophasic pulses are hypothesised to recruit cortical neurons more selectively than biphasic pulses, predicting stronger plasticity effects. Monophasic and biphasic TBS can be generated using a custom-made pulse-width modulation-based TMS device (pTMS). ObjectiveUsing pTMS, we tested the hypothesis that monophasic iTBS would induce a stronger plasticity effect than biphasic, measured as induced increases in motor corticospinal excitability. MethodsIn a repeated-measures design, thirty healthy volunteers participated in three separate sessions, where monophasic and biphasic iTBS was applied to the primary motor cortex (M1 condition) or the vertex (control condition). Plasticity was quantified as increases in motor corticospinal excitability after versus before iTBS, by comparing peak-to-peak amplitudes of motor evoked potentials (MEP) measured at baseline and over 60 min after iTBS. ResultsBoth monophasic and biphasic M1 iTBS led to significant increases in MEP amplitude. As predicted, linear mixed effects (LME) models showed that the iTBS condition had a significant effect on the MEP amplitude (χ2 (1) = 27.615, p < 0.001) with monophasic iTBS leading to significantly stronger plasticity than biphasic iTBS (t (693) = 2.311, p = 0.021). Control vertex iTBS had no effect. ConclusionsIn this study, monophasic iTBS induced a stronger motor corticospinal excitability increase than biphasic within participants. This greater physiological effect suggests that monophasic iTBS may also have potential for greater functional impact, of interest for future fundamental and clinical applications of TBS.

High-Frequency Electroporation and Chemotherapy for the Treatment of Cutaneous Malignancies: Evaluation of Early Clinical Response.

High-frequency electroporation (HF-EP) with chemotherapy is a novel therapy proposed for both curative and palliative treatment of cutaneous malignancies. The use of high-frequency biphasic pulses is thought to reduce the painful muscle contractions associated with traditional electrochemotherapy (ECT), allowing treatment administration under local anaesthesia. This proof-of-concept study investigated the efficacy and tolerability of HF-EP protocols on a variety of cutaneous malignancies. A total of 97 lesions of five different histological subtypes were treated across 25 patients. At 12 weeks post-treatment, a 91.3% overall lesion response rate was observed (complete response: 79%; partial response: 12.3%), with excellent intraprocedural patient tolerability under local anaesthetic. HF-EP with chemotherapy shows promising results regarding tumour response rates for cutaneous malignancies of varying histological subtypes when compared to traditional ECT protocols. Improved patient tolerability is important, increasing the possibility of treatment delivery under local anaesthesia and potentially broadening the treatment envelope for patients with cutaneous malignancies.

Optimized monophasic pulses with equivalent electric field for rapid-rate transcranial magnetic stimulation

Objective. Transcranial magnetic stimulation (TMS) with monophasic pulses achieves greater changes in neuronal excitability but requires higher energy and generates more coil heating than TMS with biphasic pulses, and this limits the use of monophasic pulses in rapid-rate protocols. We sought to design a stimulation waveform that retains the characteristics of monophasic TMS but significantly reduces coil heating, thereby enabling higher pulse rates and increased neuromodulation effectiveness. Approach. A two-step optimization method was developed that uses the temporal relationship between the electric field (E-field) and coil current waveforms. The model-free optimization step reduced the ohmic losses of the coil current and constrained the error of the E-field waveform compared to a template monophasic pulse, with pulse duration as a second constraint. The second, amplitude adjustment step scaled the candidate waveforms based on simulated neural activation to account for differences in stimulation thresholds. The optimized waveforms were implemented to validate the changes in coil heating. Main results. Depending on the pulse duration and E-field matching constraints, the optimized waveforms produced 12%–75% less heating than the original monophasic pulse. The reduction in coil heating was robust across a range of neural models. The changes in the measured ohmic losses of the optimized pulses compared to the original pulse agreed with numeric predictions. Significance. The first step of the optimization approach was independent of any potentially inaccurate or incorrect model and exhibited robust performance by avoiding the highly nonlinear behavior of neural responses, whereas neural simulations were only run once for amplitude scaling in the second step. This significantly reduced computational cost compared to iterative methods using large populations of candidate solutions and more importantly reduced the sensitivity to the choice of neural model. The reduced coil heating and power losses of the optimized pulses can enable rapid-rate monophasic TMS protocols.

Acute stimulation with symmetric biphasic pulses induces less ataxia compared to cathodic pulses in DBS for essential tremor

BackgroundSymmetric biphasic pulses have been shown to acutely increase the therapeutic window of ventralis intermedius deep brain stimulation (Vim-DBS) for essential tremor (ET) compared to cathodic pulses. Acute supratherapeutic stimulation can induce ataxic side effects in Vim-DBS. ObjectiveTo investigate the effect on tremor, ataxia and dysarthria of 3 h of biphasic stimulation in patients with DBS for ET. MethodsA randomized, doubled-blind, cross-over design was used to compare standard cathodic pulses with symmetric biphasic pulses (anode-first) during a 3-h period per pulse shape. During each 3-h period, all stimulation parameters were identical, except for the pulse shape. Tremor (Fahn-Tolosa-Marin Tremor Rating Scale), ataxia (International Cooperative Ataxia Rating Scale) and speech (acoustic and perceptual measures) were assessed hourly during the 3-h periods. ResultsTwelve ET patients were included. During the 3-h stimulation period, tremor control was equivalent between the two pulse shapes. Biphasic pulses elicited significantly less ataxia than cathodic pulses (p = 0.006). Diadochokinesis rate of speech was better for the biphasic pulse (p = 0.048), but other measures for dysarthria were not significantly different between the pulses. ConclusionSymmetric biphasic pulses induce less ataxia than conventional pulses after 3 h of stimulation DBS in ET patients.

