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.     

Current distance relations for fiber stimulation with pointsources

The following results are based on computer simulations and on activating function analysis. In the near field, denervated muscle fibers as well as nerve fibers with a sealed ending are easier to stimulate in the central region than with electrodes close to the end. When electrode-fiber distance is increased, the electrode location for optimal stimulation efficacy shifts from a central position to a region beyond the fiber end for cathodic stimulation and to a position above the terminating part of the fiber for anodic currents. The phenomenon becomes more pronounced with increasing distance between the electrode and fiber axis, because in the far field, the current-distance relation changes from quadratic to cubic, whereas stimulation at the fiber end obeys a rather constant quadratic law.     

条形半导体激光器注入电流的横向分布

用双连通域内的保角变换方法解二维拉普拉斯方程，得到了条形半导体激光器注入电流密度的横向分布。研究了在电阻层的电阻率比较大的情况下，中央激活区不同宽度和不同电极宽度时注入电流密度的横向分布。如果中央激活区宽度小条形电极宽度，注入电流密度在中央激活区内近似为常数，而在中央激活区外很快地衰减。     

A novel electrode array for diameter-dependent control of axonal excitability: a simulation study

Electrical extracellular stimulation of peripheral nerve activates the large-diameter motor fibers before the small ones, a recruitment order opposite the physiological recruitment of myelinated motor fibers during voluntary muscle contraction. Current methods to solve this problem require a long-duration stimulus pulse which could lead to electrode corrosion and nerve damage. The hypothesis that the excitability of specific diameter fibers can be suppressed by reshaping the profile of extracellular potential along the axon using multiple electrodes is tested using computer simulations in two different volume conductors. Simulations in a homogenous medium with a nine-contact electrode array show that the current excitation threshold (Ith) of large diameter axons (13-17 microm) (0.6-3.0 mA) is higher than that of small-diameter axons (2-7 microm) (0.4-0.7 mA) with 200-microm axon-electrode distance and 10-micros stimulus pulse. The electrode array is also tested in a three-dimensional finite-element model of the sacral root model of dog (ventral root of S3). A single cathode activates large-diameter axons before activating small axons. However, a nine-electrode array activates 50% of small axons while recruiting only 10% of large ones and activates 90% of small axons while recruiting only 50% of large ones. The simulations suggest that the near-physiological recruitment order can be achieved with an electrode array. The diameter selectivity of the electrode array can be controlled by the electrode separation and the method is independent of pulse width.     

In Vivo Electrical Stimulation Using Multichannel Photolithographic Electrode Atrays

Multichannel electrical stimulation of the auditory nerve is demonstrated in a cat model using photolithographic electrode arrays. Evoked potentials from the auditory cortex are used to map the location of fibers activated by different electrodes in the array. The evoked responses obtained are equivalent to those produced by fine wire electrodes currently used for functional stimulation of the auditory system.     

A current mirror based on single electron devices

We have fabricated Coulomb blockade devices which act as current mirrors. Each sample consists of two nominally identical one-dimensional arrays of small tunnel junctions. Each electrode of one array is capacitively coupled to two electrodes in the other array. By measuring the current voltage characteristics of the two arrays simultaneously, we observe a coupling between the currents in the two arrays. We have studied the properties both in the superconducting state and in the normal state, and we interpret the data in terms of correlated transport of charges in the two arrays. The locking between the currents in the two arrays is strongest for intermediate magnetic fields where the electrodes are still superconducting. At best we find current locking over a range of ±6.7 pA     

Soft,Flexible Freestanding Neural Stimulation and Recording Electrodes Fabricated from Reduced Graphene Oxide

There is an urgent need for conductive neural interfacing materials that exhibit mechanically compliant properties, while also retaining high strength and durability under physiological conditions. Currently, implantable electrode systems designed to stimulate and record neural activity are composed of rigid materials such as crystalline silicon and noble metals. While these materials are strong and chemically stable, their intrinsic stiffness and density induce glial scarring and eventual loss of electrode function in vivo. Conductive composites, such as polymers and hydrogels, have excellent electrochemical and mechanical properties, but are electrodeposited onto rigid and dense metallic substrates. In the work described here, strong and conductive microfibers (40–50 μm diameter) wet‐spun from liquid crystalline dispersions of graphene oxide are fabricated into freestanding neural stimulation electrodes. The fibers are insulated with parylene‐C and laser‐treated, forming “brush” electrodes with diameters over 3.5 times that of the fiber shank. The fabrication method is fast, repeatable, and scalable for high‐density 3D array structures and does not require additional welding or attachment of larger electrodes to wires. The electrodes are characterized electrochemically and used to stimulate live retina in vitro. Additionally, the electrodes are coated in a water‐soluble sugar microneedle for implantation into, and subsequent recording from, visual cortex.     

