Stability Study of Synthetic Diamond Using a Thermally Controlled Biological Environment: Application towards Long-Lasting Neural Prostheses.

This paper demonstrates, for the first time, the stability of synthetic diamond as a passive layer within neural implants. Leveraging the exceptional biocompatibility of intrinsic nanocrystalline diamond, a comprehensive review of material aging analysis in the context of in-vivo implants is provided. This work is based on electric impedance monitoring through the formulation of an analytical model that scrutinizes essential parameters such as the deposited metal resistivity, insulation between conductors, changes in electrode geometry, and leakage currents. The evolution of these parameters takes place over an equivalent period of approximately 10 years. The analytical model, focusing on a fractional capacitor, provides nuanced insights into the surface conductivity variation. A comparative study is performed between a classical polymer material (SU8) and synthetic diamond. Samples subjected to dynamic impedance analysis reveal distinctive patterns over time, characterized by their physical degradation. The results highlight the very high stability of diamond, suggesting promise for the electrode's enduring viability. To support this analysis, microscopic and optical measurements conclude the paper and confirm the high stability of diamond and its strong potential as a material for neural implants with long-life use.

Optimized Signal Analysis to Quantify the Non-Linear Behaviour of the Electrically Evoked Vestibulo-Ocular Reflex in Patients with a Vestibular Implant.

INTRODUCTION: Different eye movement analysis algorithms are used in vestibular implant research to quantify the electrically evoked vestibulo-ocular reflex (eVOR). Often, standard techniques are used as applied for quantification of the natural VOR in healthy subjects and patients with vestibular loss. However, in previous research, it was observed that the morphology of the VOR and eVOR may differ substantially. In this study, it was investigated if the analysis techniques for eVOR need to be adapted to optimize a truthful quantification of the eVOR (VOR gain, orientation of the VOR axis, asymmetry, and phase shift). METHODS: "Natural" VOR responses were obtained in six age-matched healthy subjects, and eVOR responses were obtained in eight bilateral-vestibulopathy patients fitted with a vestibular implant. Three conditions were tested: "nVOR" 1-Hz sinusoidal whole-body rotations of healthy subjects in a rotatory chair, "eVOR" 1-Hz sinusoidal electrical vestibular implant stimulation without whole-body rotations in bilateral-vestibulopathy patients, and "dVOR" 1-Hz sinusoidal whole-body rotations in bilateral-vestibulopathy patients using the chair-mounted gyroscope output to drive the electrical vestibular implant stimulation (therefore also in sync 1 Hz sinusoidal). VOR outcomes were determined from the obtained VOR responses, using three different eye movement analysis paradigms: (1) peak eye velocity detection using the raw eye traces; (2) peak eye velocity detection using full-cycle sine fitting of eye traces; (3) peak eye velocity detection using half-cycle sine fitting of eye traces. RESULTS: The type of eye movement analysis algorithm significantly influenced VOR outcomes, especially regarding the VOR gain and asymmetry of the eVOR in bilateral-vestibulopathy patients fitted with a vestibular implant. Full-cycle fitting lowered VOR gain in the eVOR condition (mean difference: 0.14 ± 0.06 95% CI, p = 0.018). Half-cycle fitting lowered VOR gain in the dVOR condition (mean difference: 0.08 ± 0.04 95% CI, p = 0.009). In the eVOR condition, half-cycle fitting was able to demonstrate the asymmetry between the excitatory and inhibitory phases of stimulation in comparison with the full-cycle fitting (mean difference: 0.19 ± 0.12 95% CI, p = 0.024). The VOR axis and phase shift did not differ significantly between eye movement analysis algorithms. In healthy subjects, no clinically significant effect of eye movement analysis algorithms on VOR outcomes was observed. CONCLUSION: For the analysis of the eVOR, the excitatory and inhibitory phases of stimulation should be analysed separately due to the inherent asymmetry of the eVOR. A half-cycle fitting method can be used as a more accurate alternative for the analysis of the full-cycle traces.

