Tripolar Electrode Research Articles

Estimating health of the implanted cochlea using psychophysical strength-duration functions and electrode configuration

It is generally believed that the efficacy of cochlear implants is partly dependent on the condition of the stimulated neural population. Cochlear pathology is likely to affect the manner in which neurons respond to electrical stimulation, potentially resulting in differences in perception of electrical stimuli across cochlear implant recipients and across the electrode array in individual cochlear implant users. Several psychophysical and electrophysiological measures have been shown to predict cochlear health in animals and were used to assess conditions near individual stimulation sites in humans. In this study, we examined the relationship between psychophysical strength-duration functions and spiral ganglion neuron density in two groups of guinea pigs with cochlear implants who had minimally-overlapping cochlear health profiles. One group was implanted in a hearing ear (N = 10) and the other group was deafened by cochlear perfusion of neomycin, inoculated with an adeno-associated viral vector with an Ntf3-gene insert (AAV.Ntf3) and implanted (N = 14). Psychophysically measured strength-duration functions for both monopolar and tripolar electrode configurations were then compared for the two treatment groups. Results were also compared to their histological outcomes. Overall, there were considerable differences between the two treatment groups in terms of their psychophysical performance as well as the relation between their functional performance and histological data. Animals in the neomycin-deafened, neurotrophin-treated, and implanted group (NNI) exhibited steeper strength-duration function slopes; slopes were positively correlated with SGN density (steeper slopes in animals that had higher SGN densities). In comparison, the implanted hearing (IH) group had shallower slopes and there was no relation between slopes and spiral ganglion density. Across all animals, slopes were negatively correlated with ensemble spontaneous activity levels (shallower slopes with higher ensemble spontaneous activity levels). We hypothesize that differences in strength-duration function slopes between the two treatment groups were related to the condition of the inner hair cells, which generate spontaneous activity that could affect the across-fiber synchrony and/or the size of the population of neural elements responding to electrical stimulation. In addition, it is likely that spiral ganglion neuron peripheral processes were present in the IH group, which could affect membrane properties of the stimulated neurons. Results suggest that the two treatment groups exhibited distinct patterns of variation in conditions near the stimulating electrodes that altered detection thresholds. Overall, the results of this study suggest a complex relationship between psychophysical detection thresholds for cochlear implant stimulation and nerve survival in the implanted cochlea. This relationship seems to depend on the characteristics of the electrical stimulus, the electrode configuration, and other biological features of the implanted cochlea such as the condition of the inner hair cells and the peripheral processes.

Acute treatment with dexketoprofen reduces penicillin induced epileptiform activity in wistar albino rats (dexketoprofen in penicillin induced seizure model)

AimDexketoprofen trometamol is one of the most commonly used anti-inflammatory analgesic agents for pain control. This study aims to investigate the effect of dexketoprofen on penicillin-induced epileptiform activity in rats. MethodIn this study, 28 male Wistar rats weighing 220–240 g were used. Tripolar electrodes were implanted under urethane anesthesia. Epileptiform activity was induced by micro-injection of 500 units (IU) penicillin into the rats’ left somatomotor cortex. Dexketoprofen (5, 25, and 50 mg/kg) was administrated intraperitoneally after 30 min of penicillin injection. Epileptiform activity was evaluated by electrocorticography (ECoG). ResultsThe low dose of dexketoprofen administration (5 mg/kg) reduced the mean spike frequency of epileptiform activity 60 min after its injection. However, 25 and 50 mg/kg dexketoprofen significantly reduced the mean spike frequency 30 min after the dexketoprofen injection compared to the control group (p < 0.05). The amplitudes of epileptiform discharges in all groups were unaffected (p > 0.05). ConclusionThis study revealed that dexketoprofen had a significant anti-seizure effect when applied at 5 mg/kg, 25 mg/kg, and 50 mg/kg (especially at 25 and 50 mg/kg), in the penicillin-induced seizure model. The obtained data revealed that dexketoprofen might play an essential role against epileptic seizures.

