An in vitro model of a retinal prosthesis

Epiretinal prostheses are being developed to bypass a degenerated photoreceptor layer and excite surviving ganglion and inner retinal cells. We used custom microfabricated multielectrode arrays with 200-microm-diameter stimulating electrodes and 10-microm-diameter recording electrodes to stimulate and record neural responses in isolated tiger salamander retina. Pharmacological agents were used to isolate direct excitation of ganglion cells from excitation of other inner retinal cells. Strength-duration data suggest that, if amplitude will be used for the coding of brightness or gray level in retinal prostheses, shorter pulses (200 micros) will allow for a smaller region in the area of the electrode to be excited over a larger dynamic range compared with longer pulses (1 ms). Both electrophysiological results and electrostatic finite-element modeling show that electrode-electrode interactions can lead to increased thresholds for sites half way between simultaneously stimulated electrodes (29.4 +/- 6.6 nC) compared with monopolar stimulation (13.3 +/- 1.7 nC, p < 0.02). Presynaptic stimulation of the same ganglion cell with both 200- and 10-microm-diameter electrodes yielded threshold charge densities of 12 +/- 6 and 7.66 +/- 1.30 nC/cm2, respectively, while the required charge was 12.5 +/- 6.2 and 19 +/- 3.3 nC.     

Effective electrode configuration for selective stimulation with inner eye prostheses

The quality of visual perception with retinal prostheses strongly depends on the local selectivity. Electrode arrays at the surface of the retina should excite exclusively cells within a local area but they are expected to co-stimulate bypassing axons originating from ganglion cells of the outer regions. Long electrodes parallel to these axons are shown to be good candidates for avoiding the co-stimulation phenomenon. Efficiency of focal excitation depends on the length and resistance of the electrodes.     

Electrical stimulation of the auditory nerve: direct current measurement in vivo

Neural prostheses use charge recovery mechanisms to ensure the electrical stimulus is charge balanced. Nucleus cochlear implants short all stimulating electrodes between pulses in order to achieve charge balance, resulting in a small residual direct current (DC). In the present study we sought to characterize the variation of this residual DC with different charge recovery mechanisms, stimulation modes, and stimulation parameters, and by modeling, to gain insight into the underlying mechanisms. In an acute study with anaesthetised guinea pigs, DC was measured in four platinum intracochlear electrodes stimulated using a Nucleus C124M cochlear implant at moderate to high pulse rates (1200-14,500 pulses/s) and stimulus intensities (0.2-1.75 mA at 26-200 microseconds/phase). Both monopolar and bipolar stimulation modes were used, and the effects of shorting or combining a capacitor with shorting for charge recovery were investigated. Residual DC increased as a function of stimulus rate, stimulus intensity, and pulse width. DC was lower for monopolar than bipolar stimulation, and lower still with capacitively coupled monopolar stimulation. Our model suggests that residual DC is a consequence of Faradaic reactions which allow charge to leak through the electrode tissue interface. Such reactions and charge leakage are still present when capacitors are used to achieve charge recovery, but anodic and cathodic reactions are balanced in such a way that the net charge leakage is zero.     

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.     

A variable range bi-phasic current stimulus driver circuitry for an implantable retinal prosthetic device

This paper reports a driver circuitry to generate bi-phasic (anodic and cathodic) current pulses for stimulating the retinal layer through electrodes which is part of a retinal prosthetic device for implants in blind patients affected by retinitis pigmentosa (RP) and age-related macular degeneration (AMD). Dual voltage architecture is used to halve the number of interface leads from the chip to the stimulation sites compared to a single voltage supply. The driver circuitry is designed to deliver currents with six bit resolution for a wide range of full scale currents up to 600 /spl mu/A. To cater to the varying stimulus requirements among patients and different regions of the retina, variable gain architecture is used to achieve fine resolution even for a narrow range of stimulus. 1:8 demultiplexing feature is embedded within the output stage thus allowing one DAC for eight outputs. A novel charge cancellation circuitry with current limiting capability is implemented to discharge the electrodes for medical safety. Measurement results of a prototype chip fabricated in 1.5-/spl mu/m CMOS technology are presented.     

In vitro comparison of the charge-injection limits of activated iridium oxide (AIROF) and platinum-iridium microelectrodes

The charge-injection limits of activated iridium oxide electrodes (AIROF) and PtIr microelectrodes with similar geometric area and shape have been compared in vitro using a stimulation waveform that delivers cathodal current pulses with current-limited control of the electrode bias potential in the interpulse period. Charge-injection limits were compared over a bias range of 0.1-0.7 V (versus Ag/AgCl) and pulse frequencies of 20, 50, and 100 Hz. The AIROF was capable of injecting between 4 and 10 times the charge of the PtIr electrode, with a maximum value of 3.9 mC/cm2 obtained at a 0.7 V bias and 20 Hz frequency.     

