A system and method to interface with multiple groups of axons in several fascicles of peripheral nerves.

BACKGROUND: Several neural interface technologies that stimulate and/or record from groups of axons have been developed. The longitudinal intrafascicular electrode (LIFE) is a fine wire that can provide access to a discrete population of axons within a peripheral nerve fascicle. Some applications require, or would benefit greatly from, technology that could provide access to multiple discrete sites in several fascicles. NEW METHOD: The distributed intrafascicular multi-electrode (DIME) lead was developed to deploy multiple LIFEs to several fascicles. It consists of several (e.g. six) LIFEs that are coiled and placed in a sheath for strength and durability, with a portion left uncoiled to allow insertion at distinct sites. We have also developed a multi-lead multi-electrode (MLME) management system that includes a set of sheaths and procedures for fabrication and deployment. RESULTS: A prototype with 3 DIME leads was fabricated and tested in a procedure in a cadaver arm. The leads were successfully routed through skin and connective tissue and the deployment procedures were utilized to insert the LIFEs into fascicles of two nerves. COMPARISON WITH EXISTING METHOD(S): Most multi-electrode systems use a single-lead, multi-electrode design. For some applications, this design may be limited by the bulk of the multi-contact array and/or by the spatial distribution of the electrodes. CONCLUSION: We have designed a system that can be used to access multiple sets of discrete groups of fibers that are spatially distributed in one or more fascicles of peripheral nerves. This system may be useful for neural-enabled prostheses or other applications.

A functional model and simulation of spinal motor pools and intrafascicular recordings of motoneuron activity in peripheral nerve.

Decoding motor intent from recorded neural signals is essential for the development of effective neural-controlled prostheses. To facilitate the development of online decoding algorithms we have developed a software platform to simulate neural motor signals recorded with peripheral nerve electrodes, such as longitudinal intrafascicular electrodes (LIFEs). The simulator uses stored motor intent signals to drive a pool of simulated motoneurons with various spike shapes, recruitment characteristics, and firing frequencies. Each electrode records a weighted sum of a subset of simulated motoneuron activity patterns. As designed, the simulator facilitates development of a suite of test scenarios that would not be possible with actual data sets because, unlike with actual recordings, in the simulator the individual contributions to the simulated composite recordings are known and can be methodically varied across a set of simulation runs. In this manner, the simulation tool is suitable for iterative development of real-time decoding algorithms prior to definitive evaluation in amputee subjects with implanted electrodes. The simulation tool was used to produce data sets that demonstrate its ability to capture some features of neural recordings that pose challenges for decoding algorithms.

Assessing the numerical accuracy of the impedance method.

The impedance method has been used extensively to calculate induced electric fields and currents in tissue as a result of applied electromagnetic fields. However, there has previously been no known method for an a priori assessment of the numerical accuracy of the results found by this method. Here, we present a method which permits an a priori assessment of the numerical accuracy of the impedance method applied to physiologically meaningful problems in bioengineering. The assessment method relies on estimating the condition number associated with the impedance matrix for problems with varying shapes, sizes, conductivities, anisotropies, and implementation strategies. Equations have been provided which predict the number of significant figures lost due to poor matrix conditioning as a function of these variables. The results show that, for problems of moderate size and uncomplicated geometry, applied fields should be measured or calculated accurately to at least five or six significant figures. As resolutions are increased and material properties are more widely divergent even more significant figures are needed. The equations provided here should ensure that solutions found from the impedance method are calculated accurately.

Differential activation of nerve fibers with magnetic stimulation in humans.

