The underlying cause of electrical stimulation-induced tissue trauma is debated. Our focus has been to study effects of generating electrochemical by-products at the electrode–electrolyte interface, using the pulse-clamp technique coupled with voltammetry to analyze charge transfer. The platinum–H2SO4 system has been a standard for analyzing electrochemistry on platinum-stimulating electrodes, even though the chemical differences between H2SO4 and the living body are obvious. Experiments were designed to determine whether phosphate-buffered saline (PBS) could serve as a more accurate emulation of living tissue. It had been rumored that platinum's performance in PBS deviates from that in H2SO4 at larger potentials. Voltammetry in PBS was performed in two potential ranges. In a conventional potential range (−0.6 V to +0.9 V versus Ag/AgCl), characteristic peaks appear very similar to published voltammograms of platinum in H2SO4. However, in an extended range (−1.0 V to +1.7 V versus Ag/AgCl), platinum exhibited additional electrochemical activity: one oxidation peak and two reduction peaks. Therefore, voltammetry was performed in NaCl and a sodium phosphate mixture (i.e. PBS components) to separate their activity. The altered electrochemical performance of platinum in PBS suggests that certain reactions on platinum at potentials outside the water window will not reflect what happens in vivo.

The objective of this study was to characterize the tissue response to multiple contact spiral nerve cuff electrodes implanted on the sciatic nerve of seven cats for 28-34 weeks. The cuffs were surrounded by fibrous tissue encapsulation consisting of foreign body cells, collagen, and fibroblasts. Focal areas of abnormal neural morphology including perineurial thickening, endoneurial fibrosis, thinly myelinated axons, and focal reduction in the density of myelinated axons were noted in five of seven nerves. In three implants, the percutaneous lead cable was destroyed by the animal pulling on the external leads. Morphological changes were observed in two of three nerves from implants sustaining no known animal induced trauma (group A), and in three of four nerves from implants damaged by the animal pulling at the leads (group B). All nerves appeared normal 2 cm proximal to the cuff. At the cuff level, small regions of one fascicle in each of two nerves (both group B) exhibited abnormalities, while the proximal and distal sections of both nerves were normal. Distal to the cuff, small regions of seven fascicles distributed among three nerves (two group A, one group B) exhibited abnormalities. These nerves were normal at the cuff level but exhibited abnormalities in individual nerve branches distal to the cuff. The incidence and characteristics of the morphological abnormalities at the cuff level are consistent with those observed in previous studies of nerve cuff electrodes, and support the hypothesis that spiral cuff electrodes can be implanted with an internal diameter less than that of the nerve and expand to accommodate the nerve without compression The pattern of morphological abnormalities indicated that mechanical trauma had occurred at some time in the past, and the distribution suggested animal intervention and the lead cable as possible causes.

We have developed an endoscopic instrument that will allow a surgeon to safely, dependably and accurately place intramuscular (IM) electrodes in the diaphragm. This instrument has been used to implant 28 IM electrodes in the diaphragms of eleven acute and four chronic dogs. All electrodes achieved full activation of the diaphragm muscle, producing tidal volumes up to 130% V(TCRIT), the critical volume necessary for basal ventilatory support, with unilateral stimulation. The surgeon is able to control the angle of the IM electrode insertion needle, which enables the needle to approach the diaphragm at an angle that is parallel to the surface of the muscle. This insures good control over the depth of needle penetration into the muscle, which greatly reduces the risk of accidentally passing the needle through the diaphragm and entering the thorax. Endoscopic placement of IM electrodes into the diaphragm opens opportunities to provide cost effective negative pressure ventilation to patients who are unable to effect sufficient ventilation by central nervous system (CNS) control of respiration.

A blind volunteer affected with retinitis pigmentosa was intracranially implanted with a selfsizing cuff electrode around her right optic nerve. The nerve cuff electrode included 4 monopolar contacts. Its leads were brought through the skin where they ended in an external connector12. After recovery from surgery, electrical activation of the implanted optic nerve was undertaken. A specially dedicated Computer Based Stimulator was used. Stimulation consisted in charge balanced biphasic rectangular pulses. The stimulation resulted consistently and exclusively in visual sensations. The thresholds have remained stable for 14 months, so far. Phosphenes were broadly distributed throughout the visual field. They were either solid surface, or organized in rows, arrays, or clusters of dots. A topological organization was observed between phosphene location and the stimulating contact. Increasing the stimulation frequency decreased the current threshold for perception. The results of this experiment are consistent with the hypothesis that a visual prosthesis, based on electrical stimulation of the optic nerve, can be developed for human subjects with retinitis pigmentosa.