A computational model of electrical stimulation of the retinal ganglion cell

Localized retinal electrical stimulation in blind volunteers results in discrete round visual percepts corresponding to the location of the stimulating electrode. The success of such an approach to provide useful vision depends on elucidating the neuronal target of surface electrical stimulation. To determine if electrodes preferentially stimulate ganglion cells directly below them or passing fibers from distant ganglion cells, we developed a compartmental model for electric field stimulation of the retinal ganglion cell (RGC). In this model a RGC is stimulated by extracellular electrical fields with active channels and realistic cell morphology derived directly from a neuronal tracing. Three membrane models were applied: a linear passive model, a Hodgkin-Huxley model with passive dendrites (HH), and a model composed of all active compartments (FCM) with five nonlinear ion channels. Idealized monopolar point and disk stimulating electrodes were positioned above the cell. For the HH and FCM models, the position of lowest cathodal threshold to propagate an action potential was over the soma. Brief (100 microseconds) cathodic stimuli were 20% (HH with disk electrode) to 73% (FCM with point-source) more effective over the soma than over the axon. In the passive model, the axon is preferentially stimulated versus the soma. Although it may be possible to electrically stimulate RGC's near their cell body at lower thresholds than at their axon, these differences are relatively small. Alternative explanations should be sought to explain the focal perceptions observed in previously reported patient trials.     

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.     

Chronic neural stimulation with thin-film, iridium oxide electrodes

Experiments were conducted to assess the effect of chronic stimulation on the electrical properties of the electrode-tissue system, as measured using electrochemical impedance spectroscopy (EIS) and cyclic voltammetry (CV). Silicon, micromachined probes with multiple iridium oxide stimulating electrodes (400-1600 micron 2) were implanted in guinea pig cortex. A 10-17 day post-operative recovery period was followed by five days of monopolar stimulation, two hours/electrode each day using biphasic, constant current stimulation (5-100 microA, 100 microseconds/phase). EIS and CV data were taken before and after stimulation. The post-stimulation impedance [at mid-range frequencies (100 Hz-100 kHz)] consistently and significantly decreased relative to prestimulation levels. Impedance magnitude increased permanently at low frequencies (< 100 Hz), correlating to a change in the charge storage capacity (the area under a cyclic voltammagram). Impedance magnitude significantly increased during the recovery period, though this increase could be mostly reversed by applying small currents. A mathematical model of the electrode-tissue system impedance was used to analyze in vivo behavior. The data and modeling results shows that applying charge to the electrode can consistently reduce the impedance of the electrode-tissue system. Analysis of explanted probes suggests that the interaction between the tissue and electrode is dependent on whether chronic pulses were applied. It is hypothesized that the interface between the tissue and metal is altered by current pulsing, resulting in a temporary impedance shift.     

A Remote Control Brain Telestimulator with Solar Cell Power Supply

A brain telestimulator system is described which can be used with primates weighing 3.0 kg or more. The 3×6×7 cm, 200 gm head-mounted receiver employs solar cells to maintain the charge on its battery, thereby permitting experiments to continue undisturbed for many months. The head unit develops across its output a cathodal, monophasic pulse whose duration, rate, and constant current are remotely controlled from the transmitter. Subject to a duty cycle of 0.1, these parameters are continuously and remotely variable: pulse repetition rate, 0-200 pulses per second; pulse duration, 0.1-3.0 ms; pulse current intensity, 0-1.0 mA with less than ± 3 percent variance for loads between 2500-10 000 ohms. Output pulse rise time is 30 , ?s. Any one of 12 electrode channels can be selected for stimulation by remote control activation of an electro-mechanical stepping switch in the head unit. Utilization of crystal control in the frequency modulated transmitter and head units permits multi-animal operation by providing separate bands in the 138 MHz region for independent stimulation of up to four animals. The sensitivity of the receiver has purposely been designed low (-35 dBm). Thus, with the present transmitter the system has a range of about 0.2 mile, which extends beyond the normal visual limits of observation of primate groups.     

