Visual-tactile shape perception in the visually restored with artificial vision.

Retinal prostheses partially restore vision to late blind patients with retinitis pigmentosa through electrical stimulation of still-viable retinal ganglion cells. We investigated whether the late blind can perform visual-tactile shape matching following the partial restoration of vision via retinal prostheses after decades of blindness. We tested for visual-visual, tactile-tactile, and visual-tactile two-dimensional shape matching with six Argus II retinal prosthesis patients, ten sighted controls, and eight sighted controls with simulated ultra-low vision. In the Argus II patients, the visual-visual shape matching performance was significantly greater than chance. Although the visual-tactile shape matching performance of the Argus II patients was not significantly greater than chance, it was significantly higher with longer duration of prosthesis use. The sighted controls using natural vision and the sighted controls with simulated ultra-low vision both performed the visual-visual and visual-tactile shape matching tasks significantly more accurately than the Argus II patients. The tactile-tactile matching was not significantly different between the Argus II patients and sighted controls with or without simulated ultra-low vision. These results show that experienced retinal prosthesis patients can match shapes across the senses and integrate artificial vision with somatosensation. The correlation of retinal prosthesis patients' crossmodal shape matching performance with the duration of device use supports the value of experience to crossmodal shape learning. These crossmodal shape matching results in Argus II patients are the first step toward understanding crossmodal perception after artificial visual restoration.

Method to remove photoreceptors from whole mount retina in vitro.

Patch clamp recordings of neurons in the inner nuclear layer of the retina are difficult to conduct in a whole mount retina preparation because surrounding neurons block the path of the patch pipette. Vertical slice preparations or dissociated retinal cells provide access to bipolar cells at the cost of severing the lateral connection between neurons. We have developed a technique to remove photoreceptors from the rodent retina that exposes inner nuclear layer neurons, allowing access for patch clamp recording. Repeated application to and removal of filter paper from the photoreceptor side of an isolated retina effectively and efficiently removes photoreceptor cells and, in degenerate retina, hypertrophied Müller cell end feet. Live-dead assays applied to neurons remaining after photoreceptor removal demonstrated mostly viable cells. Patch clamp recordings from bipolar cells reveal responses similar to those recorded in traditional slice and dissociated cell preparations. An advantage of the photoreceptor peel technique is that it exposes inner retinal neurons in a whole mount retina preparation for investigation of signal processing. A disadvantage is that photoreceptor removal alters input to remaining retinal neurons. The technique may be useful for investigations of extracellular electrical stimulation, photoreceptor DNA analysis, and nonpharmacological removal of light input.NEW & NOTEWORTHY This study reports a method for removing photoreceptors from rodent whole mount retina while preserving the architecture of the inner retina. The method enables easier access to the inner retina for studies of neural processing, such as by patch clamp recording.

Worldwide Argus II implantation: recommendations to optimize patient outcomes.

BACKGROUND: A position paper based on the collective experiences of Argus II Retinal Prosthesis System investigators to review strategies to optimize outcomes in patients with retinitis pigmentosa undergoing retinal prosthesis implantation. METHODS: Retinal surgeons, device programmers, and rehabilitation specialists from Europe, Canada, Middle East, and the United States were convened to the first international Argus II Investigator Meeting held in Ann Arbor, MI in March 2015. The recommendations from the collective experiences were collected. Factors associated with successful outcomes were determined. RESULTS: Factors leading to successful outcomes begin with appropriate patient selection, expectation counseling, and preoperative retinal assessment. Challenges to surgical implantation include presence of staphyloma and inadequate Tenon's capsule or conjunctiva. Modified surgical technique may reduce risks of complications such as hypotony and conjunctival erosion. Rehabilitation efforts and correlation with validated outcome measures following implantation are critical. CONCLUSIONS: Bringing together Argus II investigators allowed the identification of strategies to optimize patient outcomes. Establishing an on-line collaborative network will foster coordinated research efforts to advance outcome assessment and rehabilitation strategies.