Tissue damage by pulsed electrical stimulation

Repeated pulsed electrical stimulation is used in a multitude of neural interfaces; damage resulting from such stimulation was studied as a function of pulse duration, electrode size, and number of pulses using a fluorescent assay on chick chorioallontoic membrane (CAM) in vivo and chick retina in vitro. Data from the chick model were verified by repeating some measurements on porcine retina in-vitro. The electrode size varied from 100 microm to 1 mm, pulse duration from 6 micros to 6 ms, and the number of pulses from 1 to 7500. The threshold current density for damage was independent of electrode size for diameters greater than 300 microm, and scaled as 1/r2 for electrodes smaller than 200 microm. Damage threshold decreased with the number of pulses, dropping by a factor of 14 on the CAM and 7 on the retina as the number of pulses increased from 1 to 50, and remained constant for a higher numbers of pulses. The damage threshold current density on large electrodes scaled with pulse duration as approximately 1/t0.5, characteristic of electroporation. The threshold current density for repeated exposure on the retina varied between 0.061 A/cm2 at 6 ms to 1.3 A/cm2 at 6 micros. The highest ratio of the damage threshold to the stimulation threshold in retinal ganglion cells occurred at pulse durations near chronaxie-around 1.3 ms.     

Closed-loop control of ankle position using muscle afferentfeedback with functional neuromuscular stimulation

Describes a closed-loop functional neuromuscular stimulation system that uses afferent neural activity from muscle spindle fibers as feedback for controlling position of the ankle joint. Ankle extension against a load was effected by neural stimulation through a dual channel intrafascicular electrode of a fascicle of the tibial nerve that innervated the gastrocnemius muscle. Ankle joint angle was estimated from recordings of tibialis anterior and lateral gastrocnemius spindle fiber activity made with dual channel intrafascicular electrodes. Experiments were conducted in neurally intact anesthetized cats and in unanesthetized decerebrate cats to demonstrate the feasibility of this system. The system was able to reach and maintain a fixed target ankle position in the presence of a varying external moment ranging in magnitude between 7.3 and 22 N-cm opposing the action of the ankle extensor, as well as track a sinusoidal target ankle position up to a frequency of 1 Hz in the presence of a constant magnitude 22- or 37-N-cm external moment     

Spreading velocity of the active area boundary in a thyristor

The modeling, measurement, and magnitude of the plasma-spreading velocity in a modern thyristor structure is discussed. A simple model based on lateral fields present in the p-base of the thyristor is derived. This model is compared with a diffusion model by examining the validity of their predictions. Data on the effects of variations in radial position, current density, temperature, base widths, cathode-emitter short density, and gold recombination site density are presented. Basically, the data show that the spreading velocity is l) independent of radial position 2) a linear function of the log of the current density, 3)increased with increasing temperature, 4) increased with decreasing p-base width, 5) decreased cathode emitter short density, and 6) decreased recombination site density. The derived model is shown to provide a reasonable explanation for these effects which is qualitative and in some cases quantitative.     

Dipole distance for minimum threshold current to stimulate unmyelinated axons with microelectrodes

Excitation thresholds for long nerve or muscle fibers with two point sources parallel to the fiber axis depend on the dipole length. The aim of this study was to find the optimal interelectrode distance for the minimum stimulation current. For a specific electrode-fiber distance (z_el) dipole length is constrained by the energy efficacy of the electrodes requiring small interelectrode distances, and by rather low stimulation currents requiring large dipole distances. Far-field values for optimal dipole distance (approximately 1.4 *z_el) can be explained by the superposition of the positive parts of the activating functions for the monopolar elements of the dipole. A current redistribution effect in a target fiber close to the electrodes shifts the dipole length for threshold stimulation from the theoretical optimal activating function approach value towards greater dipole distances. Spike initiations in straight fibers and retinal ganglion cell axons are investigated.     

