Alejandro Barriga-Rivera

The effect of electric cross-talk in retinal neurostimulation

PURPOSE To investigate the efficacy of electric field shaping in modulating the extent and activation threshold in retinal neurostimulation. This study aims to quantify the interference of neighboring stimulation sites by assessing the shift in the activation threshold produced by a concomitant interfering stimulus. METHODS Electrical stimuli were applied to healthy retinae in a feline model (n = 4) using a 24-channel electrode array surgically implanted in the suprachoroidal space. A 96-channel penetrating electrode array was used for recording cortical responses to a number of stimulation paradigms. Data were analyzed offline. Concurrent monopolar and hexapolar stimuli were delivered at primary and interfering sites separated by up to 2.19 mm to evaluate electric cross-talk. The spike rate was fit to a sigmoidal curve to estimate the P50 threshold. The slope of the linear regression of the P50 value versus interfering current level was considered as a measure of cross-talk. RESULTS Concurrent monopolar stimulation produced a proportional drop in the P50 of approximately 20% of the interfering current level in presence of a primary monopolar and hexapolar stimulus. On the other hand, hexapolar interference did not alter activation thresholds at the primary site. CONCLUSIONS Hexapolar stimulation reduces electric cross-talk between neighboring sites and represents a technique to reduce interference between individual stimulation sites. In contrast, concurrent monopolar stimulation produces a reduction of the activation threshold of stimuli delivered nearby. Thus, a single source of subthreshold monopolar charge injection can provide benefit in the form of significant threshold reduction simultaneously at multiple stimulation sites.

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.

Cortical responses following simultaneous and sequential retinal neurostimulation with different return configurations

Researchers continue to develop visual prostheses towards safer and more efficacious systems. However limitations still exist in the number of stimulating channels that can be integrated. Therefore there is a need for spatial and time multiplexing techniques to provide improved performance of the current technology. In particular, bright and high-contrast visual scenes may require simultaneous activation of several electrodes. In this research, a 24-electrode array was suprachoroidally implanted in three normally-sighted cats. Multi-unit activity was recorded from the primary visual cortex. Four stimulation strategies were contrasted to provide activation of seven electrodes arranged hexagonally: simultaneous monopolar, sequential monopolar, sequential bipolar and hexapolar. Both monopolar configurations showed similar cortical activation maps. Hexapolar and sequential bipolar configurations activated a lower number of cortical channels. Overall, the return configuration played a more relevant role in cortical activation than time multiplexing and thus, rapid sequential stimulation may assist in reducing the number of channels required to activate large retinal areas.

Electrically evoked potentials in an ovine model for the evaluation of visual prosthesis efficacy

Visual prostheses are becoming a reality as a therapy to restore functional vision to the blind. New stimulation strategies and novel electrode designs are contributing to accelerate the development of such devices triggering the interest of scientists, clinicians and the blind community worldwide. In this scenario, there is a need for large animal models that are suitable for preclinical testing of retinal neuroprostheses. This study presents an electrophysiology assessment of an ovine model for single and simultaneous electrode stimulation from the suprachoroidal space, using symmetric biphasic current pulses with a monopolar return configuration. Visually and electrically evoked potentials were recorded using supradural surface electrodes, showing charge thresholds comparable to those in humans. This model represents an alternative to feline or canine models with analogous activation levels and an eye anatomy similar to that of humans.

Mimicking natural neural encoding through retinal electrostimulation

Retinal neuroprostheses or ‘bionic eyes’, aim to restore patterned vision to those with vision loss by electrically stimulating the remaining neurons in the degenerate retina. Despite considerable progress over the last two decades, such devices generally stimulate indiscriminately both the ‘ON’ and ‘OFF’ visual pathways in the retina, conveying highly non-physiological signals to the brain.

Progress in artificial vision through suprachoroidal retinal implants

Retinal implants have proven their ability to restore visual sensation to people with degenerative retinopathy, characterized by photoreceptor cell death and the retinas inability to sense light. Retinal bionics operate by electrically stimulating the surviving neurons in the retina, thus triggering the transfer of visual sensory information to the brain. Suprachoroidal implants were first investigated in Australia in the 1950s. In this approach, the neuromodulation hardware is positioned between the sclera and the choroid, thus providing significant surgical and safety benefits for patients, with the potential to maintain residual vision combined with the artificial input from the device. Here we review the latest advances and state of the art devices for suprachoroidal prostheses, highlight future technologies and discuss challenges and perspectives towards improved rehabilitation of vision.