Ten-Year Follow-up of a Blind Patient Chronically Implanted with Epiretinal Prosthesis Argus I.

PURPOSE: The Argus I implant is the first-generation epiretinal prosthesis approved for an investigational clinical trial by the United States Food and Drug Administration. Herein we report testing results obtained from a 10-year follow-up to study the physiologic effects of the bioelectronic visual implant after prolonged chronic electrical stimulation. DESIGN: Case report. PARTICIPANT: One man, 55 years of age when enrolled in the study, underwent surgical implantation of the Argus I in June 2004, followed by periodic tests from July 2004 through June 2014, spanning a total of 10 years. METHODS: The decade-long follow-up consisted of implant system performance tests, subject visual function evaluation, and implant-retina interface analysis. MAIN OUTCOME MEASURES: Changes in electrode impedance and perceptual threshold over the time course; subject's performance on visual function task, orientation, and mobility tests; and optical coherence tomography data, fundus imaging, and fluorescein angiography results for the assessment of subject's implant-retina physical interface. RESULTS: Electrically elicited phosphenes were present 10 years after implantation of an epiretinal stimulator. The test subject not only was able to perceive phosphenes, but also could perform visual tasks at rates well above chance. CONCLUSIONS: This decade-long follow-up report provides further support for the use of retinal prostheses as a long-lasting treatment for some types of blindness.

Axonal stimulation affects the linear summation of single-point perception in three Argus II users.

Objective.Retinal implants use electrical stimulation to elicit perceived flashes of light ('phosphenes'). Single-electrode phosphene shape has been shown to vary systematically with stimulus parameters and the retinal location of the stimulating electrode, due to incidental activation of passing nerve fiber bundles. However, this knowledge has yet to be extended to paired-electrode stimulation.Approach.We retrospectively analyzed 3548 phosphene drawings made by three blind participants implanted with an Argus II Retinal Prosthesis. Phosphene shape (characterized by area, perimeter, major and minor axis length) and number of perceived phosphenes were averaged across trials and correlated with the corresponding single-electrode parameters. In addition, the number of phosphenes was correlated with stimulus amplitude and neuroanatomical parameters: electrode-retina and electrode-fovea distance as well as the electrode-electrode distance to ('between-axon') and along axon bundles ('along-axon'). Statistical analyses were conducted using linear regression and partial correlation analysis.Main results.Simple regression revealed that each paired-electrode shape descriptor could be predicted by the sum of the two corresponding single-electrode shape descriptors (p < .001). Multiple regression revealed that paired-electrode phosphene shape was primarily predicted by stimulus amplitude and electrode-fovea distance (p < .05). Interestingly, the number of elicited phosphenes tended to increase with between-axon distance (p < .05), but not with along-axon distance, in two out of three participants.Significance.The shape of phosphenes elicited by paired-electrode stimulation was well predicted by the shape of their corresponding single-electrode phosphenes, suggesting that two-point perception can be expressed as the linear summation of single-point perception. The impact of the between-axon distance on the perceived number of phosphenes provides further evidence in support of the axon map model for epiretinal stimulation. These findings contribute to the growing literature on phosphene perception and have important implications for the design of future retinal prostheses.

Fabrication and Validation of Sub-Cellular Carbon Fiber Electrodes.

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.

Imaging the response of the retina to electrical stimulation with genetically encoded calcium indicators.

