First-In-Human Demonstration of High Frequency Electrical Motor Nerve Block: Case Report.

ABSTRACT: This feasibility study tested the capability of high frequency stimulation (HFS) to block muscle contractions elicited by electrical stimulation of the same nerve proximally. During a tendon lengthening surgery in the forearm, the anterior interosseous nerve (AIN) was exposed. A specialized nerve cuff electrode was placed around the nerve, and a stimulating probe held on the nerve 1 cm proximal to the cuff electrode delivered pulses of current causing the pronator quadratus muscle to contract. Through the cuff electrode, 20 kHz HFS was delivered to the nerve for 10 seconds during proximal stimulation. HFS amplitudes between 5 and 10 mA peak-to-peak were tested to determine which produced complete and partial block of the electrically induced contractions. The minimum HFS amplitude that produced complete block was 8 mA, with lower amplitudes producing partial block. In all trials, muscle contractions resumed immediately after HFS was turned off. This demonstration of high frequency electrical nerve block is a milestone in the road to clinical implementation of HFS mediated motor block for spasticity.

Effects on heart rate from direct current block of the stimulated rat vagus nerve.

Objective.Although electrical vagus nerve stimulation has been shown to augment parasympathetic control of the heart, the effects of electrical conduction block have been less rigorously characterized. Previous experiments have demonstrated that direct current (DC) nerve block can be applied safely and effectively in the autonomic system, but additional information about the system dynamics need to be characterized to successfully deploy DC nerve block to clinical practice.Approach.The dynamics of the heart rate (HR) from DC nerve block of the vagus nerve were measured by stimulating the vagus nerve to lower the HR, and then applying DC block to restore normal rate. DC block achieved rapid, complete block, as well as partial block at lower amplitudes.Main Results. Complete block was also achieved using lower amplitudes, but with a slower induction time. The time for DC to induce complete block was significantly predicted by the amplitude; specifically, the amplitude expressed as a percentage of the current required for a rapid, 60 s induction time. Recovery times after the cessation of DC block could occur both instantly, and after a significant delay. Both blocking duration and injected charge were significant in predicting the delay in recovery to normal conduction.Significance. While these data show that broad features such as induction and recovery can be described well by the DC parameters, more precise features of the HR, such as the exact path of the induction and recoveries, are still undefined. These findings show promise for control of the cardiac autonomic nervous system, with potential to expand to the sympathetic inputs as well.

Effects of waveform shape and electrode material on KiloHertz frequency alternating current block of mammalian peripheral nerve.

OBJECTIVES: KiloHertz frequency alternating current waveforms produce conduction block in peripheral nerves. It is not clearly known how the waveform shape affects block outcomes, and if waveform effects are frequency dependent. We determined the effects of waveform shape using two types of electrodes. MATERIALS AND METHODS: Acute in-vivo experiments were performed on 12 rats. Bipolar electrodes were used to electrically block motor nerve impulses in the sciatic nerve, as measured using force output from the gastrocnemius muscle. Three blocking waveforms were delivered (sinusoidal, square and triangular) at 6 frequencies (10-60 kHz). Bare platinum electrodes were compared with carbon black coated electrodes. We determined the minimum amplitude that could completely block motor nerve conduction (block threshold), and measured properties of the onset response, which is a transient period of nerve activation at the start of block. In-vivo results were compared with computational modeling conducted using the NEURON simulation environment using a nerve membrane model modified for stimulation in the kilohertz frequency range. RESULTS: For the majority of parameters, in-vivo testing and simulations showed similar results: Block thresholds increased linearly with frequency for all three waveforms. Block thresholds were significantly different between waveforms; lowest for the square waveform and highest for triangular waveform. When converted to charge per cycle, square waveforms required the maximum charge per phase, and triangular waveforms the least. Onset parameters were affected by blocking frequency but not by waveform shape. Electrode comparisons were performed only in-vivo. Electrodes with carbon black coatings gave significantly lower block thresholds and reduced onset responses across all blocking frequencies. For 10 and 20 kHz, carbon black coating significantly reduced the charge required for nerve block. CONCLUSIONS: We conclude that both sinusoidal and square waveforms at frequencies of 20 kHz or higher would be optimal. Future investigation of carbon black or other high charge capacity electrodes may be useful in achieving block with lower BTs and onsets. These findings will be of importance for designing clinical nerve block systems.