Scaling Effects on the Electrochemical Stimulation Performance of Au,Pt, and PEDOT:PSS Electrocorticography Arrays

The efficacy of electrical brain stimulation in combatting neurodegenerative diseases and initiating function is expected to be significantly enhanced with the development of smaller scale microstimulation electrodes and refined stimulation protocols. These benefits cannot be realized without a thorough understanding of scaling effects on electrochemical charge injection characteristics. This study fabricates and characterizes the electrochemical stimulation capabilities of Au, Pt, poly(3,4‐ethylenedioxythiophene):polystyrene sulfonate (PEDOT:PSS/Au), and PEDOT:PSS/Pt electrode arrays in the 20–2000 µm diameter range. This study observes substantial enhancement in charge injection capacity up to 9.5× for PEDOT:PSS microelectrodes compared to metal ones, and 88% lower required power for injecting the same charge density. These significant benefits are strongest for electrode diameters below 200 µm. Detailed quantitative analyses are provided, enabling optimization of charge injection capacity with potential bias and symmetric and asymmetric pulse width engineering for all diameters. These systematic analyses inform the optimal design for acute and potentially chronic implants in regards to safety and clinically effective stimulation protocols, ensure the longevity of the electrodes below critical electrochemical limits of stimulation, and demonstrate that the material choice and pulse design can lead to more energy efficiency stimulation protocols that are of critical importance for fully implanted devices.     

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.     

Optimal electrical stimulation modality for cortical esophageal evoked potentials: transmural or intraesophageal?

Esophageal electrical stimulation using short and a relatively small number of (200 micros, 0.2 Hz, n = 25) electrical pulses generates a characteristic and well defined cortical evoked potential response (EP). There are two methods of stimulation: either through intraesophageal electrodes or with transmural electrodes. The objective of this paper is to compare EP response, sensations and heart rate variability power spectra elicited by both stimulation modalities in healthy volunteers. Our results suggest that transmural stimulation is more accurately perceived and at lower intensities, produces more reproducible peaks of higher amplitude than during intraesophageal stimulation. During either mode of esophageal stimulation, power within the high-frequency component of the heart rate variability power spectrum is enhanced.     

Selective stimulation of smaller fibers in a compound nerve trunkwith single cathode by rectangular current pulses

Electrical stimulation of unmyelinated nerve fibers is analyzed, using point sources in a simple volume conductor model and a dynamic Hodgkin-Huxley model of nerve fiber. The excitation and blocking threshold of single cathode stimulation with an indifference anode at infinity are calculated by solving difference equations with axons of different diameters. The relation between the blocking threshold and the pulsewidth of single cathode stimulation is also calculated. The results suggest a method of selectively stimulating the smaller fibers in a compound nerve trunk. Two kinds of stimulation electrodes are designed to test this method. Both of them are proven to yield results in accordance with the authors' model by the animal experiments on a toad's sciatic nerve trunk. It is possible to excite the smaller fibers without exciting the larger ones in a compound nerve trunk by properly controlling the stimulus intensity. The method is likely to be used in both physiological experiments and neural prostheses     

Quantum interference control of electrical currents in GaAs

In an earlier publication, preliminary observations of the generation of electrical currents were reported in GaAs and low-temperature-grown GaAs (LT-GaAs) at 295 K using quantum interference control of single- and two-photon band-band absorption of 1.55- and 0.775-μm ultrashort optical pulses. Time-integrated currents were measured via charge collection in a metal-semiconductor-metal (MSM) electrode structure. Here we present detailed characteristics of this novel effect in terms of a simple circuit model for the MSM device and show how the injected current depends on MSM parameters as well as optical coherence, power, and polarization. For picosecond pulse excitation with peak irradiance of only 30 MW/cm^-2 (1.55 μm) and 9 kW/cm^-2 (0.775 μm), peak current densities of ~10 A/cm^-2 at peak carrier densities of 10¹⁵ cm ^-3 are inferred from the steady-state signals. This compares with 50 A/cm^-2 predicted theoretically; the discrepancy mainly reflects inefficient charge collection at the MSM electrodes     

An Asymmetric Two Electrode Cuf for Generation of Unidirectionally Propagated Action Potentials

An asymmetric two electrode cuff (ATEC) for generation of unidirectionally propagated action potentials (UPAP's) has been tested in animals. Results indicate that the design is well suited for applications of "collision block" of peripheral nerve transmission. This electrode cuff differs from a standard bipolar electrode cuff in that the anode is enclosed by an insulating sheath of larger diameter than the cuff's cathode and the electrodes are asymmetrically placed within the cuff. In all 13 animals studied, ATEC's with anodes of 1.6 or 3.4 mm diameter and with cathodes of 1.2 mm diameter generated UPAP's when used on a nerve trunk of approximately 1 mm diameter. The cuff length used was 16 mm and the cuff length asymmetry (i. e., distance from cathode to proximal end over distance from cathode to distal end) was 1.7:1. Stimuli were regulated-current rectangular pulses with exponential trailing phases. For pulse widths of 100-500 ?s, exponential (90-10 percent) fall-times of 100-500 f4s minimized total charge injection. The virtual cathode excitation typically seen in standard bipolar electrode cuffs was always adequately suppressed with the ATEC configuration. ATEC's generated UPAP's over a larger window of current amplitudes than monopolar electrodes of similar dimensions.     

