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Interphase gap as a means to reduce electrical stimulation thresholds for epiretinal prostheses.

ABSTRACT: OBJECTIVE:Epiretinal prostheses are designed to restore functional vision to the blind by electrically stimulating surviving retinal neurons. These devices have classically employed symmetric biphasic current pulses in order to maintain a balance of charge. Prior electrophysiological and psychophysical studies in peripheral nerve show that adding an interphase gap (IPG) between the two phases makes stimulation more efficient than pulses with no gap. This led us to investigate the effect of IPG duration on retinal stimulation thresholds. APPROACH:We measured retinal ganglion cell (RGC) electrical thresholds in salamander retina and phosphene perceptual thresholds in epiretinal prosthesis patients during stimulation with different IPG lengths. We also built Hodgkin-Huxley-type models of RGCs to further study how IPG affects thresholds. MAIN RESULTS:In general, there was a negative exponential correlation between threshold and IPG duration. Durations greater than or equal to ~0.5 ms reduced salamander RGC thresholds by 20-25%. Psychophysical testing in five retinal prosthesis patients indicated that stimulating with IPGs can decrease perceptual thresholds by 10-15%. Results from computational models of RGCs corroborated the observed behavior. SIGNIFICANCE:Incorporating interphase gaps can reduce the power consumption of epiretinal prostheses and increase the available dynamic range of phosphene size and brightness.

SUBMITTER: Weitz AC

PROVIDER: S-EPMC3970787 | biostudies-literature | 2014 Feb

REPOSITORIES: biostudies-literature

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Interphase gap as a means to reduce electrical stimulation thresholds for epiretinal prostheses.

Weitz Andrew C AC Behrend Matthew R MR Ahuja Ashish K AK Christopher Punita P Wei Jianing J Wuyyuru Varalakshmi V Patel Uday U Greenberg Robert J RJ Humayun Mark S MS Chow Robert H RH Weiland James D JD

Journal of neural engineering 20140201 1

<h4>Objective</h4>Epiretinal prostheses are designed to restore functional vision to the blind by electrically stimulating surviving retinal neurons. These devices have classically employed symmetric biphasic current pulses in order to maintain a balance of charge. Prior electrophysiological and psychophysical studies in peripheral nerve show that adding an interphase gap (IPG) between the two phases makes stimulation more efficient than pulses with no gap. This led us to investigate the effect ...[more]

PMID: 24654269

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Project description:Epiretinal prostheses for treating blindness activate axon bundles, causing large, arc-shaped visual percepts that limit the quality of artificial vision. Improving the function of epiretinal prostheses therefore requires understanding and avoiding axon bundle activation. This study introduces a method to detect axon bundle activation on the basis of its electrical signature and uses the method to test whether epiretinal stimulation can directly elicit spikes in individual retinal ganglion cells without activating nearby axon bundles. Combined electrical stimulation and recording from isolated primate retina were performed using a custom multielectrode system (512 electrodes, 10-μm diameter, 60-μm pitch). Axon bundle signals were identified by their bidirectional propagation, speed, and increasing amplitude as a function of stimulation current. The threshold for bundle activation varied across electrodes and retinas, and was in the same range as the threshold for activating retinal ganglion cells near their somas. In the peripheral retina, 45% of electrodes that activated individual ganglion cells (17% of all electrodes) did so without activating bundles. This permitted selective activation of 21% of recorded ganglion cells (7% of expected ganglion cells) over the array. In one recording in the central retina, 75% of electrodes that activated individual ganglion cells (16% of all electrodes) did so without activating bundles. The ability to selectively activate a subset of retinal ganglion cells without axon bundles suggests a possible novel architecture for future epiretinal prostheses.NEW & NOTEWORTHY Large-scale multielectrode recording and stimulation were used to test how selectively retinal ganglion cells can be electrically activated without activating axon bundles. A novel method was developed to identify axon activation on the basis of its unique electrical signature and was used to find that a subset of ganglion cells can be activated at single-cell, single-spike resolution without producing bundle activity in peripheral and central retina. These findings have implications for the development of advanced retinal prostheses.