Discriminability of multiple cutaneous and proprioceptive hand percepts evoked by intraneural stimulation with Utah slanted electrode arrays in human amputees.

BACKGROUND: Electrical stimulation of residual afferent nerve fibers can evoke sensations from a missing limb after amputation, and bionic arms endowed with artificial sensory feedback have been shown to confer functional and psychological benefits. Here we explore the extent to which artificial sensations can be discriminated based on location, quality, and intensity. METHODS: We implanted Utah Slanted Electrode Arrays (USEAs) in the arm nerves of three transradial amputees and delivered electrical stimulation via different electrodes and frequencies to produce sensations on the missing hand with various locations, qualities, and intensities. Participants performed blind discrimination trials to discriminate among these artificial sensations. RESULTS: Participants successfully discriminated cutaneous and proprioceptive sensations ranging in location, quality and intensity. Performance was significantly greater than chance for all discrimination tasks, including discrimination among up to ten different cutaneous location-intensity combinations (15/30 successes, p < 0.0001) and seven different proprioceptive location-intensity combinations (21/40 successes, p < 0.0001). Variations in the site of stimulation within the nerve, via electrode selection, enabled discrimination among up to five locations and qualities (35/35 successes, p < 0.0001). Variations in the stimulation frequency enabled discrimination among four different intensities at the same location (13/20 successes, p < 0.0005). One participant also discriminated among individual stimulation of two different USEA electrodes, simultaneous stimulation on both electrodes, and interleaved stimulation on both electrodes (20/24 successes, p < 0.0001). CONCLUSION: Electrode location, stimulation frequency, and stimulation pattern can be modulated to evoke functionally discriminable sensations with a range of locations, qualities, and intensities. This rich source of artificial sensory feedback may enhance functional performance and embodiment of bionic arms endowed with a sense of touch.

Restoring the High-Frequency Dynamic Visual Acuity with a Vestibular Implant Prototype in Humans.

INTRODUCTION: The vestibular implant could become a clinically useful device in the near future. This study investigated the feasibility of restoring the high-frequency dynamic visual acuity (DVA) with a vestibular implant, using the functional Head Impulse Test (fHIT). METHODS: A 72-year-old female, with bilateral vestibulopathy and fitted with a modified cochlear implant incorporating three vestibular electrodes (MED-EL, Innsbruck, Austria), was available for this study. Electrical stimulation was delivered with the electrode close to the lateral ampullary nerve in the left ear. The high-frequency DVA in the horizontal plane was tested with the fHIT. After training, the patient underwent six trials of fHIT, each with a different setting of the vestibular implant: (1) System OFF before stimulation; (2) System ON, baseline stimulation; (3) System ON, reversed stimulation; (4) System ON, positive stimulation; (5) System OFF, without delay after stimulation offset; and (6) System OFF, 25 min delay after stimulation offset. The percentage of correct fHIT scores for right and left head impulses were compared between trials. RESULTS: Vestibular implant stimulation improved the high-frequency DVA compared to no stimulation. This improvement was significant for "System ON, baseline stimulation" (p = 0.02) and "System ON, positive stimulation" (p < 0.001). fHIT scores changed from 19 to 44% (no stimulation) to maximum 75-94% (System ON, positive stimulation). CONCLUSION: The vestibular implant seems capable of improving the high-frequency DVA. This functional benefit of the vestibular implant illustrates again the feasibility of this device for clinical use in the near future.

Modeling of spike trains in auditory nerves with self-exciting point processes of the von Mises type.

This article presents the modeling of spike trains in auditory nerve fiber (ANF) models with a one-memory self-exciting point process (SEPP) of the von Mises type. The ANF models were acoustically stimulated by a synaptic current of inner hair cells, or electrically stimulated by sinusoidally amplitude-modulated pulsatile waveforms. It has been shown that the parameters of one-memory SEPP of the von Mises type could be estimated by numerically maximizing the likelihood function from sample realizations of the spike trains in response to acoustic or electric stimulus. Furthermore, it was found that period histograms of the one-memory SEPP generated artificially on the basis of the estimated von Mises parameters agreed well with those of acoustic or electric stimulus, by performing the uniform-scores test. It implies that the waveforms of pulsatile electric stimuli should be selected such that the spike trains can be represented by one-memory SEPP of the von Mises type with appropriate parameters, efficiently carrying information to the cochlear implant user's brain, like that in acoustic stimulation of the healthy ear. The findings presented in this paper may play an important role in determining optimal parameters of pulsatile electric stimuli by using one-memory SEPP of the von Mises type, and further in the design of better cochlear prostheses.