Evaluation of Activated Carbon and Platinum Black as High-Capacitance Materials for Platinum Electrodes.

The application of direct current (DC) produces a rapid and reversible nerve conduction block. However, prolonged injection of charge through a smooth platinum electrode has been found to cause damage to nervous tissue. This damage can be mitigated by incorporating high-capacitance materials (HCM) (e.g., activated carbon or platinum black) into electrode designs. HCMs increase the storage charge capacity (i.e., "Q value") of capacitive devices. However, consecutive use of these HCM electrodes degrades their surface. This paper evaluates activated carbon and platinum black (PtB) electrode designs in vitro to determine the design parameters which improve surface stability of the HCMs. Electrode designs with activated carbon and PtB concentrations were stressed using soak, bend and vibration testing to simulate destructive in vivo environments. A Q value decrease represented the decreased stability of the electrode-HCM interface. Soak test results supported the long-term Q value stabilization (mean = 44.3 days) of HCM electrodes, and both HCMs displayed unique Q value changes in response to soaking. HCM material choices, Carbon Ink volume, and application of Nafion™ affected an electrode's ability to resist Q value degradation. These results will contribute to future developments of HCM electrodes designed for extended DC application for in vivo nerve conduction block.

Scalable and reversible axonal neuromodulation of the sympathetic chain for cardiac control.

Maladaptation of the sympathetic nervous system contributes to the progression of cardiovascular disease and risk for sudden cardiac death, the leading cause of mortality worldwide. Axonal modulation therapy (AMT) directed at the paravertebral chain blocks sympathetic efferent outflow to the heart and maybe a promising strategy to mitigate excess disease-associated sympathoexcitation. The present work evaluates AMT, directed at the sympathetic chain, in blocking sympathoexcitation using a porcine model. In anesthetized porcine (n = 14), we applied AMT to the right T1-T2 paravertebral chain and performed electrical stimulation of the distal portion of the right sympathetic chain (RSS). RSS-evoked changes in heart rate, contractility, ventricular activation recovery interval (ARI), and norepinephrine release were examined with and without kilohertz frequency alternating current block (KHFAC). To evaluate efficacy of AMT in the setting of sympathectomy, evaluations were performed in the intact state and repeated after left and bilateral sympathectomy. We found strong correlations between AMT intensity and block of sympathetic stimulation-evoked changes in cardiac electrical and mechanical indices (r = 0.83-0.96, effect size d = 1.9-5.7), as well as evidence of sustainability and memory. AMT significantly reduced RSS-evoked left ventricular interstitial norepinephrine release, as well as coronary sinus norepinephrine levels. Moreover, AMT remained efficacious following removal of the left sympathetic chain, with similar mitigation of evoked cardiac changes and reduction of catecholamine release. With growth of neuromodulation, an on-demand or reactionary system for reversible AMT may have therapeutic potential for cardiovascular disease-associated sympathoexcitation.NEW & NOTEWORTHY Autonomic imbalance and excess sympathetic activity have been implicated in the pathogenesis of cardiovascular disease and are targets for existing medical therapy. Neuromodulation may allow for control of sympathetic projections to the heart in an on-demand and reversible manner. This study provides proof-of-concept evidence that axonal modulation therapy (AMT) blocks sympathoexcitation by defining scalability, sustainability, and memory properties of AMT. Moreover, AMT directly reduces release of myocardial norepinephrine, a mediator of arrhythmias and heart failure.

Fuzzy Logic Control of Heartrate by Electrical Block of Vagus Nerve.

Although vagus nerve stimulation (VNS) can be used to reduce heartrate by enhancing parasympathetic activity, a fully controllable intervention would also require a method for downregulating parasympathetic activity. A direct current (DC) block can be applied to a nerve to block its action potential conduction. This nerve block can be used to downregulate parasympathetic activity by blocking afferent reflexes. The damaging effects of reactions that occur at the electrode-nerve interface using conventional platinum electrodes can be avoided by separating the electrode from the nerve. Using a biocompatible, ionically conducting medium, the electrode and the damaging reactions can be isolated in a vessel away from the nerve. This type of electrode has been called the Separated Interface Nerve Electrode (SINE). Fuzzy logic control (FLC) is a controller approach that is well suited to physiological systems. The SINE, controlled by an FLC, was utilized to block a stimulated vagus nerve and regulate heart rate. The FLC was able to maintain the heartrate at a pre-determined setpoint while still achieving instant recovery when the block was removed.

