A new means of transcutaneous coupling for neural prostheses

Neural prostheses are electronic stimulators that activate nerves to restore sensory or motor functions. Implanted neural prostheses receive command signals and in some cases energy to recharge their batteries through the skin by telemetry. Here, we describe a new approach that eliminates the implanted stimulator. Stimulus pulse trains are passed between two surface electrodes placed on the skin. An insulated lead with conductive terminals at each end is implanted inside the body. One terminal is located under the cathodal surface electrode and the other is attached to a nerve targeted for stimulation. A fraction (10%-15%) of the current flowing between the surface electrodes is routed through the implanted lead. The nerve is stimulated when the amount of routed current is sufficient. The aims of this study were to establish some basic electrical properties of the system and test long-term stability in chronic implants. Stimulation of the nerve innervating the ankle flexors produced graded force over the full physiological range at amplitudes below threshold for evoking muscle contractions under the surface electrodes. Implants remained stable for over 8 mo. The findings provide the basis for a new family of neural prostheses.     

Implantable Myoelectric Sensors (IMESs) for Intramuscular Electromyogram Recording

We have developed a multichannel electrogmyography sensor system capable of receiving and processing signals from up to 32 implanted myoelectric sensors (IMES). The appeal of implanted sensors for myoelectric control is that electromyography (EMG) signals can be measured at their source providing relatively cross-talk-free signals that can be treated as independent control sites. An external telemetry controller receives telemetry sent over a transcutaneous magnetic link by the implanted electrodes. The same link provides power and commands to the implanted electrodes. Wireless telemetry of EMG signals from sensors implanted in the residual musculature eliminates the problems associated with percutaneous wires, such as infection, breakage, and marsupialization. Each implantable sensor consists of a custom-designed application-specified integrated circuit that is packaged into a biocompatible RF BION capsule from the Alfred E. Mann Foundation. Implants are designed for permanent long-term implantation with no servicing requirements. We have a fully operational system. The system has been tested in animals. Implants have been chronically implanted in the legs of three cats and are still completely operational four months after implantation.      

Information contained in sensory nerve recordings made withintrafascicular electrodes

Multiunit recordings were made in anesthetized cats with chronically implanted intrafascicular electrodes over a period of six months. Neural signals recorded with these electrodes consisted of activity in sensory fibers innervating a variety of cutaneous mechanoreceptors. Mechanical stimuli were used to selectively activate individual nerve fibers, and the receptive field and receptor type were identified for each unit. Over a period of six months, there was a net shift in the recorded population, but the electrodes continued to provide a representative sample of the activity in the fascicle as a whole. The total number of units from which activity could be recorded remained roughly constant with time, and individual units persisted in the recordings for up to six months. These results indicate that intrafascicular electrodes could be used to sample information carried by individual somatosensory fibers on a long term basis.     

Stereotaxic Implantation of Electrodes in the Human Brain: A Method for Long-Term Study and Treatment

A stereotaxic method for placement of electrodes in the human brain is described. Radiographic visualization of subcortical targets are discussed and error correction formulas are developed. Electrodes and fixation methods for long-term human implantation are described. Multiple stainless steel or silver bail electrodes have been implanted in 75 patients with schizophrenia, epilepsy, depression, Parkinson's disease, narcolepsy, and intractable pain. The silver ball electrode is more satisfactory for recording and stimulation. Biphasic 0.25-ms duration currents from 2-7 mA have been applied to animals and humans without evidence of structural damage.     

Long-Term Neuroelectric Signal Recording from Severed Nerves

Six recording electrode units were implanted around the severed sciatic nerves of rabbits immediately after an axotomy was performed. Voluntary and involuntary motor neuroelectric signals (including individual action potentials) were recorded from the surface of the severed nerve for as long as 142 days after implantation, the average duration being 64 days. In order to study the course of the limited duration of the signal detection, a stimulation electrode was implanted around the sciatic nerve proximal to the lesion; evoked neuroelectric signals were recorded throughout the length of the experiment. The impedance of the recording electrode was also measured throughout the length of the experiment. The behavior of the above parameters, combined with histological observations, indicated that nerve degeneration accounted for the deterioration of signal detection.     