Pudendal Nerve Block by Low-Frequency (≤1 kHz) Biphasic Electrical Stimulation

To test the hypothesis that poststimulation block of nerve conduction can be achieved by low-frequency (≤1kHz) biphasic stimulation (LFBS). A tripolar cuff electrode was placed around the pudendal nerve in cats to deliver LFBS (1kHz, 500Hz, and 100Hz). Two bipolar hook electrodes were placed central and distal to the cuff electrode to induce external urethral sphincter (EUS) contractions. A catheter was inserted into the urethra to record EUS contraction pressure. Pudendal nerve block by LFBS was confirmed by the failure of the central hook electrode stimulation to induce EUS contractions, while the distal hook electrode stimulation still induced contractions. Pudendal nerve conduction was completely blocked by LFBS at different frequencies (1kHz, 500Hz, and 100Hz) after terminating LFBS. The post-LFBS block induced at the minimal stimulation intensity and duration was fully reversible within the same time period (10-15 min on average) for the three frequencies. However, the stimulation duration to induce block significantly (p < 0.05) increased from 23 ± 8sec to 95 ± 14 sec when frequency increased from 100Hz to 1kHz. This study discovered that LFBS (≤1kHz), like high-frequency (≥5kHz) biphasic stimulation (HFBS), can induce poststimulation block. The result provides support for the theory that biphasic stimulation waveforms block axonal conduction by changing intracellular and extracellular ion concentrations. The post-LFBS block provides the opportunity to develop new neuromodulation devices for clinical applications where initial nerve firing is acceptable.

WS5.4. EMG Monitoring: Free-Run and Triggered

The recording of compound muscle action potentials (CMAPs) in response to spontaneous or electrically stimulation of the cranial, spinal, peripheral nerves or nerve root activation is known as intraoperative electromyography (EMG). EMG monitoring is widely used in surgeries when the aforementioned neural structures might be at risk. It allows early detection of surgery- related nerve injury so that proper intervention can be accordingly adopted; it also allows confirmation of the functional status of the nerve. The intraoperative monitoring team must thoroughly understand the nervous pathways that require monitoring and mapping in order to develop optimal stimulation and recording strategies for each surgical procedure. Intraoperative EMG testing includes triggered EMG (tEMG) for mapping and free-run EMG (fEMG) for monitoring purposes. Triggered EMG is used to identify the nerves and nerve root, to define a safe entry pathway to access the lesion, or to assess the functional integrity of the nerve so that the surgical plan can be modified accordingly. Clinical applications of tEMG also include confirmation of the placement of pedicle screws during spine surgery and guiding the sectioning of the lumbosacral rootlets during selective dorsal rhizotomy. The following three kinds of stimulation electrodes are available: monopolar, bipolor, and tripolar electrode. Each of the aforementioned electrodes are associated with certain strengths and weakness; thus, they can be used under different circumstances and meets most of our clinical needs. fEMG involves recording spontaneous or evoked muscle activity without interfering with the surgery. It is used as a monitoring tool to detect surgically driven mechanical irritation of the peripheral nerves and motor cranial nerves, hopefully before permanent damage occurs. It also can be applied to detect muscle activity evoked by mechanical irritation of the corticospinal tract and/or alpha motor neurons during brain tumor or intramedullary spinal cord tumor resection. There are three types of fEMG activity, referred to as the A, B and C train. Among them, the A train has been more associated with poor postoperative outcomes, although false-positive and false-negative findings do exist. Thus, the concomitant use of somatosensory and motor evoked potentials will certainly increase the sensitivity and specificity of fEMG.

A Comparison of Conventional and Tri-Polar EEG Electrodes for Decoding Real and Imaginary Finger Movements from One Hand.