Combining direct current and kilohertz frequency alternating current to mitigate onset activity during electrical nerve block.

Objective.Electrical nerve block offers the ability to immediately and reversibly block peripheral nerve conduction and would have applications in the emerging field of bioelectronics. Two modalities of electrical nerve block have been investigated-kilohertz frequency alternating current (KHFAC) and direct current (DC). KHFAC can be safely delivered with conventional electrodes, but has the disadvantage of having an onset response, which is a period of increased neural activation before block is established and currently limits clinical translation. DC has long been known to block neural conduction without an onset response but creates damaging reactive species. Typical electrodes can safely deliver DC for less than one second, but advances in high capacitance electrodes allow DC delivery up to 10 s without damage. The present work aimed to combine DC and KHFAC into a single waveform, named the combined reduced onset waveform (CROW), which can initiate block without an onset response while also maintaining safe block for long durations. This waveform consists of a short, DC pre-pulse before initiating KHFAC.Approach.Simulations of this novel waveform were carried out in the axonal simulation environment NEURON to test feasibility and gain insight into the mechanisms of action. Two sets of acute experiments were then conducted in adult Sprague-Dawley rats to determine the effectiveness of the waveform in mitigating the onset response.Main results.The CROW reduced the onset response bothin silicoandin vivo. The onset area was reduced by over 90% with the tested parameters in the acute experiments. The amplitude of the DC pulse was shown to be particularly important for effective onset mitigation, requiring amplitudes 6-8 times the DC block threshold.Significance.This waveform can reliably reduce the onset response due to KHFAC and could allow for wider clinical implementation of electrical nerve block.

A Carbon Slurry Separated Interface Nerve Electrode for Electrical Block of Nerve Conduction.

Direct current (DC) nerve block has been shown to provide a complete block of nerve conduction without unwanted neural firing. Previous work shows that high capacitance electrodes can be used to safely deliver a DC block. Another way of delivering DC safely is through a separated interface nerve electrode (SINE), such that any reactive species that are generated by the passage of DC are contained in a vessel away from the nerve. This design has been enhanced by using a high capacitance carbon "slurry" as the electrode in the external vessel to extend the capacity of the electrode (CSINE). With this new design, it was possible to provide 50 min of continuous nerve block without recharge while still maintaining complete recovery of neural signals. Up to 46 C of charge delivery was applied for a total of 4 h of nerve block with complete recovery. Because of the extended delivery time, it was possible to explore several properties of DC block that would not be revealed without the capability of a long-duration continuous block. It was possible to achieve complete block at lower values of DC if the block was applied for a longer period of time. Depending on the amount of charge applied during the block, the recovery was delayed for a period of time before complete force recovery was restored. These new properties provide novel techniques for device development to optimize charge delivery time and device powering concerns.

Measurement of block thresholds in kiloHertz frequency alternating current peripheral nerve block.

BACKGROUND: Kilohertz frequency alternating currents (KHFAC) produce rapid nerve conduction block of mammalian peripheral nerve and have potential clinical applications in reducing peripheral nerve hyperactivity. The experimental investigation of KHFAC nerve block requires a robust output measure and this has proven to be the block threshold (BT), the lowest current or voltage at which the axons of interest are completely blocked. All significant literature in KHFAC nerve block, both simulations and experimental, were reviewed to determine the block threshold method that was used. The two common methods used are the High-Low method experimentally and the Binary search method for simulations. NEW METHOD: Four methods to measure the block threshold (High-Low, High-Low-High, Binary and Random) at three frequencies (10, 20 and 30 kHz) were compared through randomized repeated experiments in the in-vivo rodent sciatic nerve-gastrocnemius model. RESULTS: The literature review showed that more than 50% of publications did not measure the block threshold. The experimental results showed no statistical difference in the BT value between the four methods. COMPARISON WITH EXISTING METHOD(S): However, there were differences in the number of significant onset responses, depending on the method. The run time for the BT determination was the shortest for the High-Low method. CONCLUSIONS: It is recommended that all research in electrical nerve block, including KHFAC, should include measurement of the BT. The High-Low method is recommended for most experimental situations but the Binary method could also be a viable option, especially where onset responses are minimal.