Long-term anesthetic protocol in rats : feasibility in electrophysiology studies in visual prosthesis

Electrical stimulation of excitable cells provides therapeutic benefits for a variety of medical conditions, including restoration of partial vision to those blinded via some types of retinal degeneration. To improve visual percepts elicited by the current technology, researchers are conducting acute electrophysiology experiments, mainly in cats. However, the rat can provide a model of a range of retinal diseases and possesses a sufficiently large eye to be used in this field. This article presents a long-term anesthetic protocol to enable electrophysiology experiments to further the development of visual prostheses. Six Long-Evans rats (aged between 14 and 16 weeks) were included in this study. Surgical anesthesia was maintained for more than 15 h by combining constant intravenous infusion of ketamine (24.0-34.5 mg/kg/h), xylazine (0.9-1.2 mg/kg/h), and inhaled isoflurane in oxygen (<0.5%). Overall heart rate, respiratory rate, and body temperature remained between 187-233 beats/min, 45-58 breaths/min, and 36-38 °C, respectively. Neural responses to 200-ms light pulses were recorded from the superior colliculus using a 32-channel neural probe at the beginning and before termination of the experiment. Robust responses were recorded from distinct functional types of retinal pathways. In addition, a platinum electrode was implanted in the retrobulbar space. The retina was electrically stimulated, and the activation threshold was determined to be 5.24 ± 0.24 μC/cm2 . This protocol may be used not only in the field of visual prosthesis research, but in other research areas requiring longer term acute experiments.

Visual Prosthesis: Interfacing Stimulating Electrodes with Retinal Neurons to Restore Vision

The bypassing of degenerated photoreceptors using retinal neurostimulators is helping the blind to recover functional vision. Researchers are investigating new ways to improve visual percepts elicited by these means as the vision produced by these early devices remain rudimentary. However, several factors are hampering the progression of bionic technologies: the charge injection limits of metallic electrodes, the mechanical mismatch between excitable tissue and the stimulating elements, neural and electric crosstalk, the physical size of the implanted devices, and the inability to selectively activate different types of retinal neurons. Electrochemical and mechanical limitations are being addressed by the application of electromaterials such as conducting polymers, carbon nanotubes and nanocrystalline diamonds, among other biomaterials, to electrical neuromodulation. In addition, the use of synthetic hydrogels and cell-laden biomaterials is promising better interfaces, as it opens a door to establishing synaptic connections between the electrode material and the excitable cells. Finally, new electrostimulation approaches relying on the use of high-frequency stimulation and field overlapping techniques are being developed to better replicate the neural code of the retina. All these elements combined will bring bionic vision beyond its present state and into the realm of a viable, mainstream therapy for vision loss.

Digital image processing for visual prosthesis: Filtering implications

Investigators around the world are working on retinal neurostimulation as it may restore functional vision to the blind. The image is captured by a camera and after being processed, a series of electrical stimuli are applied to the surviving ganglion cells of the retina. This visual perception is expected to have low resolution. Therefore, there is a need of new algorithms that present the information contained in a visual scene understandable to humans. This study presents a novel multi-resolution algorithm based on wavelet analysis to extract the useful features of an image. Participants in this experiment were able to configure a filter bank to complete a set of everyday tasks. This study shows that wavelet-based algorithms may facilitate improved functional performance in prosthetic vision.

Electrophysiology Techniques in Visual Prosthesis

Research in the field of visual prosthesis is advancing quickly with several groups around the world joining efforts to produce more effective and safe implants. In particular, new stimulation strategies are being investigated to elicit more meaningful percepts of light and to safely increase the visual acuity achieved by these devices. The synergy between in vitro, in silico and in vivo electrophysiology techniques can be exploited to accelerate research outcomes and to make them quickly available to the recipients of these implants.