Electron transfer processes occurring on platinum neural stimulating electrodes: pulsing experiments for cathodic-first, charge-imbalanced, biphasic pulses for 0.566 ⩽ k ⩽ 2.3 in rat subcutaneous tissues.

OBJECTIVE: Charge injection through platinum neural stimulation electrodes is often constrained by the Shannon limit (Shannon 1992 IEEE Trans. Biomed. Eng. 39 424-6) of k = 1.75. By leveraging the tools of electrochemistry to better understand the reactions at electrode-tissue interface, we endeavor to find a way to safely inject more charge than allowed if the traditional Shannon limit were followed. APPROACH: In previous studies on platinum electrodes using charge-balanced, cathodic-first, biphasic pulses, we noted that during the secondary anodic phase, the electrode potential moves into a range where platinum dissolution is possible when charge injection is greater than k = 1.75. Platinum dissolution products are known to be toxic to brain tissues. We hypothesize that by injecting less charge in the anodic phase than the cathodic phase, the anodic potential excursions will decrease, thereby avoiding potentials where platinum dissolution is more likely. MAIN RESULTS: Our findings show that using these charge-imbalanced pulses decreases the anodic potential excursions to a level where platinum oxidation and dissolution are less likely, and aligns the anodic potentials with those observed with charge-balanced stimulation at k < 1.75-a range widely accepted as safe for stimulation with platinum. SIGNIFICANCE: From these results, we further hypothesize that charge-imbalanced biphasic stimulation would permit more charge to be safely injected through platinum electrodes than would be permitted if the dogma of charge-balanced biphasic stimuli were followed. Testing this hypothesis in cat brain in the same manner as the experiments that formed the basis for the Shannon plot could open the door for safe charge injection through platinum electrodes at levels greater than k = 1.75.

Electron transfer processes occurring on platinum neural stimulating electrodes: pulsing experiments for cathodic-first, charge-balanced, biphasic pulses for 0.566 ⩽ k ⩽ 2.3 in rat subcutaneous tissues.

OBJECTIVE: Our mission is twofold: (1) find a way to safely inject more charge through platinum electrodes than the Shannon limit (k = 1.75) permits and (2) nurture an interest in the neural stimulation community to understand the electron transfer process occurring on neural stimulating electrodes. APPROACH: We report here on measurements of the electrode potential, performed on platinum neural stimulating electrodes in the subcutaneous space of an anesthetized rat under neural stimulation conditions. MAIN RESULTS: The results for six platinum electrodes with areas ranging from 0.2 mm2 to 12.7 mm2 were similar to prior results in sulfuric acid, except that the measured potentials were shifted negative 0.36 V because of the pH difference between the two media. The anodic 'end' potential, measured at t = 20 ms after the onset of the biphasic current pulse, was the primary focus of the data collected because previous results had shown that as charge injection crosses the Shannon limit (k = 1.75), this potential moves into a range where platinum surface oxidation and dissolution is likely to occur. The behavior of V e(t = 20 ms) over a range of electrode surface areas studied was consistent with our sulfuric acid study. Implicit, but little noticed, in Shannon's formulation is that small and large platinum electrodes behave the same in terms of k value; our data supports this idea. SIGNIFICANCE: We hypothesize that the k = 1.75 Shannon limit for safe stimulation designates a charge-injection boundary above which platinum toxicity becomes a relevant consideration for living cells around an electrode, a possibility that can be directly tested, and is a vital step forward in mission (1).

Electron transfer processes occurring on platinum neural stimulating electrodes: calculated charge-storage capacities are inaccessible during applied stimulation.

OBJECTIVE: Neural prostheses employing platinum electrodes are often constrained by a charge/charge-density parameter known as the Shannon limit. In examining the relationship between charge injection and observed tissue damage, the electrochemistry at the electrode-tissue interface should be considered. The charge-storage capacity (CSC) is often used as a predictor of how much charge an electrode can inject during stimulation, but calculating charge from a steady-state i-E curve (cyclic voltammogram) over the water window misrepresents how electrodes operate during stimulation. We aim to gain insight into why CSC predictions from classic i-E curves overestimate the amount of charge that can be injected during neural stimulation pulsing. APPROACH: In this study, we use a standard electrochemical technique to investigate how platinum electrochemistry depends on the potentials accessed by the electrode and on the electrolyte composition. MAIN RESULTS: The experiments indicate: (1) platinum electrodes must be subjected to a 'cleaning' procedure in order to expose the maximum number of surface platinum sites for hydrogen adsorption; (2) the 'cleaned' platinum surface will likely revert to an obstructed condition under typical neural stimulation conditions; (3) irreversible oxygen reduction may occur under neural stimulation conditions, so the consequences of this reaction should be considered; and (4) the presence of the chloride ion (Cl-) or proteins (bovine serum albumin) inhibits oxide formation and alters H adsorption. SIGNIFICANCE: These observations help explain why traditional CSC calculations overestimate the charge that can be injected during neural stimulation. The results underscore how careful electrochemical examination of the electrode-electrolyte interface can result in more accurate expectations of electrode performance during applied stimulation.

