Diamond/Porous Titanium Nitride Electrodes With Superior Electrochemical Performance for Neural Interfacing.

Robust devices for chronic neural stimulation demand electrode materials which exhibit high charge injection (Q inj) capacity and long-term stability. Boron-doped diamond (BDD) electrodes have shown promise for neural stimulation applications, but their practical applications remain limited due to the poor charge transfer capability of diamond. In this work, we present an attractive approach to produce BDD electrodes with exceptionally high surface area using porous titanium nitride (TiN) as interlayer template. The TiN deposition parameters were systematically varied to fabricate a range of porous electrodes, which were subsequently coated by a BDD thin-film. The electrodes were investigated by surface analysis methods and electrochemical techniques before and after BDD deposition. Cyclic voltammetry (CV) measurements showed a wide potential window in saline solution (between -1.3 and 1.2 V vs. Ag/AgCl). Electrodes with the highest thickness and porosity exhibited the lowest impedance magnitude and a charge storage capacity (CSC) of 253 mC/cm2, which largely exceeds the values previously reported for porous BDD electrodes. Electrodes with relatively thinner and less porous coatings displayed the highest pulsing capacitances (C pulse), which would be more favorable for stimulation applications. Although BDD/TiN electrodes displayed a higher impedance magnitude and a lower C pulse as compared to the bare TiN electrodes, the wider potential window likely allows for higher Q inj without reaching unsafe potentials. The remarkable reduction in the impedance and improvement in the charge transfer capacity, together with the known properties of BDD films, makes this type of coating as an ideal candidate for development of reliable devices for chronic neural interfacing.

Minimizing a Wireless Passive LC-Tank Sensor to Monitor Bladder Pressure: A Simulation Study.

In this simulation study, a wireless passive LC-tank sensor system was characterized. Given the application of continuous bladder monitoring, a specific system was proposed in terms of coil geometries and electronic circuitry. Coupling coefficients were spatially mapped by simulation, as a function of both coil distance, and longitudinal and transverse translation of the sensor relative to the antenna. Further, two interrogation schemes were outlined. One was an auto-balancing bridge for computing the sensor-system impedance. In this case, the theoretical noise limit of the analogue part of the system was found by simulations. As the full system is not necessary for obtaining a pressure reading from the sensor, a simplified circuit more suited for an implantable system was deduced. For this system, both the analogue and digital parts were simulated. First, the required ADC resolution for operating the system at a given coupling was found by simulations in the noise-free case. Then, for one selected typical operational point, noise was added gradually, and through Monte-Carlo type simulations, the system performance was obtained. Combining these results, it was found that it at least is possible to operate the proposed system for distances up to 12 mm, or equivalently for coupling coefficients above 0.005. In this case a 14 bit ADC is required, and a carrier SNR of 27 dB can be tolerated.

Influence of fibrous encapsulation on electro-chemical properties of TiN electrodes.

The aim of this study was to investigate how the electrochemical properties of porous titanium nitride stimulation electrode are affected by fibrous encapsulation in vivo. Electrochemical impedance spectroscopy (EIS), cyclic voltammetry and voltage transient (VT) measurements were performed in vivo and in phosphate buffered saline, where the encapsulation process is absent. EIS was used as a non-invasive measurement to follow the inflammation, healing and encapsulation process. EIS showed that the healing and encapsulation process lasted 3-4 weeks. The VTs increased during the first 3-4 weeks, after which they stabilized. The charge storage capacity (CSC) decreased most during the first 3-4 weeks. The increasing VTs and decreasing CSC during the first 3-4 weeks after implantation of the in vivo electrodes seem related to healing and fibrous encapsulation. It is suggested that the charge injection pathway during the encapsulation process changes, which implies that charge injection limits are underestimated with conventional methods.

Subject-Controlled, On-demand, Dorsal Genital Nerve Stimulation to Treat Urgency Urinary Incontinence; a Pilot.