A System for Neural Recording and Closed-Loop Intracortical Microstimulation in Awake Rodents

There is growing interest in intracortical microstimulation as a means of providing sensory input in neuroprosthetic systems. We believe that precisely controlling the timing and parameters of stimulation in closed loop can significantly improve the efficacy of this technique. Here, we present a system for closed-loop microstimulation in awake rodents chronically implanted with multielectrode arrays. The system interfaces with existing commercial recording and stimulating hardware. Using custom-made hardware, we can stimulate and record from electrodes on the same implanted array and significantly reduce the stimulation artifact. Stimulation sequences can either be preprogrammed or triggered by neural or behavioral events. Specifically, this system can provide feedback stimulation in response to action potentials or features in the local field potential recorded on any of the electrodes within 15 ms. It can also trigger stimulation based on behavioral events, such as real-time tracking of rat whiskers captured with high-speed video. We believe that this system, which can be recreated easily, will help to significantly refine the technique of intracortical microstimulation and advance the field of neuroprostheses.      

A method for evaluating the selectivity of electrodes implanted fornerve simulation

The scale of stimulating electrodes possible for use in functional electrical stimulation to restore motor and sensory function is rapidly approaching that of individual neurons. Although the electrodes may approach the dimensions of single nerve cells, it is unclear if the region of excitation elicited by each electrode will be correspondingly small. Previous techniques for evaluating this have either been tedious or have lacked the resolution necessary. This paper describes a method that uses the refractory interaction of the compound action potentials elicited by a stimulus pulse pair, along with high-resolution recording of those potentials, to achieve measurements of the selectivity of stimulation down to the scale of a few axon diameters. The feasibility of this technique is demonstrated in sciatic nerves of frogs (Rana Catesbiana) acutely implanted with a sapphire electrode array.     

Assessment of biocompatibility of chronically implanted polyimide and platinum intrafascicular electrodes

Longitudinal intrafascicular electrodes (LIFEs) are electrodes designed to be placed inside the peripheral nerve to improve stimulation selectivity and to increase the recording signal-to-noise ratio. We evaluated the functional and morphological effects of either Pt wire LIFEs or polyimide-based thin-film LIFEs implanted in the rat sciatic nerve for 3 mo. The newly designed thin-film LIFEs are more flexible, can be micromachined and allow placement of more active electrode sites than conventional Pt LIFEs. Functional results at 1 mo indicated an initial decline in the nerve conduction velocity and in the amplitude of muscle responses, which recovered during the following 2 mo towards normal values. Morphological results showed that both types of LIFEs induced a mild scar response and a focal but chronic inflammatory reaction, which were limited to a small area around the electrode placed in the nerve. Both types of LIFEs can be considered biocompatible and cause reversible, minimal nerve damage.     

Characteristics of Somatosensory Evoked Potentials Recorded over the Spinal Cord and Brain of Man

Evoked potentials were recorded from the skin over the lumbar and cervical portions of the spinal cord, and the scalp over the sensory cortex of the brain, using averaging techniques. Responses could be identified over the cauda equina and root entry zone in the lumbar spine to stimulation of the tibial nerve at the popliteal fossa. These responses had characteristics of nerve root and spinal cord events in their thresholds, timing, duration, and refractoriness. Stimulation of the median nerve at the wrist likewise resulted in recognizable responses over root entry portions of the cervical spinal cord. These later waves had a morphology suggestive of components arising from nerve plexus, nerve roots, and spinal cord. Responses recorded over the spinal cord were in the 1-10 ?V amplitude range. Tibial, peroneal and median nerve stimulation were used to elicit 1-20 ?V responses recorded over the cortex, which were found to be sensitive to the site, amplitude, and rate of stimulation.     

