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1.
J Neurosci ; 43(26): 4808-4820, 2023 06 28.
Artigo em Inglês | MEDLINE | ID: mdl-37268418

RESUMO

High-fidelity electronic implants can in principle restore the function of neural circuits by precisely activating neurons via extracellular stimulation. However, direct characterization of the individual electrical sensitivity of a large population of target neurons, to precisely control their activity, can be difficult or impossible. A potential solution is to leverage biophysical principles to infer sensitivity to electrical stimulation from features of spontaneous electrical activity, which can be recorded relatively easily. Here, this approach is developed and its potential value for vision restoration is tested quantitatively using large-scale multielectrode stimulation and recording from retinal ganglion cells (RGCs) of male and female macaque monkeys ex vivo Electrodes recording larger spikes from a given cell exhibited lower stimulation thresholds across cell types, retinas, and eccentricities, with systematic and distinct trends for somas and axons. Thresholds for somatic stimulation increased with distance from the axon initial segment. The dependence of spike probability on injected current was inversely related to threshold, and was substantially steeper for axonal than somatic compartments, which could be identified by their recorded electrical signatures. Dendritic stimulation was largely ineffective for eliciting spikes. These trends were quantitatively reproduced with biophysical simulations. Results from human RGCs were broadly similar. The inference of stimulation sensitivity from recorded electrical features was tested in a data-driven simulation of visual reconstruction, revealing that the approach could significantly improve the function of future high-fidelity retinal implants.SIGNIFICANCE STATEMENT This study demonstrates that individual in situ primate retinal ganglion cells of different types respond to artificially generated, external electrical fields in a systematic manner, in accordance with theoretical predictions, that allows for prediction of electrical stimulus sensitivity from recorded spontaneous activity. It also provides evidence that such an approach could be immensely helpful in the calibration of clinical retinal implants.


Assuntos
Retina , Células Ganglionares da Retina , Animais , Masculino , Feminino , Humanos , Células Ganglionares da Retina/fisiologia , Potenciais de Ação/fisiologia , Retina/fisiologia , Primatas , Estimulação Elétrica/métodos
2.
bioRxiv ; 2024 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-38712189

RESUMO

Keyboard typing with finger movements is a versatile digital interface for users with diverse skills, needs, and preferences. Currently, such an interface does not exist for people with paralysis. We developed an intracortical brain-computer interface (BCI) for typing with attempted flexion/extension movements of three finger groups on the right hand, or both hands, and demonstrated its flexibility in two dominant typing paradigms. The first paradigm is "point-and-click" typing, where a BCI user selects one key at a time using continuous real-time control, allowing selection of arbitrary sequences of symbols. During cued character selection with this paradigm, a human research participant with paralysis achieved 30-40 selections per minute with nearly 90% accuracy. The second paradigm is "keystroke" typing, where the BCI user selects each character by a discrete movement without real-time feedback, often giving a faster speed for natural language sentences. With 90 cued characters per minute, decoding attempted finger movements and correcting errors using a language model resulted in more than 90% accuracy. Notably, both paradigms matched the state-of-the-art for BCI performance and enabled further flexibility by the simultaneous selection of multiple characters as well as efficient decoder estimation across paradigms. Overall, the high-performance interface is a step towards the wider accessibility of BCI technology by addressing unmet user needs for flexibility.

3.
bioRxiv ; 2024 Feb 08.
Artigo em Inglês | MEDLINE | ID: mdl-38370697

RESUMO

People with paralysis express unmet needs for peer support, leisure activities, and sporting activities. Many within the general population rely on social media and massively multiplayer video games to address these needs. We developed a high-performance finger brain-computer-interface system allowing continuous control of 3 independent finger groups with 2D thumb movements. The system was tested in a human research participant over sequential trials requiring fingers to reach and hold on targets, with an average acquisition rate of 76 targets/minute and completion time of 1.58 ± 0.06 seconds. Performance compared favorably to previous animal studies, despite a 2-fold increase in the decoded degrees-of-freedom (DOF). Finger positions were then used for 4-DOF velocity control of a virtual quadcopter, demonstrating functionality over both fixed and random obstacle courses. This approach shows promise for controlling multiple-DOF end-effectors, such as robotic fingers or digital interfaces for work, entertainment, and socialization.

