Paul B. Matteucci

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.

Current Steering in Retinal Stimulation via a Quasimonopolar Stimulation Paradigm

PURPOSE Research to restore some degree of vision to patients suffering from retinal degeneration is becoming increasingly more promising. Several groups have chosen electrical stimulation of the remaining network of a degenerate retina as a means to generate discrete light percepts (phosphenes). Approaches vary significantly, with the greatest difference being the location of the stimulating electrode itself. METHODS Suprachoroidal positioning offers excellent mechanical stability and surgical simplicity; however, at the cost of activation thresholds and focused stimulation due to the distance from the electrodes to the target neurons. Past studies proposed a hexapolar electrode configuration to focus the cortical activation and minimize cross-talk between electrodes during concurrent stimulation. The high impedance nature of the choroid and pigment epithelium, however, cause current to shunt between the stimulating and return electrodes, resulting in even higher activation thresholds. In our study, we analyzed the effect of stimulating the feline retina using a quasimonopolar stimulation by simultaneously stimulating a hexapolar and distant monopolar return configurations. RESULTS Results of in vivo studies showed that quasimonopolar stimulation can be used to maintain the activation containment properties of hexapolar stimulation, while lowering the activation threshold to values almost equivalent to those of monopolar stimulation. CONCLUSIONS The optimal stimulus was found to be composed of a subthreshold monopolar stimulus combined with a suprathreshold hexapolar stimulation. This resulted in a decrease of activation threshold of 60% with respect to hexapolar alone, but with no discernible deleterious effect on the charge containment of a pure hexapolar stimulation.

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.

The effect of electric cross-talk in retinal neurostimulation

PURPOSE To investigate the efficacy of electric field shaping in modulating the extent and activation threshold in retinal neurostimulation. This study aims to quantify the interference of neighboring stimulation sites by assessing the shift in the activation threshold produced by a concomitant interfering stimulus. METHODS Electrical stimuli were applied to healthy retinae in a feline model (n = 4) using a 24-channel electrode array surgically implanted in the suprachoroidal space. A 96-channel penetrating electrode array was used for recording cortical responses to a number of stimulation paradigms. Data were analyzed offline. Concurrent monopolar and hexapolar stimuli were delivered at primary and interfering sites separated by up to 2.19 mm to evaluate electric cross-talk. The spike rate was fit to a sigmoidal curve to estimate the P50 threshold. The slope of the linear regression of the P50 value versus interfering current level was considered as a measure of cross-talk. RESULTS Concurrent monopolar stimulation produced a proportional drop in the P50 of approximately 20% of the interfering current level in presence of a primary monopolar and hexapolar stimulus. On the other hand, hexapolar interference did not alter activation thresholds at the primary site. CONCLUSIONS Hexapolar stimulation reduces electric cross-talk between neighboring sites and represents a technique to reduce interference between individual stimulation sites. In contrast, concurrent monopolar stimulation produces a reduction of the activation threshold of stimuli delivered nearby. Thus, a single source of subthreshold monopolar charge injection can provide benefit in the form of significant threshold reduction simultaneously at multiple stimulation sites.

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.

Towards an assistive peripheral visual prosthesis for long-term treatment of retinitis pigmentosa: evaluating mobility performance in immersive simulations

OBJECTIVE The prospective efficacy of a future peripheral retinal prosthesis complementing residual vision to raise mobility performance in non-end stage retinitis pigmentosa (RP) was evaluated using simulated prosthetic vision (SPV). APPROACH Normally sighted volunteers were fitted with a wide-angle head-mounted display and carried out mobility tasks in photorealistic virtual pedestrian scenarios. Circumvention of low-lying obstacles, path following, and navigating around static and moving pedestrians were performed either with central simulated residual vision of 10° alone or enhanced by assistive SPV in the lower and lateral peripheral visual field (VF). Three layouts of assistive vision corresponding to hypothetical electrode array layouts were compared, emphasizing higher visual acuity, a wider visual angle, or eccentricity-dependent acuity across an intermediate angle. Movement speed, task time, distance walked and collisions with the environment were analysed as performance measures. MAIN RESULTS Circumvention of low-lying obstacles was improved with all tested configurations of assistive SPV. Higher-acuity assistive vision allowed for greatest improvement in walking speeds-14% above that of plain residual vision, while only wide-angle and eccentricity-dependent vision significantly reduced the number of collisions-both by 21%. Navigating around pedestrians, there were significant reductions in collisions with static pedestrians by 33% and task time by 7.7% with the higher-acuity layout. Following a path, higher-acuity assistive vision increased walking speed by 9%, and decreased collisions with stationary cars by 18%. SIGNIFICANCE The ability of assistive peripheral prosthetic vision to improve mobility performance in persons with constricted VFs has been demonstrated. In a prospective peripheral visual prosthesis, electrode array designs need to be carefully tailored to the scope of tasks in which a device aims to assist. We posit that maximum benefit might come from application alongside existing visual aids, to further raise life quality of persons living through the prolonged early stages of RP.

