Laser patterning of platinum electrodes for safe neurostimulation.

OBJECTIVE: Laser surface modification of platinum (Pt) electrodes was investigated for use in neuroprosthetics. Surface modification was applied to increase the surface area of the electrode and improve its ability to transfer charge within safe electrochemical stimulation limits. APPROACH: Electrode arrays were laser micromachined to produce Pt electrodes with smooth surfaces, which were then modified with four laser patterning techniques to produce surface structures which were nanosecond patterned, square profile, triangular profile and roughened on the micron scale through structured laser interference patterning (SLIP). Improvements in charge transfer were shown through electrochemical impedance spectroscopy (EIS), cyclic voltammetry (CV) and biphasic stimulation at clinically relevant levels. A new method was investigated and validated which enabled the assessment of in vivo electrochemically safe charge injection limits. MAIN RESULTS: All of the modified surfaces provided electrical advantage over the smooth Pt. The SLIP surface provided the greatest benefit both in vitro and in vivo, and this surface was the only type which had injection limits above the threshold for neural stimulation, at a level shown to produce a response in the feline visual cortex when using an electrode array implanted in the suprachoroidal space of the eye. This surface was found to be stable when stimulated with more than 150 million clinically relevant pulses in physiological saline. SIGNIFICANCE: Critical to the assessment of implant devices is accurate determination of safe usage limits in an in vivo environment. Laser patterning, in particular SLIP, is a superior technique for improving the performance of implant electrodes without altering the interfacial electrode chemistry through coating. Future work will require chronic in vivo assessment of these electrode patterns.

Current steering for high resolution retinal implants.

To significantly increase the resolution achievable by a retinal prosthesis without requiring additional electrodes, a current steering technique could be utilized. In this study, a finite element model was constructed to analyze the local concentrations of charge carrying ions within a saline bath due to concurrent stimulation from two electrodes surrounded by a hexagonal arrangement of return electrodes. By altering the return pathways, tissue activation and identification of unique stimulation patterns is possible. Ag/Ag-Cl electrodes and a voltage controlled current source were developed to validate the finite element model, with the model accurately predicting saline bath measurements. The average error in the returned currents between the finite element model and experimental results was 2% relative to the stimulus current.

Performance of conducting polymer electrodes for stimulating neuroprosthetics.

OBJECTIVE: Recent interest in the use of conducting polymers (CPs) for neural stimulation electrodes has been growing; however, concerns remain regarding the stability of coatings under stimulation conditions. These studies examine the factors of the CP and implant environment that affect coating stability. The CP poly(ethylene dioxythiophene) (PEDOT) is examined in comparison to platinum (Pt), to demonstrate the potential performance of these coatings in neuroprosthetic applications. APPROACH: PEDOT is coated on Pt microelectrode arrays and assessed in vitro for charge injection limit and long-term stability under stimulation in biologically relevant electrolytes. Physical and electrical stability of coatings following ethylene oxide (ETO) sterilization is established and efficacy of PEDOT as a visual prosthesis bioelectrode is assessed in the feline model. MAIN RESULTS: It was demonstrated that PEDOT reduced the potential excursion at a Pt electrode interface by 72% in biologically relevant solutions. The charge injection limit of PEDOT for material stability was found to be on average 30× larger than Pt when tested in physiological saline and 20× larger than Pt when tested in protein supplemented media. Additionally stability of the coating was confirmed electrically and morphologically following ETO processing. It was demonstrated that PEDOT-coated electrodes had lower potential excursions in vivo and electrically evoked potentials (EEPs) could be detected within the visual cortex. SIGNIFICANCE: These studies demonstrate that PEDOT can be produced as a stable electrode coating which can be sterilized and perform effectively and safely in neuroprosthetic applications. Furthermore these findings address the necessity for characterizing in vitro properties of electrodes in biologically relevant milieu which mimic the in vivo environment more closely.

Electric crosstalk impairs spatial resolution of multi-electrode arrays in retinal implants.