Epiretinal implants for the blind are designed to stimulate surviving retinal neurons, thus bypassing the diseased photoreceptor layer. Single-unit or multielectrode recordings from isolated animal retina are commonly used to inform the design of these implants. However, such electrical recordings provide limited information about the spatial patterns of retinal activation. Calcium imaging overcomes this limitation, as imaging enables high spatial resolution mapping of retinal ganglion cell (RGC) activity as well as simultaneous recording from hundreds of RGCs. Prior experiments in amphibian retina have demonstrated proof of principle, yet experiments in mammalian retina have been hindered by the inability to load calcium indicators into mature mammalian RGCs. Here, we report a method for labeling the majority of ganglion cells in adult rat retina with genetically encoded calcium indicators, specifically GCaMP3 and GCaMP5G. Intravitreal injection of an adeno-associated viral vector targets ∼85% of ganglion cells with high specificity. Because of the large fluorescence signals provided by the GCaMP sensors, we can now for the first time visualize the response of the retina to electrical stimulation in real-time. Imaging transduced retinas mounted on multielectrode arrays reveals how stimulus pulse shape can dramatically affect the spatial extent of RGC activation, which has clear implications in prosthetic applications. Our method can be easily adapted to work with other fluorescent indicator proteins in both wild-type and transgenic mammals.

Modeling extracellular stimulation of retinal ganglion cells: theoretical and practical aspects.

Objective.Retinal prostheses use electric current to activate inner retinal neurons, providing artificial vision for blind people. Epiretinal stimulation primarily targets retinal ganglion cells (RGCs), which can be modeled with cable equations. Computational models provide a tool to investigate the mechanisms of retinal activation, and improve stimulation paradigms. However, documentation of RGC model structure and parameters is limited, and model implementation can influence model predictions.Approach.We created a functional guide for building a mammalian RGC multi-compartment cable model and applying extracellular stimuli. Next, we investigated how the neuron's three-dimensional shape will influence model predictions. Finally, we tested several strategies to maximize computational efficiency.Main results.We conducted sensitivity analyses to examine how dendrite representation, axon trajectory, and axon diameter influence membrane dynamics and corresponding activation thresholds. We optimized the spatial and temporal discretization of our multi-compartment cable model. We also implemented several simplified threshold prediction theories based on activating function, but these did not match the prediction accuracy achieved by the cable equations.Significance.Through this work, we provide practical guidance for modeling the extracellular stimulation of RGCs to produce reliable and meaningful predictions. Robust computational models lay the groundwork for improving the performance of retinal prostheses.

Patient-specific computational models of retinal prostheses.

Retinal prostheses stimulate inner retinal neurons to create visual perception for blind patients. Implanted arrays have many small electrodes, which act as pixels. Not all electrodes induce perception at the same stimulus amplitude, requiring clinicians to manually establish a visual perception threshold for each one. Phosphenes created by single-electrode stimuli can also vary in shape, size, and brightness. Computational models provide a tool to predict inter-electrode variability and automate device programming. In this study, we created statistical and patient-specific field-cable models to investigate inter-electrode variability across seven epiretinal prosthesis users. Our statistical analysis revealed that retinal thickness beneath the electrode correlated with perceptual threshold, with a significant fixed effect across participants. Electrode-retina distance and electrode impedance also correlated with perceptual threshold for some participants, but these effects varied by individual. We developed a novel method to construct patient-specific field-cable models from optical coherence tomography images. Predictions with these models significantly correlated with perceptual threshold for 80% of participants. Additionally, we demonstrated that patient-specific field-cable models could predict retinal activity and phosphene size. These computational models could be beneficial for determining optimal stimulation settings in silico, circumventing the trial-and-error testing of a large parameter space in clinic.

Patient-specific computational models of retinal prostheses.

Retinal prostheses stimulate inner retinal neurons to create visual perception for blind patients. Implanted arrays have many small electrodes. Not all electrodes induce perception at the same stimulus amplitude, requiring clinicians to manually establish a visual perception threshold for each one. Phosphenes created by single-electrode stimuli can also vary in shape, size, and brightness. Computational models provide a tool to predict inter-electrode variability and automate device programming. In this study, we created statistical and patient-specific field-cable models to investigate inter-electrode variability across seven epiretinal prosthesis users. Our statistical analysis revealed that retinal thickness beneath the electrode correlated with perceptual threshold, with a significant fixed effect across participants. Electrode-retina distance and electrode impedance also correlated with perceptual threshold for some participants, but these effects varied by individual. We developed a novel method to construct patient-specific field-cable models from optical coherence tomography images. Predictions with these models significantly correlated with perceptual threshold for 80% of participants. Additionally, we demonstrated that patient-specific field-cable models could predict retinal activity and phosphene size. These computational models could be beneficial for determining optimal stimulation settings in silico, circumventing the trial-and-error testing of a large parameter space in clinic.