Metaheuristic Optimisation Algorithms for Tuning a Bioinspired Retinal Model.

A significant challenge in neuroscience is understanding how visual information is encoded in the retina. Such knowledge is extremely important for the purpose of designing bioinspired sensors and artificial retinal systems that will, in so far as may be possible, be capable of mimicking vertebrate retinal behaviour. In this study, we report the tuning of a reliable computational bioinspired retinal model with various algorithms to improve the mimicry of the model. Its main contribution is two-fold. First, given the multi-objective nature of the problem, an automatic multi-objective optimisation strategy is proposed through the use of four biological-based metrics, which are used to adjust the retinal model for accurate prediction of retinal ganglion cell responses. Second, a subset of population-based search heuristics-genetic algorithms (SPEA2, NSGA-II and NSGA-III), particle swarm optimisation (PSO) and differential evolution (DE)-are explored to identify the best algorithm for fine-tuning the retinal model, by comparing performance across a hypervolume metric. Nonparametric statistical tests are used to perform a rigorous comparison between all the metaheuristics. The best results were achieved with the PSO algorithm on the basis of the largest hypervolume that was achieved, well-distributed elements and high numbers on the Pareto front.

Spatiotemporal characteristics of retinal response to network-mediated photovoltaic stimulation.

Subretinal prostheses aim at restoring sight to patients blinded by photoreceptor degeneration using electrical activation of the surviving inner retinal neurons. Today, such implants deliver visual information with low-frequency stimulation, resulting in discontinuous visual percepts. We measured retinal responses to complex visual stimuli delivered at video rate via a photovoltaic subretinal implant and by visible light. Using a multielectrode array to record from retinal ganglion cells (RGCs) in the healthy and degenerated rat retina ex vivo, we estimated their spatiotemporal properties from the spike-triggered average responses to photovoltaic binary white noise stimulus with 70-µm pixel size at 20-Hz frame rate. The average photovoltaic receptive field size was 194 ± 3 µm (mean ± SE), similar to that of visual responses (221 ± 4 µm), but response latency was significantly shorter with photovoltaic stimulation. Both visual and photovoltaic receptive fields had an opposing center-surround structure. In the healthy retina, ON RGCs had photovoltaic OFF responses, and vice versa. This reversal is consistent with depolarization of photoreceptors by electrical pulses, as opposed to their hyperpolarization under increasing light, although alternative mechanisms cannot be excluded. In degenerate retina, both ON and OFF photovoltaic responses were observed, but in the absence of visual responses, it is not clear what functional RGC types they correspond to. Degenerate retina maintained the antagonistic center-surround organization of receptive fields. These fast and spatially localized network-mediated ON and OFF responses to subretinal stimulation via photovoltaic pixels with local return electrodes raise confidence in the possibility of providing more functional prosthetic vision. NEW & NOTEWORTHY Retinal prostheses currently in clinical use have struggled to deliver visual information at naturalistic frequencies, resulting in discontinuous percepts. We demonstrate modulation of the retinal ganglion cells (RGC) activity using complex spatiotemporal stimuli delivered via subretinal photovoltaic implant at 20 Hz in healthy and in degenerate retina. RGCs exhibit fast and localized ON and OFF network-mediated responses, with antagonistic center-surround organization of their receptive fields.

Restoration of motor control and proprioceptive and cutaneous sensation in humans with prior upper-limb amputation via multiple Utah Slanted Electrode Arrays (USEAs) implanted in residual peripheral arm nerves.