Project description:Objective:Retinal prosthetic implants have helped improve vision in patients blinded by photoreceptor degeneration. Retinal implant users report improvements in light perception and performing visual tasks, but their ability to perceive shapes and letters is limited due to the low precision of retinal activation, which is exacerbated by axonal stimulation and high perceptual thresholds. A previous in vitro study in our lab used calcium imaging to measure the spatial activity of mouse retinal ganglion cells (RGCs) in response to electrical stimulation. Based on this study, symmetric anodic-first (SA) stimulation effectively avoided axonal activation and asymmetric anodic-first stimulation (AA) with duration ratios (ratio of the anodic to cathodic phase) greater than 10 reduced RGC activation thresholds significantly. Applying these novel stimulation strategies in clinic may increase perception precision and improve the overall patient outcomes. Approach:We combined human subject testing and computational modeling to further examine the effect of SA and AA stimuli on perception shapes and thresholds for epiretinal stimulation of RGCs. Main results:Threshold measurement in three Argus II participants indicated that AA stimulation could increase perception probabilities compared to a standard symmetric cathodic-first (SC) pulse, and this effect can be intensified by addition of an interphae gap (IPG). Our in silico RGC model predicts lower thresholds with AA and asymmetric cathodic-first (AC) stimuli compared to a SC pulse. This effect was more pronounced at shorter pulse widths. The most effective pulse for threshold reduction with short pulse durations (?0.12 ms) was AA stimulation with small duration ratios (?5) and long IPGs (?2 ms). For the 0.5 ms pulse duration, SC stimulation with IPGs longer than 0.5 ms, or asymmetric stimuli with large duration ratios (?20) were most effective in threshold reduction. Phosphene shape analysis did not reveal a significant change in percept elongation with SA stimulation. However, there was a significant increase in percept size (P < 0.01) with AA stimulation compared to the standard pulse in one participant. Significane:Including asymmetric waveform capability will provide more flexible options for optimization and personalized fitting of retinal implants.

Project description:IntroductionWe examined how pulse train electrical stimulation of the inner surface of the rabbit retina effected the resident glial cells. We used a rabbit retinal eyecup preparation model, transparent stimulus electrodes, and optical coherence tomography (OCT). The endfeet of Müller glia processes line the inner limiting membrane (ILM).MethodsTo examine how epiretinal electrode stimulation affected the Müller glia, we labeled them post stimulation using antibodies against soluble glutamine synthetase (GS). After 5 min 50 Hz pulse train stimulation 30 μm from the surface, the retina was fixed, immunostained for Müller glia, and examined using confocal microscopic reconstruction. Stimulus pulse charge densities between 133-749 μC/cm2/ph were examined.ResultsHigh charge density stimulation (442-749 μC/cm2/ph) caused significant losses in the GS immunofluorescence of the Müller glia endfeet under the electrode. This loss of immunofluorescence was correlated with stimuli causing ILM detachment when measured using OCT. Müller cells show potassium conductances at rest that are blocked by barium ions. Using 30 msec 20 μA stimulus current pulses across the eyecup, the change in transretinal resistance was examined by adding barium to the Ringer. Barium caused little change in the transretinal resistance, suggesting under low charge density stimulus pulse conditions, the Müller cell radial conductance pathway for these stimulus currents was small. To examine how epiretinal electrode stimulation affected the microglia, we used lectin staining 0-4 h post stimulation. After stimulation at high charge densities 749 μC/cm2/ph, the microglia under the electrode appeared rounded, while the local microglia outside the electrode responded to the stimulated retina by process orientation inwards in a ring by 30 min post stimulation.DiscussionOur study of glial cells in a rabbit eyecup model using transparent electrode imaging suggests that epiretinal electrical stimulation at high pulse charge densities, can injure the Müller and microglia cells lining the inner retinal surface in addition to ganglion cells.

Project description:IntroductionRetinal implants have now been approved and commercially available for certain clinical populations for over 5 years, with hundreds of individuals implanted, scores of them closely followed in research trials. Despite these numbers, however, few data are available that would help us answer basic questions regarding the nature and outcomes of artificial vision: what do recipients see when the device is turned on for the first time, and how does that change over time?MethodsSemi-structured interviews and observations were undertaken at two sites in France and the UK with 16 recipients who had received either the Argus II or IRIS II devices. Data were collected at various time points in the process that implant recipients went through in receiving and learning to use the device, including initial evaluation, implantation, initial activation and systems fitting, re-education and finally post-education. These data were supplemented with data from interviews conducted with vision rehabilitation specialists at the clinical sites and clinical researchers at the device manufacturers (Second Sight and Pixium Vision). Observational and interview data were transcribed, coded and analyzed using an approach guided by Interpretative Phenomenological Analysis (IPA).ResultsImplant recipients described the perceptual experience produced by their epiretinal implants as fundamentally, qualitatively different than natural vision. All used terms that invoked electrical stimuli to describe the appearance of their percepts, yet the characteristics used to describe the percepts varied significantly between recipients. Artificial vision for these recipients was a highly specific, learned skill-set that combined particular bodily techniques, associative learning and deductive reasoning in order to build a "lexicon of flashes"-a distinct perceptual vocabulary that they then used to decompose, recompose and interpret their surroundings. The percept did not transform over time; rather, the recipient became better at interpreting the signals they received, using cognitive techniques. The process of using the device never ceased to be cognitively fatiguing, and did not come without risk or cost to the recipient. In exchange, recipients received hope and purpose through participation, as well as a new kind of sensory signal that may not have afforded practical or functional use in daily life but, for some, provided a kind of "contemplative perception" that recipients tailored to individualized activities.ConclusionAttending to the qualitative reports of implant recipients regarding the experience of artificial vision provides valuable information not captured by extant clinical outcome measures.

Dataset Information

Interphase gap as a means to reduce electrical stimulation thresholds for epiretinal prostheses.

Publications

Interphase gap as a means to reduce electrical stimulation thresholds for epiretinal prostheses.

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