ARM-based visual processing system for prosthetic vision

A growing number of prosthetic devices have been shown to provide visual perception to the profoundly blind through electrical neural stimulation. These first-generation devices offer promising outcomes to those affected by degenerative disorders such as retinitis pigmentosa. Although prosthetic approaches vary in their placement of the stimulating array (visual cortex, optic-nerve, epi-retinal surface, sub-retinal surface, supra-choroidal space, etc.), most of the solutions incorporate an externally-worn device to acquire and process video to provide the implant with instructions on how to deliver electrical stimulation to the patient, in order to elicit phosphenized vision. With the significant increase in availability and performance of low power-consumption smart phone and personal device processors, the authors investigated the use of a commercially available ARM (Advanced RISC Machine) device as an externally-worn processing unit for a prosthetic neural stimulator for the retina. A 400 MHz Samsung S3C2440A ARM920T single-board computer was programmed to extract 98 values from a 1.3 Megapixel OV9650 CMOS camera using impulse, regional averaging and Gaussian sampling algorithms. Power consumption and speed of video processing were compared to results obtained to similar reported devices. The results show that by using code optimization, the system is capable of driving a 98 channel implantable device for the restoration of visual percepts to the blind.

Towards photorealistic and immersive virtual-reality environments for simulated prosthetic vision: integrating recent breakthroughs in consumer hardware and software.

Simulated prosthetic vision (SPV) in normally sighted subjects is an established way of investigating the prospective efficacy of visual prosthesis designs in visually guided tasks such as mobility. To perform meaningful SPV mobility studies in computer-based environments, a credible representation of both the virtual scene to navigate and the experienced artificial vision has to be established. It is therefore prudent to make optimal use of existing hardware and software solutions when establishing a testing framework. The authors aimed at improving the realism and immersion of SPV by integrating state-of-the-art yet low-cost consumer technology. The feasibility of body motion tracking to control movement in photo-realistic virtual environments was evaluated in a pilot study. Five subjects were recruited and performed an obstacle avoidance and wayfinding task using either keyboard and mouse, gamepad or Kinect motion tracking. Walking speed and collisions were analyzed as basic measures for task performance. Kinect motion tracking resulted in lower performance as compared to classical input methods, yet results were more uniform across vision conditions. The chosen framework was successfully applied in a basic virtual task and is suited to realistically simulate real-world scenes under SPV in mobility research. Classical input peripherals remain a feasible and effective way of controlling the virtual movement. Motion tracking, despite its limitations and early state of implementation, is intuitive and can eliminate between-subject differences due to familiarity to established input methods.

Smartphones as image processing systems for prosthetic vision

The feasibility of implants for prosthetic vision has been demonstrated by research and commercial organizations. In most devices, an essential forerunner to the internal stimulation circuit is an external electronics solution for capturing, processing and relaying image information as well as extracting useful features from the scene surrounding the patient. The capabilities and multitude of image processing algorithms that can be performed by the device in real-time plays a major part in the final quality of the prosthetic vision. It is therefore optimal to use powerful hardware yet to avoid bulky, straining solutions. Recent publications have reported of portable single-board computers fast enough for computationally intensive image processing. Following the rapid evolution of commercial, ultra-portable ARM (Advanced RISC machine) mobile devices, the authors investigated the feasibility of modern smartphones running complex face detection as external processing devices for vision implants. The role of dedicated graphics processors in speeding up computation was evaluated while performing a demanding noise reduction algorithm (image denoising). The time required for face detection was found to decrease by 95% from 2.5 year old to recent devices. In denoising, graphics acceleration played a major role, speeding up denoising by a factor of 18. These results demonstrate that the technology has matured sufficiently to be considered as a valid external electronics platform for visual prosthetic research.