Electron transfer processes occurring on platinum neural stimulating electrodes: a tutorial on the i(V e) profile.

The aim of this tutorial is to encourage members of the neuroprosthesis community to incorporate electron transfer processes into their thinking and provide them with the tools to do so when they design and work with neurostimulating devices. The focus of this article is on platinum because it is the most used electrode metal for devices in commercial use. The i(V e) profile or cyclic voltammogram contains information about electron transfer processes that can occur when the electrode-electrolyte interface, V e, is at a specific potential, and assumed to be near steady-state conditions. For the engineer/designer this means that if the potential is not in the range of a specific electron transfer process, that process cannot occur. An i(V e) profile, recorded at sweep rates greater than 0.1 mVs(-1), approximates steady-state conditions. Rapid transient potential excursions, like that seen with neural stimulation pulses, may be too fast for the reaction to occur, however, this means that if the potential is in the range of a specific electron transfer process it may occur and should be considered. The approach described here can be used to describe the thermodynamic electron transfer processes on other candidate electrode metals, e.g. stainless steel, iridium, carbon-based, etc.

Electron transfer processes occurring on platinum neural stimulating electrodes: pulsing experiments for cathodic-first/charge-balanced/biphasic pulses for 0.566 ≤ k ≤ 2.3 in oxygenated and deoxygenated sulfuric acid.

The application of a train of cathodic-first/charge-balanced/biphasic pulses applied to a platinum electrode resulted in a positive creep of the anodic phase potential that increases with increasing charge injection but reaches a steady-state value before 1000 pulses have been delivered. The increase follows from the fact that charge going into irreversible reactions occurring during the anodic phase must equal the charge going into irreversible reactions during the cathodic phase for charge-balanced pulses. In an oxygenated electrolyte the drift of the measured positive potential moved into the platinum oxidation region of the i(V e) profile when the charge injection level exceeds k = 1.75. Platinum dissolution may occur in this region and k = 1.75 defines a boundary between damaging and non-damaging levels on the Shannon Plot. In a very low oxygen environment, the positive potential remained below the platinum oxidation region for the highest charge injection values studied, k = 2.3. The results support the hypothesis that platinum dissolution is the defining factor for the Shannon limit, k = 1.75. Numerous instrumentation issues were encountered in the course of making measurements. The solutions to these issues are provided.

Linear summation of torque produced by selective activation of two motor fascicles.

Linear summation of torque was observed while applying selective activation to two different motor fascicles in the cat sciatic nerve. The excitatory stimulus was applied to two or more contacts housed in a four contact self-sizing spiral cuff electrode. To achieve a linear summation of torque, a delay between the two stimuli that was longer than the length of the facilitatory period but less than the length of the refractory period was used. Using a 900-micros delay between pulses, linear summation of two different torque outputs was successfully achieved in 125 out of 129 trials across five cats. These trials were performed using cuff electrodes that were in place for periods ranging up to 352 days. The results of these studies support the hypothesis that a single self-sizing spiral cuff with multiple contacts and a single lead may be used in place of several muscle-based electrodes each with its own separate lead.

Extraction force and tissue change during removal of a tined intramuscular electrode from rat gastrocnemius.

Many electrical stimulation protocols employ intramuscular electrodes for the activation of targeted muscles. Electrode displacement from the initial implant site can result in degradation of optimal stimulus parameters. Electrodes with tined tips were developed to reduce electrode migration. In the study reported here, intramuscular electrodes with polypropylene tines at the tip were implanted aseptically in the gastrocnemii of adult rats. Test electrodes were explanted immediately following implant in one group and after periods of 1, 3, 7, 14 and 28 days in others. Force as a function of displacement was recorded during removal of the electrodes. Analysis of the results showed that the electrodes were most vulnerable to movement during the first five days. Between 5 and 7 days after implantation there was significant increase in the force required to dislodge the electrode tip. Histology of muscles from which electrodes had been explanted did not show any increase in the area showing tissue changes as compared to control muscles in which the electrode remained in situ. These results indicated that electrode removal caused disruption of encapsulation tissues, with the surrounding muscle mainly unaffected by the explant process.

