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1.
Nat Commun ; 15(1): 6528, 2024 Aug 02.
Article in English | MEDLINE | ID: mdl-39095351

ABSTRACT

Cutting edge advances in electrical visual cortical prosthetics have evoked perception of shapes, motion, and letters in the blind. Here, we present an alternative optical approach using pulsed infrared neural stimulation. To interface with dense arrays of cortical columns with submillimeter spatial precision, both linear array and 100-fiber bundle array optical fiber interfaces were devised. We deliver infrared stimulation through these arrays in anesthetized cat visual cortex and monitor effects by optical imaging in contralateral visual cortex. Infrared neural stimulation modulation of response to ongoing visual oriented gratings produce enhanced responses in orientation-matched domains and suppressed responses in non-matched domains, consistent with a known higher order integration mediated by callosal inputs. Controls include dynamically applied speeds, directions and patterns of multipoint stimulation. This provides groundwork for a distinct type of prosthetic targeted to maps of visual cortical columns.


Subject(s)
Infrared Rays , Visual Cortex , Animals , Cats , Visual Cortex/physiology , Photic Stimulation/methods , Optical Fibers , Visual Prosthesis
2.
BMJ Open Ophthalmol ; 9(1)2024 Aug 05.
Article in English | MEDLINE | ID: mdl-39103235

ABSTRACT

OBJECTIVE: To quantitatively evaluate visual evoked potentials (VEPs) in prosthetic vision and simulated visual reduction. METHODS AND ANALYSIS: Four blind patients implanted with the Argus II retinal prosthesis and seven sighted controls participated. VEPs were recorded with pattern-reversal stimuli (2 cycles of a horizontal square wave grating, 0.1 cycle/degree) at 1.07 reversals per second (rps) for Argus II subjects and 3.37 rps for controls. Argus II patients had both eyes patched, viewing the pattern solely through their implant. Controls viewed the pattern monocularly, either with their best-corrected vision or with simulated visual reduction (field restriction, added blur or reduced display contrast). RESULTS: VEPs recorded in Argus II patients displayed a similar shape to normal VEPs when controls viewed the pattern without simulated visual reduction. In sighted controls, adding blur significantly delayed the P100 peak time by 8.7 ms, 95% CI (0.9, 16.6). Reducing stimulus contrast to 32% and 6% of full display contrast significantly decreased P100 amplitude to 55% (37%, 82%) and 20% (13%, 31%), respectively. Restriction on the field of view had no impact on either the amplitude or the peak latency of P100. CONCLUSION: The early visual cortex in retinal prosthesis users remains responsive to retinal input, showing a similar response profile to that of sighted controls. Pattern-reversal VEP offers valuable insights for objectively evaluating artificial vision therapy systems (AVTSs) when selecting, fitting and training implant users, but the uncertainties in the exact timing and location of electrode stimulation must be considered when interpreting the results.


Subject(s)
Blindness , Evoked Potentials, Visual , Visual Prosthesis , Humans , Evoked Potentials, Visual/physiology , Male , Female , Blindness/physiopathology , Middle Aged , Aged , Visual Acuity/physiology , Adult
5.
Sci Rep ; 14(1): 17400, 2024 07 29.
Article in English | MEDLINE | ID: mdl-39075065

ABSTRACT

The field of cortical sight restoration prostheses is making rapid progress with three clinical trials of visual cortical prostheses underway. However, as yet, we have only limited insight into the perceptual experiences produced by these implants. Here we describe a computational model or 'virtual patient', based on the neurophysiological architecture of V1, which successfully predicts the perceptual experience of participants across a wide range of previously published human cortical stimulation studies describing the location, size, brightness and spatiotemporal shape of electrically induced percepts in humans. Our simulations suggest that, in the foreseeable future the perceptual quality of cortical prosthetic devices is likely to be limited by the neurophysiological organization of visual cortex, rather than engineering constraints.