Axonal stimulation affects the linear summation of single-point perception in three Argus II users.

Purpose: Retinal implants use electrical stimulation to elicit perceived flashes of light ("phosphenes"). Single-electrode phosphene shape has been shown to vary systematically with stimulus parameters and the retinal location of the stimulating electrode, due to incidental activation of passing nerve fiber bundles. However, this knowledge has yet to be extended to paired-electrode stimulation. Methods: We retrospectively analyzed 3548 phosphene drawings made by three blind participants implanted with an Argus II Retinal Prosthesis. Phosphene shape (characterized by area, perimeter, major and minor axis length) and number of perceived phosphenes were averaged across trials and correlated with the corresponding single-electrode parameters. In addition, the number of phosphenes was correlated with stimulus amplitude and neuroanatomical parameters: electrode-retina and electrode-fovea distance as well as the electrode-electrode distance to ("between-axon") and along axon bundles ("along-axon"). Statistical analyses were conducted using linear regression and partial correlation analysis. Results: Simple regression revealed that each paired-electrode shape descriptor could be predicted by the sum of the two corresponding single-electrode shape descriptors (p < .001). Multiple regression revealed that paired-electrode phosphene shape was primarily predicted by stimulus amplitude and electrode-fovea distance (p < .05). Interestingly, the number of elicited phosphenes tended to increase with between-axon distance (p < .05), but not with along-axon distance, in two out of three participants. Conclusions: The shape of phosphenes elicited by paired-electrode stimulation was well predicted by the shape of their corresponding single-electrode phosphenes, suggesting that two-point perception can be expressed as the linear summation of single-point perception. The notable impact of the between-axon distance on the perceived number of phosphenes provides further evidence in support of the axon map model for epiretinal stimulation. These findings contribute to the growing literature on phosphene perception and have important implications for the design of future retinal prostheses.

Full-field, conformal epiretinal electrode array using hydrogel and polymer hybrid technology.

Shape-morphable electrode arrays can form 3D surfaces to conform to complex neural anatomy and provide consistent positioning needed for next-generation neural interfaces. Retinal prostheses need a curved interface to match the spherical eye and a coverage of several cm to restore peripheral vision. We fabricated a full-field array that can (1) cover a visual field of 57° based on electrode position and of 113° based on the substrate size; (2) fold to form a compact shape for implantation; (3) self-deploy into a curvature fitting the eye after implantation. The full-field array consists of multiple polymer layers, specifically, a sandwich structure of elastomer/polyimide-based-electrode/elastomer, coated on one side with hydrogel. Electrodeposition of high-surface-area platinum/iridium alloy significantly improved the electrical properties of the electrodes. Hydrogel over-coating reduced electrode performance, but the electrodes retained better properties than those without platinum/iridium. The full-field array was rolled into a compact shape and, once implanted into ex vivo pig eyes, restored to a 3D curved surface. The full-field retinal array provides significant coverage of the retina while allowing surgical implantation through an incision 33% of the final device diameter. The shape-changing material platform can be used with other neural interfaces that require conformability to complex neuroanatomy.

Post-explant profiling of subcellular-scale carbon fiber intracortical electrodes and surrounding neurons enables modeling of recorded electrophysiology.