Selective activation of the sacral anterior roots for induction of bladder voiding.

AIM: We investigated the efficacy of selective activation of the smaller diameter axons in the sacral anterior roots for electrically induced bladder voiding. MATERIALS AND METHODS: Acute experiments were conducted in five adult dogs. The anterior sacral roots S2 and S3 were implanted bilaterally with tripolar electrodes. Pressures were recorded from the bladder and from the proximal urethra and the external urethral sphincter. A detector and flow meter monitored fluid flow. A complete sacral dorsal rhizotomy was carried out. The effects of two types of pulse trains at 20 Hz were compared; quasitrapezoidal pulses (500 microsec with 500 microsec exponential decay) and interrupted rectangular (100 microsec, 2 sec on/2 sec off). Before rhizotomy, rectangular pulse trains (100 microsec) to activate all fibers were also applied. The experimental design was block randomized before and after rhizotomy. RESULTS: Quasitrapezoidal pulses showed block of sphincter activation with average minimum current for maximum suppression of 1.37 mA. All pulse types evoked average bladder pressures above the basal sphincter closure pressure. The pressure patterns in the proximal urethra closely followed the bladder pressures. Before dorsal rhizotomy, stimulation evoked a superadded increase in sphincter pressures with slow rise time. After rhizotomy, the sphincter pressure patterns followed the bladder pressures during selective activation and voiding occurred during stimulation with quasitrapezoidal trains and in between bursts with interrupted rectangular stimulation. CONCLUSIONS: Selective activation of sacral ventral roots combined with dorsal rhizotomy may provide a viable means of low-pressure continuous voiding in neurological impairment.

Phrenic nerve pacing via intramuscular diaphragm electrodes in tetraplegic subjects.

CONTEXT: Diaphragm pacing in ventilator-dependent tetraplegic subjects is usually achieved by the placement of phrenic nerve electrodes via thoracotomy. However, this technique may be accomplished less invasively via laparoscopic placement of IM electrodes, at a lower cost and with less risk of injury to the phrenic nerve. OBJECTIVE: To assess the feasibility of laparascopic placement of IM diaphragm electrodes to achieve long-term ventilatory support in ventilator-dependent tetraplegic subjects. DESIGN, SETTING, AND PARTICIPANTS: Two IM diaphragm electrodes were placed laparoscopically in each hemidiaphragm in five subjects with ventilator-dependent tetraplegia. Studies were performed either on an outpatient basis or with a single overnight hospitalization. Ventilator-dependent tetraplegic subjects were identified in whom bilateral phrenic nerve function was present, as determined by phrenic nerve conduction studies. Following electrode placement, subjects participated in a conditioning program to improve the strength and endurance of the diaphragm over a period of 15 to 25 weeks. The duration of the study was variable depending on the time necessary to determine the maximum duration that individuals could be maintained without mechanical ventilation support. MAIN OUTCOME MEASURES: Magnitude of inspired volume generation and duration of ventilatory support with bilateral diaphragm pacing alone. RESULTS: In four of the five subjects studied, initial bilateral diaphragm stimulation resulted in inspired volumes between 430 and 1,060 mL. Reconditioning of the diaphragm over several weeks resulted in substantial increases in inspired volumes to 1,100 to 1,240 mL. These subjects were comfortably maintained without mechanical ventilatory support for prolonged time periods by diaphragm pacing, by full-time ventilatory support in three subjects, and 20 h per day, in the fourth subject. No response to stimulation was observed in one subject, most likely secondary to denervation atrophy. CONCLUSIONS: Diaphragm pacing in ventilator-dependent tetraplegic subjects can be successfully achieved via laparascopic placement of IM electrodes.

A preliminary feasibility study of different implantable pulse generators technologies for diaphragm pacing system.

Diaphragm pacing stimulation (DPS) for ventilator-dependent patients provides several advantages over conventional techniques such as phrenic nerve pacing or mechanical ventilator support. To date, the only existing system for DPS uses lead electrodes, percutaneously attached to an external pulse generator (PG). However, for a widespread use of this technique it would be more appropriate to eliminate the need for percutaneous wire and use a totally implantable system. The aim of this study was to determine if it were feasible to replace the external PG by an implantable system. We present here the results of a preliminary study of two different PG, currently used in other electrical stimulation (ES) clinical applications, which could be used as implantable DPS systems. One radio-frequency-powered PG, one rechargeable battery-powered PG, and the current external PG were tested. Each was attached to the externalized part of the wires, connected to the diaphragm and tidal volume (TV) was measured in one ventilator-dependent patient who has been using the current percutaneous stimulator for 3 years. Results indicated that both implantable PGs could achieve equivalent ventilatory requirements to the current external stimulator. No significant differences were observed between the three PG systems when stimulating the electrodes as used in the patient's own chronically attached PG system. We found that TV increased with increases in charge and frequency as expected when stimulating the patient's electrodes individually and in combination with each PG system. These results are a significant step toward developing a totally implantable DPS system for the ventilator-dependant patients. Further clinical tests to demonstrate the safety and efficacy of a fully implanted DPS system are warranted.