4.
IEEE Trans Biomed Circuits Syst ; 17(4): 754-767, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37402181

RESUMO

Future high-density and high channel count neural interfaces that enable simultaneous recording of tens of thousands of neurons will provide a gateway to study, restore and augment neural functions. However, building such technology within the bit-rate limit and power budget of a fully implantable device is challenging. The wired-OR compressive readout architecture addresses the data deluge challenge of a high channel count neural interface using lossy compression at the analog-to-digital interface. In this article, we assess the suitability of wired-OR for several steps that are important for neuroengineering, including spike detection, spike assignment and waveform estimation. For various wiring configurations of wired-OR and assumptions about the quality of the underlying signal, we characterize the trade-off between compression ratio and task-specific signal fidelity metrics. Using data from 18 large-scale microelectrode array recordings in macaque retina ex vivo, we find that for an event SNR of 7-10, wired-OR correctly detects and assigns at least 80% of the spikes with at least 50× compression. The wired-OR approach also robustly encodes action potential waveform information, enabling downstream processing such as cell-type classification. Finally, we show that by applying an LZ77-based lossless compressor (gzip) to the output of the wired-OR architecture, 1000× compression can be achieved over the baseline recordings.

5.
Artigo em Inglês | MEDLINE | ID: mdl-37465143

RESUMO

Intracortical brain computer interfaces (iBCIs) decode neural activity from the cortex and enable motor and communication prostheses, such as cursor control, handwriting and speech, for people with paralysis. This paper introduces a new iBCI communication prosthesis using a 3D keyboard interface for typing using continuous, closed loop movement of multiple fingers. A participant-specific BCI keyboard prototype was developed for a BrainGate2 clinical trial participant (T5) using neural recordings from the hand-knob area of the left premotor cortex. We assessed the relative decoding accuracy of flexion/extension movements of individual single fingers (5 degrees of freedom (DOF)) vs. three groups of fingers (thumb, index-middle, and ring-small fingers, 3 DOF). Neural decoding using 3 independent DOF was more accurate (95%) than that using 5 DOF (76%). A virtual keyboard was then developed where each finger group moved along a flexion-extension arc to acquire targets that corresponded to English letters and symbols. The locations of these letter/symbols were optimized using natural language statistics, resulting in an approximately a 2× reduction in distance traveled by fingers on average compared to a random keyboard layout. This keyboard was tested using a simple real-time closed loop decoder enabling T5 to type with 31 symbols at 90% accuracy and approximately 2.3 sec/symbol (excluding a 2 second hold time) on average.

6.
bioRxiv ; 2023 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-37645934

RESUMO

Fixational eye movements alter the number and timing of spikes transmitted from the retina to the brain, but whether these changes enhance or degrade the visual signal is unclear. To quantify this, we developed a Bayesian method for reconstructing natural images from the recorded spikes of hundreds of macaque retinal ganglion cells (RGCs) of the major cell types, combining a likelihood model for RGC light responses with the natural image prior implicitly embedded in an artificial neural network optimized for denoising. The method matched or surpassed the performance of previous reconstruction algorithms, and provided an interpretable framework for characterizing the retinal signal. Reconstructions were improved with artificial stimulus jitter that emulated fixational eye movements, even when the jitter trajectory was inferred from retinal spikes. Reconstructions were degraded by small artificial perturbations of spike times, revealing more precise temporal encoding than suggested by previous studies. Finally, reconstructions were substantially degraded when derived from a model that ignored cell-to-cell interactions, indicating the importance of stimulus-evoked correlations. Thus, fixational eye movements enhance the precision of the retinal representation.

7.
J Neural Eng ; 20(4)2023 08 31.
Artigo em Inglês | MEDLINE | ID: mdl-37433293

RESUMO

Objective. Retinal implants are designed to stimulate retinal ganglion cells (RGCs) in a way that restores sight to individuals blinded by photoreceptor degeneration. Reproducing high-acuity vision with these devices will likely require inferring the natural light responses of diverse RGC types in the implanted retina, without being able to measure them directly. Here we demonstrate an inference approach that exploits intrinsic electrophysiological features of primate RGCs.Approach.First, ON-parasol and OFF-parasol RGC types were identified using their intrinsic electrical features in large-scale multi-electrode recordings from macaque retina. Then, the electrically inferred somatic location, inferred cell type, and average linear-nonlinear-Poisson model parameters of each cell type were used to infer a light response model for each cell. The accuracy of the cell type classification and of reproducing measured light responses with the model were evaluated.Main results.A cell-type classifier trained on 246 large-scale multi-electrode recordings from 148 retinas achieved 95% mean accuracy on 29 test retinas. In five retinas tested, the inferred models achieved an average correlation with measured firing rates of 0.49 for white noise visual stimuli and 0.50 for natural scenes stimuli, compared to 0.65 and 0.58 respectively for models fitted to recorded light responses (an upper bound). Linear decoding of natural images from predicted RGC activity in one retina showed a mean correlation of 0.55 between decoded and true images, compared to an upper bound of 0.81 using models fitted to light response data.Significance.These results suggest that inference of RGC light response properties from intrinsic features of their electrical activity may be a useful approach for high-fidelity sight restoration. The overall strategy of first inferring cell type from electrical features and then exploiting cell type to help infer natural cell function may also prove broadly useful to neural interfaces.