The representations of different fingers in the sensorimotor cortex are largely overlapped, which necessitate a good signal-to-noise ratio (SNR) and high spatial resolution to classify individual finger movements from one hand. Electroencephalography (EEG) recorded with disc electrodes has low SNR and poor spatial resolution. The surface Laplacian has been applied to EEG to improve the spatial resolution and selectivity of the surface electrical activity recording. Tri-polar concentric ring electrodes (TCREs) were shown to estimate the Laplacian automatically with better spatial resolution than disc electrodes. For this work, movement-related potentials (MRPs) were recorded from four TCREs and disc electrodes while 13 subjects performed real and imaginary finger movements. The MRP signals recorded with the TCREs have significantly less mutual information and coherence between neighboring locations compared to disc electrodes. The results also show that signals from TCREs generated higher accuracy compared to disc electrodes. It further shows that TCREs using temporal EEG data as features yield an average accuracy of [Formula: see text]% and [Formula: see text]% for real and imaginary finger movements, respectively, which is significantly higher than utilizing EEG spectral power changes in [Formula: see text] and [Formula: see text] bands as features. Similarly, with the disc electrodes, it achieved highest accuracy of [Formula: see text]% and [Formula: see text]% for real and imaginary finger movements, respectively, with temporal EEG data feature.

In-vivo application of low frequency alternating currents on porcine cervical vagus nerve evokes reversible nerve conduction block

BackgroundThis paper describes a method to reversibly block nerve conduction through direct application of a 1 Hz sinusoidal current waveform delivered through a bipolar nerve cuff electrode. This low frequency alternating current (LFAC) waveform was previously shown to reversibly block the effects of vagal pulse stimulation evoked bradycardia in-vivo in the anaesthetised rat model (Mintch et al. 2019). The present work measured the effectiveness of LFAC block on larger caliber myelinated vagal afferent fibers in human sized nerve bundles projecting to changes in breathing rate mediated by the Hering-Breuer (HB) reflex in anaesthetized domestic swine (n=5).MethodsTwo bipolar cuff electrodes were implanted unilaterally to the left cervical vagus nerve, which was crushed caudal to the electrodes to eliminate cardiac effects. A tripolar recording cuff electrode was placed rostral to the bipolar stimulating electrodes on the same nerve to measure changes in the compound nerve action potentials (CNAP) elicited by the vagal pulse stimulation and conditioned by the LFAC waveform. Standard pulse stimulation was applied at a sufficient level to induce a reduction in breathing rate through the HB reflex. If unblocked, the HB reflex would cause breathing to slow down and potentially halt completely. Block was quantified by the ability of LFAC to reduce the effect of the HB reflex by monitoring the respiration rate during LFAC alone, LFAC and vagal stimulation, and vagal stimulation alone.ResultsLFAC achieved 87.2 ±8.8% block (n=5) at current levels of 1.1 ±0.3 mAp (current to peak), which was well within the water window of the working electrode. CNAP showed changes that directly correlated to the effectiveness of LFAC block, which manifested itself as the slowing and amplitude reduction of components of the CNAP.ConclusionThese novel findings suggest that LFAC is a potential alternative or complementary method to other electrical blocking techniques in clinical applications.

Platinum dissolution and tissue response following long-term electrical stimulation at high charge densities

