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Unlike the exhaustive determination of cell types in the retina, key populations in the lateral geniculate nucleus of the thalamus (LGN) may have been missed. Here, we have begun to characterize the full range of extracellular neuronal responses in the LGN of awake monkeys using multi-electrodes during the presentation of colored noise visual stimuli to identify any previously overlooked signals. Extracellular spike waveforms of single units were classified into seven distinct classes, revealing previously unrecognized diversity: four negative-dominant classes that were narrow or broad, one triphasic class, and two positive-dominant classes. Based on their mapped receptive field (RF), these units were further categorized into either magnocellular (M), parvocellular (P), koniocellular (K), or non-RF (N). We found correlations between spike shape and mapped RF and response characteristics, with negative and narrow spiking waveform units predominantly associated with P and N RFs, and positive waveforms mostly linked to M RFs. Responses from positive waveforms exhibited shorter latencies, larger RF sizes, and were associated with larger eccentricities in the visual field than the other waveform classes. Additionally, N cells, those without an estimated RF, were consistently responsive to the visually presented mapping stimulus at a lower and more sustained rate than units with an RF. These findings suggest that the LGN cell population may be more diverse than previously believed.
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Over the past decade, stereotactically placed electrodes have become the gold standard for deep brain recording and stimulation for a wide variety of neurological and psychiatric diseases. Current electrodes, however, are limited in their spatial resolution and ability to record from small populations of neurons, let alone individual neurons. Here, we report on an innovative, customizable, monolithically integrated human-grade flexible depth electrode capable of recording from up to 128 channels and able to record at a depth of 10 cm in brain tissue. This thin, stylet-guided depth electrode is capable of recording local field potentials and single unit neuronal activity (action potentials), validated across species. This device represents an advance in manufacturing and design approaches which extends the capabilities of a mainstay technology in clinical neurology.
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Encéfalo , Neuronas , Humanos , Encéfalo/fisiología , Electrodos , Potenciales de Acción/fisiología , Neuronas/fisiología , Electrodos ImplantadosRESUMEN
Purpose: Electrical microstimulation techniques used in visual prostheses are designed to restore visual function following acquired blindness. Patterns of induced focal percepts, known as phosphenes, are achieved by applying localized electrical pulses to the visual pathway to bypass the impaired site in order to convey images from the external world. Here, we use a simulation of artificial vision to manipulate relationships between individual phosphenes to observe the effects on object binding and perception. We hypothesize that synchronous phosphene presentation will facilitate object perception as compared to asynchronous presentation. Methods: A model system that tracks gaze position of normal, sighted participants to present patterns of phosphenes on a computer screen was used to simulate prosthetic vision. Participants performed a reading task at varying font sizes (1.1-1.4 logMAR) and under varying levels of phosphene temporal noise while reading accuracy and speed were measured. Results: Reading performance was significantly affected by temporal noise in phosphene presentation, with increasing desynchronization leading to lower reading scores. A drop in performance was also observed when the total latency between the gaze position and phosphene update was increased without adding temporal noise. Conclusions: Object perception (here, text perception) is enhanced with synchronously presented phosphenes as compared to asynchronously presented ones. These results are fundamental for developing an efficient temporal pattern of stimulation and for the creation of high-fidelity prosthetic vision.
