Phosphene and motor transcranial magnetic stimulation thresholds are correlated: A meta-analytic investigation.

Transcranial magnetic stimulation (TMS) is commonly delivered at an intensity defined by the resting motor threshold (rMT), which is thought to represent cortical excitability, even if the TMS target area falls outside of the motor cortex. This approach rests on the assumption that cortical excitability, as measured through the motor cortex, represents a 'global' measure of excitability. Another common approach to measure cortical excitability relies on the phosphene threshold (PT), measured through the visual cortex of the brain. However, it remains unclear whether either estimate can serve as a singular measure to infer cortical excitability across different brain regions. If PT and rMT can indeed be used to infer cortical excitability across brain regions, they should be correlated. To test this, we systematically identified previous studies that measured PT and rMT to calculate an overall correlation between the two estimates. Our results, based on 16 effect sizes from eight studies, indicated that PT and rMT are correlated (ρ = 0.4), and thus one measure could potentially serve as a measure to infer cortical excitability across brain regions. Three exploratory meta-analyses revealed that the strength of the correlation is affected by different methodologies, and that PT intensities are higher than rMT. Evidence for a PT-rMT correlation remained robust across all analyses. Further research is necessary for an in-depth understanding of how cortical excitability is reflected through TMS.

Always expect the unexpected: eye position modulates visual cortex excitability in a stimulus-free environment.

Stimuli that potentially require a rapid defensive or avoidance action can appear from the periphery at any time in natural environments. de Wit et al. (Cortex 127: 120-130, 2020) recently reported novel evidence suggestive of a fundamental neural mechanism that allows organisms to effectively deal with such situations. In the absence of any task, motor cortex excitability was found to be greater whenever gaze was directed away from either hand. If modulation of cortical excitability as a function of gaze location is a fundamental principle of brain organization, then one would expect its operation to be present outside of motor cortex, including brain regions involved in perception. To test this hypothesis, we applied single-pulse transcranial magnetic stimulation (TMS) to the right lateral occipital lobe while participants directed their eyes to the left, straight-ahead, or to the right, and reported the presence or absence of a phosphene. No external stimuli were presented. Cortical excitability as reflected by the proportion of trials on which phosphenes were elicited from stimulation of the right visual cortex was greater with eyes deviated to the right as compared with the left. In conjunction with our previous findings of change in motor cortex excitability when gaze and effector are not aligned, this eye position-driven change in visual cortex excitability presumably serves to facilitate the detection of stimuli and subsequent readiness to act in nonfoveated regions of space. The existence of this brain-wide mechanism has clear adaptive value given the unpredictable nature of natural environments in which human beings are situated and have evolved.NEW & NOTEWORTHY For many complex tasks, humans focus attention on the site relevant to the task at hand. Humans evolved and live in dangerous environments, however, in which threats arise from outside the attended site; this fact necessitates a process by which the periphery is monitored. Using single-pulse transcranial magnetic stimulation (TMS), we demonstrated for the first time that eye position modulates visual cortex excitability. We argue that this underlies at least in part what we term "surveillance attention."

A Phosphenotron Device for Sensoric Spatial Resolution of Phosphenes within the Visual Field Using Non-Invasive Transcranial Alternating Current Stimulation.

This study presents phosphenotron, a device for enhancing the sensory spatial resolution of phosphenes in the visual field (VF). The phosphenotron employs a non-invasive transcranial alternating current stimulation (NITACS) to modulate brain activity by applying weak electrical currents to the scalp or face. NITACS's unique application induces phosphenes, a phenomenon where light is perceived without external stimuli. Unlike previous invasive methods, NITACS offers a non-invasive approach to create these effects. The study focused on assessing the spatial resolution of NITACS-induced phosphenes, crucial for advancements in visual aid technology and neuroscience. Eight participants were subjected to NITACS using a novel electrode arrangement around the eye orbits. Results showed that NITACS could generate spatially defined phosphene patterns in the VF, varying among individuals but consistently appearing within their VF and remaining stable through multiple stimulations. The study established optimal parameters for vibrant phosphene induction without discomfort and identified electrode positions that altered phosphene locations within different VF regions. Receiver Operating characteristics analysis indicated a specificity of 70.7%, sensitivity of 73.9%, and a control trial accuracy of 98.4%. These findings suggest that NITACS is a promising, reliable method for non-invasive visual perception modulation through phosphene generation.

Regulation of band gap and localized surface plasmon resonance by loading Au nanorods on violet phosphene nanosheets for photodynamic/photothermal synergistic anti-infective therapy.