Subject(s)
Computer Simulation , Visual Cortex , Visual Perception , Humans , Visual Cortex/physiology , Visual Perception/physiology , Photic Stimulation , Visual Prosthesis , Models, Neurological , Electric Stimulation/methods
6.
J Neural Eng ; 21(4)2024 Jul 25.
Article in English | MEDLINE | ID: mdl-38986450

ABSTRACT

Objective.The visual perception provided by retinal prostheses is limited by the overlapping current spread of adjacent electrodes. This reduces the spatial resolution attainable with unipolar stimulation. Conversely, simultaneous multipolar stimulation guided by the measured neural responses-neural activity shaping (NAS)-can attenuate excessive spread of excitation allowing for more precise control over the pattern of neural activation. However, defining effective multipolar stimulus patterns is a challenging task. Previous attempts focused on analytical solutions based on an assumed linear nonlinear model of retinal response; an analytical model inversion (AMI) approach. Here, we propose a model-free solution for NAS, using artificial neural networks (ANNs) that could be trained with data acquired from the implant.Approach.Our method consists of two ANNs trained sequentially. The measurement predictor network (MPN) is trained on data from the implant and is used to predict how the retina responds to multipolar stimulation. The stimulus generator network is trained on a large dataset of natural images and uses the trained MPN to determine efficient multipolar stimulus patterns by learning its inverse model. We validate our methodin silicousing a realistic model of retinal response to multipolar stimulation.Main results.We show that our ANN-based NAS approach produces sharper retinal activations than the conventional unipolar stimulation strategy. As a theoretical bench-mark of optimal NAS results, we implemented AMI stimulation by inverting the model used to simulate the retina. Our ANN strategy produced equivalent results to AMI, while not being restricted to any specific type of retina model and being three orders of magnitude more computationally efficient.Significance.Our novel protocol provides a method for efficient and personalized retinal stimulation, which may improve the visual experience and quality of life of retinal prosthesis users.


Subject(s)
Deep Learning , Visual Prosthesis , Humans , Retina/physiology , Neural Networks, Computer , Photic Stimulation/methods , Visual Perception/physiology
7.
PLoS One ; 19(6): e0305132, 2024.
Article in English | MEDLINE | ID: mdl-38889114

ABSTRACT

This paper proposes a retinal prosthesis edge detection (RPED) algorithm that can achieve high visual acuity and low power. Retinal prostheses have been used to stimulate retinal tissue by injecting charge via an electrode array, thereby artificially restoring the vision of visually impaired patients. The retinal prosthetic chip, which generates biphasic current pulses, should be located in the foveal area measuring 5 mm × 5 mm. When a high-density stimulation pixel array is realized in a limited area, the distance between the stimulation pixels narrows, resulting in current dispersion and high-power dissipation related to heat generation. Various edge detection methods have been proposed over the past decade to reduce these deleterious effects and achieve high-resolution pixels. However, conventional methods have the disadvantages of high-power consumption and long data processing times because many pixels are activated to detect edges. In this study, we propose a novel RPED algorithm that has a higher visual acuity and less power consumption despite using fewer active pixels than existing techniques. To verify the performance of the devised RPED algorithm, the peak signal-to-noise ratio and structural similarity index map, which evaluates the quantitative numerical value of the image are employed and compared with the Sobel, Canny, and past edge detection algorithms in MATLAB. Finally, we demonstrate the effectiveness of the proposed RPED algorithm using a 1600-pixel retinal stimulation chip fabricated using a 0.35 µm complementary metal-oxide-semiconductor process.