Reversible conduction block in peripheral nerve using electrical waveforms.

INTRODUCTION: Electrical nerve block uses electrical waveforms to block action potential propagation. MATERIALS & METHODS: Two key features that distinguish electrical nerve block from other nonelectrical means of nerve block: block occurs instantly, typically within 1 s; and block is fully and rapidly reversible (within seconds). RESULTS: Approaches for achieving electrical nerve block are reviewed, including kilohertz frequency alternating current and charge-balanced polarizing current. We conclude with a discussion of the future directions of electrical nerve block. CONCLUSION: Electrical nerve block is an emerging technique that has many significant advantages over other methods of nerve block. This field is still in its infancy, but a significant expansion in the clinical application of this technique is expected in the coming years.

Temporary persistence of conduction block after prolonged kilohertz frequency alternating current on rat sciatic nerve.

OBJECTIVE: Application of kilohertz frequency alternating current (KHFAC) waveforms can result in nerve conduction block that is induced in less than a second. Conduction recovers within seconds when KHFAC is applied for about 5-10 min. This study investigated the effect of repeated and prolonged application of KHFAC on rat sciatic nerve with bipolar platinum electrodes. APPROACH: Varying durations of KHFAC at signal amplitudes for conduction block with intervals of no stimulus were studied. Nerve conduction was monitored by recording peak Gastrocnemius muscle force utilizing stimulation electrodes proximal (PS) and distal (DS) to a blocking electrode. The PS signal traveled through the block zone on the nerve, while the DS went directly to the motor end-plate junction. The PS/DS force ratio provided a measure of conduction patency of the nerve in the block zone. MAIN RESULTS: Conduction recovery times were found to be significantly affected by the cumulative duration of KHFAC application. Peak stimulated muscle force returned to pre-block levels immediately after cessation of KHFAC delivery when it was applied for less than about 15 min. They fell significantly but recovered to near pre-block levels for cumulative stimulus of 50 ± 20 min, for the tested On/Off times and frequencies. Conduction recovered in two phases, an initial fast one (60-80% recovery), followed by a slower phase. No permanent conduction block was seen at the end of the observation period during any experiment. SIGNIFICANCE: This carry-over block effect may be exploited to provide continuous conduction block in peripheral nerves without continuous application of KHFAC.

Continuous Direct Current Nerve Block Using Multi Contact High Capacitance Electrodes.

Charge-balanced direct current (CBDC) nerve block can be used to block nerve conduction in peripheral nerves. Previous work demonstrated that the CBDC waveform could be used to achieve a 10% duty cycle of block to non-block repeatedly for at least two hours. We demonstrate that the duty cycle of this approach can be significantly increased by utilizing multiple electrode contacts and cycling the CBDC waveform between each contact in a "carousel" configuration. Using this approach, we demonstrated in an acute rat sciatic nerve preparation, that a 30% duty cycle complete block can be achieved with two contacts; and a 100% duty cycle block (>95% complete block) can be achieved with four contacts. This latter configuration utilized a 4-s block plateau, with 3 s between successive plateaus at each contact and a recharge phase amplitude that was 34% of the block amplitude. Further optimization of the carousel approach can be achieved to improve block effectiveness and minimize total electrode length. This approach may have significant clinical use in cases where a partial or complete block of peripheral nerve activity is required. In one example case, we achieved continuous block for 22 min without degradation of nerve conduction. Future study will be required to further optimize this technique and to demonstrate safety for chronic human use.

Characterization of high capacitance electrodes for the application of direct current electrical nerve block.

Direct current (DC) can briefly produce a reversible nerve conduction block in acute experiments. However, irreversible reactions at the electrode-tissue interface have prevented its use in both acute and chronic settings. A high capacitance material (platinum black) using a charge-balanced waveform was evaluated to determine whether brief DC block (13 s) could be achieved repeatedly (>100 cycles) without causing acute irreversible reduction in nerve conduction. Electrochemical techniques were used to characterize the electrodes to determine appropriate waveform parameters. In vivo experiments on DC motor conduction block of the rat sciatic nerve were performed to characterize the acute neural response to this novel nerve block system. Complete nerve motor conduction block of the rat sciatic nerve was possible in all experiments, with the block threshold ranging from -0.15 to -3.0 mA. DC pulses were applied for 100 cycles with no nerve conduction reduction in four of the six platinum black electrodes tested. However, two of the six electrodes exhibited irreversible conduction degradation despite charge delivery that was within the initial Q (capacitance) value of the electrode. Degradation of material properties occurred in all experiments, pointing to a possible cause of the reduction in nerve conduction in some platinum black experiments .