OBJECTIVES: To evaluate the effect of subject-controlled, on-demand, dorsal genital nerve (DGN) stimulation on non-neurogenic urgency urinary incontinence (UUI) in a domestic setting. MATERIALS AND METHODS: Non-neurogenic patients >18 years with overactive bladder symptoms and UUI were included. Exclusion criteria were mainly stress urinary incontinence. Patients underwent 1 week of subject-controlled, on-demand, DGN stimulation, delivered by a percutaneously placed electrode near the DGN connected to an external stimulator (pulse-rate 20 Hz, pulse-width 300 µs). Patients activated the stimulator when feeling the urge to void and stimulated for 30 s. The amplitude was set at the highest tolerable level. A bladder diary including a severity score of the UUI episodes/void (scores: 0 = none, 1 = drops, 2 = dashes, 3 = soaks) and a padtest was kept 3 days prior to, during, and 3 days after the test period. The subjective improvement was also scored. RESULTS: Seven patients (4 males/3 females) were enrolled, the mean age was 55 years (range 23-73). Six completed the test week. In the remaining patient the electrode migrated and was removed. 5/6 finalized the complete bladder diary, 1/6 recorded only the heavy incontinence episodes (score = 3). 4/6 completed the padtest. In all patients who finalized the bladder diary the number of UUI episodes decreased, in 3/5 with ≥60%. The heavy incontinence episodes (score = 3) were resolved in 2/6 patients, and improved ≥80% in the other 4. The severity score of the UUI episodes/void was improved with ≥ 60% in 3/5 patients. The mean subjective improvement was 73%. CONCLUSION: This feasibility study indicates that subject-controlled, on-demand DGN stimulation using a percutaneously placed electrode is possible over a longer time period, in a home setting, with a positive effect on non-neurogenic overactive bladder symptoms with UUI. Although the placement is an easy procedure, it is difficult to fixate the electrode to keep it in the correct position. Improvements in hardware, like a better fixated electrode and an easy to control stimulator, are necessary to make SODGNS a treatment possibility in the future.

Electrochemical properties of titanium nitride nerve stimulation electrodes: an in vitro and in vivo study.

The in vivo electrochemical behavior of titanium nitride (TiN) nerve stimulation electrodes was compared to their in vitro behavior for a period of 90 days. Ten electrodes were implanted in two Göttingen minipigs. Four of these were used for electrical stimulation and electrochemical measurements. Five electrodes were kept in Ringer's solution at 37.5°C, of which four were used for electrical stimulation and electrochemical measurements. The voltage transients measured in vivo were 13 times greater than in vitro at implantation and they continued to increase with time. The electrochemical properties in vivo and the tissue resistance (Rtissue) followed a similar trend with time. There was no consistent significant difference between the electrochemical properties of the in vivo and in vitro electrodes after the implanted period. The differences between the in vivo and in vitro electrodes during the implanted period show that the evaluation of electrochemical performance of implantable stimulation electrodes cannot be substituted with in vitro measurements. After the implanted period, however, the performance of the in vivo and in vitro electrodes in saline was similar. In addition, the changes observed over time during the post-implantation period regarding the electrochemical properties of the in vivo electrodes and Rtissue were similar, which indicates that these changes are due to the foreign body response to implantation.

Subject-controlled stimulation of dorsal genital nerve to treat neurogenic detrusor overactivity at home.

AIMS: To investigate the effects of subject controlled dorsal genital nerve (DGN) electrical stimulation on neurogenic detrusor overactivity (NDO) in subjects at home. METHODS: Subjects underwent a 5-day study at home with DGN stimulation. Stimulation was provided with surface electrodes placed either on the dorsal penile shaft in males and on or close to the clitoris in females. The days 1 and 5 were with no stimulation whereas days 2-4 were with stimulation. Two urodynamic studies were performed at the beginning and at the end of the study. A bladder diary was obtained. RESULTS: Eleven subjects with NDO and with urge incontinence were included. One subject stopped the protocol before the end of the 5-day trial and two did not undergo the second urodynamic study. The subjects showed a statistically significant increase in bladder capacities compared to baseline (P = 0.047). Mean volume per day voided significantly increased over the study within the subjects. Differences between day 1 and day 5 were statistically significant (P = 0.028). CONCLUSIONS: The feasibility and the globally positive outcomes of the study indicate that the stimulation of the dorsal genital nerve can be an option for the treatment of the NDO.