PO-04-071 PULSE FIELD ABLATION AND LESION FORMATION USING A UNIQUE INTEGRATED MULTIELECTRODE FOCAL, LINEAR, AND LOOP ABLATION CATHETER

Pulse field ablation (PFA) is a promising energy modality for cardiac ablation due to its speed, tissue selectivity, and potential ability to create consistent transmural lesions Evaluate PFA lesions created using an innovative catheter design combining focal, linear and pulmonary vein (PV) ablation PEF ablation was performed using an 8F bidirectional linear catheter with a 2mm tip and 4 ring electrodes through which a 3.5F loop catheter (6 to 9 rings, 3mm length on 19mm diameter) can be inserted and deployed beyond the tip (Figure, A). In 8 swine, R-wave gated biphasic pulse trains of voltage between 600 and 700V were delivered sequentially and simultaneously to the loop or linear catheter electrode pairs. The linear catheter is compatible with any commercially available 8.5F transseptal sheath. Porcine intracardiac tissue was ablated in vivo targeting the superior vena cava (SVC), right atrium (RA), RA appendage (RAA), cavotricuspid isthmus, left atrium, PVs, and right ventricle. Electrogram (EGM) amplitudes/morphology and pre- and post-ablation pacing thresholds were assessed. Triphenyl tetrazolium chloride (infused 20 minutes before euthanasia) or tetrazolium blue stain was used to demarcate and measure the lesions. Histopathologic analysis of all cardiac tissues was performed, esophageal pre and post ablation phrenic nerve stimulation were done. EGM attenuation and pacing thresholds increase were documented (see Table). Focal: PFA was delivered from the distal electrode pair of the linear catheter. Lesion measured 10.3±2.6 mm diameter, 3.15±1.56 mm depth (Figure, B). Linear: PFA was delivered to 5 electrodes of the linear catheter (Figure, C). Lesion dimension range: width: 4 - 20mm, length: 12 to 20mm. Loop: PFA was delivered sequentially via loop catheter electrode pairs to PVs resulting in transmural lesions with 2.02 ± 0.94mm depth measured at the thickest area of affected myocardium (Figure, D). Simultaneous biphasic PEF was delivered by loop electrode pairs to the RAA and SVC, resulting in transmural lesions. RAA lesion measured 132mm2 surface area with average EGM attenuation 87% ± 2% and pacing thresholds increased post ablation (p=0.00), 4.0 ± 2.1 mA pre, 18.5 ± 4.2 mA post (Figure, E) No esophageal or phrenic injuries were documented. The combined linear, focal, and circular PFA ablation device demonstrated acute lesion success and each configuration has the potential to create effective transmural lesions in the atrium.Tabled 1TableEGM % Reduction*Pacing Threshold (mA)*Lesion DimensionsFocal lesion in atrial tissue88% ± 3.8% (N=7)Pre-ablation: 2.23 ± 1.83 mAPost-ablation: 19.3 ± 2.23 mA (N=9)Diameter: 10.3 ± 2.6 mm (N=15)Surface area: 87.6 ± 41.8 mm2 (N=15)Depth: 3.15 ± 1.56 mm (N=11)**10/11 lesions transmural (1 lesion was not assessed).Linear lesions in RA and LA95% ± 5% (N=7)Pre-ablation: 2.02 ± 1.78 mAPost-ablation: 15.1 ± 5.92 mA (N=29)Width: 8.86 ± 4.93 mm (N=9)Length: 17.17 ± 3.71 mm (N=9)Surface area: 156 ± 103 mm2 (N=9)Loop lesions in SVC and PV88% ± 5% (N=53)Pre-ablation: 3.5 ± 2.8 mAPost-ablation: 18.3 ± 3.2 mA (N=80)Transmural lesions,Depth: 2.02 ± 0.94mm (N=10) Open table in a new tab

Development of a flexible embedded neurostimulator for animal robots

The neural stimulator is a core component of animal robots. While the control effect of animal robots is influenced by various factors, the performance of the neural stimulator plays a decisive role in regulating animal robots. In order to optimize animal robots, embedded neural stimulators had been developed using flexible printed circuit board technology. This innovation not only enabled the stimulator to generate parameter-adjustable biphasic current pulses through control signals, but also optimized its carrying mode, material, and size, overcoming the disadvantages of traditional backpack or head-inserted stimulators, which have poor concealment and are prone to infection. Static, in vitro, and in vivo performance tests of the stimulator demonstrated that it not only had precise pulse waveform output capability, but also was lightweight and small in size. It had excellent in vivo performance in both laboratory and outdoor environments. Our study has high practical significance for the application of animal robots.