Subject(s)
Algorithms , Visual Acuity , Visual Prosthesis , Humans , Visual Acuity/physiology , Retina/physiology , Retina/diagnostic imaging , Signal-To-Noise Ratio
8.
Biomaterials ; 311: 122674, 2024 Dec.
Article in English | MEDLINE | ID: mdl-38897028

ABSTRACT

Clinical results with photovoltaic subretinal prosthesis (PRIMA) demonstrated restoration of sight via electrical stimulation of the interneurons in degenerated retina, with resolution matching the 100 µm pixel size. Since scaling the pixels below 75 µm in the current bipolar planar geometry will significantly limit the penetration depth of the electric field and increase stimulation threshold, we explore the possibility of using smaller pixels based on a novel 3-dimensional honeycomb-shaped design. We assessed the long-term biocompatibility and stability of these arrays in rats by investigating the anatomical integration of the retina with flat and 3D implants and response to electrical stimulation over lifetime - up to 32-36 weeks post-implantation in aged rats. With both flat and 3D implants, signals elicited in the visual cortex decreased after the day of implantation by more than 3-fold, and gradually recovered over the next 12-16 weeks. With 25 µm high honeycomb walls, the majority of bipolar cells migrate into the wells, while amacrine and ganglion cells remain above the cavities, which is essential for selective network-mediated stimulation of the retina. Retinal thickness and full-field stimulation threshold with 40 µm-wide honeycomb pixels were comparable to those with planar devices - 0.05 mW/mm2 with 10 ms pulses. However, fewer cells from the inner nuclear layer migrated into the 20 µm-wide wells, and stimulation threshold increased over 12-16 weeks, before stabilizing at about 0.08 mW/mm2. Such threshold is still significantly lower than 1.8 mW/mm2 with a previous design of flat bipolar pixels, confirming the promise of the 3D honeycomb-based approach to high resolution subretinal prosthesis.


Subject(s)
Retina , Visual Prosthesis , Animals , Retina/physiology , Rats , Electric Stimulation , Rats, Long-Evans , Follow-Up Studies , Electrodes, Implanted
9.
J Neurosci Methods ; 408: 110169, 2024 Aug.
Article in English | MEDLINE | ID: mdl-38782123

ABSTRACT

BACKGROUND: Neuroprostheses are used to electrically stimulate the brain, modulate neural activity and restore sensory and motor function following injury or disease, such as blindness, paralysis, and other movement and psychiatric disorders. Recordings are often made simultaneously with stimulation, allowing the monitoring of neural signals and closed-loop control of devices. However, stimulation-evoked artifacts may obscure neural activity, particularly when stimulation and recording sites are nearby. Several methods have been developed to remove stimulation artifacts, but it remains challenging to validate and compare these methods because the 'ground-truth' of the neuronal signals may be contaminated by artifacts. NEW METHOD: Here, we delivered stimulation to the visual cortex via a high-channel-count prosthesis while recording neuronal activity and stimulation artifacts. We quantified the waveforms and temporal properties of stimulation artifacts from the cortical visual prosthesis (CVP) and used them to build a dataset, in which we simulated the neuronal activity and the stimulation artifacts. We illustrate how to use the simulated data to evaluate the performance of six software-based artifact removal methods (Template subtraction, Linear interpolation, Polynomial fitting, Exponential fitting, SALPA and ERAASR) in a CVP application scenario. RESULTS: We here focused on stimulation artifacts caused by electrical stimulation through a high-channel-count cortical prosthesis device. We find that the Polynomial fitting and Exponential fitting methods outperform the other methods in recovering spikes and multi-unit activity. Linear interpolation and Template subtraction recovered the local-field potentials. CONCLUSION: Polynomial fitting and Exponential fitting provided a good trade-off between the quality of the recovery of spikes and multi-unit activity (MUA) and the computational complexity for a cortical prosthesis.