Dorsal genital nerve stimulation in patients with detrusor overactivity: a systematic review.

This study evaluates the outcome of trials to stimulate the dorsal genital nerve (DGN) in patients with lower urinary tract dysfunction. The aim of most studies was to suppress detrusor overactivity in patients with overactive bladder (OAB) syndrome by DGN stimulation. A literature search was performed using Pub Med, Web of Science, and Scopus databases (1980 to April 2012) for clinical trials of DGN stimulation in patients with detrusor overactivity. Seventeen studies were found in the literature. In the studies, different patterns of DGN stimulation were applied. The patterns were either continuous, conditional, or semi-conditional; on an acute or on a chronic basis. DGN stimulation lead to improvement of bladder capacity and reduction in urgency and/or incontinence episodes in many patients. The outcomes of conditional stimulation were comparable to continuous stimulation with respect to improvement of bladder capacity. The publications give evidence that DGN stimulation increases bladder capacity and suppresses involuntary detrusor contractions. Implantable DGN stimulation electrodes can open the way for more prolonged studies in larger patient groups to assess the effectiveness of chronic DGN stimulation in patients with OAB syndrome. Chronic DGN stimulation seems to be of value in the management of OAB syndrome.

Gastric transit and small intestinal transit time and motility assessed by a magnet tracking system.

BACKGROUND: Tracking an ingested magnet by the Magnet Tracking System MTS-1 (Motilis, Lausanne, Switzerland) is an easy and minimally-invasive method to assess gastrointestinal transit. The aim was to test the validity of MTS-1 for assessment of gastric transit time and small intestinal transit time, and to illustrate transit patterns detected by the system. METHODS: A small magnet was ingested and tracked by an external matrix of 16 magnetic field sensors (4 × 4) giving a position defined by 5 coordinates (position: x, y, z, and angle: θ, φ). Eight healthy subjects were each investigated three times: (1) with a small magnet mounted on a capsule endoscope (PillCam); (2) with the magnet alone and the small intestine in the fasting state; and (3) with the magnet alone and the small intestine in the postprandial state. RESULTS: Experiment (1) showed good agreement and no systematic differences between MTS-1 and capsule endoscopy when assessing gastric transit (median difference 1 min; range: 0-6 min) and small intestinal transit time (median difference 0.5 min; range: 0-52 min). Comparing experiments (1) and (2) there were no systematic differences in gastric transit or small intestinal transit when using the magnet-PillCam unit and the much smaller magnetic pill. In experiments (2) and (3), short bursts of very fast movements lasting less than 5% of the time accounted for more than half the distance covered during the first two hours in the small intestine, irrespective of whether the small intestine was in the fasting or postprandial state. The mean contraction frequency in the small intestine was significantly lower in the fasting state than in the postprandial state (9.90 min-1 vs. 10.53 min-1) (p = 0.03). CONCLUSION: MTS-1 is reliable for determination of gastric transit and small intestinal transit time. It is possible to distinguish between the mean contraction frequency of small intestine in the fasting state and in the postprandial state.

Surgical access for electrical stimulation of the pudendal and dorsal genital nerves in the overactive bladder: a review.

PURPOSE: The anatomy of the pudendal nerve and its nerve branches, especially the dorsal nerve of the penis and clitoris (dorsal genital nerves), and the clinical application of electrical stimulation of these nerves in patients with overactive bladder syndrome and detrusor overactivity are reviewed. MATERIALS AND METHODS: A literature search was performed using the PubMed® database and reference lists of relevant studies to obtain articles concerning the anatomy as well as the electrical stimulation of the pudendal nerve and its nerve branches in patients with overactive bladder syndrome. RESULTS: According to the anatomy, electrical stimulation of the pudendal nerve and the dorsal genital nerves to suppress involuntary detrusor contractions is possible at several sites along their course from the sacral nerves to the penis or clitoris. The nerves are accessible by minimally invasive percutaneous methods. Stimulation of the pudendal nerve and dorsal genital nerves effectively increases bladder capacity, and inhibits involuntary detrusor contractions and overactive bladder symptoms. CONCLUSIONS: More clinically applied studies are recommended for stimulation of the dorsal genital nerves to assess its value and feasibility because most studies have been performed in an acute and experimental setting. The preferred type of electrode is not known, but if wire electrodes can be implanted and fixated well by a minimally invasive procedure, cuff electrodes are not necessary. Before deciding on continuous or conditional stimulation, chronic clinical studies are recommended because acute studies remain inconclusive. The feasibility of conditional stimulation depends on the availability of a reliable and clinically applicable detrusor activity sensor.

