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Multielectrode arrays for interfacing with neurons are of great interest for a wide range of medical applications. However, current electrodes cause damage over time. Ultra small carbon fibers help to address issues but controlling the electrode site geometry is difficult. Here we propose a methodology to create small, pointed fiber electrodes (SPFe). We compare the SPFe to previously made blowtorched fibers in characterization. The SPFe result in small site sizes [Formula: see text] with consistently sharp points (20.8 ± 7.64°). Additionally, these electrodes were able to record and/or stimulate neurons multiple animal models including rat cortex, mouse retina, Aplysia ganglia and octopus axial cord. In rat cortex, these electrodes recorded significantly higher peak amplitudes than the traditional blowtorched fibers. These SPFe may be applicable to a wide range of applications requiring a highly specific interface with individual neurons.

Retinal prostheses aim to improve visual perception in patients blinded by photoreceptor degeneration. However, shape and letter perception with these devices is currently limited due to low spatial resolution. Previous research has shown the retinal ganglion cell (RGC) spatial activity and phosphene shapes can vary due to the complexity of retina structure and electrode-retina interactions. Visual percepts elicited by single electrodes differ in size and shapes for different electrodes within the same subject, resulting in interference between phosphenes and an unclear image. Prior work has shown that better patient outcomes correlate with spatially separate phosphenes. In this study we use calcium imaging, in vitro retina, neural networks (NN), and an optimization algorithm to demonstrate a method to iteratively search for optimal stimulation parameters that create focal RGC activation. Our findings indicate that we can converge to stimulation parameters that result in focal RGC activation by sampling less than 1/3 of the parameter space. A similar process implemented clinically can reduce time required for optimizing implant operation and enable personalized fitting of retinal prostheses.

Goal: Retinal prosthesis performance is limited by the variability of elicited phosphenes. The stimulating electrode's position with respect to retinal ganglion cells (RGCs) affects both perceptual threshold and phosphene shape. We created a modeling framework incorporating patient-specific anatomy and electrode location to investigate RGC activation and predict inter-electrode differences for one Argus II user., Methods: We used ocular imaging to build a three-dimensional finite element model characterizing retinal morphology and implant placement. To predict the neural response to stimulation, we coupled electric fields with multi-compartment cable models of RGCs. We evaluated our model predictions by comparing them to patient-reported perceptual threshold measurements., Results: Our model was validated by the ability to replicate clinical impedance and threshold values, along with known neurophysiological trends. Inter-electrode threshold differences in silico correlated with in vivo results., Conclusions: We developed a patient-specific retinal stimulation framework to quantitatively predict RGC activation and better explain phosphene variations.

This paper presents a fully intraocular self-calibrating epiretinal prosthesis with 512 independent channels in 65 nm CMOS. A novel digital calibration technique matches the biphasic currents of each channel independently while the calibration circuitry is shared among every 4 channels. Dual-band telemetry for power and data with on-chip rectifier and clock recovery reduces the number of off-chip components. The rectifier utilizes unidirectional switches to prevent reverse conduction loss in the power transistors and achieves an efficiency > 80%. The data telemetry implements a phase-shift keying (PSK) modulation scheme and supports data rates up to 20 Mb/s. The system occupies an area of 4.5 ×3.1 mm². It features a pixel size of 0.0169 mm² and arbitrary waveform generation per channel. In vitro measurements performed on a Pt/Ir concentric bipolar electrode in phosphate buffered saline (PBS) are presented. A statistical measurement over 40 channels from 5 different chips shows a current mismatch with μ = 1.12 μA and σ = 0.53 μA. The chip is integrated with flexible MEMS origami coils and parylene substrate to provide a fully intraocular implant.

Retinal prostheses have restored light perception to people worldwide who have poor or no vision as a consequence of retinal degeneration. To advance the quality of visual stimulation for retinal implant recipients, a higher number of stimulation channels is expected in the next generation retinal prostheses, which poses a great challenge to system design and verification. This paper presents a system verification platform dedicated to the development of retinal prostheses. The system includes primary processing, dual-band power and data telemetry, a high-density stimulator array, and two methods for output verification. End-to-end system validation and individual functional block characterization can be achieved with this platform through visual inspection and software analysis. Custom-built software running on the computers also provides a good way for testing new features before they are realized by the ICs. Real-time visual feedbacks through the video displays make it easy to monitor and debug the system. The characterization of the wireless telemetry and the demonstration of the visual display are reported in this paper using a 256-channel retinal prosthetic IC as an example.

Precise positioning of a stimulating electrode in the eye is not possible by simple visualization. However, reliable measurement of responses to retinal stimulation requires consistent positioning. The present study focuses on impedance measurement techniques to sense the proximity of the electrode to the retina. A platinum-iridium stimulation electrode was placed inside the rat eye and impedance was recorded at different positions of the stimulating electrode relative to the retina. The presence of robust electrically evoked response in the superior colliculus indicates that the electrode may not have to be in absolute contact in order to elicit a neural response. Optical coherence tomography imaging confirmed the distance-impedance relationship.