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Fosfenos , Prótesis Visuales , Humanos , Simulación por Computador , Ceguera , LecturaRESUMEN
With the advent of multiple visual prosthesis devices to treat blindness, the question of how potential patients view such interventions becomes important in order to understand the levels of expectation and acceptance, and the perceived risk-reward balance across the different device approaches. Building on previous work on single device approaches done with blind individuals in Chicago and Detroit, USA, Melbourne, Australia, and Bejing, China, we investigated attitudes in blind individuals in Athens, Greece with coverage expanded to three of the contemporary approaches, Retinal, Thalamic, and Cortical. We presented an informational lecture on the approaches, had potential participants fill out a preliminary Questionnaire 1, then organized selected subjects into focus groups for guided discussion on visual prostheses, and finally had these subjects fill out a more detailed Questionnaire 2. We report here the first quantitative data that compares multiple prosthesis approaches. Our primary findings are that for these potential patients, perceived risk continues to outweigh perceived benefits, with the Retinal approach having the least negative overall impression and the Cortical approach the most negative. Concerns about the quality of restored vision were primary. Factors that drove the choice of hypothetical participation in a clinical trial were age and years of blindness. Secondary factors focused on positive clinical outcomes. The focus groups served to swing the impressions of each approach from neutrality toward the extremes of a Likert scale, and shifted the overall willingness to participate in a clinical trial from neutral to negative. These results, coupled with informal assessment of audience questions after the informational lecture, suggest that a substantial improvement in performance over currently available devices will be necessary before visual prostheses gain wide acceptance.
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Prótesis Visuales , Humanos , Visión Ocular , Ceguera/terapia , Implantación de Prótesis , ActitudRESUMEN
Simulated artificial vision is used in visual prosthesis design to answer questions about device usability. We previously reported a striking increase in equivalent visual acuity with daily use of a simulation of artificial vision in an active task, reading sentences, that required high levels of subject engagement, but passive activities are more likely to dominate post-implant experience. Here, we investigated the longitudinal effects of a passive task, watching videos. Eight subjects used a simulation of a thalamic visual prosthesis with 1000 phosphenes to watch 23 episodes of classic American television in daily, 25-min sessions, for a period of 1 month with interspersed reading tests that quantified reading accuracy and reading speed. For reading accuracy, we found similar dynamics to the early part of the learning process in our previous report, here leading to an improvement in visual acuity of 0.15 ± 0.05 logMAR. For reading speed, however, no change was apparent by the end of training. We found that single reading sessions drove about twice the improvement in acuity of single video sessions despite being only half as long. We conclude that while passive viewing tasks may prove useful for post-implant rehabilitation, active tasks are likely to be preferable.
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Visión Ocular , Prótesis Visuales , Humanos , Fosfenos , Trastornos de la Visión , Agudeza VisualRESUMEN
The visual pathway is retinotopically organized and sensitive to gaze position, leading us to hypothesize that subjects using visual prostheses incorporating eye position would perform better on perceptual tasks than with devices that are merely head-steered. We had sighted subjects read sentences from the MNREAD corpus through a simulation of artificial vision under conditions of full gaze compensation, and head-steered viewing. With 2000 simulated phosphenes, subjects (n = 23) were immediately able to read under full gaze compensation and were assessed at an equivalent visual acuity of 1.0 logMAR, but were nearly unable to perform the task under head-steered viewing. At the largest font size tested, 1.4 logMAR, subjects read at 59 WPM (50% of normal speed) with 100% accuracy under the full-gaze condition, but at 0.7 WPM (under 1% of normal) with below 15% accuracy under head-steering. We conclude that gaze-compensated prostheses are likely to produce considerably better patient outcomes than those not incorporating eye movements.
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Fijación Ocular/fisiología , Lectura , Visión Ocular/fisiología , Vías Visuales/fisiología , Prótesis Visuales , Adolescente , Adulto , Femenino , Humanos , Masculino , Pruebas de Visión , Agudeza Visual/fisiología , Adulto JovenRESUMEN
Visual prosthesis devices designed to restore sight to the blind have been under development in the laboratory for several decades. Clinical translation continues to be challenging, due in part to gaps in our understanding of critical parameters such as how phosphenes, the electrically-generated pixels of artificial vision, can be combined to form images. In this review we explore the effects that synchronous and asynchronous electrical stimulation across multiple electrodes have in evoking phosphenes. Understanding how electrical patterns influence phosphene generation to control object binding and perception of visual form is fundamental to creation of a clinically successful prosthesis.