Mapping the phrenic nerve motor point: the key to a successful laparoscopic diaphragm pacing system in the first human series.

BACKGROUND: For patients with high spinal cord injury and chronic respiratory insufficiency, electrically induced diaphragm pacing is an alternative to long-term positive pressure ventilation. The goal of this study was to laparoscopically assess the phrenic nerve motor point of the diaphragm and then implant electrodes to produce chronic negative pressure ventilation. METHODS: Patients undergoing elective laparoscopic procedures (volunteer patient group) underwent a series of electrical stimuli (2 to 24 mA at 100-microsecond pulse widths) with a mapping probe to identify the motor point through qualitative visualization of diaphragm motion and quantitative measurement of the abdominal pressure to assess the strength of the contraction. After Food and Drug Administration and Institutional Review Board approval, tetraplegic patients (spinal cord injured patient group) who were ventilator dependent underwent mapping and implantation of electrodes for pacing in both diaphragms. RESULTS: In the volunteer group, 28 patients underwent 3 to 50 stimulations per diaphragm to identify the motor points. Throughout this series the surgical tools and software were improved to allow rapid motor point location with a grid-mapping algorithm. In the spinal cord injured group, 5 of 6 patients had electrodes successfully implanted at the motor point to produce adequate tidal volumes. The one failure caused a change in our inclusion criteria to include fluoroscopic confirmation of diaphragm movement during surface nerve stimulation. Three patients are completely free of the ventilator, and the other 2 are progressively increasing their time off the ventilator with conditioning. CONCLUSIONS: Mapping and implantation of the electrodes can be done laparoscopically, providing for a low-risk, cost-effective, outpatient, diaphragm pacing system that will support the respiratory needs of patients.

Selective and independent activation of four motor fascicles using a four contact nerve-cuff electrode.

Any one of the four motor nerves in the cat sciatic nerve could be activated selectively and independently, from threshold to saturation, using a self-sizing spiral cuff electrode containing four radially placed monopolar contacts. These studies were carried out in nine adult cats with acute implants. Of the 36 possible fascicles, 23 fascicles could be activated selectively with current stimuli applied to a single contact and ten of the remaining fascicles could be activated selectively with current stimuli applied to two contacts, "field steering." In three experiments, time constraints precluded attempting selective activation through "field steering" techniques. In eight of the ten cases where "field steering" was used, a positive and a negative current source (anodic steering) were required to achieve the desired fascicle and in the remaining two cases, two negative current sources (cathodic steering) were required. The relative distance from the electrode contacts to each fascicle was well correlated to the order in which each fascicle was activated. In seven experiments, carried out in two animals, selective activation was verified by collision block techniques. The results of these experiments support the hypothesis that selective and independent activation of any of four motor fascicles in the cat sciatic nerve is possible using a four contact self-sizing spiral cuff electrode. Furthermore, in a more general case, these results support the concept of a "tunable" electrode that is capable of "steering" the excitation from an undesirable location to a preferred location.

Characterization of the human diaphragm muscle with respect to the phrenic nerve motor points for diaphragmatic pacing.

Diaphragm pacing from laparoscopically placed electrodes is an alternative to conventional phrenic pacers that use electrodes placed in direct contact with the nerve in the neck or chest. The challenge with the laparoscopic approach is determining where to implant the electrodes, as the phrenic nerves are not visible from the abdomen. The objective of this study was to locate the phrenic nerve "motor points" in the human diaphragm muscle from an abdominal perspective. Twenty-five cadavers were examined by excising the diaphragm muscle and assessing for the thickness of the muscle, the motor point area, and the accessibility of the motor point from the abdominal approach. The data indicate the average thickness of the muscle in the motor point region was 3.0 mm for the left and 2.9 mm for the right hemidiaphragm. The average motor point area was 73 mm2 for the left and 58.7 mm2 for the right hemidiaphragm. The motor points were accessible from an abdominal approach, but the motor point on the right hemidiaphragm was located on the central tendon in many cases (12 of 25). Thus, although the nerves branch prior to entry into the muscle on the right side, several well-placed electrodes could still activate the entire nerve. In this study, we have characterized the human diaphragm muscle in the motor point region and found that it is feasible to place laparoscopically intramuscular electrodes in the motor point region. This is the foundation for the laparoscopically placed diaphragm pacing device that has been utilized in a small series of patients.