Absence of Arrhythmogenicity with Biphasic Pulsed Electric Fields Delivered to Porcine Airways.

Pulsed electric field (PEF) technologies treat many types of tissue. Many systems mandate synchronization to the cardiac cycle to avoid the induction of cardiac arrhythmias. Significant differences between PEF systems make the assessment of cardiac safety from one technology to another challenging. A growing body of evidence suggests that shorter duration biphasic pulses obviate the need for cardiac synchronization, even when delivered in a monopolar fashion. This study theoretically evaluates the risk profile of different PEF parameters. It then tests a monopolar, biphasic, microsecond-scale PEF technology for arrhythmogenic potential. PEF applications of increasing likelihood to induce an arrhythmia were delivered. The energy was delivered throughout the cardiac cycle, including both single and multiple packets, and then with concentrated delivery on the t-wave. There were no sustained changes to the electrocardiogram waveform or to the cardiac rhythm, despite delivering energy during the most vulnerable phase of the cardiac cycle, and delivery of multiple packets of PEF energy across the cardiac cycle. Only isolated premature-atrial contractions (PAC) were observed. This study provides evidence that certain varieties of biphasic, monopolar PEF delivery do not require synchronized energy delivery to prevent harmful arrhythmias.

Intra-cochlear differences in the spread of excitation between biphasic and triphasic pulse stimulation in cochlear implants: A modeling and experimental study

Triphasic pulse stimulation can prevent unpleasant facial nerve stimulation in cochlear implant users. Using electromyographic measurements on facial nerve effector muscles, previous studies have shown that biphasic and triphasic pulse stimulations produce different input-output functions. However, little is known about the intracochlear effects of triphasic stimulation and how these may contribute to the amelioration of facial nerve stimulation.The present study used a computational model of implanted human cochleae to investigate the effect of pulse shape on the intracochlear spread of excitation. Biphasic and triphasic pulse stimulations were simulated from three different cochlear implant electrode contact positions. To validate the model results, experimental spread of excitation measurements were conducted with biphasic and triphasic pulse stimulation from three different electrode contact positions in 13 cochlear implant users.The model results depict differences between biphasic and triphasic pulse stimulations depending on the position of the stimulating electrode contact. While biphasic and triphasic pulse stimulations from a medial or basal electrode contact caused similar extents of neural excitation, differences between the pulse shapes were observed when the stimulating contact was located in the cochlear apex. In contrast, the experimental results showed no difference between the biphasic and triphasic initiated spread of excitation for any of the tested contact positions. The model was also used to study responses of neurons without peripheral processes to mimic the effect of neural degeneration. For all three contact positions, simulated degeneration shifted the neural responses towards the apex. Biphasic pulse stimulation showed a stronger response with neural degeneration compared to without degeneration, while triphasic pulse stimulation showed no difference.As previous measurements have demonstrated an ameliorative effect of triphasic pulse stimulation on facial nerve stimulation from medial electrode contact positions, the results imply that a complementary effect located at the facial nerve level must be responsible for reducing facial nerve stimulation.

Immediate effects and duration of a short and single application of transcutaneous auricular vagus nerve stimulation on P300 event related potential.

Transcutaneous auricular vagus nerve stimulation (taVNS) is a neuromodulatory technique that stimulates the auricular branch of the vagus nerve. The modulation of the locus coeruleus-norepinephrine (LC-NE) network is one of the potential working mechanisms of this method. Our aims were 1-to investigate if short and single applications of taVNS can modulate the P300 cognitive event-related potential (ERP) as an indirect marker that reflects NE brain activation under control of the LC, and 2-to evaluate the duration of these changes. 20 healthy volunteers executed an auditory oddball paradigm to obtain P300 and reaction time (RT) values. Then a 7 min active or sham taVNS period was initiated and simultaneously a new P300 paradigm was performed. We successively repeated the paradigm on 4 occasions with different time intervals up to 56 min after the stimulation onset. During active taVNS an immediate and significant effect of increasing the amplitude and reducing the latency of P300, as well as a shortening in the RT was observed. This effect was prolonged in time up to 28 min. The values then returned to pre-stimulation levels. Sham stimulation did not generate changes. Our results, demonstrate differential facilitating effects in a concrete time window after taVNS. Literature about the modulatory effect of taVNS over P300 ERP shows a wide spread of results. There is not a standardized system for taVNS and currently the great heterogeneity of stimulation approaches concerning targets and parameters, make it difficult to obtain conclusions about this relationship. Our study was designed optimizing several stimulation settings, such as a customized earbud stimulator, enlarged stimulating surface, simultaneous stimulation over the cymba and cavum conchae, a Delayed Biphasic Pulse Burst and current controlled stimulation that adjusted the output voltage and guaranteed the administration of a preset electrical dose. Under our stimulation conditions, targeting vagal nerve fibers via taVNS modulates the P300 in healthy participants. The optimal settings of modulatory function of taVNS on P300, and their interdependency is insufficiently studied in the literature, but our data provides several easily optimizable parameters, that will produce more robust results in future.