Subject(s)
Artifacts , Electric Stimulation , Visual Cortex , Visual Prosthesis , Visual Cortex/physiology , Electric Stimulation/methods , Electric Stimulation/instrumentation , Animals , Macaca mulatta , Signal Processing, Computer-Assisted , Neurons/physiology , Male
10.
Sensors (Basel) ; 24(9)2024 Apr 23.
Article in English | MEDLINE | ID: mdl-38732784

ABSTRACT

Artificial retinas have revolutionized the lives of many blind people by enabling their ability to perceive vision via an implanted chip. Despite significant advancements, there are some limitations that cannot be ignored. Presenting all objects captured in a scene makes their identification difficult. Addressing this limitation is necessary because the artificial retina can utilize a very limited number of pixels to represent vision information. This problem in a multi-object scenario can be mitigated by enhancing images such that only the major objects are considered to be shown in vision. Although simple techniques like edge detection are used, they fall short in representing identifiable objects in complex scenarios, suggesting the idea of integrating primary object edges. To support this idea, the proposed classification model aims at identifying the primary objects based on a suggested set of selective features. The proposed classification model can then be equipped into the artificial retina system for filtering multiple primary objects to enhance vision. The suitability of handling multi-objects enables the system to cope with real-world complex scenarios. The proposed classification model is based on a multi-label deep neural network, specifically designed to leverage from the selective feature set. Initially, the enhanced images proposed in this research are compared with the ones that utilize an edge detection technique for single, dual, and multi-object images. These enhancements are also verified through an intensity profile analysis. Subsequently, the proposed classification model's performance is evaluated to show the significance of utilizing the suggested features. This includes evaluating the model's ability to correctly classify the top five, four, three, two, and one object(s), with respective accuracies of up to 84.8%, 85.2%, 86.8%, 91.8%, and 96.4%. Several comparisons such as training/validation loss and accuracies, precision, recall, specificity, and area under a curve indicate reliable results. Based on the overall evaluation of this study, it is concluded that using the suggested set of selective features not only improves the classification model's performance, but aligns with the specific problem to address the challenge of correctly identifying objects in multi-object scenarios. Therefore, the proposed classification model designed on the basis of selective features is considered to be a very useful tool in supporting the idea of optimizing image enhancement.


Subject(s)
Artificial Intelligence , Neural Networks, Computer , Retina , Retina/diagnostic imaging , Humans , Image Enhancement/methods , Algorithms , Image Processing, Computer-Assisted/methods , Visual Prosthesis
11.
Nat Commun ; 15(1): 4481, 2024 May 27.
Article in English | MEDLINE | ID: mdl-38802397

ABSTRACT

Retinal degeneration, a leading cause of irreversible low vision and blindness globally, can be partially addressed by retina prostheses which stimulate remaining neurons in the retina. However, existing electrode-based treatments are invasive, posing substantial risks to patients and healthcare providers. Here, we introduce a completely noninvasive ultrasonic retina prosthesis, featuring a customized ultrasound two-dimensional array which allows for simultaneous imaging and stimulation. With synchronous three-dimensional imaging guidance and auto-alignment technology, ultrasonic retina prosthesis can generate programmed ultrasound waves to dynamically and precisely form arbitrary wave patterns on the retina. Neuron responses in the brain's visual center mirrored these patterns, evidencing successful artificial vision creation, which was further corroborated in behavior experiments. Quantitative analysis of the spatial-temporal resolution and field of view demonstrated advanced performance of ultrasonic retina prosthesis and elucidated the biophysical mechanism of retinal stimulation. As a noninvasive blindness prosthesis, ultrasonic retina prosthesis could lead to a more effective, widely acceptable treatment for blind patients. Its real-time imaging-guided stimulation strategy with a single ultrasound array, could also benefit ultrasound neurostimulation in other diseases.


