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Temporal interactions during paired-electrode stimulation in two retinal prosthesis subjects.

ABSTRACT: Since 2002, six blind patients have undergone implantation of an epiretinal 4 × 4 electrode array designed to directly stimulate the remaining cells of the retina after severe photoreceptor degeneration due to retinitis pigmentosa. This study was conducted to investigate how the brightness of percepts is affected by pulse timing across electrodes in two of these patients.Subjects compared the perceived brightness of a standard stimulus (synchronous pulse trains presented across pairs of electrodes) to the perceived brightness of a test stimulus (pulse trains across the electrode pair phase shifted by 0.075, 0.375, 1.8, or 9 ms). The current amplitude necessary for each phase-shifted test stimulus to match the brightness of the standard was determined.Depending on the electrode pair, interactions between electrodes were either facilitatory (the perceived brightness produced by stimulating the pair of electrodes was greater than that produced by stimulating either electrode alone) or suppressive (the perceived brightness produced by stimulating the pair of electrodes was less than that produced by stimulating either electrode alone). The amount of interaction between electrodes decreased as a function of increased separation both in time (the phase-shift between pulse trains) and space (center-to-center distance between the electrode pair).For visual prostheses to represent visual scenes that are changing in both space and time requires the development of spatiotemporal models describing the effects of stimulation across multiple electrodes. During multielectrode stimulation, interactions between electrodes have a significant influence on subjective brightness that includes both facilitatory and suppressive effects, and these interactions can be described with a simple computational model. (ClinicalTrials.gov number, NCT00279500.).

SUBMITTER: Horsager A

PROVIDER: S-EPMC3053297 | biostudies-literature | 2011 Jan

REPOSITORIES: biostudies-literature

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Temporal interactions during paired-electrode stimulation in two retinal prosthesis subjects.

Horsager Alan A Boynton Geoffrey M GM Greenberg Robert J RJ Fine Ione I

Investigative ophthalmology & visual science 20110101 1

<h4>Purpose</h4>Since 2002, six blind patients have undergone implantation of an epiretinal 4 × 4 electrode array designed to directly stimulate the remaining cells of the retina after severe photoreceptor degeneration due to retinitis pigmentosa. This study was conducted to investigate how the brightness of percepts is affected by pulse timing across electrodes in two of these patients.<h4>Methods</h4>Subjects compared the perceived brightness of a standard stimulus (synchronous pulse trains pr ...[more]

PMID: 20720224

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Project description:PURPOSE:The Argus II epiretinal prosthesis has been developed to provide partial restoration of vision to subjects blinded from outer retinal degenerative disease. Participants were surgically implanted with the system in the United States and Europe in a single arm, prospective, multicenter clinical trial. The purpose of this investigation was to determine which factors affect electrical thresholds in order to inform surgical placement of the device. METHODS:Electrode-retina and electrode-fovea distances were determined using SD-OCT and fundus photography, respectively. Perceptual threshold to electrical stimulation of electrodes was measured using custom developed software, in which current amplitude was varied until the threshold was found. Full field stimulus light threshold was measured using the Espion D-FST test. Relationships between electrical threshold and these three explanatory variables (electrode-retina distance, electrode-fovea distance, and monocular light threshold) were quantified using regression. RESULTS:Regression analysis showed a significant correlation between electrical threshold and electrode-retina distance (R2 = 0.50, P = 0.0002; n = 703 electrodes). 90.3% of electrodes in contact with the macula (n = 207) elicited percepts at charge densities less than 1 mC/cm2/phase. These threshold data also correlated well with ganglion cell density profile (P = 0.03). A weaker, but still significant, inverse correlation was found between light threshold and electrical threshold (R2 < 0.52, P = 0.01). Multivariate modeling indicated that electrode-retina distance and light threshold are highly predictive of electrode threshold (R2 = 0.87; P < 0.0005). CONCLUSIONS:Taken together, these results suggest that while light threshold should be used to inform patient selection, macular contact of the array is paramount. TRANSLATIONAL RELEVANCE:Reported Argus II clinical study results are in good agreement with prior in vitro and in vivo studies, and support the development of higher-density systems that employ smaller diameter electrodes. (clinicaltrials.gov identifier: NCT00407602).