Objective. Established guidelines for safe levels of electrical stimulation for neural prostheses are based on a limited range of the stimulus parameters used clinically. Recent studies have reported particulate platinum (Pt) associated with long-term clinical use of these devices, highlighting the need for more carefully defined safety limits. We previously reported no adverse effects of Pt corrosion products in the cochleae of guinea pigs following 4 weeks of electrical stimulation using charge densities far greater than the published safe limits for cochlear implants. The present study examines the histopathological effects of Pt within the cochlea following continuous stimulation at a charge density well above the defined safe limits for periods up to 6 months. Approach. Six cats were bilaterally implanted with Pt electrode arrays and unilaterally stimulated using charge balanced current pulses at a charge density of 267 μC cm−2 phase−1 using a tripolar electrode configuration. Electrochemical measurements were made throughout the implant duration and evoked potentials recorded at the outset and on completion of the stimulation program. Cochleae were examined histologically for particulate Pt, tissue response, and auditory nerve survival; electrodes were examined for surface corrosion; and cochlea, brain, kidney, and liver tissue analysed for trace levels of Pt. Main results. Chronic stimulation resulted in both a significant increase in tissue response and particulate Pt within the tissue capsule surrounding the electrode array compared with implanted, unstimulated control cochleae. Importantly, there was no stimulus-induced loss of auditory neurons (ANs) or increase in evoked potential thresholds. Stimulated electrodes were significantly more corroded compared with unstimulated electrodes. Trace analysis revealed Pt in both stimulated and control cochleae although significantly greater levels were detected within stimulated cochleae. There was no evidence of Pt in brain or liver; however, trace levels of Pt were recorded in the kidneys of two animals. Finally, increased charge storage capacity and charge injection limit reflected the more extensive electrode corrosion associated with stimulated electrodes. Significance. Long-term electrical stimulation of Pt electrodes at a charge density well above existing safety limits and nearly an order of magnitude higher than levels used clinically, does not adversely affect the AN population or reduce neural function, despite a stimulus-induced tissue response and the accumulation of Pt corrosion product. The mechanism resulting in Pt within the unstimulated cochlea is unclear, while the level of Pt observed systemically following stimulation at these very high charge densities does not appear to be of clinical significance.

Poststimulation Block of Pudendal Nerve Conduction by High-Frequency (kHz) Biphasic Stimulation in Cats

To determine the relationship between various parameters of high-frequency biphasic stimulation (HFBS) and the recovery period of post-HFBS block of the pudendal nerve in cats. A tripolar cuff electrode was implanted on the pudendal nerve to deliver HFBS in ten cats. Two hook electrodes were placed central or distal to the cuff electrode to stimulate the pudendal nerve and induce contractions of external urethral sphincter (EUS). A catheter was inserted toward the distal urethra to slowly perfuse the urethra and record the back-up pressure generated by EUS contractions. After determining the block threshold (T), HFBS (6 or 10 kHz) of different durations (1, 5, 10, 20, 30 min) and intensities (1T or 2T) was used to produce the post-HFBS block. HFBS at 10 kHz and 1T intensity must be applied for at least 30 min to induce post-HFBS block. However, 10 kHz HFBS at a higher intensity (2T) elicited post-HFBS block after stimulation of only 10 min; and 10 kHz HFBS at 2T for 30 min induced a longer-lasting (1-3 h) post-HFBS block that fully recovered with time. HFBS of 5-min duration at 6 kHz produced a longer period (20.4 ± 2.1 min, p < 0.05, N = 5 cats) of post-HFBS block than HFBS at 10 kHz (9.5 ± 2.1 min). HFBS of longer duration, higher intensity, and lower frequency can produce longer-lasting reversible post-HFBS block. This study is important for developing new methods to block nerve conduction by HFBS.

Epileptogenesis-induced changes of hippocampal-piriform connectivity

ObjectiveTissue remodeling has been described in brain circuits that are involved in the generation and propagation of epileptic seizures. Human and animal studies suggest that the anterior piriform cortex (aPC) is crucial for seizure expression in focal epilepsies. Here, we investigate the effect of kainic-acid (KA)-induced seizures on the effective connectivity of the aPC with bilateral hippocampal CA3 regions using cerebro-cerebral evoked potentials (CCEPs). MethodsAdult male Sprague-Dawley rats were implanted with a tripolar electrode in the left aPC for stimulation and recording, and with unipolar recording electrodes in bilateral CA3 regions. Single pulse stimulations were given to the aPC and CCEPs were averaged before KA injections and after the emergence of spontaneous recurrent seizures (SRS). Similar recordings at equivalent time intervals were obtained from animals that received saline injections instead of KA (controls). ResultsIn the experimental group, the percentage change of increased amplitude of the contralateral (but not ipsilateral) CA3 CCEPs between pre-KA injection and after the emergence of SRS was significantly greater than in controls. No significant single-pulse-induced spectral change responses were observed in either epileptic or control rats when comparing pre- and post-stimulus time intervals. Also, we found no correlation between seizure frequency and the extent of amplitude changes in the CCEPs. ConclusionsIn the KA model, epileptogenesis results in plastic changes that manifest as an amplification of evoked potential amplitudes recorded in the contralateral hippocampus in response to single-pulse stimulation of the aPC. These results suggest epileptogenesis-induced facilitation of interhemispheric connectivity between the aPC and the hippocampus. Since the amplitude increase of the contralateral CCEP is a possible in vivo biomarker of epilepsy, any intervention (e.g. neuromodulatory) that can reverse this phenomenon may hold a potential antiepileptic efficacy.