Assuntos
Degeneração Retiniana , Células Ganglionares da Retina , Animais , Células Ganglionares da Retina/fisiologia , Potenciais de Ação/fisiologia , Estimulação Elétrica/métodos , Retina/fisiologia , Macaca
8.
bioRxiv ; 2023 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-37873182

RESUMO

How does the motor cortex combine simple movements (such as single finger flexion/extension) into complex movements (such hand gestures or playing piano)? Motor cortical activity was recorded using intracortical multi-electrode arrays in two people with tetraplegia as they attempted single, pairwise and higher order finger movements. Neural activity for simultaneous movements was largely aligned with linear summation of corresponding single finger movement activities, with two violations. First, the neural activity was normalized, preventing a large magnitude with an increasing number of moving fingers. Second, the neural tuning direction of weakly represented fingers (e.g. middle) changed significantly as a result of the movement of other fingers. These deviations from linearity resulted in non-linear methods outperforming linear methods for neural decoding. Overall, simultaneous finger movements are thus represented by the combination of individual finger movements by pseudo-linear summation.

9.
bioRxiv ; 2023 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-37986895

RESUMO

Identifying neuronal cell types and their biophysical properties based on their extracellular electrical features is a major challenge for experimental neuroscience and the development of high-resolution brain-machine interfaces. One example is identification of retinal ganglion cell (RGC) types and their visual response properties, which is fundamental for developing future electronic implants that can restore vision. The electrical image (EI) of a RGC, or the mean spatio-temporal voltage footprint of its recorded spikes on a high-density electrode array, contains substantial information about its anatomical, morphological, and functional properties. However, the analysis of these properties is complex because of the high-dimensional nature of the EI. We present a novel optimization-based algorithm to decompose electrical image into a low-dimensional, biophysically-based representation: the temporally-shifted superposition of three learned basis waveforms corresponding to spike waveforms produced in the somatic, dendritic and axonal cellular compartments. Large-scale multi-electrode recordings from the macaque retina were used to test the effectiveness of the decomposition. The decomposition accurately localized the somatic and dendritic compartments of the cell. The imputed dendritic fields of RGCs correctly predicted the location and shape of their visual receptive fields. The inferred waveform amplitudes and shapes accurately identified the four major primate RGC types (ON and OFF midget and parasol cells), a substantial advance. Together, these findings may contribute to more accurate inference of RGC types and their original light responses in the degenerated retina, with possible implications for other electrical imaging applications.

10.
Neuron ; 110(4): 698-708.e5, 2022 02 16.
Artigo em Inglês | MEDLINE | ID: mdl-34932942

RESUMO

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.


Assuntos
Retina , Células Ganglionares da Retina , Animais , Feminino , Macaca , Masculino , Estimulação Luminosa , Retina/fisiologia , Células Ganglionares da Retina/fisiologia , Visão Ocular
11.
J Neural Eng ; 19(6)2022 12 19.
Artigo em Inglês | MEDLINE | ID: mdl-36533865

RESUMO

Objective. Vision restoration with retinal implants is limited by indiscriminate simultaneous activation of many cells and cell types, which is incompatible with reproducing the neural code of the retina. Recent work has shown that primate retinal ganglion cells (RGCs), which transmit visual information to the brain, can be directly electrically activated with single-cell, single-spike, cell-type precision - however, this possibility has never been tested in the human retina. In this study we aim to characterize, for the first time, direct in situ extracellular electrical stimulation of individual human RGCs.Approach. Extracellular electrical stimulation of individual human RGCs was conducted in three human retinas ex vivo using a custom large-scale, multi-electrode array capable of simultaneous recording and stimulation. Measured activation properties were compared directly to extensive results from macaque.Main results. Precise activation was in many cases possible without activating overlying axon bundles, at low stimulation current levels similar to those used in macaque. The major RGC types could be identified and targeted based on their distinctive electrical signatures. The measured electrical activation properties of RGCs, combined with a dynamic stimulation algorithm, was sufficient to produce an evoked visual signal that was nearly optimal given the constraints of the interface.Significance. These results suggest the possibility of high-fidelity vision restoration in humans using bi-directional epiretinal implants.