BACKGROUND: Despite advances in sophisticated robotic hands, intuitive control of and sensory feedback from these prostheses has been limited to only 3-degrees-of-freedom (DOF) with 2 sensory percepts in closed-loop control. A Utah Slanted Electrode Array (USEA) has been used in the past to provide up to 81 sensory percepts for human amputees. Here, we report on the advanced capabilities of multiple USEAs implanted in the residual peripheral arm nerves of human amputees for restoring control of 5 DOF and sensation of up to 131 proprioceptive and cutaneous hand sensory percepts. We also demonstrate that USEA-restored sensory percepts provide a useful source of feedback during closed-loop virtual prosthetic hand control. METHODS: Two 100-channel USEAs were implanted for 4-5 weeks, one each in the median and ulnar arm nerves of two human subjects with prior long-duration upper-arm amputations. Intended finger and wrist positions were decoded from neuronal firing patterns via a modified Kalman filter, allowing subjects to control many movements of a virtual prosthetic hand. Additionally, USEA microstimulation was used to evoke numerous sensory percepts spanning the phantom hand. Closed-loop control was achieved by stimulating via an electrode of the ulnar-nerve USEA while recording and decoding movement via the median-nerve USEA. RESULTS: Subjects controlled up to 12 degrees-of-freedom during informal, 'freeform' online movement decode sessions, and experienced up to 131 USEA-evoked proprioceptive and cutaneous sensations spanning the phantom hand. Independent control was achieved for a 5-DOF real-time decode that included flexion/extension of the thumb, index, middle, and ring fingers, and the wrist. Proportional control was achieved for a 4-DOF real-time decode. One subject used a USEA-evoked hand sensation as feedback to complete a 1-DOF closed-loop virtual-hand movement task. There were no observed long-term functional deficits due to the USEA implants. CONCLUSIONS: Implantation of high-channel-count USEAs enables multi-degree-of-freedom control of virtual prosthetic hand movement and restoration of a rich selection of both proprioceptive and cutaneous sensory percepts spanning the hand during the short 4-5 week post-implant period. Future USEA use in longer-term implants and in closed-loop may enable restoration of many of the capabilities of an intact hand while contributing to a meaningful embodiment of the prosthesis.

Semiconductor nanorod-carbon nanotube biomimetic films for wire-free photostimulation of blind retinas.

We report the development of a semiconductor nanorod-carbon nanotube based platform for wire-free, light induced retina stimulation. A plasma polymerized acrylic acid midlayer was used to achieve covalent conjugation of semiconductor nanorods directly onto neuro-adhesive, three-dimensional carbon nanotube surfaces. Photocurrent, photovoltage, and fluorescence lifetime measurements validate efficient charge transfer between the nanorods and the carbon nanotube films. Successful stimulation of a light-insensitive chick retina suggests the potential use of this novel platform in future artificial retina applications.

Effects of chronic cochlear electrical stimulation after an extended period of profound deafness on primary auditory cortex organization in cats.

Extended periods of deafness have profound effects on central auditory system function and organization. Neonatal deafening results in loss of the normal cochleotopic organization of the primary auditory cortex (AI), but environmentally-derived intracochlear electrical stimulation, via a cochlear implant, initiated shortly after deafening, can prevent this loss. We investigated whether such stimulation initiated after an extended period of deafness can restore cochleotopy. In two groups of neonatally-deafened cats, a multi-channel intracochlear electrode array was implanted at 8 weeks of age. One group received only minimal stimulation, associated with brief recordings at 4-6-week intervals, over the following 6 months to check the efficacy of the implant. In the other group, this 6-month period was followed by 6 months of near-continuous intracochlear electrical stimulation from a modified clinical cochlear implant system. We recorded multi-unit clusters in the auditory cortex and used two different methods to define the region of interest in the putative AI. There was no evidence of cochleotopy in any of the minimally stimulated animals, confirming our earlier finding. In three of six chronically stimulated cats there was clear evidence of AI cochleotopy, and in a fourth cat in which the majority of penetrations were in the anterior auditory field there was clear evidence of cochleotopy in that field. The finding that chronic intracochlear electrical stimulation after an extended period of deafness is able to restore cochleotopy in some (but not all) cases has implications for the performance of patients implanted after an extended period of deafness.