Impedance pneumography signals were characterised during diaphragm pacing using stimulating and recording electrodes placed on the abdominal surface of the diaphragm. These measurements were useful for the detection of muscle contraction without confounding effects from stimulus artifacts. Impedance pneumography signals were measured using 23 epimysial electrodes implanted in seven dogs with 1–5 experiments on each electrode. The polarity of the change in impedance associated with diaphragm pacing differed for each recording electrode and its configuration. Thirty-four of 57 cases produced increased impedance, 11 produced decreased impedance and the remaining 12 depended on the level of diaphragm activation. Impedance pneumography signals were useful for detecting complete airway obstruction. The mean difference between the impedance measured during open and obstructed airway conditions was 80% of the open airway impedance signal. The difference between open and obstructed airway impedance measurements was a mean of 2.3 times larger with a recording electrode on the same hemidiaphragm as the stimulating electrode, compared to an electrode placed on the opposite hemidiaphragm (p<0.05, paired t test, four dogs). In addition, the differences between open and completely obstructed airways were a mean of 2.8 times larger when the second recording electrode was placed on the thorax at the fifth intercostal space, compared to the ninth intercostal space (p<0.05, two-factor ANOVA, one dog, two replicates). It was concluded that impedance pneumograph circuitry could be incorporated into an existing diaphragm pacer using electrodes placed on the diaphragm to provide valuable measurements of the function of the device.

Electrode location is of vital importance to diaphragm pacing devices using electrodes implanted on the diaphragm. Complete phrenic nerve recruitment with a single epimysial electrode implanted on the abdominal surface of the diaphragm required placement within 1 cm of the motor point. Recruitment could be increased further using multiple electrodes, provided the electrodes were implanted on opposite sides of the phrenic nerve motor point. The location of the implanted electrode relative to the phrenic nerve motor point also affected the relation between the stimulus interpulse interval (IPI) and the measured tidal volume. Specifically, we found that electrodes implanted lateral to the phrenic nerve motor point had different tidal volume--IPI relations than electrodes placed anterior or posterior to the motor point. We concluded that properly placed epimysial electrodes are required to obtain adequate phrenic nerve recruitment for full time ventilation and knowledge of the relative location of the electrode with respect to motor point is necessary to predict the tidal volume produced by a specific IPI.

The objective of this investigation was to measure the input-output (I-O) properties of chronically implanted nerve cuff electrodes. Silicone rubber spiral nerve cuff electrodes, containing 12 individual platinum electrode contacts, were implanted on the sciatic nerve of seven adult cats for 28-34 weeks. Measurements of the torque generated at the ankle joint by electrical stimulation of the sciatic nerve were made every 1-2 weeks for the first 6 weeks post-implant and every 3-5 weeks between 6 weeks and 32 weeks post-implant. In three implants the percutaneous lead cable was irreparably damaged by the animal within 4 weeks after implant and further testing was not possible. One additional lead cable was irreparably damaged by the animal at 17 weeks post-implant. The three remaining implants functioned for 28, 31, and 32 weeks. Input-output curves of ankle joint torque as a function of stimulus current amplitude were repeatable within an experimental session, but there were changes in I-O curves between sessions. The degree of variability in I-O properties differed between implants and between different contacts within the same implant. After 8 weeks, the session to session changes in the stimulus amplitude required to generate 50% of the maximum torque (I50) were smaller (15+/-19%, mean +/- s.d.) than the changes in I50 measured between 1 week and 8 weeks post-implant (34+/-42%). Furthermore, the I-O properties were more stable across changes in limb position in the late post-implant period than in acutely implanted cuff electrodes. These results suggest that tissue encapsulation acted to stabilize chronically implanted cuff electrodes. Electrode movement relative to the nerve, de- and regeneration of nerve fibers, and the inability to precisely reproduce limb position in the measurement apparatus all may have contributed to the variability in I-O properties.