Fibre-selective recording from peripheral nerves using a multiple-contact cuff: report on pilot pig experiments.

A single cuff electrode with multiple-contacts permits fibre selective recording from peripheral nerves. This has been demonstrated in frog nerve in vitro and earth worm before. In this paper we apply this method successfully to the peripheral median nerve of pig in vivo. Compound action potentials (CAPs) were electrically excited at the median nerve close to the wrist of the forelimb. The CAPs were recorded by a recording nerve cuff located proximal to the stimulation cuff. Applying simple mathematical routines allowed for generating a profile of nerve fibre activation as a function of propagation velocity.

Rectal evacuation and antegrade colonic luminal transport by sacral anterior root stimulation in pigs.

PURPOSE: Electrical sacral anterior root stimulation with a selective anodal block may relieve difficulties with bowel evacuation by selective colorectal activation and anal sphincter suppression. This study compares rectal evacuation induced by anodal block with that induced by unselective stimulation. METHODS: The sacral anterior roots were stimulated with cuff electrodes in seven chloralose-anesthetized minipigs. Anodal block and unselective stimulation were applied in random order and compared by anorectal manometry and by the obtained colorectal evacuation. Evacuation was quantified scintigraphically after retrograde radioactive paste installation. RESULTS: Unselective stimulation evoked sphincter activation which obstructed rectal evacuation during the 30-second stimulation period, after which poststimulation evacuation occurred (mean, 13%; P < 0.05). Anodal block reduced the anal canal pressure by median 83% compared with unselective stimulation. With unrestrained evacuation, a different evacuation pattern (mean, 18%; P < 0.05) occurred within the first ten seconds of the stimulation period and evacuated volume was higher (P = 0.08). Colonic evacuation reached a mean of 17% with unselective stimulation and 11% with anodal block. CONCLUSION: Anodal block and unselective sacral root stimulation induce rectal evacuation and colonic luminal transport in pigs. However, anodal block may improve stimulation-induced defecation by enabling a near-physiologic defecation pattern.

Pelvic nerve stimulation evokes nitric oxide mediated distal rectal relaxation in pigs.

PURPOSE: Pelvic nerve stimulation evokes a complex motility response in the pig rectum with a proximal decrease and a distal increase in cross-sectional area. This study investigated whether the distal increase in the cross-sectional area is because of smooth muscle relaxation mediated by nitric oxide. METHODS: The pelvic nerves were stimulated with cuff electrodes in ten chloralose-anesthetized minipigs. Pressure, volume, and cross-sectional areas at five positions in the rectum were obtained during stimulation to examine the effect of N(G)-nitro-L-arginine (an inhibitor of nitric oxide synthase) injection. RESULTS: Stimulation evoked a median pressure decrease of 13 cm H(2)O (range, 0-27; P < 0.05; n = 10) in the anal canal, a pressure increase of 6 cm H(2)O (range,-15 to 30; P < 0.05; n = 10) in the rectum and a decrease of 39 mL (range, 30-63; P < 0.05; n = 6) in rectal volume. Rectal cross-sectional areas decreased 33 percent (range, 5-56; P < 0.02; n = 7) in the proximal part and increased 32 percent (range, 9-67; P < 0.02; n = 8) in the distal part. N(G)-nitro-L-arginine eliminated the increase in the distal rectal cross-sectional area (n = 5) and the decrease in anal canal pressure (n = 9) in all tested animals. CONCLUSION: Pelvic nerve stimulation evokes distal rectal relaxation in pigs, sensitive to N(G)-nitro-L-arginine, which suggests that this smooth muscle response is mediated by nitric oxide.