Active multi-electrode arrays are used in vision prostheses, including optic nerve cuffs and cortical and retinal implants for stimulation of neural tissue. For retinal implants, arrays with up to 1500 electrodes are used in clinical trials. The ability to convey information with high spatial resolution is critical for these applications. To assess the extent to which spatial resolution is impaired by electric crosstalk, finite-element simulation of electric field distribution in a simplified passive tissue model of the retina is performed. The effects of electrode size, electrode spacing, distance to target cells, and electrode return configuration (monopolar, tripolar, hexagonal) on spatial resolution is investigated in the form of a mathematical model of electric field distribution. Results show that spatial resolution is impaired with increased distance from the electrode array to the target cells. This effect can be partly compensated by non-monopolar electrode configurations and larger electrode diameters, albeit at the expense of lower pixel densities due to larger covering areas by each stimulation electrode. In applications where multi-electrode arrays can be brought into close proximity to target cells, as presumably with epiretinal implants, smaller electrodes in monopolar configuration can provide the highest spatial resolution. However, if the implantation site is further from the target cells, as is the case in suprachoroidal approaches, hexagonally guarded electrode return configurations can convey higher spatial resolution.

Advancements in electrode design and laser techniques for fabricating micro-electrode arrays as part of a retinal prosthesis.

Retinal micro-electrode arrays (MEAs) for a visual prosthesis were fabricated by laser structuring of platinum (Pt) foil and liquid silicone rubber. A new design was created using a folding technique to create a multi-layered array from a single Pt sheet. This method allowed a reduction in both the electrode pitch, and the overall width of the array, while maintaining coplanar connection points for more stable interconnections to other components of the system. The design also included a section which could be rolled to create a cylindrical segment in order to minimise the size of the exit in the sclera after implantation. A picosecond mode-locked 532 nm laser system was investigated as a replacement for the nanosecond Q-switched 1064 nm laser currently in use. Trials showed that the ps system could produce high quality electrode tracks with a minimum pitch of 30 µm, less than 40% the pitch achievable with the ns laser. A method was investigated for the cutting of Pt foils without damaging the underlying silicone by laser machining to a depth just below the thickness of the foil. Initial samples showed promise with full penetration of the foil only occurring at cross points of the laser paths. The ps laser was also used to create roughened surfaces, in order to increase the electrochemical surface area of the electrodes. Surfaces were imaged using a scanning electron microscope, and compared to surfaces roughened with the ns laser. The ps laser was seen to offer a reduction in feature size, as well as an increase in control over the appearance of the electrode surface.

Responses of starburst amacrine cells to prosthetic stimulation of the retina.

Recent advances in the design and development of retinal implants have made these devices a promising therapeutic strategy for restoring sight to the blind. Over the last decade a plethora of studies have investigated the responses of the retinal ganglion cells (RGCs) to electrical stimulation under a variety of stimulus configurations. Similar to the RGCs, the amacrine cells also survive in large numbers following retinal neural degeneration. However, with the exception of two previous reports, where the responses of the amacrine cells were measured indirectly, these cells have thus far received little attention in the context of prosthetic stimulation. In this study we focused on the starburst amacrine cells (SACs), a particularly well-characterized amacrine cell among the approximately two-dozen types known to exist in the retina. Using whole-cell patch clamp recordings in the whole-mount rabbit retina, we investigated the temporal responses of the SACs following subretinal biphasic pulse stimulation. These cells responded to the stimuli with oscillatory membrane potentials that lasted for tens to hundreds of milliseconds, with the response amplitude increasing as a function of stimulus strength. Furthermore, the SAC responses originated primarily from the presynaptic inputs they receive, rather than through direct activation of these cells by the electrical stimuli.

Discrete cortical responses from multi-site supra-choroidal electrical stimulation in the feline retina.

Exploration into electrical stimulation of the retina has thus far focussed primarily upon the development of prostheses targeted at one of two sites of intervention - the epi- and sub-retinal surfaces. These two approaches have sound, logical merit owing to their proximity to retinal neurons and their potential to deliver stimuli via the surviving retinal neural networks respectively. There is increasing evidence, however, that electric field effects, electrode engineering limitations, and electrode-tissue interactions limit the spatial resolution that once was hoped could be elicited from electrical stimulation at epi- and sub-retinal sites. An alternative approach has been proposed that places a stimulating electrode array within the supra-choroidal space - that is, between the sclera and the choroid. Here we investigate whether discrete, cortical activity patterns can be elicited via electrical stimulation of a feline retina using a custom, 14 channel, silicone rubber and Pt electrode array arranged in two hexagons comprising seven electrodes each. Cortical responses from Areas 17/18 were acquired using a silicon-based, multi-channel, penetrating probe developed at IMTEK, University of Freiburg, within the European research project NeuroProbes. Multi-unit spike activity was recorded in synchrony with the presentation of electrical stimuli. Results show that distinct cortical response patterns could be elicited from each hexagon separated by 1.8 mm (center-to-center) with a center-to-center electrode spacing within each hexagon of 0.55 mm. This lends support that higher spatial resolution may also be discerned.