In the face of the serious threat to human health and the economic burden caused by bacterial antibiotic resistance, 2D phosphorus nanomaterials have been widely used as antibacterial agents. Violet phosphorus nanosheets (VPNSs) are an exciting bandgap-adjustable 2D nanomaterial due to their good physicochemical properties, yet the study of VPNS-based antibiotics is still in its infancy. Here, a composite of gold nanorods (AuNRs) loaded onto VPNS platforms (VPNS/AuNR) is constructed to maximize the potential of VPNSs for antimicrobial applications. The loading with AuNRs not only enhances the photothermal performance via a localized surface plasmon resonance (LSPR) effect, but also enhances the light absorption capacity due to the narrowing of the band gap of the VPNSs, thus increasing the ROS generation capacity. The results demonstrate that VPNS/AuNR exhibits outstanding antibacterial properties and good biocompatibility. Attractively, VPNS/AuNR is then extensively tested for treating skin wound infections, suggesting promising in vivo antibacterial and wound-healing features. Our findings may open a novel direction to develop a versatile VPNS-based treatment platform, which can significantly boost the progress of VPNS exploration.

Bypassing input to V1 in visual awareness: A TMS-EROS investigation.

Early visual cortex (V1-V3) is believed to be critical for normal visual awareness by providing the necessary feedforward input. However, it remains unclear whether visual awareness can occur without further involvement of early visual cortex, such as re-entrant feedback. It has been challenging to determine the importance of feedback activity to these areas because of the difficulties in dissociating this activity from the initial feedforward activity. Here, we applied single-pulse transcranial magnetic stimulation (TMS) over the left posterior parietal cortex to elicit phosphenes in the absence of direct visual input to early visual cortex. Immediate neural activity after the TMS pulse was assessed using the event-related optical signal (EROS), which can measure activity under the TMS coil without artifacts. Our results show that: 1) The activity in posterior parietal cortex 50 ms after TMS was related to phosphene awareness, and 2) Activity related to awareness was observed in a small portion of V1 140 ms after TMS, but in contrast (3) Activity in V2 was a more robust correlate of awareness. Together, these results are consistent with interactive models proposing that sustained and recurrent loops of activity between cortical areas are necessary for visual awareness to emerge. In addition, we observed phosphene-related activations of the anteromedial cuneus and lateral occipital cortex, suggesting a functional network subserving awareness comprising these regions, the parietal cortex and early visual cortex.

Axonal stimulation affects the linear summation of single-point perception in three Argus II users.

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.

Towards biologically plausible phosphene simulation for the differentiable optimization of visual cortical prostheses.

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.

Mapping the routes of perception: Hemispheric asymmetries in signal propagation dynamics.

The visual system has long been considered equivalent across hemispheres. However, an increasing amount of data shows that functional differences may exist in this regard. We therefore tried to characterize the emergence of visual perception and the spatiotemporal dynamics resulting from the stimulation of visual cortices in order to detect possible interhemispheric asymmetries. Eighteen participants were tested. Each of them received 360 transcranial magnetic stimulation (TMS) pulses at phosphene threshold intensity over left and right early visual areas while electroencephalography was being recorded. After each single pulse, participants had to report the presence or absence of a phosphene. Local mean field power analysis of TMS-evoked potentials showed an effect of both site (left vs. right TMS) of stimulation and hemisphere (ipsilateral vs. contralateral to the TMS): while right TMS determined early stronger activations, left TMS determined later stronger activity in contralateral electrodes. The interhemispheric signal propagation index revealed differences in how TMS-evoked activity spreads: left TMS-induced activity diffused contralaterally more than right stimulation. With regard to phosphenes perception, distinct electrophysiological patterns were found to reflect similar perceptual experiences: left TMS-evoked phosphenes are associated with early occipito-parietal and frontal activity followed by late central activity; right TMS-evoked phosphenes determine only late, fronto-central, and parietal activations. Our results show that left and right occipital TMS elicits differential electrophysiological patterns in the brain, both per se and as a function of phosphene perception. These distinct activation patterns may suggest a different role of the two hemispheres in processing visual information and giving rise to perception.

Light flashes and other sensory illusions perceived in space travel and on ground, including proton and heavy ion therapies.