Comparison of joint torque evoked with monopolar and tripolar-cuff electrodes.

Using a self-sizing spiral-cuff electrode placed on the sciatic nerve of the cat, the joint torque evoked with stimulation applied to contacts in a monopolar configuration was judged to be the same as the torque evoked by stimulation applied to contacts in a tripolar configuration. Experiments were carried out in six acute cat preparations. In each experiment, a 12-contact electrode was placed on the sciatic nerve and used to effect both the monopolar and tripolar electrode configurations. The ankle torque produced by electrically evoked isometric muscle contraction was measured in three dimensions: plantar flexion, internal rotation, and inversion. Based on the recorded ankle torque, qualitative and quantitative comparisons were performed to determine if any significant difference existed in the pattern or order in which motor nerve fibers were recruited. No significant difference was found at a 98% confidence interval in either the recruitment properties or the repeatability of the monopolar and tripolar configurations. Further, isolated activation of single fascicles within the sciatic nerve was observed. Once nerve fibers in a fascicle were activated, recruitment of that fascicle was modulated over the full range before "spill-over" excitation occurred in neighboring fascicles. These results indicate that a four contact, monopolar nerve-cuff electrode is a viable substitute for a 12 contact, tripolar nerve-cuff electrode. The results of this study are also consistent with the hypothesis that multicontact self-sizing spiral-cuff electrodes can be used in motor prostheses to provide selective control of many muscles. These findings should also apply to other neuroprostheses employing-cuff electrodes on nerve trunks.

Phrenic nerve pacing in a tetraplegic patient via intramuscular diaphragm electrodes.

In patients with ventilator-dependent tetraplegia, phrenic nerve pacing (PNP) provides significant clinical advantages compared with mechanical ventilation. This technique however generally requires a thoracotomy with its associated risks and in-patient hospital stay and carries some risk of phrenic nerve injury. We have developed a method by which the phrenic nerves can be activated via intramuscular diaphragm electrodes. In one patient with ventilator-dependent tetraplegia, two intramuscular diaphragm electrodes were implanted into each hemidiaphragm near the phrenic nerve motor points via laparoscopic surgery. The motor points were identified employing a previously devised mapping technique. Because inspired volumes were suboptimal on the right, a second laparoscopic procedure was necessary to position electrodes near the anterior and posterior branches of the right phrenic nerve. During bilateral stimulation, inspired volume was 580 ml. After a reconditioning program of progressively increasing diaphragm pacing, maximum inspired volumes on the left and right hemidiaphragms increased significantly. Maximum combined bilateral stimulation was 1120 ml. Importantly, the patient has been able to comfortably tolerate full-time pacing. If confirmed in additional patients, PNP with intramuscular diaphragm electrodes via laparoscopic surgery may provide a less invasive and less costly alternative to conventional PNP.

Selective suppression of sphincter activation during sacral anterior nerve root stimulation.

The purpose of this work was to electrically activate small-diameter motor fibers in the sacral anterior roots innervating the urinary bladder, without activating the large-diameter fibers to the sphincter. Quasitrapezoidal current pulses were applied through tripolar spiral nerve electrodes on selected anterior sacral roots during acute experiments on eight dogs, maintained under pentobarbital anesthesia. Pressures were recorded from the bladder and sphincter with catheter-mounted gauges. Stimulation with biphasic quasitrapezoidal pulses showed decrease in sphincter recruitment with increasing pulse amplitudes. The minimum current amplitude that resulted in maximum sphincter suppression was used to stimulate the roots with trains of 20 Hz pulses, with 60 mL of saline filling the bladder. Pressures were also recorded when 100 micros rectangular pulse trains at 20 Hz, both continuous and intermittent, were applied. Trains of stimuli were applied before and after dorsal root rhizotomy. Suppression of sphincter activation was defined to be a percentage, [(Maximum pressure -Minimum pressure)/Maximum pressure x100. The results from 22 roots in eight animals show that with single pulses, the average percentage suppression of sphincter activation was 76.3% (+/-14.0). The minimum current for maximum sphincter suppression was 1.29 mA (+/-0.62). The average bladder pressure evoked was 50 cm of water during pulse train stimulation, with no significant difference due to pulse type. With pulse trains, the sphincter pressures were significantly higher when the bladder was filled. Evacuation of fluid occurred in three animals with average flow rates of 1.0 mL/s.