Recording of spontaneous vagus nerve activity during Pentylenetetrazol-induced seizures in rats

BackgroundVagus nerve stimulation is a treatment for refractory epilepsy. The vagus nerve carries parasympathetic information and innervates multiple organs. As seizures are commonly associated with autonomic manifestations, we believe that biomarkers for diseases affecting autonomic functions such as epilepsy can be found in vagus nerve signals. New methodWe present a method to record vagus nerve electroneurogram (VENG) and detect in the VENG single unit activity in anesthetized rats during Pentylenetetrazol induced seizures using a true tripolar cuff electrode. ResultsThe VENG consisted of high amplitude bursts and lower amplitude bursts synchronous to respiration and heartbeat respectively. The average spikes exhibited a triphasic shape with duration below 1.5ms and root mean square amplitude varied between 5.5 +/- 0.2 μV and 11.4 +/- 3.1 μV depending on the type of recording. An increase of the contact distance resulted in a signal amplitude increase. Application of Lidocaine led to a total disappearance of the recorded spontaneous spiking of the nerve. Comparison with existing methodsTrue tripolar cuff electrodes exhibited a better performance in terms of artefact rejection, stability and reproducibility of the signal compared to commonly used hook electrodes which is of special interest in seizures where important motion and EMG artifacts are expected. ConclusionWe present a new method to record single unit activity of the vagus nerve during acute chemically induced seizures in rats and verified the neural origin of the recorded signals. This recording method might be a powerful tool to develop seizure biomarkers based on VENG.

Modeling and simulation of deep brain stimulation electrodes with various active contacts

Deep brain stimulation provides electrical stimulation to the target brain region through implant electrode. Some of the electrodes cannot produce desired field distribution for greater therapeutic efficacy because of their configuration. This paper aims at analyzing electric field distribution for electrodes with various combinations of active contacts to get an optimum electrode for greater therapeutic efficacy of the neurological patients. Various electrode configurations including monopolar, bipolar, tripolar, and quadripolar are simulated by COMSOL multiphysics (5.0 a). The potential distribution is calculated by using Laplace’s equation. The current density on the electrode contacts is determined by integrating the total amount of current delivered by the electrode. The simulation results confirm that tripolar electrode configuration provides highly concentrated electric field distribution and electrical current at the surface of the electrodes than the rest of the configurations. The tripolar electrode configuration can localize the current delivery into specific populations of neurons to avoid undesirable axon activation. Hence, it can be applied to obtain maximum therapeutic efficacy for particular neurological disorders.

Integration of tri-polar microelectrodes for performance enhancement of an impedance biosensor

This paper demonstrates the effect of microelectrodes configuration on the sensitivity and accuracy of the micro-electrical impedance spectroscopy (μEIS). Bi-polar and tri-polar microelectrodes configurations were presented, fabricated and experimentally used to extract the electrical parameters of Human Bone Osteosarcoma Epithelial (U2OS) viable and dead cells. A comparison between the experimental results are presented and discussed. These experimental results show that the tri-polar electrode configuration has higher sensitivity compared to bi-polar configuration.