Most of the astronauts experience visual illusions, apparent flashes of light (LF) in absence of light. The first reported observation of this phenomenon was in July 1969 by Buzz Aldrin, in the debriefing following the Apollo 11 mission. Several ground-based experiments in the 1970s tried to clarify the mechanisms behind these light flashes and to evaluate possible related risks. These works were supported by dedicated experiments in space on the following Apollo flights and in Low Earth Orbit (LEO). It was soon demonstrated that the LF could be caused by charged particles (present in the space radiation) traveling through the eye, and, possibly, some other visual cortical areas. In the 1990s the interest in these phenomena increased again and additional experiments in Low Earth Orbit and others ground-based were started. Recently patients undergoing proton and heavy ion therapy for eye or head and neck tumors have reported the perception of light flashes, opening a new channel to investigate these phenomena. In this paper the many LF studies will be reviewed, presenting an historical and scientific perspective consistent with the combined set of observations, offering a single comprehensive summary aimed to provide further insights on these phenomena. While the light flashes appear not to be a risk by themselves, they might provide information on the amount of radiation induced radicals in the astronauts' eyes. Understanding their generation mechanisms might also support radiation countermeasures development. However, even given the substantial progress outlined in this paper, many questions related to their generation are still under debate, so additional studies are suggested. Finally, it is also conceivable that further LF investigations could provide evidence about the possible interaction of single particles in space with brain function, impacting with the crew ability to optimally perform a mission.

Utilization of brain scans to create realistic phosphene maps for cortical visual prosthesis simulation studies.

It has been shown that we can restore sensations of light by stimulating the visual cortex. Cortical prosthetic vision consists of light perception in the visual field named phosphenes. Phosphenes are like pixels on a monitor which we can control to form the desired perception. However, the locations of phosphenes evoked vary between individuals. One of the biggest challenges is how to utilize phosphenes to present recognizable patterns that represent real-world scenes. Because of the difficulties of recruiting participants, and the risks of neurosurgery, researchers have used computer simulations to investigate the outcome of cortical visual prostheses. Previous simulations used regular phosphene maps, which may overestimate the visual ability cortical visual prosthesis can provide. This study aims to develop a more realistic simulation for cortical visual prostheses. We derived realistic phosphene maps using an existing cortical retinotopy dataset and decided implant placement by considering neurosurgery restrictions. We rendered some visual stimuli to evaluate the usability of those phosphene maps. The results indicate that presenting information on phosphenes maps may be more challenging than previously estimated.

The Influence of Phosphene Synchrony in Driving Object Binding in a Simulation of Artificial Vision.

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.

A novel simulation paradigm utilising MRI-derived phosphene maps for cortical prosthetic vision.

Objective.We developed a realistic simulation paradigm for cortical prosthetic vision and investigated whether we can improve visual performance using a novel clustering algorithm.Approach.Cortical visual prostheses have been developed to restore sight by stimulating the visual cortex. To investigate the visual experience, previous studies have used uniform phosphene maps, which may not accurately capture generated phosphene map distributions of implant recipients. The current simulation paradigm was based on the Human Connectome Project retinotopy dataset and the placement of implants on the cortices from magnetic resonance imaging scans. Five unique retinotopic maps were derived using this method. To improve performance on these retinotopic maps, we enabled head scanning and a density-based clustering algorithm was then used to relocate centroids of visual stimuli. The impact of these improvements on visual detection performance was tested. Using spatially evenly distributed maps as a control, we recruited ten subjects and evaluated their performance across five sessions on the Berkeley Rudimentary Visual Acuity test and the object recognition task.Main results.Performance on control maps is significantly better than on retinotopic maps in both tasks. Both head scanning and the clustering algorithm showed the potential of improving visual ability across multiple sessions in the object recognition task.Significance.The current paradigm is the first that simulates the experience of cortical prosthetic vision based on brain scans and implant placement, which captures the spatial distribution of phosphenes more realistically. Utilisation of evenly distributed maps may overestimate the performance that visual prosthetics can restore. This simulation paradigm could be used in clinical practice when making plans for where best to implant cortical visual prostheses.

Abnormal visual and olfactory sensations during radiation therapy: a prospective study.