Objective.Characterizing the relationship between neuron spiking and the signals that electrodes record is vital to defining the neural circuits driving brain function and informing clinical brain-machine interface design. However, high electrode biocompatibility and precisely localizing neurons around the electrodes are critical to defining this relationship.Approach.Here, we demonstrate consistent localization of the recording site tips of subcellular-scale (6.8µm diameter) carbon fiber electrodes and the positions of surrounding neurons. We implanted male rats with carbon fiber electrode arrays for 6 or 12+ weeks targeting layer V motor cortex. After explanting the arrays, we immunostained the implant site and localized putative recording site tips with subcellular-cellular resolution. We then 3D segmented neuron somata within a 50µm radius from implanted tips to measure neuron positions and health and compare to healthy cortex with symmetric stereotaxic coordinates.Main results.Immunostaining of astrocyte, microglia, and neuron markers confirmed that overall tissue health was indicative of high biocompatibility near the tips. While neurons near implanted carbon fibers were stretched, their number and distribution were similar to hypothetical fibers placed in healthy contralateral brain. Such similar neuron distributions suggest that these minimally invasive electrodes demonstrate the potential to sample naturalistic neural populations. This motivated the prediction of spikes produced by nearby neurons using a simple point source model fit using recorded electrophysiology and the mean positions of the nearest neurons observed in histology. Comparing spike amplitudes suggests that the radius at which single units can be distinguished from others is near the fourth closest neuron (30.7 ± 4.6µm,X-± S) in layer V motor cortex.Significance.Collectively, these data and simulations provide the first direct evidence that neuron placement in the immediate vicinity of the recording site influences how many spike clusters can be reliably identified by spike sorting.

Preservation of retinotopic map in retinal degeneration.

Retinal degenerations trigger the loss of photoreceptors and cause the remaining de-afferented neural retina to undergo remodeling. Concerns over this potential retinal synaptic reorganization following visual loss have raised questions regarding the usefulness of visual restoration via retinal electrical stimulation. We have used quantitative positron emission tomography (PET) and 2-deoxy-2-[18F]fluoro-d-glucose (FDG) to objectively evaluate the connection between the retina and the primary visual cortex under both light and transcorneal electrical stimulation (TcES) in five subjects with retinal degeneration (RD) who have had more than ten years of light-perception-only best visual acuity and five age-matched normal-sighted controls. All subjects underwent quantitative PET with FDG as the metabolic tracer during stimulation of the right eye under both light stimulation condition and transcorneal electrical stimulation (TcES) using ERG-Jet contact lens electrode. Cortical activation maps from each stimulation condition were obtained using statistical parametric mapping. TcES phosphene threshold current and qualitative visual cortex activation from both stimulation conditions were compared between the two subject groups. Average phosphene threshold current was 0.72 ± 0.18 mA for the five normal-sighted controls and 3.08 ± 2.01 mA for the retinal degenerative subjects. Phosphene threshold current was significantly higher in retinal degenerative subjects compared to normal-sighted controls (p < 0.05). We found both light stimulation and TcES resulted in retinotopically mapped primary visual cortex activation in both groups. In addition, the patterns of early visual area activation between the two subject groups are more similar during TcES than light stimulation. Our findings suggest primary visual cortex continues to maintain its retinotopy in RD subjects despite prolonged visual loss.

Mechanical characteristics of the porcine retina in low temperatures.

BACKGROUND: We previously observed that the stiffness of the porcine retina was significantly higher when deforming at room temperature than at body temperature. The present study further investigates this phenomenon by examining the mechanical properties of the retina in saline at temperature lower than room temperature. METHODS: Tensile testing was performed on a total of 15 retinal strips dissected from pig eyes. Equal amount of strips from the dissection were tested at 37.0 ± 0.3°C, 26.1 ± 0.1°C, and 7.8 ± 1.2°C. Their transition modulus, stress, and strain were measured for statistical analysis. RESULTS: The transition modulus, the transition stress, and the transition strain of the retinal strips were found to be 11.12 ± 6.10 kPa, 0.12 ± 0.07 kPa, and 0.016 ± 0.001, respectively, at 37.0°C. These values were 111.25 ± 88.16 kPa, 1.11 ± 0.85 kPa, and 0.016 ± 0.001 at 26.1°C, and 125.13 ± 63.61 kPa, 1.30 ± 0.50 kPa, and 0.017 ± 0.003 at 7.8°C, respectively. The differences of the transition modulus and the transition stress at between 37.0°C and 26.1°C and at between 37.0°C and 7.8°C were statistically significant (P < 0.05). There were no significant differences in these values at between 26.1°C and 7.8°C. CONCLUSION: These findings suggest that lowering the temperature of the retina from body temperature is potentially useful to decrease retinal damage in posterior eye surgeries by increasing the resistance of the retina to mechanical deformation.