Laparoscopic mapping of the phrenic nerve motor points using test stimulation was conducted for the implant of epimysial electrodes for diaphragm pacing in dogs. Both visual assessment of muscle activation and measurements of recruitment were useful for identifying an implant location resulting in a mean electrode placement approximately 14 mm from the phrenic nerve motor points in 16 dogs. Postmortem analysis of the stimulus test site locations and corresponding recruitment curves suggested that the phrenic nerve motor points could be predicted during the laparoscopic procedure to within 4.5 mm of the anatomical motor point.

A blind volunteer with retinitis pigmentosa was chronically implanted with a self-sizing spiral cuff electrode around an optic nerve. Electrical stimuli applied to the nerve produced localized visual sensations that were broadly distributed throughout the visual field and could be varied by changing the stimulating conditions. These results demonstrate the potential for constructing a visual prosthesis, based on electrical stimulation of the optic nerve, for blind subjects who have intact retinal ganglion cells.

Epimysial electrodes stapled to the abdominal surface of the diaphragm produced a chronic inflammatory response that appeared to be mediated by mechanical stresses placed on the encapsulation tissue by periodic diaphragm contraction. The tissue response surrounding 34 epimysial electrodes implanted in 11 dogs was studied three months post implant. The tissue response was characterized by a capsule having a mean thickness of 1.24 mm between the electrode and the muscle, while having only a very thin capsule on the back, or abdominal side of the electrode. The tissue response between the electrode and the muscle was comprised of two tissue layers: a layer of granulation tissue and a layer of collagen. The granulation tissue layer contained evidence of acute inflammatory processes including the presence of polymorphonuclear leukocytes in 68% of the samples. Granulation layer thickness was inversely correlated with back encapsulation indicating a reduction in granulation tissue for mechanically stabilized electrodes. In addition, encapsulation tissue surrounding the granulation layer was comprised of collagen fibers with an oblique orientation and an extraperitoneal locale suggesting mechanical load transfers between the electrode and the surrounding tissue. As a result, the histological response to epimysial electrodes implanted on the diaphragm suggests that mechanical loading, induced by movement associated with the contraction of adjacent muscle, must be a consideration for devices that employ epimysial electrodes.

The objective of this research was to develop a technique to excite selectively nerve fibers distant from an electrode without exciting nerve fibers close to the electrode. The shape of the stimulus current waveform was designed based on the nonlinear conductance properties of neuronal sodium channels. Models of mammalian peripheral myelinated axons and experimental measurements on cat sciatic nerve were used to determine the effects of subthreshold polarization on neural excitability and recruitment. Subthreshold membrane depolarization generated a transient decrease in neural excitability and thus an increase in the threshold for stimulation by a subsequent stimulus pulse. The decrease in excitability increased as the duration and amplitude of the subthreshold depolarization were increased, and the increase in threshold was greater for fibers close to the electrode. When a depolarizing stimulus pulse was applied immediately after the subthreshold depolarization, nerve fibers far from the electrode could be stimulated without stimulating fibers close to the electrode. Subthreshold depolarizing prepulses inverted the current-distance relationship and allowed selective stimulation of nerve fibers far from the electrode.

Choice of stimulus parameters is an important consideration in the design of neural prosthetic systems. The objective of this study was to determine the effect of rectangular stimulus pulsewidth (PW) on the selectivity of peripheral nerve stimulation. Computer simulations using a cable model of a mammalian myelinated nerve fiber indicated that shorter PW's increased the difference between the threshold currents of fibers lying at different distances from an electrode. Experimental measurements of joint torque generated by peripheral nerve stimulation demonstrated that shorter PW's generated larger torques before spillover and created a larger dynamic range of currents between threshold and spillover. Thus, shorter PW's allowed more spatially selective stimulation of nerve fibers. Analysis of the response of a passive cable model to different duration stimuli indicated that PW dependent contributions of distributed sources to membrane polarization accounted for the observed differences in selectivity.