Urethral sphincter EMG as event detector for Neurogenic detrusor overactivity.

The aim of this study was to investigate the feasibility of using external urethral sphincter electromyogram (EMG) (EUSEMG) to detect the onset of detrusor contractions in patients with both neurogenic detrusor overactivity (NDO) and detrusor sphincter dyssynergia (DSD). Detrusor pressure (Pdet) and EUSEMG was recorded in 23 neurogenic patients during slow artificial bladder filling. The time delay between the onset of a detrusor contraction and the onset of EUSEMG activity was calculated together with the detrusor pressure increase related to this delay. Of 23 patients enrolled, 12 patients showed both NDO and DSD. Of these 12 patients, 10 had a strong correlation between detrusor pressure and EUSEMG. One patient in this group was excluded due to a storage pressure above 30 cm H2O. Two detection methods were applied on the remaining 9 patients. Method 1 was a root mean square (RMS)-integrator with simple thresholding. This approach had a good sensitivity but also a poor specificity (many false-positive detections). Detection method 2 included a kurtosis-based scaling function, which was multiplied to a similar RMS-integrator as used in method 1. Onset detection occurred before Pdet exceeded 18 cm H2O with both methods. However, method 1 resulted in 14.1 +/- 12.8 false-positive detections during one bladder filling. Pdet at onset detection was on average 1.0 +/- 1.1 cmH2 0 higher with detection method 2 but the number of false-positives was reduced by 95.8%. This paper demonstrates the feasibility of using EUSEMG to estimate the onset of a detrusor contraction in selected patients.

Acute urodynamic effects of posterior tibial nerve stimulation on neurogenic detrusor overactivity in patients with MS.

OBJECTIVES: The aim of this study was to investigate whether acute electrical stimulation of the posterior tibial nerve could suppress detrusor contractions in multiple sclerosis (MS) patients with neurogenic detrusor overactivity. METHODS: Two successive slow-fill cystometries (16 ml/min) were carried out in eight MS patients with neurogenic detrusor overactivity. The first filling served as control without stimulation. In the second filling, electrical stimulation using needle electrodes was applied automatically to the posterior tibial nerve when the detrusor pressure exceeded 10 cm H(2)O. An additional filling in which the needle electrodes were replaced by surface electrodes was carried out in three patients. RESULTS: The control filling showed detrusor overactivity in eight patients, but electrical stimulation of the posterior tibial nerve failed to suppress detrusor contractions in all tested patients. CONCLUSIONS: Although neuromodulative effects may be obtained with therapeutic electrical stimulation of the posterior tibial nerve, no acute effects were demonstrated. For this reason, electrical stimulation of pudendal afferents remains the only option if acute suppression of a detrusor contraction is required.

Event driven electrical stimulation of the dorsal penile/clitoral nerve for management of neurogenic detrusor overactivity in multiple sclerosis.

AIMS: The aim of this study was to evaluate the effect of automatic event driven electrical stimulation on the dorsal penile/clitoral nerve for management of neurogenic detrusor overactivity in patients suffering from Multiple Sclerosis. METHODS: A total of 10 patients participated in the study. Detrusor pressure was recorded during physiological filling of the bladder and electrical stimulation was applied with surface electrodes whenever the detrusor pressure exceeded 10 cm H(2)O. RESULTS: In seven of the eight patients, where neurogenic detrusor overactivity was observed an average of 12 detrusor contractions could be inhibited by stimulation. In one patient, however, stimulation failed to inhibit the detrusor contractions. The average increase in bladder volume from first suppressed detrusor contraction until leakage was 94% (range: 22-366%). On average, the time from first suppressed contraction until leakage was 15 min and 50 sec (range: 4 min 58 sec-32 min 5 sec) with an average physiological filling rate of 8 ml/min. Urgency was effectively suppressed at the onset of stimulation. CONCLUSIONS: The results indicate that involuntary detrusor contractions in patients with multiple sclerosis can effectively be inhibited with event driven stimulation, hereby improving bladder capacity and reducing the number of incontinence episodes. However, the used method for detecting detrusor contractions is not suitable in a chronic setting and alternative techniques needs to be investigated if stimulation should be applied automatically.