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Corteza Visual , Prótesis Visuales , Estimulación Eléctrica , Fosfenos , Visión OcularRESUMEN
Common causes of blindness are diseases that affect the ocular structures, such as glaucoma, retinitis pigmentosa, and macular degeneration, rendering the eyes no longer sensitive to light. The visual pathway, however, as a predominantly central structure, is largely spared in these cases. It is thus widely thought that a device-based prosthetic approach to restoration of visual function will be effective and will enjoy similar success as cochlear implants have for restoration of auditory function. In this article the authors review the potential locations for stimulation electrode placement for visual prostheses, assessing the anatomical and functional advantages and disadvantages of each. Of particular interest to the neurosurgical community is placement of deep brain stimulating electrodes in thalamic structures that has shown substantial promise in an animal model. The theory of operation of visual prostheses is discussed, along with a review of the current state of knowledge. Finally, the visual prosthesis is proposed as a model for a general high-fidelity machine-brain interface.
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Ceguera/terapia , Estimulación Encefálica Profunda/métodos , Prótesis e Implantes , Tálamo/fisiología , Interfaz Usuario-Computador , Vías Visuales/fisiología , Percepción Visual/fisiología , Animales , Electrodos Implantados , Humanos , Modelos Animales , Procedimientos Neuroquirúrgicos/métodos , Diseño de Prótesis , Implantación de Prótesis , Retina/fisiología , Visión Ocular/fisiología , Corteza Visual/fisiologíaRESUMEN
Visual prostheses serve to restore visual function following acquired blindness. Acquired blindness (as opposed to congenital blindness) has many causes, including diseases such as retinitis pigmentosa, glaucoma, and macular degeneration, or trauma such as caused by automobile accident or blast damage from explosions. Many of the blindness-causing diseases target the retina or other ocular structure. Often, despite the loss of sensitivity to light, the remainder of the visual pathway is still functional, enabling electrical devices to deliver effective and meaningful visual information to the brain via arrays of electrodes. These arrays can be placed in any part of the early visual pathway, such as the retina, optic nerve, lateral geniculate nucleus, or visual cortex. A camera or other imaging source is used to drive electrical stimulation of remaining healthy cells or structures to create artificial vision and provide restoration of function. In this review, each approach to visual prostheses is described, including advantages and disadvantages as well as assessments of the current state of the art. Most of the work to-date has been targeting stimulation of (a) the retina, with three devices approved for general use and two more in clinical testing; (b) the lateral geniculate nucleus, with efforts still in the pre-clinical stage; and (c) the cortex, with three devices in clinical testing and none currently approved for general use despite the longest history of investigation of the three major approaches. Each class of device has different medical indications, and different levels of invasiveness required for implantation. All contemporary devices deliver relatively poor vision. There has been remarkable progress since the first proof-of-concept demonstration that used stimulation of the primary visual cortex, with the field exploring all viable options for restoration of function. Much of the progress has been recent, driven by advances in microelectronics and biocompatibility. With three devices currently approved for general use in various parts of the world, and a handful of additional devices well along in the pipeline toward approval, prospects for wide deployment of a device-based therapy to treat acquired blindness are good.
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Ceguera/terapia , Terapia por Estimulación Eléctrica , Nervio Óptico/fisiología , Corteza Visual/fisiología , Prótesis Visuales , Ensayos Clínicos como Asunto , HumanosRESUMEN
Many cortical structures have elevated firing rates during working memory, but it is not known how the activity is maintained. To investigate whether reverberating activity is important, we studied the temporal structure of local field potential (LFP) activity and spiking from area LIP in two awake macaques during a memory-saccade task. Using spectral analysis, we found spatially tuned elevated power in the gamma band (25-90 Hz) in LFP and spiking activity during the memory period. Spiking and LFP activity were also coherent in the gamma band but not at lower frequencies. Finally, we decoded LFP activity on a single-trial basis and found that LFP activity in parietal cortex discriminated between preferred and anti-preferred direction with approximately the same accuracy as the spike rate and predicted the time of a planned movement with better accuracy than the spike rate. This finding could accelerate the development of a cortical neural prosthesis.