Subject(s)
Blindness , Retina , Visual Prosthesis , Retina/diagnostic imaging , Retina/physiology , Animals , Blindness/therapy , Blindness/physiopathology , Retinal Degeneration/therapy , Retinal Degeneration/diagnostic imaging , Ultrasonic Waves , Humans , Neurons/physiology , Ultrasonography/methods , Vision, Ocular/physiology
12.
Nat Commun ; 15(1): 3086, 2024 Apr 10.
Article in English | MEDLINE | ID: mdl-38600063

ABSTRACT

Bioinspired bionic eyes should be self-driving, repairable and conformal to arbitrary geometries. Such eye would enable wide-field detection and efficient visual signal processing without requiring external energy, along with retinal transplantation by replacing dysfunctional photoreceptors with healthy ones for vision restoration. A variety of artificial eyes have been constructed with hemispherical silicon, perovskite and heterostructure photoreceptors, but creating zero-powered retinomorphic system with transplantable conformal features remains elusive. By combining neuromorphic principle with retinal and ionoelastomer engineering, we demonstrate a self-driven hemispherical retinomorphic eye with elastomeric retina made of ionogel heterojunction as photoreceptors. The receptor driven by photothermoelectric effect shows photoperception with broadband light detection (365 to 970 nm), wide field-of-view (180°) and photosynaptic (paired-pulse facilitation index, 153%) behaviors for biosimilar visual learning. The retinal photoreceptors are transplantable and conformal to any complex surface, enabling visual restoration for dynamic optical imaging and motion tracking.


Subject(s)
Visual Prosthesis , Bionics , Retina , Vision, Ocular , Visual Perception
13.
J Neural Eng ; 21(2)2024 Mar 19.
Article in English | MEDLINE | ID: mdl-38452381

ABSTRACT

Objective.Retinal prostheses evoke visual precepts by electrically stimulating functioning cells in the retina. Despite high variance in perceptual thresholds across subjects, among electrodes within a subject, and over time, retinal prosthesis users must undergo 'system fitting', a process performed to calibrate stimulation parameters according to the subject's perceptual thresholds. Although previous work has identified electrode-retina distance and impedance as key factors affecting thresholds, an accurate predictive model is still lacking.Approach.To address these challenges, we (1) fitted machine learning models to a large longitudinal dataset with the goal of predicting individual electrode thresholds and deactivation as a function of stimulus, electrode, and clinical parameters ('predictors') and (2) leveraged explainable artificial intelligence (XAI) to reveal which of these predictors were most important.Main results.Our models accounted for up to 76% of the perceptual threshold response variance and enabled predictions of whether an electrode was deactivated in a given trial with F1 and area under the ROC curve scores of up to 0.732 and 0.911, respectively. Our models identified novel predictors of perceptual sensitivity, including subject age, time since blindness onset, and electrode-fovea distance.Significance.Our results demonstrate that routinely collected clinical measures and a single session of system fitting might be sufficient to inform an XAI-based threshold prediction strategy, which has the potential to transform clinical practice in predicting visual outcomes.


Subject(s)
Visual Prosthesis , Humans , Artificial Intelligence , Electrodes, Implanted , Retina/physiology , Machine Learning , Electric Stimulation/methods
14.
J Neural Eng ; 21(2)2024 Apr 08.
Article in English | MEDLINE | ID: mdl-38457841

ABSTRACT

Objective.Retinal implants use electrical stimulation to elicit perceived flashes of light ('phosphenes'). Single-electrode phosphene shape has been shown to vary systematically with stimulus parameters and the retinal location of the stimulating electrode, due to incidental activation of passing nerve fiber bundles. However, this knowledge has yet to be extended to paired-electrode stimulation.Approach.We retrospectively analyzed 3548 phosphene drawings made by three blind participants implanted with an Argus II Retinal Prosthesis. Phosphene shape (characterized by area, perimeter, major and minor axis length) and number of perceived phosphenes were averaged across trials and correlated with the corresponding single-electrode parameters. In addition, the number of phosphenes was correlated with stimulus amplitude and neuroanatomical parameters: electrode-retina and electrode-fovea distance as well as the electrode-electrode distance to ('between-axon') and along axon bundles ('along-axon'). Statistical analyses were conducted using linear regression and partial correlation analysis.Main results.Simple regression revealed that each paired-electrode shape descriptor could be predicted by the sum of the two corresponding single-electrode shape descriptors (p < .001). Multiple regression revealed that paired-electrode phosphene shape was primarily predicted by stimulus amplitude and electrode-fovea distance (p < .05). Interestingly, the number of elicited phosphenes tended to increase with between-axon distance (p < .05), but not with along-axon distance, in two out of three participants.Significance.The shape of phosphenes elicited by paired-electrode stimulation was well predicted by the shape of their corresponding single-electrode phosphenes, suggesting that two-point perception can be expressed as the linear summation of single-point perception. The impact of the between-axon distance on the perceived number of phosphenes provides further evidence in support of the axon map model for epiretinal stimulation. These findings contribute to the growing literature on phosphene perception and have important implications for the design of future retinal prostheses.