环形电极压电驱动器极化电压和力学性能分析

提出一种新型环形电极压电驱动器,运用ABAQUS软件对此驱动器进行电场和力学分析。着重研究环形电极分支中心距和电极宽度对极化电压和驱动性能的影响,并与普通形电极压电驱动器的极化电压和驱动性能对比。结果表明,环形电极压电驱动器的极化电压为普通形电极的1/2,环形电极结构降低压电驱动器对极化电压的要求;减小电极分支中心距、增大电极宽度,有利于降低环形电极压电驱动器的极化电压;当工作电压为90 V时,环形电极压电驱动器的径向夹持力达到普通形电极的5.2倍,径向自由位移达到普通形电极的2.6倍。     

A method to improve the estimation of conduction velocitydistributions over a short segment of nerve

Accurate, noninvasive determination of the distribution of conduction velocities (DCV) among fibers of a peripheral nerve has the potential to improve both clinical diagnoses of pathology and longitudinal studies of the progress of disease or the efficacy of treatments. Current techniques rely on long distances of propagation to increase the amount of temporal dispersion in the compound signals and reduce the relative effect of errors in the forward model. The method described in this paper attempts to reduce errors in DCV estimation through transfer function normalization and, thereby, eliminate the need for long segments of nerve. Compound action potential (CAP) signals are recorded from several, equally spaced electrodes in an array spanning only a 10-cm length of nerve. Relative nerve-to-electrode transfer functions (NETF's) between the nerve and each of the array electrodes are estimated by comparing discrete Fourier transforms of the array signals. NETF's are normalized along the array so that waveform differences can be attributed to the effects of temporal dispersion between recordings, and more accurate DCV estimates can be calculated from the short nerve segment. The method is tested using simulated and real CAP data. DCV estimates are improved for simulated signals. The normalization procedure results in DCV's that qualitatively match those from the literature when used on actual CAP recordings.     

A new technique for transmission of signals from implantabletransducers

To reduce space requirements for implant electronics in in vivo telemetry applications, the purpose of this project was to develop and test a new data transmission method that utilizes the ionic properties of bodily fluids as the transmission medium. Motivated by an interest in using the new method to transmit information from a sensor which measures tension in anterior cruciate ligament (ACL) grafts, a sine wave was injected into a cadaver leg using platinum electrodes implanted into the lateral femoral epicondyle. The signal was detected by electromyogram (EMG) surface electrodes. The effect of transmission frequency, the current injected, interelectrode separation, distance of the electrodes from the joint line, and the surface of electrode placement on the signal attenuation was studied. The logarithmic relation between attenuation and frequency was constant from 2 kHz until 10 kHz. For frequencies above 10 kHz, the attenuation increased linearly at the rate of 1 dB/octave. Attenuation was inversely sensitive to both current and interelectrode separation with larger separations and currents giving less attenuation. Attenuation was significantly less for the lateral thigh surface than for the anterior surface and increased with increasing distance from the joint line for both surfaces. For the application of interest here, suitable values of transmission variables to avoid the possible negative consequences of injecting current into living tissue are a current of 3 mA injected at a frequency of 37 kHz. The values of reception variables for minimum attenuation are wide interelectrode separation (5 cm) with the electrodes placed 5 cm proximal of the joint line on the lateral surface of the thigh. With the exception of the surface which is application dependent, these values of the reception variables should also be appropriate for other applications     

Dynamic current density of the disk electrode double-layer

With applied potential, the current distribution at the surface of a disk electrode is spatially nonuniform and time dependent. This distribution is important to control in applications that desire a uniform current density profile or minimal corrosion. We examine the current density profile of a capacitive disk electrode subjected to a voltage-step using finite element analysis software to solve the system of partial differential equations. In detailed analyses we show quantitatively that the current density shifts from peripheral enhancement to near-uniformity following 1/2 of the lumped element time constant. As charging continues, the current density is slightly enhanced in the central region. We present curves for the evolution of local "time constants" as time progresses and calculate their effective values. The model is intended to be the basis of future work to control the corrosion profile of biologically implantable electrodes of arbitrary shape. Data suggest a means to control corrosion by retarding the edges of a stimulus pulse. Additionally, smaller electrodes may be more effective in fully utilizing surface area for charge transfer due to their shorter time constants.     

The nerve-electrode interface of the cochlear implant: currentspread

One of the fundamental facets of the cochlear implant that must be understood to predict accurately the effect of an electrical stimulus on the auditory nerve is the nerve-electrode interface. One aspect of this interface is the degree to which current delivered by an electrode spreads to neurons distant from it. This paper reports a direct mapping of this current spread using recordings from single units from the cat auditory nerve. Large variations were seen in the degree to which the different units are selective in responding to electrodes at different positions within the scala tympani. Three types of units could be identified based on the selectiveness of their response to the different electrodes in a linear array. The first type of unit exhibited a gradual increase in threshold as the stimulating site was moved from more apical to more basal locations within the scala tympani. The second type of unit exhibited a sharp local minimum, with rapid increases in threshold in excess of 6 dB/mm in the vicinity of the minimum. At electrode sites distant from the local minima the rate of change of the threshold approached that of the first type of units. The final type of unit also demonstrated a gradual change in threshold with changing electrode position, however, two local minima, one apical and one basal, could be identified. These three types are hypothesized to correspond to units which originate apical to the electrode array, along the electrode array and basal to the electrode array     