BACKGROUND: Earlier observations in our lab had indicated that large, time-varying magnetic fields could elicit action potentials that travel in only one direction in at least some of the myelinated axons in peripheral nerves. The objective of this study was to collect quantitative evidence for magnetically induced unidirectional action potentials in peripheral nerves of human subjects. A magnetic coil was maneuvered to a location on the upper arm where physical effects consistent with the creation of unidirectional action potentials were observed. Electromyographic (EMG) and somatosensory evoked potential (SEP) recordings were then made from a total of 20 subjects during stimulation with the magnetic coil. RESULTS: The relative amplitudes of the EMG and SEP signals changed oppositely when the current direction in the magnetic coil was reversed. This effect was consistent with current direction in the coil relative to the arm for all subjects. CONCLUSION: A differential evocation of motor and sensory fibers was demonstrated and indicates that it may be possible to induce unidirectional action potentials in myelinated peripheral nerve fibers with magnetic stimulation.

Differential activation and block of peripheral nerve fibers by magnetic fields.

The ability to noninvasively and reversibly block conduction in peripheral nerves would have several clinical applications. As an initial step in this direction, we investigated the possibility of magnetically generating and differentially blocking activity in mammalian peripheral nerve fibers in vitro. Compound action potentials at each end of individual explanted phrenic nerves were recorded in response to currents induced at the midpoint of the nerve with an externally placed magnetic coil. Current in the coil was then reversed and the recordings repeated. In all cases, the area under the compound action potential on the virtual anode side of the magnetic stimulus was reduced (mean of 18.2 +/- 8.8%) in comparison to the area on the virtual cathode side. This indicates that peripheral nerve activity can be differentially induced by magnetic stimulation. Extension of this effect to the point of generating unidirectional action potentials in vivo may prove clinically useful in a number of contexts, such as reducing contractures secondary to spasticity and generating magnetically induced anesthesia in limbs. Further investigations of this effect seem warranted.

Intraspinal microstimulation using cylindrical multielectrodes.

A cylindrical multielectrode system specifically designed for intraspinal microstimulation was mechanically and electrically evaluated in the ventral horn of the feline lumbo-sacral spinal cord. Electrode insertions proved to be straight as evaluated from radiographs. Impedances were measured in situ and force recruitment curves from quadriceps muscles were collected over a wide range of stimulus parameters. For a given charge, higher current amplitudes produced greater forces than proportionally longer pulse durations, indicating that charge is not the sole indicator of evoked force in applications utilizing electrical stimulation. Overlap measurements for calculating current-distance constants were collected at a variety of current amplitudes, electrode pair separations, and pair orientations in the spinal grey matter. Forces obtained in the majority of these trials demonstrated an order effect, presumably due to asymmetric neuronal connectivity within the spinal cord. In the cases showing no order effect, the dorso-ventral electrode pair orientation yielded a higher average current-distance constant (278 microA/mm2) than either the medio-lateral or rostro-caudal electrode pair orientations (197 microA/mm2). Specifications of an array of cylindrical multielectrodes for use in future intraspinal microstimulation prostheses were updated.

Microfabricated cylindrical multielectrodes for neural stimulation.

The effects of spinal cord injuries are likely to be ameliorated with the help of functional electrical stimulation of the spinal cord, a technique that may benefit from a new style of electrode: the cylindrical multielectrode. This paper describes the specifications for, fabrication techniques for, and in vitro evaluation of cylindrical multielectrodes. Four tip shapes were tested to determine which shape required the lowest peak force and would, therefore, be expected to minimize dimpling during implantation. The impedance of the electrode interface was monitored for changes due to insertion as well as repetitive delivery of current pulses. The charge delivery capacity was determined by testing with safe (< or = 0.6 mC/cm2) and damaging levels (> or = 0.8 mC/cm2) of charge density. The results of these tests suggest that this electrode design could be used to stimulate neurons in the ventral horn of the spinal cord.

Direct neural sensory feedback and control of a prosthetic arm.