Project description:PurposeTo assess the safety and efficacy of chronic electrical stimulation of the retina with a suprachoroidal visual prosthesis.MethodsSeven normally-sighted feline subjects were implanted for 96-143 days with a suprachoroidal electrode array and six were chronically stimulated for 70-105 days at levels that activated the visual cortex. Charge balanced, biphasic, current pulses were delivered to platinum electrodes in a monopolar stimulation mode. Retinal integrity/function and the mechanical stability of the implant were assessed monthly using electroretinography (ERG), optical coherence tomography (OCT) and fundus photography. Electrode impedances were measured weekly and electrically-evoked visual cortex potentials (eEVCPs) were measured monthly to verify that chronic stimuli were suprathreshold. At the end of the chronic stimulation period, thresholds were confirmed with multi-unit recordings from the visual cortex. Randomized, blinded histological assessments were performed by two pathologists to compare the stimulated and non-stimulated retina and adjacent tissue.ResultsAll subjects tolerated the surgical and stimulation procedure with no evidence of discomfort or unexpected adverse outcomes. After an initial post-operative settling period, electrode arrays were mechanically stable. Mean electrode impedances were stable between 11-15 kΩ during the implantation period. Visually-evoked ERGs & OCT were normal, and mean eEVCP thresholds did not substantially differ over time. In 81 of 84 electrode-adjacent tissue samples examined, there were no discernible histopathological differences between stimulated and unstimulated tissue. In the remaining three tissue samples there were minor focal fibroblastic and acute inflammatory responses.ConclusionsChronic suprathreshold electrical stimulation of the retina using a suprachoroidal electrode array evoked a minimal tissue response and no adverse clinical or histological findings. Moreover, thresholds and electrode impedance remained stable for stimulation durations of up to 15 weeks. This study has demonstrated the safety and efficacy of suprachoroidal stimulation with charge balanced stimulus currents.

Project description:BackgroundVisual cortical prostheses (VCPs) have the potential to restore visual function to patients with acquired blindness. Successful implementation of VCPs requires the ability to reliably map the location of the phosphene produced by stimulation of each implanted electrode.ObjectiveTo evaluate the efficacy of different approaches to phosphene mapping and propose simple improvements to mapping strategy.MethodsWe stimulated electrodes implanted in the visual cortex of five blind and fifteen sighted patients. We tested two fixation strategies, unimanual fixation, where subjects placed a single index finger on a tactile fixation point and bimanual fixation, where subjects overlaid their right index finger over their left on the tactile point. In addition, we compared absolute mapping in which a single electrode was stimulated on each trial, and relative mapping with sequences containing stimulation of three to five phosphenes on each trial. Trial-to-trial variability present in relative mapping sequences was quantified.ResultsPhosphene mapping was less precise in blind subjects than in sighted subjects (2DRMS, 16 ± 2.9° vs. 1.9 ± 0.93°; t (18) = 18, p = <0.001). Within blind subjects, bimanual fixation resulted in more consistent phosphene localization than unimanual fixation (BS1: 4.0 ± 2.6° vs. 19 ± 4.7°, t (79) = 24, p < 0.001; BS2 4.1 ± 2.0° vs. 12 ± 2.7°, t (65) = 19, p < 0.001). Multi-point relative mapping had similar baseline precision to absolute mapping (BS1: 4.7 ± 2.6° vs. 3.9 ± 2.0°; BS2: 4.1 ± 2.0° vs. 3.2 ± 1.1°) but improved significantly when trial-to-trial translational variability was removed. Although multi-point mapping methods did reveal more of the functional organization expected in early visual cortex, subjects tended to artificially regularize the spacing between phosphenes. We attempt to address this issue by fitting a standard logarithmic map to relative multi-point sequences.ConclusionsRelative mapping methods, combined with bimanual fixation, resulted in the most precise estimates of phosphene organization. These techniques, combined with use of a standard logarithmic model of visual cortex, may provide a practical way to improve the implementation of a VCP.

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Temporal interactions during paired-electrode stimulation in two retinal prosthesis subjects.

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Temporal interactions during paired-electrode stimulation in two retinal prosthesis subjects.

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