Microelectrode array for chronic deep-brain microstimulation and recording

We have developed an array of microelectrodes that is suitable for long-term implantation into the subthalamic nucleus (STN) or the globus pallidus and is able to record from single neurons, as well as deliver localized microstimulation. This device can be used to investigate the mechanisms by which deep brain stimulation can ameliorate the symptoms of Parkinson's disease and other movement disorders, and also may be the basis for a new clinical tool for the treatment of Parkinson's disease, by capitalizing on the high spatial specificity of intranuclear microstimulation. The array includes 16 activated iridium microelectrodes, 5-6 mm in length, within a cluster approximately 1.8 mm in diameter. We have fabricated the array using materials carrying the USP Category VI classification, and we have developed an apparatus and a procedure for implanting the microelectrode arrays into the deep brain. Ten arrays have been implanted into the STN of domestic cats, and one into the internal segment of the globus pallidus, for 140-415 days. During that time, we were able to record action potentials from individual neurons, on 4 to 8 of the 16 channels. The microelectrode' active surface areas ranged from 500 to 2000 microm2. Controlled-current pulses, 26.5 microA in amplitude and 150 micros/phase in duration (4 nC/phase) were used to excite neurons in the cat's STN. In addition to direct activation, the stimulus modulated the neuronal activity over a distance of at least 1.2 mm from the site of stimulation. These parameters did not induce histologically detectable changes around the tip sites after 35 hours of stimulation at 100 Hz (7 hours of stimulation per day, on 5 successive days), if the electrode' active surface area was 1000 microm2 or greater.     

Carbon-loaded Teflon electrodes for chronic EEG recordings in microwave research.

Conventional metal electrodes can cause serious modification and intensification of the rate of energy absorption in tissues during exposure of animals to microwaves. Carbon-loaded Teflon with a conductivity close to that of tissue has been implanted and maintained for four to six months at cortical and subcortical locations in rabbits. The EEG and its spectrum as recorded from the carbon-loaded Teflon electrodes are comparable to those recorded from conventional metal electrodes. Histological examination showed good tissue compatibility. Recordings made during acute exposure of rabbits to microwave radiation (2450-MHz) at 100 mW/cm2 showed no electromagnetic interference. The results indicate that carbon-loaded Teflon electrodes can be implanted chronically to record the EEG in animals during the course of microwave radiation.     

Charge density and charge per phase as cofactors in neural injuryinduced by electrical stimulation

The possibility of neural injury during prolonged electrical stimulation of the brain imposes some constraints on the use of this technique for therapeutic and experimental applications. Stimulating electrodes of various sizes were used to investigate the interactions of two stimulus parameters, charge density and charge per phase, in determining the threshold of neural injury induced by electrical stimulation. Platinum electrodes ranging in size from 0.002 to 0.5 cm2 were implanted over the parietal cortex of adult cats. Penetrating microelectrodes fabricated from iridium, with surface areas of 65 +/- 3 x 10(-6) cm2 were inserted into the parietal cortex. Ten days after implantation, the electrodes were pulsed continuously for 7h using charge balanced, current regulated, symmetric pulse pairs, 400 microseconds per phase in duration, at a repetition rate of 50 Hz. The animals were perfused immediately after the stimulation for histologic evaluation of the brain tissue subjacent to the electrode sites. The results show that charge density (as measured at the surface of the stimulating electrode), and charge per phase, interact in a synergistic manner to determine the threshold of stimulation-induced neural injury. This interaction occurs over a wide range of both parameters; for charge density from at least 10 to 800 microC/cm2 and, for charge per phase, from at least 0.05 to 5.0 microC per phase. The significance of these findings in elucidating the mechanisms underlying stimulation-induced injury is discussed.     

Design and fabrication of neurostimulator implants—selected problems

In many therapeutic processes the future medicine will go away from the traditional pharmacological methods and will apply active stimulation of organs with implanted neurostimulators. The classical examples are nowadays the pacemakers. From the inspiration of Pathophysiology Department in Collegium Medicum of Jagiellonian University the Institute of Electron Technology undertook the research work in the field of implanted neurostimulators. The authors presented in the paper the hitherto achieved results of research works, including the analysis of electrical signals course in excited and non-excited vagus nerve and impedance measurement of nerve fibre, necessary for determining the parameters of neurostimulator such as the amplitude, duration and the repetition rate of stimulator pulses. From the point of view of circuit theory neurostimulator is a kind of self-excited or microprocessor controlled pulse generator. In the paper the structure of neurostimulator is presented and the choice of electrodes material and encapsulation resin is explained, taking into account the problem of biocompatibility. Some experimental results of laboratory tests on experimental animals with implanted neurostimulators are shown.     