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Memoria a Corto Plazo/fisiología , Neuronas/fisiología , Lóbulo Parietal/fisiología , Potenciales de Acción/fisiología , Animales , Macaca mulatta , Masculino , Lóbulo Parietal/citología , Estimulación Luminosa , Movimientos Sacádicos/fisiología , Procesamiento de Señales Asistido por Computador , Vigilia/fisiologíaRESUMEN
Despite appearing automatic and effortless, perceiving the visual world is a highly complex process that depends on intact visual and oculomotor function. Understanding the mechanisms underlying spatial updating (i.e., gaze contingency) represents an important, yet unresolved issue in the fields of visual perception and cognitive neuroscience. Many questions regarding the processes involved in updating visual information as a function of the movements of the eyes are still open for research. Beyond its importance for basic research, gaze contingency represents a challenge for visual prosthetics as well. While most artificial vision studies acknowledge its importance in providing accurate visual percepts to the blind implanted patients, the majority of the current devices do not compensate for gaze position. To-date, artificial percepts to the blind population have been provided either by intraocular light-sensing circuitry or by using external cameras. While the former commonly accounts for gaze shifts, the latter requires the use of eye-tracking or similar technology in order to deliver percepts based on gaze position. Inspired by the need to overcome the hurdle of gaze contingency in artificial vision, we aim to provide a thorough overview of the research addressing the neural underpinnings of eye compensation, as well as its relevance in visual prosthetics. The present review outlines what is currently known about the mechanisms underlying spatial updating and reviews the attempts of current visual prosthetic devices to overcome the hurdle of gaze contingency. We discuss the limitations of the current devices and highlight the need to use eye-tracking methodology in order to introduce gaze-contingent information to visual prosthetics.
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Simulations of artificial vision are used to provide the researcher an opportunity to explore different aspects of visual prosthesis device design by observing subject performance on various tasks viewed through the simulation. Such studies typically use normal, sighted subjects to measure performance at a given point in time. Relatively few studies examine performance changes longitudinally to quantitatively assess the benefits from a training plan that would be akin to post-implantation rehabilitation. Here, we had six normal, sighted subjects use a standard reading task with daily practice over eight weeks to understand the effects of an intensive training schedule on adaptation to artificial sight. Subjects read 40 MNREAD-style sentences per session, with a new set each session, that were presented at five font sizes (logMAR 1.0-1.4) and through three center-weighted phosphene patterns (2,000, 1,000, 500 phosphenes). We found that subjects improved their reading accuracy across sessions, and that the training lead to an increase of reading speed that was equivalent to a doubling of available phosphenes. Most importantly, the hardest condition, while initially illegible, supported functional reading after training. Consistent with experience-driven neuroplastic changes, gaps in the training schedule lead to transient decreases in reading speed, but, surprisingly, not reading accuracy. Our findings contribute to our larger project of developing a thalamic visual prosthesis and to post-implant rehabilitation strategies.
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Lectura , Tálamo/fisiología , Prótesis Visuales , Adulto , Femenino , Humanos , Masculino , Tiempo de Reacción , Adulto JovenRESUMEN
Visual perceptual grouping, the process of forming global percepts from discrete elements, is experience-dependent. Here we show that the learning time course in an animal model of artificial vision is predicted primarily from the density of visual elements. Three naïve adult non-human primates were tasked with recognizing the letters of the Roman alphabet presented at variable size and visualized through patterns of discrete visual elements, specifically, simulated phosphenes mimicking a thalamic visual prosthesis. The animals viewed a spatially static letter using a gaze-contingent pattern and then chose, by gaze fixation, between a matching letter and a non-matching distractor. Months of learning were required for the animals to recognize letters using simulated phosphene vision. Learning rates increased in proportion to the mean density of the phosphenes in each pattern. Furthermore, skill acquisition transferred from trained to untrained patterns, not depending on the precise retinal layout of the simulated phosphenes. Taken together, the findings suggest that learning of perceptual grouping in a gaze-contingent visual prosthesis can be described simply by the density of visual activation.