Multifunctional Nanobiomaterials for Neural Interfaces

Neural electrodes are designed to interface with the nervous system and provide control signals for neural prostheses. However, robust and reliable chronic recording and stimulation remains a challenge for neural electrodes. Here, a novel method for the fabrication of soft, low impedance, high charge density, and controlled releasing nanobiomaterials that can be used for the surface modification of neural microelectrodes to stabilize the electrode/tissue interface is reported. The fabrication process includes electrospinning of anti‐inflammatory drug‐incorporated biodegradable nanofibers, encapsulation of these nanofibers by an alginate hydrogel layer, followed by electrochemical polymerization of conducting polymers around the electrospun drug‐loaded nanofibers to form nanotubes and within the alginate hydrogel scaffold to form cloud‐like nanostructures. The three‐dimensional conducting polymer nanostructures significantly decrease the electrode impedance and increase the charge capacity density. Dexamethasone release profiles show that the alginate hydrogel coating slows down the release of the drug, significantly reducing the burst effect. These multifunctional materials are expected to be of interest for a variety of electrode/tissue interfaces in biomedical devices.     

Scalable Microstructured Photoconductive Terahertz Emitters

The development of scalable emitters for pulsed broadband terahertz (THz) radiation is reviewed. Their large active area in the 1 – 100 mm² range allows for using the full power of state-of-the-art femtosecond lasers for excitation of charge carriers. Large fields for acceleration of the photogenerated carriers are achieved at moderate voltages by interdigitated electrodes. This results in efficient emission of single-cycle THz waves. THz field amplitudes in the range of 300 V/cm and 17 kV/cm are reached for excitation with 10 nJ pulses from Ti:sapphire oscillators and for excitation with 5 μJ pulses from amplified lasers, respectively. The corresponding efficiencies for conversion of near-infrared to THz radiation are 2.5 × 10^-4 (oscillator excitation) and 2 × 10^-3 (amplifier excitation). In this article the principle of operation of scalable emitters is explained and different technical realizations are described. We demonstrate that the scalable concept provides freedom for designing optimized antenna patterns for different polarization modes. In particular emitters for linearly, radially and azimuthally polarized radiation are discussed. The success story of photoconductive THz emitters is closely linked to the development of mode-locked Ti:sapphire lasers. GaAs is an ideal photoconductive material for THz emitters excited with Ti:sapphire lasers, which are widely used in research laboratories. For many applications, especially in industrial environments, however, fiber-based lasers are strongly preferred due to their lower cost, compactness and extremely stable operation. Designing photoconductive emitters on InGaAs materials, which have a low enough energy gap for excitation with fiber lasers, is challenging due to the electrical properties of the materials. We discuss why the challenges are even larger for microstructured THz emitters as compared to conventional photoconductive antennas and present first results of emitters suitable for excitation with ytterbium-based fiber lasers. Furthermore an alternative concept, namely the lateral photo-Dember emitter, is presented. Due to the strong THz output scalable emitters are well suited for THz systems with fast data acquisition. Here the application of scalable emitters in THz spectrometers without mechanical delay stages, providing THz spectra with 1 GHz spectral resolution and a signal-to-noise ratio of 37 dB within 1 s, is presented. Finally a few highlight experiments with radiation from scalable THz emitters are reviewed. This includes a brief discussion of near-field microscopy experiments as well as an overview over gain studies of quantum-cascade lasers.     

利用单电极不对称双向脉冲刺激实现哺乳动物有髓神经纤维选择性兴奋的仿真研究

本研究的目的是要从理论上探讨利用单电极双向脉冲刺激实现哺乳动物神经纤维选择性刺激,(即当刺激一束神经时,不兴奋粗神经而兴奋细神经)的可能性.双向脉冲刺激可以降低刺激脉冲对神经纤维产生的电化学损伤.为研究哺乳动物有髓神经纤维的电特性,建立了一个基于简单的无穷大、各向同性的容积导体模型的仿真系统.利用该仿真系统,采用"不对称但电荷平衡"的双向脉冲刺激,计算了神经纤维的兴奋和阻断阈值与纤维直径、纤维-电极间距离的关系.结果表明:在距电极一定距离内采用该双向脉冲刺激模式确实可以实现哺乳动物有髓神经纤维的选择性兴奋.     

Capacitance tomography sensor without CMOS switches

Usually, CMOS switches are used to select excitation and detection electrodes in electrical capacitance tomography (ECT) systems. However, these switches cause charge injection or coupling leakage problems. An ECT sensor is described which does not use any switches directly connected to the measurement electrodes. The potentials on the electrodes are digitally controlled and the excitation field of the sensor is totally flexible. Experimental results show that the circuit performs well as either an excitation or a detection channel