Venous Sinus Stent to Treat Paralysis.

Transvenous treatment of paralysis is a concept less than a decade old. The Stentrode (Synchron, Inc, New York, USA) is a novel electrode on stent device intended to be implanted in the superior sagittal sinus adjacent to the motor cortex. Initial animal studies in sheep demonstrated the safety of the implant as well as its accuracy in detecting neural signals at both short and long term. Early human trials have shown the safety of the device and demonstrated the use of the Stentrode system in facilitating patients with paralysis to carry out daily activities such as texting, email, and personal finance. This is an emerging technology with promise, although certainly more research is required to better understand the capabilities and limitations of the device.

Ethical Considerations of Neuralink and Brain-Computer Interfaces.

Neuralink is a neurotechnology company founded by Elon Musk in 2016, which has been quietly developing revolutionary technology allowing for ultra-high precision bidirectional communication between external devices and the brain. In this paper, we explore the multifaceted ethical considerations surrounding neural interfaces, analyzing potential societal impacts, risks, and call for a need for responsible innovation. Despite the technological, medical, medicolegal, and ethical challenges ahead, neural interface technology remains extremely promising and has the potential to create a new era of medicine.

Structural and functional changes of deep layer pyramidal neurons surrounding microelectrode arrays implanted in rat motor cortex.

Devices capable of recording or stimulating neuronal signals have created new opportunities to understand normal physiology and treat sources of pathology in the brain. However, it is possible that the tissue response to implanted electrodes may influence the nature of the signals detected or stimulated. In this study, we characterized structural and functional changes in deep layer pyramidal neurons surrounding silicon or polyimide-based electrodes implanted in the motor cortex of rats. Devices were captured in 300 µm-thick tissue slices collected at the 1 or 6 week time point post-implantation, and individual neurons were assessed using a combination of whole-cell electrophysiology and 2-photon imaging. We observed disrupted dendritic arbors and a significant reduction in spine densities in neurons surrounding devices. These effects were accompanied by a decrease in the frequency of spontaneous excitatory post-synaptic currents, a reduction in sag amplitude, an increase in spike frequency adaptation, and an increase in filopodia density. We hypothesize that the effects observed in this study may contribute to the signal loss and instability that often accompany chronically implanted electrodes. STATEMENT OF SIGNIFICANCE: Implanted electrodes in the brain can be used to treat sources of pathology and understand normal physiology by recording or stimulating electrical signals generated by local neurons. However, a foreign body response following implantation undermines the performance of these devices. While several studies have investigated the biological mechanisms of device-tissue interactions through histology, transcriptomics, and imaging, our study is the first to directly interrogate effects on the function of neurons surrounding electrodes using single-cell electrophysiology. Additionally, we provide new, detailed assessments of the impacts of electrodes on the dendritic structure and spine morphology of neurons, and we assess effects for both traditional (silicon) and newer polymer electrode materials. These results reveal new potential mechanisms of electrode-tissue interactions.

An in-silico framework for modeling optimal control of neural systems.

Introduction: Brain-machine interfaces have reached an unprecedented capacity to measure and drive activity in the brain, allowing restoration of impaired sensory, cognitive or motor function. Classical control theory is pushed to its limit when aiming to design control laws that are suitable for large-scale, complex neural systems. This work proposes a scalable, data-driven, unified approach to study brain-machine-environment interaction using established tools from dynamical systems, optimal control theory, and deep learning. Methods: To unify the methodology, we define the environment, neural system, and prosthesis in terms of differential equations with learnable parameters, which effectively reduce to recurrent neural networks in the discrete-time case. Drawing on tools from optimal control, we describe three ways to train the system: Direct optimization of an objective function, oracle-based learning, and reinforcement learning. These approaches are adapted to different assumptions about knowledge of system equations, linearity, differentiability, and observability. Results: We apply the proposed framework to train an in-silico neural system to perform tasks in a linear and a nonlinear environment, namely particle stabilization and pole balancing. After training, this model is perturbed to simulate impairment of sensor and motor function. We show how a prosthetic controller can be trained to restore the behavior of the neural system under increasing levels of perturbation. Discussion: We expect that the proposed framework will enable rapid and flexible synthesis of control algorithms for neural prostheses that reduce the need for in-vivo testing. We further highlight implications for sparse placement of prosthetic sensor and actuator components.