Conducting polymer electrodes for visual prostheses.

Conducting polymers (CPs) have the potential to provide superior neural interfaces to conventional metal electrodes by introducing more efficient charge transfer across the same geometric area. In this study the conducting polymer poly(ethylene dioxythiophene) (PEDOT) was coated on platinum (Pt) microelectrode arrays. The in vitro electrical characteristics were assessed during biphasic stimulation regimes applied between electrode pairs. It was demonstrated that PEDOT could reduce the potential excursion at a Pt electrode interface by an order of magnitude. The charge injection limit of PEDOT was found to be 15 x larger than Pt. Additionally, PEDOT coated electrodes were acutely implanted in the suprachoroidal space of a cat retina. It was demonstrated that PEDOT coated electrodes also had lower potential excursions in vivo and electrically evoked potentials (EEPs) could be detected within the vision cortex.

A transparent electrode array for simultaneous cortical potential recording and intrinsic signal optical imaging.

Intrinsic signal optical imaging (ISOI) is a technique that enables researchers to relate changes in cortical activity in response to stimuli by measuring changes in hemoglobin oxygenation and local blood volume. As the time course of these changes - local blood volume in particular - is of the order of seconds, the neural activity that initiates these changes is only indirectly acquired in ISOI. To better correlate these events, it is beneficial to simultaneously record both the evoked cortical potentials and ISOI. In this study we present a novel, transparent, recording array that allows the combination of optical imaging with electrical recordings without the use of metal electrodes in the observation field. Pilot data were recorded after visual and electrical stimuli of the eye to prove the concept.

Direct activation of retinal ganglion cells with subretinal stimulation.

Recent advances in the design and implementation of vision prostheses have made these devices a promising therapeutic option for restoring sight to blind patients in the near future. The success of vision prostheses in providing clinically useful vision, however, depends critically on our understanding of the retinal neural mechanisms evoked during electrical stimulation, and how these mechanisms can be controlled precisely to elicit the desired visual percept. We demonstrate here that subretinal stimulation can reliably elicit stimulus- locked short latency (< or = 2 ms) responses. To our knowledge, this is the first report of such responses using the subretinal paradigm. These responses could be readily distinguished from within the stimulus artifacts using cell-attached extracellular recording or whole-cell patch clamp. The thresholds for these short latency responses were determined for ON, OFF and ON- OFF type retinal ganglion cell classes across cathodic biphasic pulses of 0.1-5.0ms. No significant difference was found for the mean latency and the threshold for the different cell types over the pulse range tested.

A CMOS retinal neurostimulator capable of focussed, simultaneous stimulation.

Restoring vision to the blind by way of medical device technology has been an objective of several research teams for a number of years. It is known that spots of light-phosphenes-can be elicited by way of electrical stimulation of surviving retinal neurons. Beyond this our understanding of prosthetic vision remains rudimentary. We have designed and manufactured an integrated circuit neurostimulator with substantial versatility, able to provide focussed, simultaneous stimulation using current sources and sinks, steering the current to the intended site of stimulation. The ASIC utilizes high-voltage CMOS transistors in key circuits, to manage voltage compliance issues (due to an unknown or changing electrode/tissue interface impedance) given the relatively high stimulation thresholds necessary to elicit physiological excitation of retinal neurons. In addition, a unique multiplexing system comprised of electrodes arranged in a hexagonal mosaic is used, wherein each electrode can be addressed to be a stimulating electrode and all adjacent electrodes serve as the return path. This allows for simultaneous stimulation to be delivered while appropriately managing cross-talk between the stimulating electrodes. Test results indicate highly linear current sources and sinks (differential nonlinearity error of 0.13 least significant bits -2.6 microA), with the ASIC clearly able to provide focussed stimulation using electrodes immersed in a saline solution.

Rehabilitation regimes based upon psychophysical studies of prosthetic vision.

