In vivo electrical stimulation of the optic nerve and hybrid computational model for neuroprosthetic applications

Blindness affects millions of people worldwide, dramatically decreasing their quality of life. Retinal dystrophies, such as age related macular degeneration and Retinitis Pigmentosa, which are leading causes of blindness in industrialized countries, currently have no cure. However, in both of these diseases, parts of the visual pathway remain intact and functional, and can elicit visual percepts when stimulated. Here, we are performing electrical stimulation of the optic nerve in rabbits that could lead to the development of a new neuroprosthetic device for sight restoration in blind patients. We opted to stimulate the optic nerve with a modified version of the SELINE electrode, a 12-channels flexible implant, shown to be biocompatible and able to selectively recruit different fascicles in the rat sciatic nerve. After optimization of the stimulation parameters, we demonstrated that the amplitude of the stimulating current and the number of stimulating pulses could modulate the intensity of the response in the visual cortex. We are now investigating more complex multi-channel stimulating protocols in order to show the possibility to selectively recruit different portions of the optic nerve. Lastly, we are currently developing a computational model of the optic nerve. It combines a 3D finite element method that allows to determine the voltage distribution generated in the optic nerve and a biophysical model of the optic nerve axons and their ionic channels dynamics that predicts which axonal population is recruited.

Spatially selective activation of the visual cortex via intraneural stimulation of the optic nerve

Fiorenzo Artoni, Vivien Gaillet, Diego Ghezzi, Dario Lipucci Di Paola, Silvestro Micera, Ariastity Mega Pratiwi, Paola Vagni

Retinal prostheses can restore a functional form of vision in patients affected by dystrophies of the outer retinal layer. Beyond clinical utility, prostheses for the stimulation of the optic nerve, the visual thalamus or the visual cortex could also serve as tools for studying the visual system. Optic-nerve stimulation is particularly promising because it directly activates nerve fibres, takes advantage of the high-level information processing occurring downstream in the visual pathway, does not require optical transparency and could be effective in cases of eye trauma. Here we show, in anaesthetized rabbits and with support from numerical modelling, that an intraneural electrode array with high mechanical stability placed in the intracranial segment of the optic nerve induces, on electrical stimulation, selective activation patterns in the visual cortex. These patterns are measured as electrically evoked cortical potentials via an ECoG array placed in the contralateral cortex. The intraneural electrode array should enable further investigations of the effects of electrical stimulation in the visual system and could be further developed as a visual prosthesis for blind patients.

2019

A machine-learning algorithm correctly classifies cortical evoked potentials from both visual stimulation and electrical stimulation of the optic nerve

Eleonora Borda, Vivien Gaillet, Diego Ghezzi, Elodie Geneviève Zollinger

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 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.

IOP PUBLISHING LTD2021

Fabrication and validation of an intraneural interface tailored for optic nerve stimulation

Eleonora Borda

Technological progress in materials science and microengineering along with new discoveries in neuroscience have contributed to restore lost or impaired sensory functions by closely interfacing with the nervous system. Electronic devices have begun to be integrated within the body to artificially reproduce or record the electrical encoding of neural signals, the language of the nervous system. This has allowed us to restore the impaired communication between the missing or defective organ and the brain. As evidence of this, cochlear implants have returned hearing to millions of people world wide. On the other hand, there is no suitable solution yet for the 43 millions people who are currently blind. Nevertheless, several research groups and companies are trying to tackle this issue. So far, different devices have demonstrated the capability of restoring a certain degree of artificial vision, however, with limited success in delivering meaningful improvements in daily life activities. This is because, unlike hearing, vision is an extremely complex sense and requires higher stimulation resolution. Limitations of retinal prostheses have pushed further the investigation of other targets along the visual pathway, such as the optic nerve, the thalamus and the visual cortex. Among these, our group has started to explore the possibility of stimulating the optic nerve. The main advantages are the direct stimulation of the axon fibers and the access to the entire visual field with only one device. It is also interesting because it could work for those patients who are not eligible for retinal prostheses, due to severe eye trauma or retinal detachment, and it does not require optical transparency.In this thesis, we investigate stimulation strategies and materials to improve the outcome of optic nerve prostheses and make them one step closer to a viable option for blind patients. We first propose the use of machine learning algorithms to classify cortical activity upon electrical stimulation of the optic nerve. Secondly, we investigate a strategy to achieve higher spatial selectivity of the optic nerve stimulation. We design a three-dimensional (3D) multilayer concentric bipolar (CB) configuration and fabricate a modified version of the OpticSELINE. We validate the efficacy of the novel design during in-vivo experiments on rabbits and find that cortical activation is reduced when using the 3D multilayer CB electrodes compared to the classic monopolar configuration. In parallel, we explore the use of novel polymers, namely Off-Stoichiometry Thiol- Ene Epoxy (OSTE+), to design conformable neural interfaces. Their chemistry makes them a suitable candidate for easy integration in cleanroom processes and they show superior adhesion properties with respect to standard thin films currently in use. Hence, we characterise their usability as substrate and encapsulation for neural interfaces in-vitro and in-vivo. Lastly, we propose an alternative fabrication technique, ink-jet printing of platinum on flexible substrates, for neurophysiology applications. Altogether, the findings highlighted in this thesis will hopefully lead to a more in-depth investigation of the optic nerve prosthesis and can also be relevant for other applications in the field of neuroprosthetics.