A non-invasive method was developed to determine the input-output (I/O) properties of peripheral nerve stimulating electrodes. An apparatus was fabricated to measure the 3-dimensional (3-D) isometric torque generated at the cat ankle joint by electrical activation of the sciatic nerve. The performance of the apparatus was quantified, and the utility of the method was demonstrated by measuring the recruitment properties of multiple contact nerve cuff electrodes. Torque-twitch waveforms, recruitment curves of peak torque as a function of stimulus current amplitude, and 2-D joint torque vectors were used to analyze the recruitment properties of the cuff. The peak of the twitch torque was an accurate measure of excitation even for muscles having fibers with varying speeds of contraction. The evoked twitch waveforms and torque vectors generated by selective stimulation of individual nerve branches with a hook electrode were compared to those produced by stimulation of the nerve trunk with the cuff electrode. These data allowed determination of the regions of the nerve trunk that were activated by different electrode geometries and stimulus parameters. The positional stability of electrode recruitment properties could be quantified by measuring I/O characteristics at different limb positions. The methods described are useful for characterization of neural stimulating electrodes and for studies of motor system physiology.

Nerve-based stimulating electrodes provide the technology for advancing the function of motor system neural prostheses. The goal of this work was to measure and quantify the recruitment properties of a 12 contact spiral nerve cuff electrode. The cuff was implanted on the cat sciatic nerve trunk, which consists of at least four distinct motor fascicles, and the torque generated at the ankle joint by selective stimulation of the nerve was recorded in nine acute experiments. Comparisons of torques generated with the cuff to torques generated by selective stimulation of individual nerve branches indicated that the cuff allowed selective activation of individual nerve fascicles. Selectivity was dependent on the relative location of the electrode contacts and the nerve fascicles, as well as the size and relative spacing of neighboring fascicles. Selective stimulation of individual nerve fascicles allowed independent and graded control of dorsiflexion and plantarflexion torques in all nine experiments. Field steering currents improved selectivity as reflected by significant increases in the maximum torques that could be generated before spillover to other fascicles, significant increases in the difference between the current amplitude at spillover and the current amplitude at threshold, and significant increases in the slope of the current distance relationship.

Nerve cuff electrodes have been shown to be safe and able to activate selectively specific fascicles in a nerve trunk. Selectivity has been shown using a cuff with four radially placed tripoles thus requiring twelve contacts and twelve lead wires. This study evaluates a simplified cuff electrode, consisting of four radially placed monopole electrodes, requiring only four lead wires, and compares the results to the tripolar electrode configuration. Experiments were performed on two cats, each with an electrode that was implanted for over six months. Results from a correlation analysis and a torque vector likeness measure indicated that the recruitment characteristics of the two configurations were similar in 6 of 8 cases

The limits of present electrode technology are being reached in current motor prostheses for restoring functional movement in paralyzed people. Improved devices require electrodes and stimulation methods that will activate muscles selectively and independently with less implanted hardware. A practical functional neuromuscular stimulation (FNS) system may need to employ extraneural, intraneural, epimysial, or intramuscular electrodes or a combination of these types. The limitations of current muscle electrodes and the anatomy of peripheral nerve innervation of muscle have pointed to stimulation of peripheral nerve trunks as a promising area for investigation. Attempts to use conventional (extraneural) peripheral nerve electrodes for selective activation of muscles in chronic applications have met with only limited success. Intraneural (intrafascicular) electrodes offer the advantages of greater selectivity and lower power requirements, but these may be offset by the difficulty of inserting delicate electrodes through the collagenous epineurium and perineurium while avoiding unacceptable amounts of trauma. Cuff electrodes require more power than intrafascicular ones but may provide more stable recruitment patterns over time, and the opportunity for retrieval and replacement

The authors review recent efforts to design stimulus waveforms for selective electrical stimulation of the nervous system. Two types of selectivity are considered. Fiber diameter selectivity refers to the ability to activate one group of nerve fibers having a common diameter without activating nerve fibers having different diameters. Spatial selectivity refers to the ability to activate nerve fibers in a localized region without activating nerve fibers in neighboring regions. The fundamental principles governing the response of excitable nerve fibers to imposed stimuli are reviewed and used to design waveforms. The emphasis of the presentation is on excitation of peripheral myelinated nerve fibers, The underlying principles, however, are broadly applicable to all excitable membranes