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Objective. Optic nerve’s intraneural stimulation is an emerging neuroprosthetic approach to provide artificial vision to totally blind patients. An open question is the possibility to evoke individual non-overlapping phosphenes via selective intraneural optic nerve stimulation. To begin answering this question, first, we aim at showing in preclinical experiments with animals that each intraneural electrode could evoke a distinguishable activity pattern in the primary visual cortex. Approach. We performed both patterned visual stimulation and patterned electrical stimulation in healthy rabbits while recording evoked cortical activity with an electrocorticogram array in the primary visual cortex. Electrical stimulation was delivered to the optic nerve with the intraneural array OpticSELINE. We used a support vector machine algorithm paired to a linear regression model to classify cortical responses originating from visual stimuli located in different portions of the visual field and electrical stimuli from the different electrodes of the OpticSELINE. Main results. Cortical activity induced by visual and electrical stimulation could be classified with nearly 100% accuracy relative to the specific location in the visual field or electrode in the array from which it originated. For visual stimulation, the accuracy increased with the separation of the stimuli and reached 100% for separation higher than 7°. For electrical stimulation, at low current amplitudes, the accuracy increased with the distance between electrodes, while at higher current amplitudes, the accuracy was nearly 100% already for the shortest separation. Significance. Optic nerve’s intraneural stimulation with the OpticSELINE induced discernible cortical activity patterns. These results represent a necessary condition for an optic nerve prosthesis to deliver vision with non-overlapping phosphene. However, clinical investigations will be required to assess the translation of these results into perceptual phenomena.

Objective. Intraneural nerve interfaces often operate in a monopolar configuration with a common and distant ground electrode. This configuration leads to a wide spreading of the electric field. Therefore, this approach is suboptimal for intraneural nerve interfaces when selective stimulation is required. Approach. We designed a multilayer electrode array embedding three-dimensional concentric bipolar electrodes. First, we validated the higher stimulation selectivity of this new electrode array compared to classical monopolar stimulation using simulations. Next, we compared them in-vivo by intraneural stimulation of the rabbit optic nerve and recording evoked potentials in the primary visual cortex. Main results. Simulations showed that three-dimensional concentric bipolar electrodes provide a high localisation of the electric field in the tissue so that electrodes are electrically independent even for high electrode density. Experiments in-vivo highlighted that this configuration restricts spatial activation in the visual cortex due to the fewer fibres activated by the electric stimulus in the nerve. Significance. Highly focused electric stimulation is crucial to achieving high selectivity in fibre activation. The multilayer array embedding three-dimensional concentric bipolar electrodes improves selectivity in optic nerve stimulation. This approach is suitable for other neural applications, including bioelectronic medicine.

Objective: Intraneural nerve interfaces often operate in a monopolar configuration with a common and distant ground electrode. This configuration leads to a wide spreading of the electric field. Therefore, this approach is suboptimal for intraneural nerve interfaces when selective stimulation is required. Approach: We designed a multilayer electrode array embedding three-dimensional concentric bipolar electrodes. First, we validated the higher stimulation selectivity of this new electrode array compared to classical monopolar stimulation using simulations. Next, we compared them in-vivo by intraneural stimulation of the rabbit optic nerve and recording evoked potentials in the primary visual cortex. Main results: Simulations showed that three-dimensional concentric bipolar electrodes provide a high localisation of the electric field in the tissue so that electrodes are electrically independent even for high electrode density. Experiments in-vivo highlighted that this configuration leads to evoked responses with lower amplitude and more localised cortical patterns due to the fewer fibres activated by the electric stimulus in the nerve. Significance: Highly focused electric stimulation is crucial to achieving high selectivity in fibre activation. The multilayer array embedding three-dimensional concentric bipolar electrodes improves selectivity in optic nerve stimulation. This approach is suitable for other neural applications, including bioelectronic medicine.

Retinal prostheses have been developed to restore a functional form of vision in patients affected by outer retinal layer dystrophies. Other approaches, namely optic nerve, thalamic, and cortical prostheses are under investigation to expand this toolbox both as clinical devices and as tools for fundamental research. Optic nerve stimulation is attractive since it bypasses the entire retinal network and directly activates nerve fibers. At the same time, it still takes advantage of the high-level information processing occurring downstream in the visual cortex. Here we show that a new intraneural electrode array (OpticSELINE) is effective in inducing the activation of the visual cortex upon electrical stimulation of the optic nerve. We also demonstrate that intraneural optic nerve stimulation induces selective cortical activation patterns depending on the stimulating electrode, thus suggesting that the OpticSELINE possesses spatial selectivity in fiber stimulation. In conclusion, the OpticSELINE can be used both as visual prosthesis for blind patients and as tool to further investigate the effect of the electrical stimulation in the visual system.

No abstract

Objective: Optic nerve's intraneural stimulation is an emerging neuroprosthetic approach to provide artificial vision to totally blind patients. An open question is the possibility to evoke individual non-overlapping phosphenes via selective intraneural optic nerve stimulation. To begin answering this question, first, we aim at showing in preclinical experiments with animals that each intraneural electrode could evoke a distinguishable activity pattern in the primary visual cortex. Approach: We performed both patterned visual stimulation and patterned electrical stimulation in healthy rabbits while recording evoked cortical activity with an electrocorticogram array in the primary visual cortex. Electrical stimulation was delivered to the optic nerve with the intraneural array OpticSELINE. We used a support vector machine algorithm paired to a linear regression model to classify cortical responses originating from visual stimuli located in different portions of the visual field and electrical stimuli from the different electrodes of the OpticSELINE. Main results: Cortical activity induced by visual and electrical stimulation could be classified with nearly 100% accuracy relative to the specific location in the visual field or electrode in the array from which it originated. For visual stimulation, the accuracy increased with the separation of the stimuli and reached 100% for separation higher than 7 degrees. For electrical stimulation, at low current amplitudes, the accuracy increased with the distance between electrodes, while at higher current amplitudes, the accuracy was nearly 100% already for the shortest separation. Significance: Optic nerve's intraneural stimulation with the OpticSELINE induced discernible cortical activity patterns. These results represent a leap forward for intraneural optic nerve stimulation towards artificial vision.

No abstract