Gait phase information provided by sensory nerve activity duringwalking: applicability as state controller feedback for FES

In this study, we extracted gait-phase information from natural sensory nerve signals of primarily cutaneous origin recorded in the forelimbs of cats during walking on a motorized treadmill. Nerve signals were recorded in seven cats using nerve cuff or patch electrodes chronically implanted on the median, ulnar, and/or radial nerves. Features in the electroneurograms that were related to paw contact and lift-off were extracted by threshold detection. For four cats, a state controller model used information from two nerves (either median and radial, or ulnar and radial) to predict the timing of palmaris longus activity during walking. When fixed thresholds were used across a variety of walking conditions, the model predicted the timing of EMG activity with a high degree of accuracy (average error = 7.8%, standard deviation = 3.0%, n = 14). When thresholds were optimized for each condition, predictions were further improved (average error = 5.5%, standard deviation = 2.3%, n = 14). The overall accuracy with which EMG timing information could be predicted using signals from two cutaneous nerves for two constant walking speeds and three treadmill inclinations for four cats suggests that natural sensory signals may be implemented as a reliable source of feedback for closed-loop control of functional electrical stimulation (FES).     

Long-term intramuscular electrical activation of the phrenic nerve:safety and reliability

The safety and reliability of a system for long-term intramuscular electrical activation of the phrenic nerve was evaluated in seven dogs. In this system, electrodes are implanted bilaterally into the diaphragm without directly contacting the phrenic nerve using a laparoscope to direct placement. Five dogs underwent chronic bilateral intramuscular diaphragm stimulation (IDS) for 61 to 183 days at stimulus parameters selected to evoke at least 120% of the animal's basal ventilation. Two dogs maintained as controls did not undergo chronic stimulation. The safety and reliability of the system was evaluated in terms of tissue responses to the electrode, alterations in diaphragm muscle, pulmonary function, electrode reliability, and cardiac activation. No adverse responses to the electrode or stimulation were found. The histochemistry of chronically stimulated diaphragm suggested transformation towards type I (oxidative metabolism) muscle fibers. Two IDS electrodes dislodged out of a total of 32 IDS electrodes implanted. Both electrodes dislodged within seven days of implant. All IDS electrodes had stable and repeatable recruitment properties. No IDS electrode mechanical failures were found and no electrode corrosion was observed. It is concluded from these experiments that intramuscular activation of the phrenic nerve will present a minimal risk to human patients who are good candidates for clinical studies using this technique     

Chronic measurement of the stimulation selectivity of the flat interface nerve electrode

The flat interface nerve electrode (FINE) is an attempt to improve the stimulation selectivity of extraneural electrodes. By reshaping peripheral nerves into elliptical cylinders, central fibers are moved closer to the nerve-electrode interface, and additional surface area is created for contact placement. The goals of this study were to test the hypothesis that greater nerve reshaping leads to improved selectivity and to examine the chronic recruitment properties of the FINE. Three FINEs were developed to reshape peripheral nerves to different degrees. Four electrodes of each type were implanted on the sciatic nerves of 12 cats and tested for selectivity over at least three months. There was physiologic evidence of nerve injury in two cats with the tightest cuffs, but the other animals behaved normally. All cuff types were capable of selectively activating branches of the sciatic nerve, as well as groups of fibers within branches. The electrodes that moderately reshaped the nerves demonstrated the most selectivity. Both the selectivity measurements and the recruitment curve characteristics were stable throughout the implant period. From an electrophysiological standpoint, the FINE is a viable alternative for neuroprosthetic devices. A histological analysis of the nerves is under way to evaluate the safety of the FINE.     

Long-term intramuscular electrical activation of the phrenic nerve:efficacy as a ventilatory prosthesis

