Focal Activation of Primary Visual Cortex Following Supra-choroidal Electrical Stimulation of the Retina: Intrinsic Signal Imaging and Linear Model Analysis

UNLABELLED: We performed optical intrinsic signal imaging of cat primary visual cortex (Area 17 and 18) while delivering bipolar electrical stimulation to the retina by way of a supra-choroidal electrode array. Using a general linear model (GLM) analysis we identified statistically significant (p < 0.01) activation in a localized region of cortex following supra-threshold electrical stimulation at a single retinal locus. OUR RESULTS: (1) demonstrate that intrinsic signal imaging combined with linear model analysis provides a powerful tool for assessing cortical responses to prosthetic stimulation, and (2) confirm that supra-choroidal electrical stimulation can achieve localized activation of the cortex consistent with focal activation of the retina

Survey of electrically evoked responses in the retina-stimulus preferences and oscillation among neurons

Electrical stimulation is an important tool in neuroscience research and clinically. In the retina, extensive work has revealed how the retinal ganglion cells respond to extracellular electrical stimulation. But little is known about the responses of other neuronal types, and more generally, how the network responds to stimulation. We conducted a survey of electrically evoked responses, over a range of pulse amplitudes and pulse widths, for 21 cell types spanning the inner two layers of the rabbit retina. It revealed: (i) the evoked responses of some neurons were charge insensitive; (ii) pulse-width sensitivity varied between cell types, allowing preferential recruitment of cell types; and (iii) 10-20 Hz damped oscillations across retinal layers. These oscillations were generated by reciprocal excitatory/inhibitory synapses, at locations as early as the cone-horizontal-cell synapses. These results illustrate at cellular resolution how a network responds to extracellular stimulation, and could inform the development of bioelectronic implants for treating blindness

On the use of test gases of various radii to investigate molecular sieving in leak channels

Evidence of the effect of molecule size (molecular sieving) was discovered in leak channels similar to those found in hermetically sealed implantable bionics. A range of test gases of different molecular sizes was used to investigate the relative leak rates of several different samples. A contemporary model of molecular sieving is shown to be in partial agreement with our data

Proceedings of the Annual International Conference of the IEEE Engineering in Medicine and Biology Society, EMBS

© 2017 IEEE. Retinal neuromodulation is an emerging therapeutic approach to restore functional vision to those suffering retinal photoreceptor degeneration. The retina encodes visual information and transmits it to the brain. Replicating this retinal code through electrical stimulation is essential to improving the performance of visual prostheses. In doing so, the first step relies on precise neural recordings from visual centers that allow studying the response of these neurons to electrical stimulation of the retina. This paper demonstrates the feasibility of a rat model to conduct highly reliable electrophysiological studies in the field of retinal neuromodulation. A disc electrode, implanted in the retrobulbar space was used to stimulate the retina of Long-Evans rats. Buzsaki multi-electro arrays were inserted in the superior colliculus (SC) to record electrical activity propagated from the retinal ganglion cells (RGCs). Activation thresholds calculated from local field potentials (visual cortex) and from neural spikes (SC) were contrasted. Both values were comparable to those in humans and in other animal models, and were slightly higher when estimated from SC recordings. However, differences were not statistically significant

High-amplitude electrical stimulation can reduce elicited neuronal activity in visual prosthesis

Retinal electrostimulation is promising a successful therapy to restore functional vision. However, a narrow stimulating current range exists between retinal neuron excitation and inhibition which may lead to misperformance of visual prostheses. As the conveyance of representation of complex visual scenes may require neighbouring electrodes to be activated simultaneously, electric field summation may contribute to reach this inhibitory threshold. This study used three approaches to assess the implications of relatively high stimulating conditions in visual prostheses: (1) in vivo, using a suprachoroidal prosthesis implanted in a feline model, (2) in vitro through electrostimulation of murine retinal preparations, and (3) in silico by computing the response of a population of retinal ganglion cells. Inhibitory stimulating conditions led to diminished cortical activity in the cat. Stimulus-response relationships showed non-monotonic profiles to increasing stimulating current. This was observed in vitro and in silico as the combined response of groups of neurons (close to the stimulating electrode) being inhibited at certain stimulating amplitudes, whilst other groups (far from the stimulating electrode) being recruited. These findings may explain the halo-like phosphene shapes reported in clinical trials and suggest that simultaneous stimulation in retinal prostheses is limited by the inhibitory threshold of the retinal ganglion cells

Mediating retinal ganglion cell spike rates using high-frequency electrical stimulation

Recent retinal studies have directed more attention to sophisticated stimulation strategies based on high-frequency (>1.0 kHz) electrical stimulation (HFS). In these studies, each retinal ganglion cell (RGC) type demonstrated a characteristic stimulus-strength-dependent response to HFS, offering the intriguing possibility of focally targeting retinal neurons to provide useful visual information by retinal prosthetics. Ionic mechanisms are known to affect the responses of electrogenic cells during electrical stimulation. However, how these mechanisms affect RGC responses is not well understood at present, particularly when applying HFS. Here, we investigate this issue via an in silico model of the RGC. We calibrate and validate the model using an in vitro retinal preparation. An RGC model based on accurate biophysics and realistic representation of cell morphology, was used to investigate how RGCs respond to HFS. The model was able to closely replicate the stimulus-strength-dependent suppression of RGC action potentials observed experimentally. Our results suggest that spike inhibition during HFS is due to local membrane hyperpolarization caused by outward membrane currents near the stimulus electrode. In addition, the extent of HFS-induced inhibition can be largely altered by the intrinsic properties of the inward sodium current. Finally, stimulus-strength-dependent suppression can be modulated by a wide range of stimulation frequencies, under generalized electrode placement conditions. In vitro experiments verified the computational modeling data. This modeling and experimental approach can be extended to further our understanding on the effects of novel stimulus strategies by simulating RGC stimulus-response profiles over a wider range of stimulation frequencies and electrode locations than have previously been explored