Epiretinal prostheses for the blind bypass diseased photosensitive cells in the retina, directly stimulating retinal neurons electrically and evoking signals that are relayed to the brain. Current clinical implants have few electrodes and provide limited visual acuity. Acuity may be improved by identifying electrode array design features and operational details that enhance or interfere with visual percept formation. We labeled all retinal ganglion cells in whole mount retina with a calcium reporter and then measured the number and pattern of cells responding, over a range of electrode diameters and stimulus durations. Span of the response scaled with electrode diameter for electrodes 60 μm and larger. Short stimulation pulse widths selectively activated cells nearest the electrode. Our measurements in the salamander retina suggest that the spatial resolution is 150 μm, which on a human retina is equivalent to 0.55(°) of human visual field and corresponding Snellen acuity of 20/660. Reading large print could be possible with such a prosthesis., (© 2011 IEEE)

In this paper, the thermal elevation in the human body due to the operation of a dual-unit epiretinal prosthesis to restore partial vision to the blind affected by irreversible retinal degeneration is presented. An accurate computational model of a 60-electrode device dissipating 97 mW power, currently under clinical trials is developed and positioned in a 0.25 mm resolution, heterogeneous model of the human head to resemble actual conditions of operation of the prosthesis. A novel simple finite difference scheme combining the explicit and the alternating-direction implicit (ADI) method has been developed and validated with existing methods. Simulation speed improvement up to 11 times was obtained for the the head model considered in this work with very good accuracy. Using this method, solutions of the bioheat equation were obtained for different placements of the implant. Comparison with in-vivo experimental measurements showed good agreement.

Dysfunction of the seventh cranial nerve often results in facial paralysis and loss of the ability to blink the eye, which can lead to corneal scarring, diminished vision, and potential loss of the eye. This study investigated the potential of electrical stimulation of the orbicularis oculi muscle as a means of restoring blink function. An animal model of orbicularis paralysis was created by sectioning the seventh cranial nerve in rabbit. Twenty paralyzed and five normal rabbits were acutely implanted with a subcutaneous stimulating electrode near the margin of the upper eyelid. Biphasic current controlled stimulation pulses were delivered between implanted contacts at the medial and lateral edges of the eyelid. Strength-duration curves for lid twitch threshold were generated, and quantitative measurements of lid closure were made for systematically varied parameters including pulse amplitude, pulse width, number of pulses delivered, and duration of paralysis prior to stimulation. Normal rabbits achieved a greater degree of lid closure due to electrical stimulation than rabbits that had been surgically paralyzed. Of rabbits that had been paralyzed, those demonstrating evidence of at least partial reinnervation achieved a greater degree of lid closure than those demonstrating persistent denervation. Trains of 10 ms biphasic pulses delivered at 50 Hz were found to be the most effective means of eliciting lid closure for the range of parameters tested.

Experiments were conducted to assess the effect of stimulating electrode parameters (size, position, and waveform shape) on electrically elicited ganglion cell action potentials from isolated rabbit retina. Thirty-eight isolated rabbit retinas were stimulated with bipolar stimulating electrodes (either 125 or 25 microm in diameter) positioned on either the ganglion or the photoreceptor side. Recording electrodes were placed between the optic disc and the stimulating electrodes. Cathodic-first, biphasic, current waveforms of varying pulse durations (0.1, 0.5, 1 ms) were used. For the four conditions tested (125-electrode and 25-microm electrode, ganglion cell, and photoreceptor positions) threshold currents ranged from 6.7 to 23.6 microA, depending on location and pulse duration. With 1-ms pulse duration, no statistically significant difference was seen between threshold currents when either size electrode was used to stimulate either the ganglion cell side or the photoreceptor side. For all groups, the threshold currents using the 1-ms pulse were lower than those using 0.1 ms, but the 0.1-ms pulses used less charge. These experiments provide a number of valuable insights into the relative effects of several stimulation parameters critical to the development of an implanted electronic retinal prosthesis.

Three test subjects blind from retinitis pigmentosa were implanted with retinal prostheses as part of a FDA-approved clinical trial. The implant consisted of an extraocular unit that contained electronics for wireless data, power, and generation of stimulus current, and an intraocular unit that consisted of 16 platinum stimulating electrodes arranged in a 4 x 4 pattern within a silicone rubber substrate. The array was held to the retina by a small tack. The stimulator was connected to the array by a multiwire cable and was controlled by a computer based external system that allowed precise control over each electrode. Perception thresholds and electrode impedance were obtained on each electrode from the subjects over several months of testing. The electrode distance from the retina was determined from optical coherence tomography imaging of the array and retina. Across all subjects, average thresholds ranged from 24-702 microA (1-ms pulse). The data show that proximity to the retina played a role in determining the threshold and impedance, but only for electrodes that were greater than 0.5 mm from the retina.