In vivo feasibility of epiretinal stimulation using ultrananocrystalline diamond electrodes.

OBJECTIVE: Due to their increased proximity to retinal ganglion cells (RGCs), epiretinal visual prostheses present the opportunity for eliciting phosphenes with low thresholds through direct RGC activation. This study characterised the in vivo performance of a novel prototype monolithic epiretinal prosthesis, containing Nitrogen incorporated ultrananocrystalline (N-UNCD) diamond electrodes. APPROACH: A prototype implant containing up to twenty-five 120 × 120 µm N-UNCD electrodes was implanted into 16 anaesthetised cats and attached to the retina either using a single tack or via magnetic coupling with a suprachoroidally placed magnet. Multiunit responses to retinal stimulation using charge-balanced biphasic current pulses were recorded acutely in the visual cortex using a multichannel planar array. Several stimulus parameters were varied including; the stimulating electrode, stimulus polarity, phase duration, return configuration and the number of electrodes stimulated simultaneously. MAIN RESULTS: The rigid nature of the device and its form factor necessitated complex surgical procedures. Surgeries were considered successful in 10/16 animals and cortical responses to single electrode stimulation obtained in eight animals. Clinical imaging and histological outcomes showed severe retinal trauma caused by the device in situ in many instances. Cortical measures were found to significantly depend on the surgical outcomes of individual experiments, phase duration, return configuration and the number of electrodes stimulated simultaneously, but not stimulus polarity. Cortical thresholds were also found to increase over time within an experiment. SIGNIFICANCE: The study successfully demonstrated that an epiretinal prosthesis containing diamond electrodes could produce cortical activity with high precision, albeit only in a small number of cases. Both surgical approaches were highly challenging in terms of reliable and consistent attachment to and stabilisation against the retina, and often resulted in severe retinal trauma. There are key challenges (device form factor and attachment technique) to be resolved for such a device to progress towards clinical application, as current surgical techniques are unable to address these issues.

Optimizing growth and post treatment of diamond for high capacitance neural interfaces.

Electrochemical and biological properties are two crucial criteria in the selection of the materials to be used as electrodes for neural interfaces. For neural stimulation, materials are required to exhibit high capacitance and to form intimate contact with neurons for eliciting effective neural responses at acceptably low voltages. Here we report on a new high capacitance material fabricated using nitrogen included ultrananocrystalline diamond (N-UNCD). After exposure to oxygen plasma for 3 h, the activated N-UNCD exhibited extremely high electrochemical capacitance greater than 1 mF/cm(2), which originates from the special hybrid sp(2)/sp(3) structure of N-UNCD. The in vitro biocompatibility of the activated N-UNCD was then assessed using rat cortical neurons and surface roughness was found to be critical for healthy neuron growth, with best results observed on surfaces with a roughness of approximately 20 nm. Therefore, by using oxygen plasma activated N-UNCD with appropriate surface roughness, and considering the chemical and mechanical stability of diamond, the fabricated neural interfaces are expected to exhibit high efficacy, long-term stability and a healthy neuron/electrode interface.

Development of a Magnetic Attachment Method for Bionic Eye Applications.

Successful visual prostheses require stable, long-term attachment. Epiretinal prostheses, in particular, require attachment methods to fix the prosthesis onto the retina. The most common method is fixation with a retinal tack; however, tacks cause retinal trauma, and surgical proficiency is important to ensure optimal placement of the prosthesis near the macula. Accordingly, alternate attachment methods are required. In this study, we detail a novel method of magnetic attachment for an epiretinal prosthesis using two prostheses components positioned on opposing sides of the retina. The magnetic attachment technique was piloted in a feline animal model (chronic, nonrecovery implantation). We also detail a new method to reliably control the magnet coupling force using heat. It was found that the force exerted upon the tissue that separates the two components could be minimized as the measured force is proportionately smaller at the working distance. We thus detail, for the first time, a surgical method using customized magnets to position and affix an epiretinal prosthesis on the retina. The position of the epiretinal prosthesis is reliable, and its location on the retina is accurately controlled by the placement of a secondary magnet in the suprachoroidal location. The electrode position above the retina is less than 50 microns at the center of the device, although there were pressure points seen at the two edges due to curvature misalignment. The degree of retinal compression found in this study was unacceptably high; nevertheless, the normal structure of the retina remained intact under the electrodes.

Spatiotemporal interactions in the visual cortex following paired electrical stimulation of the retina.