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Ojo Artificial , Aprendizaje , Percepción Visual , Animales , Macaca mulattaRESUMEN
The psychophysics of reading with artificial sight has received increasing attention as visual prostheses are becoming a real possibility to restore useful function to the blind through the coarse, pseudo-pixelized vision they generate. Studies to date have focused on simulating retinal and cortical prostheses; here we extend that work to report on thalamic designs. This study examined the reading performance of normally sighted human subjects using a simulation of three thalamic visual prostheses that varied in phosphene count, to help understand the level of functional ability afforded by thalamic designs in a task of daily living. Reading accuracy, reading speed, and reading acuity of 20 subjects were measured as a function of letter size, using a task based on the MNREAD chart. Results showed that fluid reading was feasible with appropriate combinations of letter size and phosphene count, and performance degraded smoothly as font size was decreased, with an approximate doubling of phosphene count resulting in an increase of 0.2 logMAR in acuity. Results here were consistent with previous results from our laboratory. Results were also consistent with those from the literature, despite using naive subjects who were not trained on the simulator, in contrast to other reports.
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Mapping neuronal responses in the lateral geniculate nucleus (LGN) is key to understanding how visual information is processed in the brain. This paper focuses on our current knowledge of the dynamics the receptive field (RF) as broken down into the classical receptive field (CRF) and the extra-classical receptive field (ECRF) in primate LGN. CRFs in the LGN are known to be similar to those in the retinal ganglion cell layer in terms of both spatial and temporal characteristics, leading to the standard interpretation of the LGN as a relay center from retina to primary visual cortex. ECRFs have generally been found to be large and inhibitory, with some differences in magnitude between the magno-, parvo-, and koniocellular pathways. The specific contributions of the retina, thalamus, and visual cortex to LGN ECRF properties are presently unknown. Some reports suggest a retinal origin for extra-classical suppression based on latency arguments and other reports have suggested a thalamic origin for extra-classical suppression. This issue is complicated by the use of anesthetized animals, where cortical activity is likely to be altered. Thus further study of LGN ECRFs is warranted to reconcile these discrepancies. Producing descriptions of RF properties of LGN neurons could be enhanced by employing preferred naturalistic stimuli. Although there has been significant work in cats with natural scene stimuli and noise that statistically imitates natural scenes, we highlight a need for similar data from primates. Obtaining these data may be aided by recent advancements in experimental and analytical techniques that permit the efficient study of nonlinear RF characteristics in addition to traditional linear factors. In light of the reviewed topics, we conclude by suggesting experiments to more clearly elucidate the spatial and temporal structure of ECRFs of primate LGN neurons.
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Mapeo Encefálico/métodos , Cuerpos Geniculados/fisiología , Campos Visuales/fisiología , Vías Visuales/fisiología , Animales , Humanos , Macaca , Estimulación Luminosa/métodos , Corteza Visual/fisiología , Percepción Visual/fisiologíaRESUMEN
Simulation in normally sighted individuals is a crucial tool to evaluate the performance of potential visual prosthesis designs prior to human implantation of a device. Here, we investigated the effects of electrode count on visual acuity, learning rate and response time in 16 normally sighted subjects using a simulated thalamic visual prosthesis, providing the first performance reports for thalamic designs. A new letter recognition paradigm using a multiple-optotype two-alternative forced choice task was adapted from the Snellen eye chart, and specifically devised to be readily communicated to both human and non-human primate subjects. Validation of the method against a standard Snellen acuity test in 21 human subjects showed no significant differences between the two tests. The novel task was then used to address three questions about simulations of the center-weighted phosphene patterns typical of thalamic designs: What are the expected Snellen acuities for devices with varying numbers of contacts, do subjects display rapid adaptation to the new visual modality, and can response time in the task provide clues to the mechanisms of perception in low-resolution artificial vision? Population performance (hit rate) was significantly above chance when viewing Snellen 20/200 optotypes (Log MAR 1.0) with 370 phosphenes in the central 10 degrees of vision, ranging to Snellen 20/800 (Log MAR 1.6) with 25 central phosphenes. Furthermore, subjects demonstrated learning within the 1-2 hours of task experience indicating the potential for an effective rehabilitation and possibly better visual performance after a longer period of training. Response time differences suggest that direct letter perception occurred when hit rate was above 75%, whereas a slower strategy like feature-based pattern matching was used in conditions of lower relative resolution. As pattern matching can substantially boost effective acuity, these results suggest post-implant therapy should specifically address feature detection skills.