Subject(s)
Retina , Visual Prosthesis , Humans , Retrospective Studies , Retina/physiology , Phosphenes , Axons , Electric Stimulation , Perception
15.
J Neural Eng ; 21(2)2024 Apr 10.
Article in English | MEDLINE | ID: mdl-38547529

ABSTRACT

Objective.Neuromodulation, particularly electrical stimulation, necessitates high spatial resolution to achieve artificial vision with high acuity. In epiretinal implants, this is hindered by the undesired activation of distal axons. Here, we investigate focal and axonal activation of retinal ganglion cells (RGCs) in epiretinal configuration for different sinusoidal stimulation frequencies.Approach.RGC responses to epiretinal sinusoidal stimulation at frequencies between 40 and 100 Hz were tested inex-vivophotoreceptor degenerated (rd10) isolated retinae. Experiments were conducted using a high-density CMOS-based microelectrode array, which allows to localize RGC cell bodies and axons at high spatial resolution.Main results.We report current and charge density thresholds for focal and distal axon activation at stimulation frequencies of 40, 60, 80, and 100 Hz for an electrode size with an effective area of 0.01 mm2. Activation of distal axons is avoided up to a stimulation amplitude of 0.23µA (corresponding to 17.3µC cm-2) at 40 Hz and up to a stimulation amplitude of 0.28µA (14.8µC cm-2) at 60 Hz. The threshold ratio between focal and axonal activation increases from 1.1 for 100 Hz up to 1.6 for 60 Hz, while at 40 Hz stimulation frequency, almost no axonal responses were detected in the tested intensity range. With the use of synaptic blockers, we demonstrate the underlying direct activation mechanism of the ganglion cells. Finally, using high-resolution electrical imaging and label-free electrophysiological axon tracking, we demonstrate the extent of activation in axon bundles.Significance.Our results can be exploited to define a spatially selective stimulation strategy avoiding axonal activation in future retinal implants, thereby solving one of the major limitations of artificial vision. The results may be extended to other fields of neuroprosthetics to achieve selective focal electrical stimulation.


Subject(s)
Retina , Visual Prosthesis , Retina/physiology , Retinal Ganglion Cells/physiology , Microelectrodes , Axons/physiology , Electric Stimulation/methods
16.
J Neural Eng ; 21(1)2024 02 23.
Article in English | MEDLINE | ID: mdl-38364290