Combined KHFAC + DC nerve block without onset or reduced nerve conductivity after block.

OBJECTIVE: Kilohertz frequency alternating current (KHFAC) waveforms have been shown to provide peripheral nerve conductivity block in many acute and chronic animal models. KHFAC nerve block could be used to address multiple disorders caused by neural over-activity, including blocking pain and spasticity. However, one drawback of KHFAC block is a transient activation of nerve fibers during the initiation of the nerve block, called the onset response. The objective of this study is to evaluate the feasibility of using charge balanced direct current (CBDC) waveforms to temporarily block motor nerve conductivity distally to the KHFAC electrodes to mitigate the block onset-response. APPROACH: A total of eight animals were used in this study. A set of four animals were used to assess feasibility and reproducibility of a combined KHFAC + CBDC block. A following randomized study, conducted on a second set of four animals, compared the onset response resulting from KHFAC alone and combined KHFAC + CBDC waveforms. To quantify the onset, peak forces and the force-time integral were measured during KHFAC block initiation. Nerve conductivity was monitored throughout the study by comparing muscle twitch forces evoked by supra-maximal stimulation proximal and distal to the block electrodes. Each animal of the randomized study received at least 300 s (range: 318-1563 s) of cumulative dc to investigate the impact of combined KHFAC + CBDC on nerve viability. MAIN RESULTS: The peak onset force was reduced significantly from 20.73 N (range: 18.6-26.5 N) with KHFAC alone to 0.45 N (range: 0.2-0.7 N) with the combined CBDC and KHFAC block waveform (p < 0.001). The area under the force curve was reduced from 6.8 Ns (range: 3.5-21.9 Ns) to 0.54 Ns (range: 0.18-0.86 Ns) (p < 0.01). No change in nerve conductivity was observed after application of the combined KHFAC + CBDC block relative to KHFAC waveforms. SIGNIFICANCE: The distal application of CBDC can significantly reduce or even completely prevent the KHFAC onset response without a change in nerve conductivity.

Direct current contamination of kilohertz frequency alternating current waveforms.

Kilohertz frequency alternating current (KHFAC) waveforms are being evaluated in a variety of physiological settings because of their potential to modulate neural activity uniquely when compared to frequencies in the sub-kilohertz range. However, the use of waveforms in this frequency range presents some unique challenges regarding the generator output. In this study we explored the possibility of undesirable contamination of the KHFAC waveforms by direct current (DC). We evaluated current- and voltage-controlled KHFAC waveform generators in configurations that included a capacitive coupling between generator and electrode, a resistive coupling and combinations of capacitive with inductive coupling. Our results demonstrate that both voltage- and current-controlled signal generators can unintentionally add DC-contamination to a KHFAC signal, and that capacitive coupling is not always sufficient to eliminate this contamination. We furthermore demonstrated that high value inductors, placed in parallel with the electrode, can be effective in eliminating DC-contamination irrespective of the type of stimulator, reducing the DC contamination to less than 1 µA. This study highlights the importance of carefully designing the electronic setup used in KHFAC studies and suggests specific testing that should be performed and reported in all studies that assess the neural response to KHFAC waveforms.

Reversible nerve conduction block using kilohertz frequency alternating current.

OBJECTIVES: The features and clinical applications of balanced-charge kilohertz frequency alternating currents (KHFAC) are reviewed. Preclinical studies of KHFAC block have demonstrated that it can produce an extremely rapid and reversible block of nerve conduction. Recent systematic analysis and experimentation utilizing KHFAC block have resulted in a significant increase in interest in KHFAC block, both scientifically and clinically. MATERIALS AND METHODS: We review the history and characteristics of KHFAC block, the methods used to investigate this type of block, the experimental evaluation of block, and the electrical parameters and electrode designs needed to achieve successful block. We then analyze the existing clinical applications of high-frequency currents, comparing the early results with the known features of KHFAC block. RESULTS: Although many features of KHFAC block have been characterized, there is still much that is unknown regarding the response of neural structures to rapidly fluctuating electrical fields. The clinical reports to date do not provide sufficient information to properly evaluate the mechanisms that result in successful or unsuccessful treatment. CONCLUSIONS: KHFAC nerve block has significant potential as a means of controlling nerve activity for the purpose of treating disease. However, early clinical studies in the use of high-frequency currents for the treatment of pain have not been designed to elucidate mechanisms or allow direct comparisons to preclinical data. We strongly encourage the careful reporting of the parameters utilized in these clinical studies, as well as the development of outcome measures that could illuminate the mechanisms of this modality.