Human trials of prototype visual prostheses have successfully elicited visual percepts (phosphenes) in the visual field of implant recipients blinded through retinitis pigmentosa and age-related macular degeneration. Researchers are progressing rapidly towards a device that utilizes individual phosphenes as the elementary building blocks to compose a visual scene. This form of prosthetic vision is expected, in the near term, to have low resolution, large inter-phosphene gaps, distorted spatial distribution of phosphenes, restricted field of view, an eccentrically located phosphene field and limited number of expressible luminance levels. In order to fully realize the potential of these devices, there needs to be a training and rehabilitation program which aims to assist the prosthesis recipients to understand what they are seeing, and also to adapt their viewing habits to optimize the performance of the device. Based on the literature of psychophysical studies in simulated and real prosthetic vision, this paper proposes a comprehensive, theoretical training regime for a prosthesis recipient: visual search, visual acuity, reading, face/object recognition, hand-eye coordination and navigation. The aim of these tasks is to train the recipients to conduct visual scanning, eccentric viewing and reading, discerning low-contrast visual information, and coordinating bodily actions for visual-guided tasks under prosthetic vision. These skills have been identified as playing an important role in making prosthetic vision functional for the daily activities of their recipients.

A wearable real-time image processor for a vision prosthesis.

Rapid progress in recent years has made implantable retinal prostheses a promising therapeutic option in the near future for patients with macular degeneration or retinitis pigmentosa. Yet little work on devices that encode visual images into electrical stimuli have been reported to date. This paper presents a wearable image processor for use as the external module of a vision prosthesis. It is based on a dual-core microprocessor architecture and runs the Linux operating system. A set of image-processing algorithms executes on the digital signal processor of the device, which may be controlled remotely via a standard desktop computer. The results indicate that a highly flexible and configurable image processor can be built with the dual-core architecture. Depending on the image-processing requirements, general-purpose embedded microprocessors alone may be inadequate for implementing image-processing strategies required by retinal prostheses.

Focal activation of the feline retina via a suprachoroidal electrode array.

This paper presents the results of the first investigations into the use of bipolar electrical stimulation of the retina with a suprachoroidal vision prosthesis, and the effects of different electrode configurations on localization of responses on the primary visual cortex. Cats were implanted with electrodes in the suprachoroidal space, and electrically evoked potentials were recorded on the visual cortex. Responses were elicited to bipolar and monopolar stimuli, with each stimulating electrode coupled with either six-return electrodes, two-return electrodes, or a single-return electrode. The average charge threshold to elicit a response with bipolar stimulation and six-return electrodes was 76.47+/-8.76 nC. Bipolar stimulation using six-return electrodes evoked responses half the magnitude of those elicited with a single or two-return electrodes. Monopolar stimulation evoked a greater magnitude, and area of cortical activation than bipolar stimulation. This study showed that suprachoroidal, bipolar stimulation can elicit localized activity in the primary visual cortex, with the extent of localization and magnitude of response dependent on the electrode configuration.

Efficacy of supra-choroidal, bipolar, electrical stimulation in a vision prosthesis.

The key to successful, clinical application of therapeutic neurostimulators lies primarily with the safety and efficacy of their electrode-tissue interfaces. The authors posit that for electrical stimulation of the visual system, supra-choroidal electrode placement provides a safe, stable and readily-accessible site for implantation and the provision of electrical stimulation. The present paper explores the efficacy of supra-choroidal electrical stimulation of retinal neurons. Based upon recordings made with surface electrodes placed on the primary visual cortex, areas of activation in the cortex were shown to change when different areas on the supra-choroidal space were stimulated. Finally, the threshold to elicit a response from neurons in the visual cortex, was found to be 77.55 +/- 29.85 nC.

A dual band wireless power and FSK data telemetry for biomedical implants.

A dual-link coil arrangement and a novel digital frequency-shift keying (FSK) demodulator are presented. The primary application of this system is for inductively powered biomedical implants. The implant is provided with data and power via two separate links. Two sets of coils are used in an arrangement such that the magnetic interference between the two pairs is minimized. The demodulator circuitry presented relies solely on delaying elements, utilizing a delayed digital FSK signal to sample the original digital FSK signal. A synchronized clock can be derived from the FSK signals alone, however, by utilizing the power signal to obtain a synchronized clock, a higher data rate and a decrease in complexity of the receiver circuitry can be achieved. The system was implemented on the bench and experimentally tested at a data rate of 2.083 Mbps with zero bit error rate while receiving a 4.17/6.25 MHz FSK carrier signal synchronized with 2.083 MHz clock derived from the power carrier. The power link was set to provide 58mW.

A wideband frequency-shift keying demodulation technique for inductively powered biomedical implants.