Bi-directional electrical recording and stimulation of the intact retina with a screen-printed soft probe: a feasibility study.

Introduction: Electrophysiological investigations of intact neural circuits are challenged by the gentle and complex nature of neural tissues. Bi-directional electrophysiological interfacing with the retina, in its intact form, is particularly demanding and currently there is no feasible approach to achieve such investigations. Here we present a feasibility study of a novel soft multi-electrode array suitable for bi-directional electrophysiological study of the intact retina. Methods: Screen-printed soft electrode arrays were developed and tested. The soft probes were designed to accommodate the curvature of the retina in the eye and offer an opportunity to study the retina in its intact form. Results: For the first time, we show both electrical recording and stimulation capabilities from the intact retina. In particular, we demonstrate the ability to characterize retina responses to electrical stimulation and reveal stable, direct, and indirect responses compared with ex-vivo conditions. Discussion: These results demonstrate the unique performances of the new probe while also suggesting that intact retinas retain better stability and robustness than ex-vivo retinas making them more suitable for characterizing retina responses to electrical stimulation.

Electrothermal Microactuators With Peg Drive Improve Performance for Brain Implant Applications.

This paper presents a new actuation scheme for in-plane bidirectional translation of polysilicon microelectrodes. The new Chevron-peg actuation scheme uses microelectromechanical systems (MEMS) based electrothermal microactuators to move microelectrodes for brain implant applications. The design changes were motivated by specific needs identified by the in vivo testing of an earlier generation of MEMS microelectrodes that were actuated by the Chevron-latch type of mechanism. The microelectrodes actuated by the Chevron-peg mechanism discussed here show improved performance in the following key areas: higher force generation capability (111 µN per heat strip compared to 50 µN), reduced power consumption (91 mW compared to 360 mW), and reliable performance with consistent forward and backward movements of microelectrodes. Failure analysis of the Chevron-latch and the Chevron-peg type of actuation schemes showed that the latter is more robust to wear over four million cycles of operation. The parameters for the activation waveforms for Chevron-peg actuators were optimized using statistical analysis. Waveforms with a 1-ms time period and a 1-Hz frequency of operation showed minimal error between the expected and the actual movement of the microelectrodes. The new generation of Chevron-peg actuators and microelectrodes are therefore expected to enhance the longevity and performance of implanted microelectrodes in the brain. [2011-0341].

Upward Shifts in the Internal Representation of Frequency Can Persist Over a 3-Year Period for Cochlear Implant Patients Fit With a Relatively Short Electrode Array.

Patients fit with cochlear implants (CIs) commonly indicate at the time of device fitting and for some time after, that the speech signal sounds abnormal. A high pitch or timbre is one component of the abnormal percept. In this project, our aim was to determine whether a number of years of CI use reduced perceived upshifts in frequency spectrum and/or voice fundamental frequency. The participants were five individuals who were deaf in one ear and who had normal hearing in the other ear. The deafened ears had been implanted with a 18.5 mm electrode array which resulted in signal input frequencies being directed to locations in the spiral ganglion (SG) that were between one and two octaves higher than the input frequencies. The patients judged the similarity of a clean signal (a male-voice sentence) presented to their implanted ear and candidate, implant-like, signals presented to their normal-hearing (NH) ear. Matches to implant sound quality were obtained, on average, at 8 months after device activation (see section "Time 1") and at 35 months after activation (see section "Time 2"). At Time 1, the matches to CI sound quality were characterized, most generally, by upshifts in the frequency spectrum and in voice pitch. At Time 2, for four of the five patients, frequency spectrum values remained elevated. For all five patients F0 values remained elevated. Overall, the data offer little support for the proposition that, for patients fit with shorter electrode arrays, cortical plasticity nudges the cortical representation of the CI voice toward more normal, or less upshifted, frequency values between 8 and 35 months after device activation. Cortical plasticity may be limited when there are large differences between frequencies in the input signal and the locations in the SG stimulated by those frequencies.