ABSTRACT

Objective.Retinal prosthetics offer partial restoration of sight to patients blinded by retinal degenerative diseases through electrical stimulation of the remaining neurons. Decreasing the pixel size enables increasing prosthetic visual acuity, as demonstrated in animal models of retinal degeneration. However, scaling down the size of planar pixels is limited by the reduced penetration depth of the electric field in tissue. We investigated 3-dimensional (3d) structures on top of photovoltaic arrays for enhanced penetration of the electric field, permitting higher resolution implants.Approach.3D COMSOL models of subretinal photovoltaic arrays were developed to accurately quantify the electrodynamics during stimulation and verified through comparison to flat photovoltaic arrays. Models were applied to optimize the design of 3D electrode structures (pillars and honeycombs). Return electrodes on honeycomb walls vertically align the electric field with bipolar cells for optimal stimulation. Pillars elevate the active electrode, thus improving proximity to target neurons. The optimized 3D structures were electroplated onto existing flat subretinal prostheses.Main results.Simulations demonstrate that despite exposed conductive sidewalls, charge mostly flows via high-capacitance sputtered iridium oxide films topping the 3D structures. The 24µm height of honeycomb structures was optimized for integration with the inner nuclear layer cells in the rat retina, whilst 35µm tall pillars were optimized for penetrating the debris layer in human patients. Implantation of released 3D arrays demonstrates mechanical robustness, with histology demonstrating successful integration of 3D structures with the rat retinain-vivo.Significance. Electroplated 3D honeycomb structures produce vertically oriented electric fields, providing low stimulation thresholds, high spatial resolution, and high contrast for pixel sizes down to 20µm. Pillar electrodes offer an alternative for extending past the debris layer. Electroplating of 3D structures is compatible with the fabrication process of flat photovoltaic arrays, enabling much more efficient retinal stimulation.


Subject(s)
Artificial Limbs , Retinal Degeneration , Visual Prosthesis , Humans , Rats , Animals , Prostheses and Implants , Retina/physiology , Neurons/physiology , Electric Stimulation , Electrodes, Implanted
17.
Adv Healthc Mater ; 13(15): e2304169, 2024 06.
Article in English | MEDLINE | ID: mdl-38324245

ABSTRACT

Brain interfaces that can stimulate neurons, cause minimal damage, and work for a long time will be central for future neuroprosthetics. Here, the long-term performance of highly flexible, thin polyimide shanks with several small (<15 µm) electrodes during electrical microstimulation of the visual cortex, is reported. The electrodes exhibit a remarkable stability when several billions of electrical pulses are applied in vitro. When the devices are implanted in the primary visual cortex (area V1) of mice and the animals are trained to detect electrical microstimulation, it is found that the perceptual thresholds are 2-20 microamperes (µA), which is far below the maximal currents that the electrodes can withstand. The long-term functionality of the devices in vivo is excellent, with stable performance for up to more than a year and little damage to the brain tissue. These results demonstrate the potential of thin floating electrodes for the long-term restoration of lost sensory functions.


Subject(s)
Electrodes, Implanted , Polymers , Visual Perception , Animals , Mice , Visual Perception/physiology , Polymers/chemistry , Mice, Inbred C57BL , Visual Prosthesis/chemistry , Electric Stimulation , Visual Cortex/physiology
18.
Elife ; 132024 Feb 22.
Article in English | MEDLINE | ID: mdl-38386406

ABSTRACT

Blindness affects millions of people around the world. A promising solution to restoring a form of vision for some individuals are cortical visual prostheses, which bypass part of the impaired visual pathway by converting camera input to electrical stimulation of the visual system. The artificially induced visual percept (a pattern of localized light flashes, or 'phosphenes') has limited resolution, and a great portion of the field's research is devoted to optimizing the efficacy, efficiency, and practical usefulness of the encoding of visual information. A commonly exploited method is non-invasive functional evaluation in sighted subjects or with computational models by using simulated prosthetic vision (SPV) pipelines. An important challenge in this approach is to balance enhanced perceptual realism, biologically plausibility, and real-time performance in the simulation of cortical prosthetic vision. We present a biologically plausible, PyTorch-based phosphene simulator that can run in real-time and uses differentiable operations to allow for gradient-based computational optimization of phosphene encoding models. The simulator integrates a wide range of clinical results with neurophysiological evidence in humans and non-human primates. The pipeline includes a model of the retinotopic organization and cortical magnification of the visual cortex. Moreover, the quantitative effects of stimulation parameters and temporal dynamics on phosphene characteristics are incorporated. Our results demonstrate the simulator's suitability for both computational applications such as end-to-end deep learning-based prosthetic vision optimization as well as behavioral experiments. The modular and open-source software provides a flexible simulation framework for computational, clinical, and behavioral neuroscientists working on visual neuroprosthetics.