Additive Inhibition of Reflex Bladder Activity Induced by Bilateral Pudendal Neuromodulation in Cats.

ObjectiveTo determine the inhibitory effect on bladder activity induced by bilateral pudendal neuromodulation.MethodsIn 10 cats under anesthesia, two tripolar cuff electrodes were implanted bilaterally on the pudendal nerves for stimulation. A double lumen catheter was inserted into the bladder through the urethra to infuse saline and measure bladder pressure. During repeated cystometrograms (CMGs) pudendal nerve stimulation (PNS: 5 Hz, 0.2 ms, 5–15 min) was applied unilaterally or bilaterally at 1- or 2-times intensity threshold (T) for inducing anal sphincter twitching. PNS inhibition was indicated by the increase in bladder capacity measured by CMGs.ResultsUnilateral PNS at 1T did not significantly increase bladder capacity, but at 2T significantly (p < 0.05) increased bladder capacity by about 30%. Bilateral PNS at 1T also failed to increase bladder capacity, but at 2T significantly (p < 0.05) increased bladder capacity by about 60%, indicating an additive effect induced by the bilateral 2T PNS. Unilateral 1T PNS did not enhance the inhibitory effect induced by contra-lateral 2T PNS.ConclusionThis study in anesthetized cats reveals that an additive inhibition of reflex bladder activity can be induced by bilateral pudendal neuromodulation, indicating that bilateral PNS might achieve better therapeutic efficacy in treating overactive bladder (OAB) than unilateral PNS.

Interaction of Sodium Valproate With Low-Frequency Electrical Stimulation During Kindlingn.

Introduction:The interaction between antiepileptic drugs and brain electrical stimulation is a potential therapy to control seizures in patients with pharmacoresistance to drugs. So, the present study aimed to design to determine the effect of a subeffective dose of sodium valproate combined with low-frequency electrical stimulation during kindling.Methods:One tripolar electrode was implanted stereotactically in the CA1 hippocampus of male Wistar rats. One week after surgery, the rats were kindled by electrical stimulation of hippocampus in a rapid manner (12 stimulations/day) for 6 days with sodium valproate alone or combined with low-frequency electrical stimulation (four packages contained 200 monophasic square wave pulses of 0.1-ms duration at 1 Hz, immediately after kindling stimulations). The duration of afterdischarge, maximum latency to stages 4 and 5, and the maximum duration of these stages were recorded by electromadule during kindling.Results:Application of sodium valproate with low-frequency electrical stimulation caused a reduction in cumulative afterdischarge duration. The maximum latency to the onset of stage 5 seizure increased after sodium valproate application alone, without having a significant effect on the fourth stage. Our findings showed reductions in the seizures duration and increasing in the latency times of both stages after the application of sodium valproate with low-frequency electrical stimulation.Conclusion:It seems that usage of sodium valproate with low-frequency electrical stimulation during kindling was more effective to suppress the epileptic activity than its administration alone and may have a critical role on the antiepileptic effects of sodium valproate.

Neural Signal Blocking Based on Spike Trapping Principle: Effect of Electrode and Pulse Parameters

Electrical stimulation of nerves to treat neurological disorders has been extensively studied. In this paper, a proactive blocking method, spike trapping, is introduced, which was previously referred to as the “antimissile strategy”. Acute experiments on sciatic nerve–gastrocnemius muscle preparations of bullfrogs were performed to explore the parameters of this blocking method, including the size, spacing, and placement of the electrodes, as well as the widths of the cathodic triangular pulses used to trap the evoked neural signals. The block threshold voltage decreased with increasing electrode spacing and for larger diameter when the tripolar platinum wire electrodes were placed longitudinally on the same side of the sciatic nerve. However, there was no statistically significant difference between the minimum pulse widths which requires achieving nerve block with different electrode spacing or size. Placing bipolar electrodes of asymmetrical shape and size on the opposite sides across the nerve, the block threshold and the minimum pulse width both decreased first and then increased as a function of increasing anode width. Whether the electrodes is placed longitudinally along the nerve with tripolar configuration or transversely across the nerve with bipolar configuration, the nerve conduction can be instantaneously blocked without undesired excitation using the spike trapping strategy.