The efficacy of a system for long-term intramuscular activation of the phrenic nerve as a ventilatory prosthesis was evaluated in seven dogs. Five dogs underwent chronic bilateral intramuscular diaphragm stimulation (IDS) for 61 to 183 days at stimulus parameters selected to evoke at least 120% of the animal's basal ventilation. Two dogs maintained as controls did not undergo chronic stimulation. The ability of IDS to provide long-term ventilation without diaphragm fatigue was evaluated in terms of the ventilatory capacity of IDS, the effects of chronic IDS on diaphragm contractile properties, and the phrenic nerve recruitment properties of chronic IDS electrodes. Hemi-diaphragms with electrodes placed within 2 cm of the phrenic nerve trunk could be completely activated by 25 mA pulses having a 100 μs pulse width. The tidal volume evoked by IDS in this study was 167% (±48 s.d.) of that required for full-time basal ventilation without diaphragm fatigue. Evoked tidal volume increased after 8 to 9 weeks of chronic IDS for stimulus pulse intervals longer than 50 ms. Electrode recruitment properties were stable for both active and passive implanted electrodes. It is concluded from these studies that with properly placed electrodes IDS is capable of providing reliable full-time ventilatory support without fatiguing the diaphragm     

Design and clinical application of a double helix electrode forfunctional electrical stimulation

An electrode, designed to be implanted without a surgical incision, was developed for skeletal muscle stimulation. Stainless steel, Teflon-insulated wire was wound into a helical lead around a polypropylene core and then rewound into a double helix configuration for stress relief during muscle contractions. The electrode tip was augmented with stainless steel barbs to increase anchoring strength. Electrodes were implanted with the help of specially modified hypodermic needles, sheaths, and passing tubes. 775 electrodes were implanted in a five year period in 22 subjects; accumulated implant time was 1,080 electrode years. 453 electrodes (65%) continue to produce strong, stable, muscle contractions. Electrode longevity varied with the location of implant. Electrodes were removed because of (1) inability to locate and properly place the electrode in a suitable site for stimulation during surgery (28, 4%), (2) unwanted changes in muscle response to stimulation (91, 12%) one-third occurring during the first six weeks post implant), (3) increase in electrode impedance (74, 10%) assumed breakage, mostly occurring during the first year after implant), (4) intolerable pain during stimulation (8, 1%), and (5) infection (4, 0.5%). 67 (8%) electrodes were removed by accident or when the subjects left the program. This double helix electrode design has proven practical for achieving chronic stimulation of selected muscles in hemiplegic, paraplegic, stroke and brain-injured subjects with minimally invasive surgery     

Selective activation of distant nerve by surface electrode array

Neural prostheses for restoring lost functions can benefit from selective activation of nerves with limited number and density of electrodes. Here, we show by simulations and animal experiments that multipoint simultaneous stimulation with a surface electrode array can selectively activate nerves in a bundle at a desired location in between the array or at a desired depth, which are referred to as lateral or depth-wise gating stimulation, respectively. The stimulation broadly generates action potentials with cathodic source electrodes, and simultaneously blocks unnecessary propagation with downstream anodic gate electrodes. In general, stimulation with a small diameter electrode can affect a nearly hemispherical region, while a large electrode is effective at a more vertically compressed region, i.e., a surface of nerve bundle. The gating stimulation takes advantage of the size effects by utilizing an asymmetrical electrode array. The array of the lateral gating stimulation is designed to have four electrodes; a pair of large source electrodes and a pair of small gate electrodes. The depth-wise gating stimulation array consists of two electrodes; a large gate and small source electrodes. The simulation first demonstrated that appropriate combination of currents at the source and gate electrodes can change recruitment patterns of nerves with lateral or depth-wise selectivity as desired. We then applied the lateral gating stimulation on the rat spinal cords and obtained a preliminary support for the feasibility.     

Ceramic-based multisite electrode arrays for chronic single-neuron recording

A method is described for the manufacture of a microelectrode array for chronic, multichannel, single neuron recording. The ceramic-based, multisite electrode array has four recording sites patterned onto a ceramic shaft the size of a single typical microwire electrode. The sites and connecting wires are applied to the ceramic substrate using a reverse photolithographic procedure. Recording sites (22 x 80 microm) are separated by 200 microm along the shaft. A layer of alumina insulation is applied over the whole array (exclusive of recording sites) by ion-beam assisted deposition. These arrays were capable of recording single neuron activity from each of their recording sites for at least three weeks during chronic implantation in the somatosensory cortex of rats, and several sites had recordings that lasted for more than 8 weeks. The vertical arrangement of the recording sites on these electrodes is ideal for simultaneously recording across the different layers of brain areas such as the cerebral cortex and hippocampus in chronic preparations.