Evidence indicates that user acceptance of modern artificial limbs by amputees would be significantly enhanced by a system that provides appropriate, graded, distally referred sensations of touch and joint movement, and that the functionality of limb prostheses would be improved by a more natural control mechanism. We have recently demonstrated that it is possible to implant electrodes within individual fascicles of peripheral nerve stumps in amputees, that stimulation through these electrodes can produce graded, discrete sensations of touch or movement referred to the amputee's phantom hand, and that recordings of motor neuron activity associated with attempted movements of the phantom limb through these electrodes can be used as graded control signals. We report here that this approach allows amputees to both judge and set grip force and joint position in an artificial arm, in the absence of visual input, thus providing a substrate for better integration of the artificial limb into the amputee's body image. We believe this to be the first demonstration of direct neural feedback from and direct neural control of an artificial arm in amputees.

Residual function in peripheral nerve stumps of amputees: implications for neural control of artificial limbs.

PURPOSE: It is not known whether motor and sensory pathways associated with a missing or denervated limb remain functionally intact over periods of many months or years after amputation or chronic peripheral nerve transection injury. We examined the extent to which activity on chronically severed motor nerve fibers could be controlled by human amputees and whether distally referred tactile and proprioceptive sensations could be induced by stimulation of sensory axons in the nerve stumps. METHODS: Amputees undergoing elective stump procedures were invited to participate in this study. Longitudinal intrafascicular electrodes were threaded percutaneously and implanted in severed nerves of human amputees. The electrodes were interfaced to an amplifier and stimulator system controlled by a laptop computer. Electrophysiologic tests were conducted for 2 consecutive days after recovery from the surgery. RESULTS: It was possible to record volitional motor nerve activity uniquely associated with missing limb movements. Electrical stimulation through the implanted electrodes elicited discrete, unitary, graded sensations of touch, joint movement, and position, referring to the missing limb. CONCLUSIONS: These findings indicate that both central and peripheral motor and somatosensory pathways retain significant residual connectivity and function for many years after limb amputation. This implies that peripheral nerve interfaces could be used to provide amputees with prosthetic limbs that have more natural feel and control than is possible with current myoelectric and body-powered control systems.

Fabrication and characteristics of an implantable, polymer-based, intrafascicular electrode.

We describe new manufacturing techniques and physical properties of an improved polymer-based longitudinal intrafascicular electrode (polyLIFE). Modifications were made to correct: (1) poor metal film adhesion and fatigue resistance, (2) inconsistent insulation adhesion and control over recording/stimulation zone length, and (3) insufficient tensile strength for clinical use. Metal adhesion was significantly improved by both plasma treatment and fiber rotation (about the long axis) during metal deposition. Fatigue resistance was improved by reduction in sputtering energy (time x power) combined with long axis rotation, resulting in thin metal films that were 250 times more resistant to cyclic bending fatigue. Insulation adhesion was enhanced with the application of an adhesion-promoting silicone (MED2-4013, Nusil), while the recording/stimulation zone length was controlled to 1 +/- 0.2mm (mean +/- S.D.). The polyLIFE was made more robust by the inclusion of three individually metallized fibers, improving its tensile strength by a factor of 4 while producing minimal changes to its overall stiffness. However, the metallized fiber redundancy did not significantly affect fatigue resistance. The manufacturing changes described in this study enable the construction of more mechanically robust polyLIFEs, which should provide greater success when chronically implanted in peripheral nerves.

Long-term biocompatibility of implanted polymer-based intrafascicular electrodes.

Polymer-based longitudinal intrafascicular electrodes (polyLIFEs) were chronically implanted into the sciatic nerve of white New Zealand rabbits (n=8) for a period of 6 months (hereafter referred to as the long-term group). The impact of the implantation procedure, as observed 6 months post surgery, was evaluated in a sham-treated control group (n=9). The contralateral sciatic nerve served as the control for each animal. Nerve-fiber counts, fiber diameters, and myelin thickness were estimated at the level of the implant site, 1.5 cm proximally, and 1.5 cm distally for both nerves in sham-treated and long-term groups. Implantation of polyLIFEs had no significant effect on fiber counts, nerve-fiber diameter, or myelin thickness. A slight increase in connective tissue in the vicinity of the implant site was evident in the long-term group, including a thin but dense capsule immediately surrounding the implanted electrode.