Progressive Retinal Degeneration Increases Cortical Response Latency of Light Stimulation but Not of Electric Stimulation.

Purpose: The brain is known to change functionally and structurally in response to blindness, but less is known about the effects of restoration of cortical input on brain function. Here, we present a preliminary study to observe alterations in visual and electrical evoked cortical potentials as a function of age in a clinically relevant animal model of retinitis pigmentosa. Methods: We recorded brain potentials elicited by light (visual evoked potentials [VEPs]) or corneal electrical stimulation (electrical evoked response [EER]) in retinal degenerate animal model LE-P23H-1. We used a linear mixed model to examine the effects of age on latency and amplitude of VEP and EER age groups P120, P180, and P360. Results: VEP N1, P1, and N2 latency and amplitude were analyzed across animal age. For 1 Hz VEP, N1 latency increased significantly with animal age (slope = 0.053 ± 0.020 ms/day, P < 0.01). For 10 Hz VEP, N1, P1, and N2 latency increased significantly with animal age (slope = 0.104 ± 0.011, 0.135 ± 0.011, 0.087 ± 0.023 ms/day, and P < 0.001 for all VEP peaks). Conversely, EER latency did not change with age. Signal amplitude of VEP or EER did not change with age. Conclusions: Cortical potentials evoked by electrical stimulation of the retina do not diminish in spite of continued retinal degeneration in P23H rats. Translational Relevance: These findings suggest that retinal bioelectronic treatments of retinitis pigmentosa will activate cortex consistently despite variations in outer retinal degeneration. Clinical studies of retinal stimulation should consider varying retinitis pigmentosa genotypes as part of the experimental design.

Retinal ganglion cell desensitization is mitigated by varying parameter constant excitation pulse trains.

Retinal prostheses partially restore vision in patients blinded by retinitis pigmentosa (RP) and age-related macular degeneration (AMD). One issue that limits the effectiveness of retinal stimulation is the desensitization of the retina response to repeated pulses. Rapid fading of percepts is reported in clinical studies. We studied the retinal output evoked by fixed pulse trains vs. pulse trains that have variable parameters pulse-to-pulse. We used the current clamp to record RGC spiking in the isolated mouse retina. Trains of biphasic current pulses at different frequencies and amplitudes were applied. The main results we report are: (1) RGC desensitization was induced by increasing stimulus frequency, but was unrelated to stimulus amplitude. Desensitization persisted when the 20 Hz stimulation pulses were applied to the retinal ganglion cells at 65 µA, 85 µA, and 105 µA. Subsequent pulses in the train evoked fewer spikes. There was no obvious desensitization when 2 Hz stimulation pulse trains were applied. (2) Blocking inhibitory GABAA receptor increased spontaneous activity but did not reduce desensitization. (3) Pulse trains with constant charge or excitation (based on strength-duration curves) but varying pulse width, amplitude, and shape increased the number of evoked spikes/pulse throughout the pulse train. This suggests that retinal desensitization can be partially overcome by introducing variability into each pulse.

Spatial Transcriptomics as a Novel Approach to Redefine Electrical Stimulation Safety.