Assuntos
Células Ganglionares da Retina , Próteses Visuais , Animais , Humanos , Células Ganglionares da Retina/fisiologia , Estimulação Elétrica/métodos , Retina/fisiologia , Eletrodos , Macaca , Potenciais de Ação/fisiologia , Estimulação Luminosa/métodos
12.
J Neural Eng ; 17(5): 055002, 2020 10 22.
Artigo em Inglês | MEDLINE | ID: mdl-33089827

RESUMO

A future artificial retina that can restore high acuity vision in blind people will rely on the capability to both read (observe) and write (control) the spiking activity of neurons using an adaptive, bi-directional and high-resolution device. Although current research is focused on overcoming the technical challenges of building and implanting such a device, exploiting its capabilities to achieve more acute visual perception will also require substantial computational advances. Using high-density large-scale recording and stimulation in the primate retina with an ex vivo multi-electrode array lab prototype, we frame several of the major computational problems, and describe current progress and future opportunities in solving them. First, we identify cell types and locations from spontaneous activity in the blind retina, and then efficiently estimate their visual response properties by using a low-dimensional manifold of inter-retina variability learned from a large experimental dataset. Second, we estimate retinal responses to a large collection of relevant electrical stimuli by passing current patterns through an electrode array, spike sorting the resulting recordings and using the results to develop a model of evoked responses. Third, we reproduce the desired responses for a given visual target by temporally dithering a diverse collection of electrical stimuli within the integration time of the visual system. Together, these novel approaches may substantially enhance artificial vision in a next-generation device.


Assuntos
Órgãos Artificiais , Cegueira , Retina , Animais , Estimulação Elétrica , Percepção Visual
13.
Elife ; 92020 11 04.
Artigo em Inglês | MEDLINE | ID: mdl-33146609

RESUMO

The visual message conveyed by a retinal ganglion cell (RGC) is often summarized by its spatial receptive field, but in principle also depends on the responses of other RGCs and natural image statistics. This possibility was explored by linear reconstruction of natural images from responses of the four numerically-dominant macaque RGC types. Reconstructions were highly consistent across retinas. The optimal reconstruction filter for each RGC - its visual message - reflected natural image statistics, and resembled the receptive field only when nearby, same-type cells were included. ON and OFF cells conveyed largely independent, complementary representations, and parasol and midget cells conveyed distinct features. Correlated activity and nonlinearities had statistically significant but minor effects on reconstruction. Simulated reconstructions, using linear-nonlinear cascade models of RGC light responses that incorporated measured spatial properties and nonlinearities, produced similar results. Spatiotemporal reconstructions exhibited similar spatial properties, suggesting that the results are relevant for natural vision.


Vision begins in the retina, the layer of tissue that lines the back of the eye. Light-sensitive cells called rods and cones absorb incoming light and convert it into electrical signals. They pass these signals to neurons called retinal ganglion cells (RGCs), which convert them into electrical signals called spikes. Spikes from RGCs then travel along the optic nerve to the brain. They are the only source of visual information that the brain receives. From this information, the brain constructs our entire visual world. The primate retina contains roughly 20 types of RGCs. Each encodes a different visual feature, such as the presence of bright spots of a certain size, or information about texture and movement. But exactly what input each RGC sends to the brain, and how the brain uses this information, is unclear. Brackbill et al. set out to answer these questions by measuring and analyzing the electrical activity in isolated retinas from macaque monkeys. Studying the macaque retina was important because the primate visual system differs from that of other species in several ways. These include the numbers and types of RGCs present in the retina. These primates are also similar to humans in their high-resolution central vision and trichromatic color vision. Using electrode arrays to monitor hundreds of RGCs at the same time, Brackbill et al. recorded the responses of macaque retinas to real-life images of landscapes, objects, animals or people. Based on these recordings, plus existing knowledge about RGC responses, Brackbill et al. then attempted to reconstruct the original images using just the electrical activity recorded. The resulting reconstructions were similar across all retinas tested. Moreover, they showed a striking resemblance to the original images. These results made it possible to comprehend how the light-response properties of each cell represent visual information that can be used by the brain. Understanding how macaque retinas work in natural conditions is critical to decoding how our own retinas process and convey information. A better knowledge of how the brain uses this input to generate images could ultimately make it possible to design artificial retinas to restore vision in patients with certain forms of blindness.