PURPOSE: Retinal prostheses use spatiotemporal patterns of electrical stimulation across multiple electrodes to provide visual percepts to blind patients. It is generally assumed that percepts produced by individual electrodes are independent of one another, which may not be the case. In this study, we aimed to quantify interactions between pairs of electrical stimuli delivered to the retina. METHODS: Normally sighted cats were implanted with a suprachoroidal electrode array. The retina was stimulated with a paired-pulse paradigm that consisted of a conditioning stimulus followed by a test stimulus, while recording multiunit activity in the visual cortex. Conditioning current, and spatial and temporal separation between the conditioning and test stimuli were varied. Cortical interactions were quantified by changes in multiunit activity elicited by stimulation with the paired-pulse paradigm, compared to stimulation of the test stimulus alone (control). RESULTS: Interactions varied as a function of conditioning current and temporal separation between the two stimulating pulses. Cortical activity increased compared to the control condition at an interstimulus delay of 1.025 ms and was significantly suppressed for delays between 20 and 90 ms, returning to near control levels for longer delays. The level of interactions increased when the conditioning current was increased. Interactions were found to be similar for electrode separations up to 3 mm. CONCLUSIONS: Interactions between sequential stimulation of pairs of electrodes in a suprachoroidal retinal prosthesis occur for delays up to 100 ms and electrode separations of several millimeters. Knowledge of these spatiotemporal interactions is essential for developing effective patterns of stimulation for retinal prostheses.

Visual cortex responses to single- and simultaneous multiple-electrode stimulation of the retina: implications for retinal prostheses.

PURPOSE: The aim of this study was to compare simultaneous stimulation of multiple electrodes to single-electrode stimulation in a retinal prosthesis. METHODS: A platinum electrode array was implanted into the suprachoroidal space in six normally sighted anesthetized cats. Multiunit activity from the primary visual cortex in response to retinal stimulation was recorded. Cortical thresholds, yield of responses, dynamic ranges, and the spread of retinal activation were measured for three modes of stimulation: single electrode, half-row (six-electrode horizontal line), and column (seven-electrode vertical line). RESULTS: Stimulation of the best half-rows and columns was found to elicit activity with higher yield and lower charge thresholds per electrode compared to the best single electrodes. Dynamic ranges between the three modes were similar. As expected, peak voltages measured for columns and half-rows were lower than those measured for single electrodes. Spread of retinal activation, determined by the increase in threshold with distance in the retina from the best site, was found to be similar between single- and multiple-electrode stimulation but dependent on orientation. CONCLUSIONS: The lower thresholds, higher yield, equivalent dynamic ranges, and equivalent spread of retinal activation observed from simultaneous stimulation of multiple electrodes may be due to current and/or neural summation within the retina. Such stimulation techniques could be useful for the presentation of lines and edges of objects using a suprachoroidal retinal stimulator with low voltage compliance. Furthermore, the results suggest that more complex visual processing strategies in addition to sequential stimulation of individual electrodes should be considered for retinal prostheses.

Visual cortex responses to suprachoroidal electrical stimulation of the retina: effects of electrode return configuration.

A clinically effective retinal prosthesis must evoke localized phosphenes in a retinotopic manner in response to stimulation of each of the retinal electrodes, evoke brightness cues over a wide dynamic range and function within safe stimulus limits. The effects of varying return configuration for retinal stimulation are currently unknown. To investigate this, we implanted a flexible, 7 × 12 electrode array into the suprachoroidal space of normally-sighted, anesthetized cats. Multi-unit activity in the primary visual cortex was recorded in response to electrical stimulation using various return configurations: monopolar vitreous (MPV), common ground (CG), hexagonal (HX), monopolar remote (MPR) and bipolar (BP_N). MPV stimulation was found to be the most charge efficient and was most likely to induce cortical activity within safe charge limits. HX and CG stimulation were found to exhibit greater retinal selectivity compared to the MPV return at the expense of lower cortical yield and higher P50 charge levels, while cortical selectivity was unaffected by choice of return. Responses using MPR and widely spaced BP_N configurations were similar to those using the MPV return. These results suggest that choice of return configuration for a retinal prosthesis will be balanced between resolution and stimulation within safe charge limits.

Evaluation of stimulus parameters and electrode geometry for an effective suprachoroidal retinal prosthesis.

Several approaches have been proposed for placement of retinal prostheses: epiretinal, subretinal and suprachoroidal. We aimed to systematically evaluate the effectiveness of varying a range of stimulus parameters and electrode geometry for a suprachoroidal electrode array, using cortical evoked responses to monopolar electrical stimulation in cats. Our results indicate that charge thresholds were not dependent on electrode size, pulse widths or position of the return electrode tested, but were dependent on the number of sites stimulated in parallel. Further, we found that the combination of monopolar stimulation with large diameter electrodes, wide pulse widths and parallel stimulation minimized the voltage requirements for stimulation. These results provide useful insights for the design specifications of a low voltage suprachoroidal stimulator.