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Tálamo/fisiología , Agudeza Visual , Prótesis Visuales , Adulto , Electrodos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Adulto JovenRESUMEN
In this paper, placement parameters for microstimulation electrodes in a visual prosthesis are evaluated based on retinotopic models of macaque and human lateral geniculate nucleus. Phosphene patterns were simulated for idealized microwire electrodes as well as for currently available clinical electrodes. For idealized microwire electrodes, spacing as large as 600 microm in three dimensions would allow for over 250 phosphenes per visual hemifield in macaques, and over 800 in humans.
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Simulación por Computador , Electrodos Implantados , Microelectrodos , Modelos Neurológicos , Tálamo/fisiología , Percepción Visual , Animales , Encéfalo/fisiología , Fóvea Central/fisiología , Haplorrinos , Humanos , Microtecnología/instrumentación , Método de Montecarlo , Fosfenos/fisiología , Prótesis e Implantes , Estadísticas no ParamétricasRESUMEN
Electrical stimulation of the visual system might serve as the foundation for a prosthetic device for the blind. We examined whether microstimulation of the dorsal lateral geniculate nucleus of the thalamus can generate localized visual percepts in alert monkeys. To assess electrically generated percepts, an eye-movement task was used with targets presented on a computer screen (optically) or through microstimulation of the lateral geniculate nucleus (electrically). Saccades (fast, direct eye movements) made to electrical targets were comparable to saccades made to optical targets. Gaze locations for electrical targets were well predicted by measured visual response maps of cells at the electrode tips. With two electrodes, two distinct targets could be independently created. A sequential saccade task verified that electrical targets were processed not in motor coordinates, but in visual spatial coordinates. Microstimulation produced predictable visual percepts, showing that this technique may be useful for a visual prosthesis.
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Órganos Artificiales , Tálamo/fisiología , Percepción Visual/fisiología , Animales , Electrodos , Electrofisiología , Femenino , Macaca , Masculino , Reproducibilidad de los ResultadosRESUMEN
Electrical stimulation of the thalamus has been widely used to test for the existence of monosynaptic input to cortical neurons, typically with stimulation currents that evoke cortical spikes with high probability. We stimulated the lateral geniculate nucleus (LGN) of the thalamus and recorded monosynaptically evoked spikes from layer 4 neurons in visual cortex. We found that with moderate currents, cortical spikes were evoked with low to moderate probability and their occurrence was modulated by ongoing sensory (visual) input. Furthermore, when repeated at 8-12 Hz, electrical stimulation of the thalamic afferents caused such profound inhibition that cortical spiking activity was suppressed, aside from electrically evoked monosynaptic spikes. Visual input to layer 4 cortical cells between electrical stimuli must therefore have derived exclusively from LGN afferents. We used white-noise visual stimuli to make a 2D map of the receptive field of each cortical simple cell during repetitive electrical stimulation in the LGN. The receptive field of electrically evoked monosynaptic spikes (and thus of the thalamic input alone) was significantly elongated. Its primary subfield was comparable to that of the control receptive field, but secondary (flanking) subfields were weaker. These findings extend previous results from intracellular recordings, but also demonstrate the effectiveness of an extracellular method of measuring subthreshold afferent input to cortex.