Sensitivity and selectivity of intraneural stimulation using a silicon electrode array

Artificial electrical stimulation of peripheral nerves needs the development of multielectrode devices which stimulate individual fibers or small groups in a selective and sensitive way. To this end, a multielectrode array in silicon technology has been developed, as well as experimental paradigms and model calculations for sensitivity and selectivity measures. The array consists of twelve platinum electrode sites (10 x 50 microns at 50 microns interdistance) on a 45 microns thick tip-shaped silicon substrate and a Si3N4 insulating glass cover layer. The tip is inserted in the peroneal nerve of the rat during acute experiments to stimulate alpha motor fibers of the extensor digitorum longus muscle. Sensitivity calculations and experiments show a cubic dependence of the number of stimulated motor units on current amplitude of the stimulatory pulse (recruitment curves), starting at single motor level. Selectivity was tested by a method based on the refractory properties of neurons. At the lowest stimulus levels (for one motor unit) selectivity is maximal when two electrodes are separated by 200-250 microns, which was estimated also on theoretical grounds. The study provides clues for future designs of two- and three-dimensional devices.     

The effect of stimulus parameters on the recruitment characteristics of direct nerve stimulation

The effect of stimulus parameters on the recruitment characteristics of motor nerve was studied for regulated current monophasic and balanced charge biphasic stimuli. Results of a nerve model investigation indicated that the threshold difference between different diameter nerve fibers would be dependent on pulse width, the choice between monophasic and biphasic stimuli, and the delay between the primary cathodic and secondary anodic pulses. Threshold difference increased with decreasing pulse width, the greatest effects evident for pulses less than 100 ?s. Biphasic stimulation with no delay between pulses provided greater threshold separation than monophasic stimulation or biphasic stimulation with delay. Animal experiments, in which recruitment in a nerve trunk composed of mixed diameter nerve fibers was examined, showed a decrease in recruitment slope with a decrease in pulse width and with the use of a biphasic, zero delay pulse. These results were examined through muscle force measurements using both a metal loop electrode encircling the nerve trunk and a nerve cuff electrode, i. e., a loop electrode in an insulating tube.     

Long-term stimulation and recording with a penetrating microelectrode array in cat sciatic nerve

We studied the consequences of long-term implantation of a penetrating microelectrode array in peripheral nerve over the time course of 4-6 mo. Electrode arrays without lead wires were implanted to test the ability of different containment systems to protect the array and nerve during contractions of surrounding muscles. Treadmill walking was monitored and the animals showed no functional deficits as a result of implantation. In a different set of experiments, electrodes with lead wires were implanted for up to 7 mo and the animals were tested at 2-4 week intervals at which time stimulation thresholds and recorded sensory activity were monitored for every electrode. It was shown that surgical technique highly affected the long-term stimulation results. Results between measurement sessions were compared, and in the best case, the stimulation properties stabilized in 80% of the electrodes over the course of the experiment (162 days). The recorded sensory signals, however, were not stable over time. A histological analysis performed on all implanted tissues indicated that the morphology and fiber density of the nerve around the electrodes were normal.     

Optimal Electrode Designs for Electrosurgery, Defibrillation, and External Cardiac Pacing

We have developed a simple and easily modifiable two-dimensional finite element computer model of the human torso, which allows us to predict current delivery from arbitrarily placed and designed electrodes. Using this model, the performance of many variations from the commonly used gelled-pad electrode, applied to a torso of uniform and isotropic resistivity, has been examined by independently varying the thickness, width, and resistivity of the gel layer, as well as the width of the conducting plate. We compared the electrode performances on the basis of their ability to maintain a uniform current density at the electrode-body interface, which is thought to be of critical concern in avoiding burn, pain, and other complications in electrosurgery, external cardiac pacing, and defibrillation. In addition to studying the effects of geometric and electrical design variations, we have isolated two electrode designs of particular importance: 1) a simple plate electrode with a uniformly high resistivity gel layer and intermediate conducting plate width, which could be used for low-energy applications such as external cardiac pacing, and 2) an annular electrode in which the resistivity of the gel varies as a function of distance to the electrode center, which could be used for high-energy applications such as electrosurgery and defibrillation, as well as for external cardiac pacing.