A digital wideband frequency-shift keying (FSK) demodulator is presented. The primary application of this system is for inductively powered biomedical implants. By providing both the data and the power to the implant via an inductive link, the need for a battery and the interconnect wires are eliminated. This reduces revision surgeries that may take place for maintenance purposes, provides extra safety measures in the case of failures and reduces the risk of infection. However these devices are challenged by power requirements and size availability at the receiving site and often require a high data rate. These challenges lead to the need for an efficient demodulation technique, as traditional methods often do not overcome the restrictions that prevail. The demodulator circuitry presented relies solely on delaying elements, utilising a delayed FSK carrier to sample the incoming FSK waveform. The system architecture is based on a digital environment and both the data and a synchronised clock are derived concurrently. This can be achieved with the coherent-FSK modulated raw binary data stream without the need of any additional baseband coding schemes. The demodulator circuitry was simulated up to a data rate of 5 Mbps while receiving a 5/10 MHz FSK carrier. The system was also implemented on the bench and experimentally tested at a data rate of 1.042 Mbps with no detectable bit error rate while receiving a 4.16/6.25 MHz FSK carrier signal.

A quantitative analysis of head movement behaviour during visual acuity assessment under prosthetic vision simulation.

In most current vision prosthesis designs, head movement is the sole director of visual gaze and scanning due to the head-mounted nature of the camera. Study of this unnatural behaviour may provide insight into improved prosthesis designs and rehabilitation procedures. In this paper, we conducted a psychophysical study to investigate the characteristics of head movements of normally sighted subjects undergoing a visual acuity task in simulated prosthetic vision (SPV). In 12 naïve, untrained subjects, we recorded spontaneous changes in the amount of head movements during SPV sessions compared to control (normal vision) sessions. The observed behaviour continued to be refined until five or six sessions of practice. Increased head movement velocity was shown to be correlated to improved visual acuity performance, up to 0.3 logMAR, an equivalent of detecting details at half the physical size compared to complete deprivation of head movements. We postulate that visual scanning can as much as double the spatial frequency information in prosthetic vision. Increased head movement velocity observed when subjects were attempting smaller test items and for low-pass filtering schemes with higher cut-off frequencies may be further evidence that higher frequency content may be available through visual scanning, unconsciously driving subjects to increase head movement velocity.

Simulating auditory and visual sensorineural prostheses: a comparative review.

Microelectronic vision prosthesis proposes to render luminous spots (so-called phosphenes) in the visual field of the otherwise blind subject by way of an implanted array of stimulating electrodes, and in doing so restore some spatial vision. There are now many research teams worldwide working towards a therapeutic device, analogous to the cochlear implant, for the profoundly blind. Despite the similarities between the cochlear implant and vision prostheses, there are few instances in the literature where the two approaches are compared and contrasted with a mind to informing the science and engineering of the latter. This is the focus of the present review; specifically, our interest is psychophysics and signal processing. Firstly, we examine the cochlear implant, and review a handful of psychophysical work: the acoustic simulation of cochlear implants and the method used. We focus on the use of normally hearing subjects (played coloured noise bands or sine waves) as a means of investigating cochlear-implant efficacy and speech processing algorithms. These results provide guidance to vision researchers, for they address the interpretation of simulation data, and flag key areas, such as 'artificial' perception in the presence of noise, that require experimental work in coming years. Secondly, we provide an up-to-date review of the body of analogous psychophysical work: the visual simulation, involving normal observers, of microelectronic vision prosthesis. These simulations allow predictions as to the likely clinical efficacy of the prosthesis; indeed, results to date suggest that a number on the order of 100 implanted electrodes will afford subjects mobility and recognition of faces (and other complex stimuli), while even fewer electrodes facilitate reading printed text and very simple visuomanual tasks. Further, the simulations allow investigations of image and signal processing strategies, plus they provide researchers in the field, and other interested persons, a perceptual experience that approximates what a prosthesis will likely afford implantees.

Bank note recognition for the vision impaired.

Blind Australians find great difficulty in recognising bank notes. Each note has the same feel, with no Braille markings, irregular edges or other tangible features. In Australia, there is only one device available that can assist blind people recognise their notes. Internationally, there are devices available; however they are expensive, complex and have not been developed to cater for Australian currency. This paper discusses a new device, the MoneyTalker that takes advantage of the largely different colours and patterns on each Australian bank note and recognises the notes electronically, using the reflection and transmission properties of light. Different coloured lights are transmitted through the inserted note and the corresponding sensors detect distinct ranges of values depending on the colour of the note. Various classification algorithms were studied and the final algorithm was chosen based on accuracy and speed of recognition. The MoneyTalker has shown an accuracy of more than 99%. A blind subject has tested the device and believes that it is usable, compact and affordable. Based on the devices that are available currently in Australia, the MoneyTalker is an effective alternative in terms of accuracy and usability.