The effect of vitamin D3 and paricalcitol on penicillin-induced epileptiform activity in rats

AimEpilepsy is a disease characterized by seizures which impair human life considerably. Vitamin D is of different systemic effects on metabolism and its deficiency is known to have a high prevalence among epilepsy patients. Paricalcitol, a vitamin D receptor agonist, has relatively fewer side effects. This study aimed to investigate the anticonvulsant effect of vitamin D3 (cholecalciferol) and paricalcitol on penicillin-induced epileptiform activity. Method21 male Wistar rat weighing 180−240 g were used. After anesthetized by 1.25 g/kg urethane intraperitoneally (i.p.), rats were placed in the stereotaxic frame and tripolar electrodes were placed on the skull. The single microinjection of penicillin (2.5 μl, 500 IU, i.c.) into left sensorimotor cortex induced epileptiform activity. A single dose of 60.000 IU/kg (i.p.) vitamin D3 was administered 14 days before intracortical penicillin (500 IU) injection. Paricalcitol (10 μg/kg, i.p.) was administered 30 min before intracortical penicillin (500 IU) administration and recorded for the following 180 min. ResultsVitamin D3 pretreatment and paricalcitol diminished the frequency of epileptiform activity (p < 0.001) without changing the amplitude (p > 0.05) compared to the penicillin-injected group. Vitamin D3 pretreatment and paricalcitol led to an important delay in the onset of penicillin-induced epileptiform activity (p < 0.001 and p < 0.05, respectively). Vitamin D3 increased the latency of penicillin-induced epileptic activity compared to paricalcitol group (p < 0.001). ConclusionResults indicate that vitamin D3 and paricalcitol decreased the frequency and increased the latency of the penicillin-induced epileptic activity. Vitamin D3 was more effective than paricalcitol.

Low pressure voiding induced by a novel implantable pudendal nerve stimulator.

To validate the functionality of an implantable pudendal nerve stimulator under development for Food and Drug Administration approval to restore bladder function after spinal cord injury. In nine cats under anesthesia, two tripolar cuff electrodes were implanted bilaterally on the pudendal nerves and one bipolar cuff electrode was implanted on the right pudendal nerve central to the tripolar cuff electrode. The pudendal nerve stimulator was implanted subcutaneously on the left lower back along the lumbosacral spine and connected to the cuff electrodes. In five cats, a double lumen catheter was inserted into the bladder through the urethra to infuse saline and measure bladder pressure and another catheter was inserted into the distal urethra to perfuse and measure the back pressure caused by urethral contraction. In four cats, a bladder catheter was inserted into the bladder dome and the urethra was left open so that voiding could occur without urethral outlet obstruction. The implantable pudendal nerve stimulator was controlled wirelessly and successfully provided the required stimulation waveforms to different cuff electrodes. Pudendal nerve stimulation (PNS) at 5 Hz increased bladder capacity to about 200% of control capacity. PNS at 20 to 30 Hz induced large (80-100 cmH2 O) bladder contractions under isovolumetric conditions. When combined with ipsilateral or bilateral pudendal nerve block induced by 6 to 10 kHz stimulation, PNS at 20 to 30 Hz elicited low pressure (<40 cmH 2 O) efficient (70%) voiding. The implantable stimulator generated the required stimulation waveforms and successfully induced low pressure efficient voiding in anesthetized cats.

Stimulation Pattern Efficiency in Percutaneous Auricular Vagus Nerve Stimulation: Experimental Versus Numerical Data.