Current standards for safe delivery of electrical stimulation to the central nervous system are based on foundational studies which examined post-mortem tissue for histological signs of damage. This set of observations and the subsequently proposed limits to safe stimulation, termed the "Shannon limits," allow for a simple calculation (using charge per phase and charge density) to determine the intensity of electrical stimulation that can be delivered safely to brain tissue. In the three decades since the Shannon limits were reported, advances in molecular biology have allowed for more nuanced and detailed approaches to be used to expand current understanding of the physiological effects of stimulation. Here, we demonstrate the use of spatial transcriptomics (ST) in an exploratory investigation to assess the biological response to electrical stimulation in the brain. Electrical stimulation was delivered to the rat visual cortex with either acute or chronic electrode implantation procedures. To explore the influence of device type and stimulation parameters, we used carbon fiber ultramicroelectrode arrays (7 µm diameter) and microwire electrode arrays (50 µm diameter) delivering charge and charge density levels selected above and below reported tissue damage thresholds (range: 2-20 nC, 0.1-1 mC/cm2). Spatial transcriptomics was performed using Visium Spatial Gene Expression Slides (10x Genomics, Pleasanton, CA, United States), which enabled simultaneous immunohistochemistry and ST to directly compare traditional histological metrics to transcriptional profiles within each tissue sample. Our data give a first look at unique spatial patterns of gene expression that are related to cellular processes including inflammation, cell cycle progression, and neuronal plasticity. At the acute timepoint, an increase in inflammatory and plasticity related genes was observed surrounding a stimulating electrode compared to a craniotomy control. At the chronic timepoint, an increase in inflammatory and cell cycle progression related genes was observed both in the stimulating vs. non-stimulating microwire electrode comparison and in the stimulating microwire vs. carbon fiber comparison. Using the spatial aspect of this method as well as the within-sample link to traditional metrics of tissue damage, we demonstrate how these data may be analyzed and used to generate new hypotheses and inform safety standards for stimulation in cortex.

Integration of artificial vision with non-visual peripheral cues to guide mobility.

Visual prostheses can improve vision for people with severe vision loss, but low image resolution and lack of peripheral vision limit their effectiveness. To address both problems, we developed a prototype advanced video processing system with a headworn depth camera and feature detection capabilities. We used computer vision algorithms to detect landmarks representing a goal and plan a path towards the goal, while removing unnecessary distractors from the video. If the landmark fell outside the visual prosthesis's field-of-view (20 degrees central vision) but within the camera's field-of-view (70 degrees), we provided vibrational cues to the left or right temple to guide the user in pointing the camera. We evaluated an Argus II retinal prosthesis participant with significant vision loss who could not complete the task (finding a door in a large room) with either his remaining vision or his retinal prosthesis. His success rate improved to 57%, 37.5%, and 100% while requiring 52.3, 83.0, and 58.8 seconds to reach the door using only vibration feedback, retinal prosthesis with modified video, and retinal prosthesis with modified video and vibration feedback, respectively. This case study demonstrates a possible means of augmenting artificial vision. Clinical Relevance- Retinal prostheses can be enhanced by adding computer vision and non-visual cues.

Both electrical stimulation thresholds and SMI-32-immunoreactive retinal ganglion cell density correlate with age in S334ter line 3 rat retina.

Electrical stimulation threshold and retinal ganglion cell density were measured in a rat model of retinal degeneration. We performed in vivo electrophysiology and morphometric analysis on normal and S334ter line 3 (RD) rats (ages 84-782 days). We stimulated the retina in anesthetized animals and recorded evoked responses in the superior colliculus. Current pulses were delivered with a platinum-iridium (Pt-Ir) electrode of 75-µm diameter positioned on the epiretinal surface. In the same animals used for electrophysiology, SMI-32 immunolabeling of the retina enabled ganglion cell counting. An increase in threshold currents positively correlated with age of RD rats. SMI-32-labeled retinal ganglion cell density negatively correlated with age of RD rats. ANOVA shows that RD postnatal day (P)100 and P300 rats have threshold and density similar to normal rats, but RD P500 and P700 rats have threshold and density statistically different from normal rats (P < 0.05). Threshold charge densities were within the safety limits of Pt for all groups and pulse configurations, except at RD P600 and RD P700, where pulses were only safe up to 1- and 0.2-ms duration, respectively. Preservation of ganglion cells may enhance the efficiency and safety of electronic retinal implants.