Spatially Patterned Bi-electrode Epiretinal Stimulation for Axon Avoidance at Cellular Resolution

Objective: Epiretinal prostheses are designed to restore vision to people blinded by photoreceptor degenerative diseases by stimulating surviving retinal ganglion cells (RGCs), which carry visual signals to the brain. However, inadvertent stimulation of RGCs at their axons can result in non-focal visual percepts, limiting the quality of artificial vision. Theoretical work has suggested that axon activation can be avoided with current stimulation designed to minimize the second spatial derivative of the induced extracellular voltage along the axon. However, this approach has not been verified experimentally at the resolution of single cells. Approach: In this work, a custom multi-electrode array (512 electrodes, 10 μm diameter, 60 μm pitch) was used to stimulate and record RGCs in macaque retina ex vivo at single-cell, single-spike resolution. RGC activation thresholds resulting from bi-electrode stimulation, which consisted of bipolar currents simultaneously delivered through two electrodes straddling an axon, were compared to activation thresholds from traditional single-electrode stimulation. Results: Across three retinal preparations, the bi-electrode stimulation strategy reduced somatic activation thresholds while increasing axonal activation thresholds, thus favoring selective somatic activation. Furthermore, individual examples revealed rescued selective activation of somas that was not possible with any individual electrode. Significance: This work suggests that a bi-electrode epiretinal stimulation strategy can reduce inadvertent axonal activation at cellular resolution, for high-fidelity artificial vision.

Effect of Number of Electrodes Used to Elicit Electrical Stapedius Reflex Thresholds in Cochlear Implants

<b><i>Introduction:</i></b> When mapping cochlear implant (CI) patients with limited reporting abilities, the lowest electrical stimulus level that produces a stapedial reflex (i.e., the electrical stapedius reflex threshold [eSRT]) can be measured to estimate the upper bound of stimulation on individual or a subset of CI electrodes. However, eSRTs measured for individual electrodes or a subset of electrodes cannot be used to predict the global adjustment of electrical stimulation levels needed to achieve comfortable loudness sensations that can be readily used in a speech coding strategy. In the present study, eSRTs were measured for 1-, 4-, and 15-electrode stimulation to (1) determine changes in eSRT levels as a function of the electrode stimulation mode and (2) determine which stimulation mode eSRT levels best approximate comfortable loudness levels from patients’ clinical maps. <b><i>Methods:</i></b> eSRTs were measured with the 3 different electrical stimulation configurations in 9 CI patients and compared with behaviorally measured, comfortable loudness levels or M-levels from patients’ clinical maps. <b><i>Results:</i></b> A linear, mixed-effects, repeated-measures analysis revealed significant differences (<i>p</i> &#x3c; 0.01) between eSRTs measured as a function of the stimulation mode. No significant differences (<i>p</i> = 0.059) were measured between 15-electrode eSRTs and M-levels from patients’ clinical maps. The eSRTs measured for 1- and 4-electrode stimulation differed significantly (<i>p</i> &#x3c; 0.05) from the M-levels on the corresponding electrodes from the patients’ clinical map. <b><i>Conclusion:</i></b> eSRT profiles based on 1- or 4-electrode stimulation can be used to determine comfortable loudness level on either individual or a subset of electrodes, and 15-electrode eSRT profiles can be used to determine the upper bound of electrical stimulation that can be used in a speech coding strategy.

Feasibility of Using Adjunctive Optogenetic Technologies in Cardiomyocyte Phenotyping – from the Single Cell to the Whole Heart

In 1791, Galvani established that electricity activated excitable cells. In the two centuries that followed, electrode stimulation of neuronal, skeletal and cardiac muscle became the adjunctive method of choice in experimental, electrophysiological, and clinical arenas. This approach underpins breakthrough technologies like implantable cardiac pacemakers that we currently take for granted. However, the contact dependence, and field stimulation that electrical depolarization delivers brings inherent limitations to the scope and experimental scale that can be achieved. Many of these were not exposed until reliable in vitro stem-cell derived experimental materials, with genotypes of interest, were produced in the numbers needed for multi-well screening platforms (for toxicity or efficacy studies) or the 2D or 3D tissue surrogates required to study propagation of depolarization within multicellular constructs that mimic clinically relevant arrhythmia in the heart or brain. Here the limitations of classical electrode stimulation are discussed. We describe how these are overcome by optogenetic tools which put electrically excitable cells under the control of light. We discuss how this enables studies in cardiac material from the single cell to the whole heart scale. We review the current commercial platforms that incorporate optogenetic stimulation strategies, and summarize the global literature to date on cardiac applications of optogenetics. We show that the advantages of optogenetic stimulation relevant to iPS-CM based screening include independence from contact, elimination of electrical stimulation artefacts in field potential measuring approaches such as the multi-electrode array, and the ability to print re-entrant patterns of depolarization at will on 2D cardiomyocyte monolayers.

Correlation between Argus II array–retina distance and electrical thresholds of stimulation is improved by measuring the entire array

Purpose: To describe two methods of measuring Argus II array–retina distance and to correlate array–retina distance to electrode stimulation thresholds. Methods: This was a case series of eight patients implanted with the Argus II. Spectral domain-optical coherence tomography array–retina distance was measured by two methods and correlated to corresponding electrode thresholds: (1) array–retina distance at each array corner and the largest array–retina distance and (2) using manual optical coherence tomography segmentation, the average array–retina distance was determined for each group of four electrodes. Patients 1–5 and 6–8 were analyzed separately due to a different threshold programming software. Results: The Spearman’s rank coefficient between array–retina distance and thresholds was −0.006 ( p = 0.98) for patients 1–5, and 0.16 ( p = 0.59) for patients 6–8 with the first method. The Spearman’s rank coefficient was 0.25 ( p < 0.001) for patients 1–5 and 0.36 ( p < 0.001) for patients 6–8 with the second method. Conclusion: There is a positive correlation between array–retina distance and threshold measurements when measuring the entire array but not when using a faster measurement method of four corners and largest array–retina distance.