Electrical stimulation to induce propulsive contractions in the porcine descending colon.

Electrical stimulation of the colon can improve transit in slow-transit constipation, or enable controlled emptying in colostomy patients. Preliminary studies showed that sequential stimulation of consecutive colon segments induced serial contractions resulting in colonic propulsion. This study was performed to optimize the stimulation parameters. The electrodes were inserted under the serosa of the descending colon of pigs. Charge-balanced rectangular pulses at 10 Hz were delivered in consecutive sessions. Electrically evoked contractions (ECs) were monitored using impedance planimetry and manometry. The luminal pressure and cross-sectional area (CSA), the latency and velocity of CSA decrease, and the wall tension were compared for ECs induced using 3 ms pulses of 9, 12, 15, and 30 mA. When using 15 mA, ECs induced by 0.03, 0.3, and 3 ms long pulses were compared. A current increase from 9 to 30 mA induced a significant increase in the pressure generated by contraction. The increase in pulse duration from 0.03 to 3 ms resulted in shorter latency, faster contraction, higher pressure, and higher wall tension. It is concluded that, at a frequency of 10 Hz, the best combination of current and pulse duration to elicit propulsive contractions in the descending colon of pigs is 15 mA and 3 ms.

Intraoperative recording of sacral root nerve signals in humans.

Electroneurographic signals were intraoperatively recorded from the S3 sacral nerve root in two SCI patients. The aim of this study was to record afferent nerve signals in response to mechanical stimulation of the urinary bladder, rectum, and dermatome. Such signals could be used in an implantable neuroprosthesis to treat neurogenic detrusor overactivity. In both patients a neural response was recorded from the dermatome and the rectum, but from the bladder only in one patient. The results were consistent with results from animal and other human studies. Further studies are however, needed because the number of subjects investigated remains low.

Muscular vs. Neural Activation in Propulsion Induced by Electrical Stimulation in the Descending Colon of Rats.

The present experiments were performed on rat colon to study neurogenic and myogenic elicited propulsion induced by 0.3 and 30 msec long current pulses. The colon segments were stimulated sequentially and randomly. The obtained contractions displaced the intraluminal content in individual propulsion steps. The propulsion steps differed in displacement onset latency, distance, and velocity; the latency decreased while the distance and velocity increased from the proximal to the distal colon segments when performing sequential stimulation; the propulsion steps differed in latency when stimulation was performed randomly; the latency in the first propulsion step was three times longer when using 0.3 vs. 30 msec long pulses. When inhibiting cholinergic transmission by atropine, the propulsion induced by 0.3 msec pulses was blocked, while partially inhibited when using 30 msec pulses. Inhibiting nitric oxide synthesis by N(G) -nitro-L-arginine methyl ester (L-NAME) blocked propulsion induced by both of the pulse durations. In conclusion, electrical stimulation induces propulsion when using both 0.3 and 30 msec long pulses; stimulation using 0.3 msec pulses activates neurons, whereas 30 msec pulses depolarize muscles; in the absence of nitrergic transmission, propulsion cannot be induced by electrical stimulation.

Colon emptying induced by sequential electrical stimulation in rats.

Electrical stimulation could be used to induce colon emptying. The present experiments were performed to establish a stimulation pattern to optimize the stimulation parameters and to test neural involvement in propulsion induced by electrical stimulation. Colon segments were sequentially stimulated using rectangular pulses. The resulting propulsive activity displaced intraluminal content in consecutive propulsion steps. The propulsion steps differed in displacement latency, distance, and velocity along the stimulated colon. Increasing the pulse duration or amplitude resulted in a decrease of the latency. Increasing the stimulation amplitude doubled the displacement distance. The frequencies tested in the present study did not affect propulsion. Inhibition of cholinergic and nitrergic pathways inhibited propulsion. Electrical stimulation can induce colonic propulsion. Motor differences are present along the descending colon. The most suitable combination of pulse parameters regarding colon stimulation is 0.3 ms, 5 mA, 10 Hz. Neural circuits are involved in propulsion when using these values.