Percutaneous electrical stimulation of the auricular vagus nerve (pVNS) is an electroceutical technology. The selection of stimulation patterns is empirical, which may lead to under-stimulation or over-stimulation. The objective is to assess the efficiency of different stimulation patterns with respect to individual perception and to compare it with numerical data based on in-silico ear models. Monophasic (MS), biphasic (BS) and triphasic stimulation (TS) patterns were tested in volunteers. Different clinically-relevant perception levels were assessed. In-silico models of the human ear were created with embedded fibers and vessels to assess different excitation levels. TS indicates experimental superiority over BS which is superior to MS while reaching different perception levels. TS requires about 57% and 35% of BS and MS magnitude, respectively, to reach the comfortable perception. Experimental thresholds decrease from non-bursted to bursted stimulation. Numerical results indicate a slight superiority of BS and TS over MS while reaching different excitation levels, whereas the burst length has no influence. TS yields the highest number of asynchronous action impulses per stimulation symbol for the used tripolar electrode set-up. The comparison of experimental and numerical data favors the novel TS pattern. The analysis separates excitatory pVNS effects in the auricular periphery, as accounted by in-silico data, from the combination of peripheral and central pVNS effects in the brain, as accounted by experimental data. The proposed approach moves from an empirical selection of stimulation patterns towards efficient and optimized pVNS settings.

Spontaneous epileptiform activity in a rat model of bilateral subcortical band heterotopia.

SummaryObjectiveMalformations of cortical development are common causes of intellectual disability and epilepsy, yet there is a crucial lack of relevant preclinical models associating seizures and cortical malformations. Here, we describe a novel rat model with bilateral subcortical band heterotopia (SBH) and examine whether this model develops spontaneous epileptic seizures.MethodsTo generate bilateral SBH in rats, we combined RNAi‐mediated knockdown of Dcx and in utero electroporation with a tripolar electrode configuration enabling simultaneous transfection of the two brain hemispheres. To determine whether bilateral SBH leads to epileptiform activity, rats of various ages were implanted for telemetric electrocorticographic recordings and histopathological examination was carried out at the end of the recording sessions.ResultsBy 2 months, rats with bilateral SBH showed nonconvulsive spontaneous seizures consisting of spike‐and‐wave discharges (SWDs) with dominant frequencies in the alpha and theta bands and secondarily in higher‐frequency bands. SWDs occurred during both the dark and the light period, but were more frequent during quiet awake state than during sleep. Also, SWDs were more frequent and lasted longer at older ages. No sex differences were found. Although frequencies and durations of SWDs were found to be uncorrelated with the size of SBH, SWDs were initiated in some occasions from brain hemispheres comprising a larger SBH. Lastly, SWDs exhibited absence‐like pharmacological properties, being temporarily alleviated by ethosuximide administration.SignificanceThis novel model of bilateral SBH with spontaneous epilepsy may potentially provide valuable new insights into causality between cortical malformations and seizures, and help translational research aiming at designing novel treatment strategies for epilepsy.

The effect of duloxetine on penicillin-induced epileptiform activity in rats

ABSTRACTAim: Previous studies showed the existence of a relationship between epilepsy and depression. Duloxetine is a potent and selective inhibitor of serotonin and norepinephrine reuptake (SNRI) used in the treatment of the major depressive disorder. The aim of the present study was to investigate the effect of duloxetine on penicillin-induced epileptiform activity in an experimental rat model of acute partial epilepsy.Method: In this study, 35 male rats weighing 200–240 g were used. Under urethane anesthesia, tripolar electrodes were placed for electrocorticography (ECoG) recording. Duloxetine, at 1, 5, 10 or 30 mg/kg rates, was administered intraperitoneally 30 minutes after intracortical penicillin (500 IU) injection.Results: Duloxetine administrations of 1, 5, 10 and 30 mg/kg increased the mean frequency of epileptiform activity 10 minutes after Duloxetine injection compared to the control group (p < 0.05) without changing amplitude in all groups (p > 0.05).Conclusion: The results showed proconvulsant effect of duloxetine in penicillin-induced epileptiform activity and indicated that it could pose complications risk for people with partial epilepsy.