Assuntos
Células Ganglionares da Retina/fisiologia , Visão Ocular/fisiologia , Animais , Macaca fascicularis , Macaca mulatta , Microeletrodos , Estimulação Luminosa , Retina/fisiologia
14.
Elife ; 92020 03 09.
Artigo em Inglês | MEDLINE | ID: mdl-32149600

RESUMO

Responses of sensory neurons are often modeled using a weighted combination of rectified linear subunits. Since these subunits often cannot be measured directly, a flexible method is needed to infer their properties from the responses of downstream neurons. We present a method for maximum likelihood estimation of subunits by soft-clustering spike-triggered stimuli, and demonstrate its effectiveness in visual neurons. For parasol retinal ganglion cells in macaque retina, estimated subunits partitioned the receptive field into compact regions, likely representing aggregated bipolar cell inputs. Joint clustering revealed shared subunits between neighboring cells, producing a parsimonious population model. Closed-loop validation, using stimuli lying in the null space of the linear receptive field, revealed stronger nonlinearities in OFF cells than ON cells. Responses to natural images, jittered to emulate fixational eye movements, were accurately predicted by the subunit model. Finally, the generality of the approach was demonstrated in macaque V1 neurons.


Assuntos
Células Ganglionares da Retina/fisiologia , Córtex Visual/fisiologia , Potenciais de Ação , Algoritmos , Animais , Simulação por Computador , Fixação Ocular , Funções Verossimilhança , Macaca fascicularis , Macaca mulatta , Modelos Neurológicos , Dinâmica não Linear , Estimulação Luminosa , Córtex Visual/citologia
15.
Neuron ; 103(4): 658-672.e6, 2019 08 21.
Artigo em Inglês | MEDLINE | ID: mdl-31227309

RESUMO

The functions of the diverse retinal ganglion cell types in primates and the parallel visual pathways they initiate remain poorly understood. Here, unusual physiological and computational properties of the ON and OFF smooth monostratified ganglion cells are explored. Large-scale multi-electrode recordings from 48 macaque retinas revealed that these cells exhibit irregular receptive field structure composed of spatially segregated hotspots, quite different from the classic center-surround model of retinal receptive fields. Surprisingly, visual stimulation of different hotspots in the same cell produced spikes with subtly different spatiotemporal voltage signatures, consistent with a dendritic contribution to hotspot structure. Targeted visual stimulation and computational inference demonstrated strong nonlinear subunit properties associated with each hotspot, supporting a model in which the hotspots apply nonlinearities at a larger spatial scale than bipolar cells. These findings reveal a previously unreported nonlinear mechanism in the output of the primate retina that contributes to signaling spatial information.


Assuntos
Células Ganglionares da Retina/classificação , Potenciais de Ação , Animais , Contagem de Células , Eletrofisiologia/métodos , Macaca fascicularis , Macaca mulatta , Modelos Neurológicos , Dinâmica não Linear , Técnicas de Patch-Clamp , Estimulação Luminosa , Células Ganglionares da Retina/fisiologia , Células Ganglionares da Retina/efeitos da radiação , Visão Ocular/fisiologia
16.
Front Syst Neurosci ; 8: 128, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25104927

RESUMO

Eye-specific thalamic inputs converge in the primary visual cortex (V1) and form the basis of binocular vision. For normal binocular perceptions, such as depth and stereopsis, binocularly matched orientation preference between the two eyes is required. A critical period of binocular matching of orientation preference in mice during normal development is reported in literature. Using a reaction diffusion model we present the development of RF and orientation selectivity in mouse V1 and investigate the binocular orientation preference matching during the critical period. At the onset of the critical period the preferred orientations of the modeled cells are mostly mismatched in the two eyes and the mismatch decreases and reaches levels reported in juvenile mouse by the end of the critical period. At the end of critical period 39% of cells in binocular zone in our model cortex is orientation selective. In literature around 40% cortical cells are reported as orientation selective in mouse V1. The starting and the closing time for critical period determine the orientation preference alignment between the two eyes and orientation tuning in cortical cells. The absence of near neighbor interaction among cortical cells during the development of thalamo-cortical wiring causes a salt and pepper organization in the orientation preference map in mice. It also results in much lower % of orientation selective cells in mice as compared to ferrets and cats having organized orientation maps with pinwheels.

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