Alternating current and infrared produce an onset-free reversible nerve block.

Nerve block can eliminate spasms and chronic pain. Kilohertz frequency alternating current (KHFAC) produces a safe and reversible nerve block. However, KHFAC-induced nerve block is associated with an undesirable onset response. Optical inhibition using infrared (IR) laser light can produce nerve block without an onset response, but heats nerves. Combining KHFAC with IR inhibition [alternating current and infrared (ACIR)] produces a rapidly reversible nerve block without an onset response. ACIR can be used to rapidly and reversibly provide onset-free nerve block in the unmyelinated nerves of the marine mollusk Aplysia californica and may have significant advantages over either modality alone. ACIR may be of great clinical utility in the future.

Dynamics and sensitivity analysis of high-frequency conduction block.

The local delivery of extracellular high-frequency stimulation (HFS) has been shown to be a fast acting and quickly reversible method of blocking neural conduction and is currently being pursued for several clinical indications. However, the mechanism for this type of nerve block remains unclear. In this study, we investigate two hypotheses: (1) depolarizing currents promote conduction block via inactivation of sodium channels and (2) the gating dynamics of the fast sodium channel are the primary determinate of minimal blocking frequency. Hypothesis 1 was investigated using a combined modeling and experimental study to investigate the effect of depolarizing and hyperpolarizing currents on high-frequency block. The results of the modeling study show that both depolarizing and hyperpolarizing currents play an important role in conduction block and that the conductance to each of three ionic currents increases relative to resting values during HFS. However, depolarizing currents were found to promote the blocking effect, and hyperpolarizing currents were found to diminish the blocking effect. Inward sodium currents were larger than the sum of the outward currents, resulting in a net depolarization of the nodal membrane. Our experimental results support these findings and closely match results from the equivalent modeling scenario: intra-peritoneal administration of the persistent sodium channel blocker ranolazine resulted in an increase in the amplitude of HFS required to produce conduction block in rats, confirming that depolarizing currents promote the conduction block phenomenon. Hypothesis 2 was investigated using a spectral analysis of the channel gating variables in a single-fiber axon model. The results of this study suggested a relationship between the dynamical properties of specific ion channel gating elements and the contributions of corresponding conductances to block onset. Specifically, we show that the dynamics of the fast sodium inactivation gate are too slow to track the high-frequency changes in membrane potential during HFS, and that the behavior of the fast sodium current was dominated by the low-frequency depolarization of the membrane. As a result, in the blocked state, only 5.4% of nodal sodium channels were found to be in the activatable state in the node closest to the blocking electrode, resulting in conduction block. Moreover, we find that the corner frequency for the persistent sodium channel activation gate corresponds to the frequency below which high-frequency stimuli of arbitrary amplitude are incapable of inducing conduction block.

Electrical conduction block in large nerves: high-frequency current delivery in the nonhuman primate.

Recent studies have made significant progress toward the clinical implementation of high-frequency conduction block (HFB) of peripheral nerves. However, these studies were performed in small nerves, and questions remain regarding the nature of HFB in large-diameter nerves. This study in nonhuman primates shows reliable conduction block in large-diameter nerves (up to 4.1 mm) with relatively low-threshold current amplitude and only moderate nerve discharge prior to the onset of block.

Separated interface nerve electrode prevents direct current induced nerve damage.

Direct current, DC, can be used to quickly and reversibly block activity in excitable tissue, or to quickly and reversibly increase or decrease the natural excitability of a neuronal population. However, the practical use of DC to control neuronal activity has been extremely limited due to the rapid tissue damage caused by its use. We show that a separated interface nerve electrode, SINE, is a much safer method to deliver DC to excitable tissue and may be valuable as a laboratory research tool or potentially for clinical treatment of disease.