Subject(s)
Phosphenes , Visual Prosthesis , Animals , Humans , Computer Simulation , Software , Blindness/therapy
19.
J Neural Eng ; 21(1)2024 02 09.
Article in English | MEDLINE | ID: mdl-38290151

ABSTRACT

Objective.Current retinal prosthetics are limited in their ability to precisely control firing patterns of functionally distinct retinal ganglion cell (RGC) types. The aim of this study was to characterise RGC responses to continuous, kilohertz-frequency-varying stimulation to assess its utility in controlling RGC activity.Approach.We usedin vitropatch-clamp experiments to assess electrically-evoked ON and OFF RGC responses to frequency-varying pulse train sequences. In each sequence, the stimulation amplitude was kept constant while the stimulation frequency (0.5-10 kHz) was changed every 40 ms, in either a linearly increasing, linearly decreasing or randomised manner. The stimulation amplitude across sequences was increased from 10 to 300µA.Main results.We found that continuous stimulation without rest periods caused complex and irreproducible stimulus-response relationships, primarily due to strong stimulus-induced response adaptation and influence of the preceding stimulus frequency on the response to a subsequent stimulus. In addition, ON and OFF populations showed different sensitivities to continuous, frequency-varying pulse trains, with OFF cells generally exhibiting more dependency on frequency changes within a sequence. Finally, the ability to maintain spiking behaviour to continuous stimulation in RGCs significantly reduced over longer stimulation durations irrespective of the frequency order.Significance.This study represents an important step in advancing and understanding the utility of continuous frequency modulation in controlling functionally distinct RGCs. Our results indicate that continuous, kHz-frequency-varying stimulation sequences provide very limited control of RGC firing patterns due to inter-dependency between adjacent frequencies and generally, different RGC types do not display different frequency preferences under such stimulation conditions. For future stimulation strategies using kHz frequencies, careful consideration must be given to design appropriate pauses in stimulation, stimulation frequency order and the length of continuous stimulation duration.


Subject(s)
Retinal Ganglion Cells , Visual Prosthesis , Retinal Ganglion Cells/physiology , Action Potentials/physiology , Electric Stimulation/methods
20.
Nat Nanotechnol ; 19(5): 688-697, 2024 May.
Article in English | MEDLINE | ID: mdl-38225357

ABSTRACT

Electronic retinal prostheses for stimulating retinal neurons are promising for vision restoration. However, the rigid electrodes of conventional retinal implants can inflict damage on the soft retina tissue. They also have limited selectivity due to their poor proximity to target cells in the degenerative retina. Here we present a soft artificial retina (thickness, 10 µm) where flexible ultrathin photosensitive transistors are integrated with three-dimensional stimulation electrodes of eutectic gallium-indium alloy. Platinum nanoclusters locally coated only on the tip of these three-dimensional liquid-metal electrodes show advantages in reducing the impedance of the stimulation electrodes. These microelectrodes can enhance the proximity to the target retinal ganglion cells and provide effective charge injections (72.84 mC cm-2) to elicit neural responses in the retina. Their low Young's modulus (234 kPa), owing to their liquid form, can minimize damage to the retina. Furthermore, we used an unsupervised machine learning approach to effectively identify the evoked spikes to grade neural activities within the retinal ganglion cells. Results from in vivo experiments on a retinal degeneration mouse model reveal that the spatiotemporal distribution of neural responses on their retina can be mapped under selective localized illumination areas of light, suggesting the restoration of their vision.


Subject(s)
Microelectrodes , Visual Prosthesis , Visual Prosthesis/chemistry , Animals , Mice , Retinal Ganglion Cells/physiology , Retinal Degeneration/therapy , Retinal Degeneration/pathology , Retina , Electrodes, Implanted , Platinum/chemistry
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