Multichannel stimulation module as a tool for animal studies on cortical neural prostheses.

Intracortical microstimulation to the visual cortex is thought to be a feasible technique for inducing localized phosphenes in patients with acquired blindness, and thereby for visual prosthesis. In order to design effective stimuli for the prosthesis, it is important to elucidate relationships between the spatio-temporal patterns of stimuli and the resulting neural responses and phosphenes through pre-clinical animal studies. However, the physiological basis of effective spatial patterns of the stimuli for the prosthesis has been little investigated in the literature, at least partly because that the previously developed multi-channel stimulation systems were designed specifically for the clinical use. In the present, a 64-channel stimulation module was developed as a scalable tool for animal experiments. The operations of the module were verified by not only dry-bench tests but also physiological animal experiments in vivo. The results demonstrated its usefulness for examining the stimulus-response relationships in a quantitative manner, and for inducing the multi-site neural excitations with a multi-electrode array. In addition, this stimulation module could be used to generate spatially patterned stimuli with up to 4,096 channels in a dynamic way, in which the stimulus patterns can be updated at a certain frame rate in accordance with the incoming visual scene. The present study demonstrated that our stimulation module is applicable to the physiological and other future studies in animals on the cortical prostheses.

Individual variability of neural computations in the primate retina.

Variation in the neural code contributes to making each individual unique. We probed neural code variation using ∼100 population recordings from major ganglion cell types in the macaque retina, combined with an interpretable computational representation of individual variability. This representation captured variation and covariation in properties such as nonlinearity, temporal dynamics, and spatial receptive field size and preserved invariances such as asymmetries between On and Off cells. The covariation of response properties in different cell types was associated with the proximity of lamination of their synaptic input. Surprisingly, male retinas exhibited higher firing rates and faster temporal integration than female retinas. Exploiting data from previously recorded retinas enabled efficient characterization of a new macaque retina, and of a human retina. Simulations indicated that combining a large dataset of retinal recordings with behavioral feedback could reveal the neural code in a living human and thus improve vision restoration with retinal implants.

Electrophysiological investigation of intact retina with soft printed organic neural interface.

Objective.Understanding how the retina converts a natural image or an electrically stimulated one into neural firing patterns is the focus of on-going research activities.Ex vivo, the retina can be readily investigated using multi electrode arrays (MEAs). However, MEA recording and stimulation from an intact retina (in the eye) has been so far insufficient.Approach.In the present study, we report new soft carbon electrode arrays suitable for recording and stimulating neural activity in an intact retina. Screen-printing of carbon ink on 20µm polyurethane (PU) film was used to realize electrode arrays with electrodes as small as 40µm in diameter. Passivation was achieved with a holey membrane, realized using laser drilling in a thin (50µm) PU film. Plasma polymerized 3.4-ethylenedioxythiophene was used to coat the electrode array to improve the electrode specific capacitance. Chick retinas, embryonic stage day 13, both explanted and intact inside an enucleated eye, were used.Main results.A novel fabrication process based on printed carbon electrodes was developed and yielded high capacitance electrodes on a soft substrate.Ex vivoelectrical recording of retina activity with carbon electrodes is demonstrated. With the addition of organic photo-capacitors, simultaneous photo-electrical stimulation and electrical recording was achieved. Finally, electrical activity recordings from an intact chick retina (inside enucleated eyes) were demonstrated. Both photosensitive retinal ganglion cell responses and spontaneous retina waves were recorded and their features analyzed.Significance.Results of this study demonstrated soft electrode arrays with unique properties, suitable for simultaneous recording and photo-electrical stimulation of the retina at high fidelity. This novel electrode technology opens up new frontiers in the study of neural tissuein vivo.