PURPOSE: Patients sometimes report phosphene and phantosmia during radiation therapy (RT). However, the detail features and related factors are not well understood. Our prospective study aimed to investigate the characteristics of phantosmias and phosphenes, to identify factors that influence the occurrence, intensity and hedonic (pleasantness/unpleasantness) ratings of such sensations during RT. METHODS: We included a total of 106 patients (37 women), who underwent RT in regions of the brain, ear, nose, throat (ENT), and other areas of the body for a duration of 43 ± 5 days. Medical history and treatment parameters were collected in a structured medical interview. Olfactory function was measured using the Sniffin' Stick Odor Identification Test at baseline. Phantosmia and phosphene were recorded weekly based on a self-report questionnaire. RESULTS: There were 37% of the patients experiencing phantosmias, 51% experiencing phosphenes, and 29% simultaneously experiencing both sensations. Phosphenes were typically perceived as a flashily blue, white and/or purple light, phantosmias were typically perceived as a chemical-like, metallic or burnt smell. Younger age (F = 7.81, p < 0.01), radiation in the brain region (χ2 = 14.05, p = 0.02), absence of taste problems (χ2 = 10.28, p = 0.01), and proton RT (χ2 = 10.57, p = 0.01) were related to these abnormal sensations. History of chemical/dust exposure predicted lower intensity (B = -1.52, p = 0.02) and lower unpleasantness (B = 0.49, p = 0.03) of phantosmia. In contrast, disease (tumor) duration (B = 0.11, p < 0.01), food allergy (B = 2.77, p < 0.01), and epilepsy (B = -1.50, p = 0.02) influence phosphenes intensity. Analgesics intake predicted a higher pleasantness of the phosphenes (B = 0.47, p < 0.01). CONCLUSIONS: Phantosmias and phosphenes are common during RT. The treatment settings and individual arousal level influence the occurrence, intensity and hedonic of such abnormal sensations. Phantosmias and phosphenes may involve more central neural than peripheral mechanism, and they could be elicited with activation of areas that are not regarded to be part of the olfactory or visual network.

Estimating Phosphene Locations Using Eye Movements of Suprachoroidal Retinal Prosthesis Users.

Purpose: Accurate mapping of phosphene locations from visual prostheses is vital to encode spatial information. This process may involve the subject pointing to evoked phosphene locations with their finger. Here, we demonstrate phosphene mapping for a retinal implant using eye movements and compare it with retinotopic electrode positions and previous results using conventional finger-based mapping. Methods: Three suprachoroidal retinal implant recipients (NCT03406416) indicated the spatial position of phosphenes. Electrodes were stimulated individually, and the subjects moved their finger (finger based) or their eyes (gaze based) to the perceived phosphene location. The distortion of the measured phosphene locations from the expected locations (retinotopic electrode locations) was characterized with Procrustes analysis. Results: The finger-based phosphene locations were compressed spatially relative to the expected locations all three subjects, but preserved the general retinotopic arrangement (scale factors ranged from 0.37 to 0.83). In two subjects, the gaze-based phosphene locations were similar to the expected locations (scale factors of 0.72 and 0.99). For the third subject, there was no apparent relationship between gaze-based phosphene locations and electrode locations (scale factor of 0.07). Conclusions: Gaze-based phosphene mapping was achievable in two of three tested retinal prosthesis subjects and their derived phosphene maps correlated well with the retinotopic electrode layout. A third subject could not produce a coherent gaze-based phosphene map, but this may have revealed that their phosphenes were indistinct spatially. Translational Relevance: Gaze-based phosphene mapping is a viable alternative to conventional finger-based mapping, but may not be suitable for all subjects.

Amplitude modulating frequency overrides carrier frequency in tACS-induced phosphene percept.

The amplitude modulated (AM) neural oscillation is an essential feature of neural dynamics to coordinate distant brain areas. The AM transcranial alternating current stimulation (tACS) has recently been adopted to examine various cognitive functions, but its neural mechanism remains unclear. The current study utilized the phosphene phenomenon to investigate whether, in an AM-tACS, the AM frequency could modulate or even override the carrier frequency in phosphene percept. We measured the phosphene threshold and the perceived flash rate/pattern from 12 human subjects (four females, aged from 20-44 years old) under tACS that paired carrier waves (10, 14, 18, 22 Hz) with different envelope conditions (0, 2, 4 Hz) over the mid-occipital and left facial areas. We also examined the phosphene source by adopting a high-density stimulation montage. Our results revealed that (1) phosphene threshold was higher for AM-tACS than sinusoidal tACS and demonstrated different carrier frequency functions in two stimulation montages. (2) AM-tACS slowed down the phosphene flashing and abolished the relation between the carrier frequency and flash percept in sinusoidal tACS. This effect was independent of the intensity change of the stimulation. (3) Left facial stimulation elicited phosphene in the upper-left visual field, while occipital stimulation elicited equally distributed phosphene. (4) The near-eye electrodermal activity (EDA) measured under the threshold-level occipital tACS was greater than the lowest power sufficient to elicit retinal phosphene. Our results show that AM frequency may override the carrier frequency and determine the perceived flashing frequency of AM-tACS-induced phosphene.

Clinical Progress and Optimization of Information Processing in Artificial Visual Prostheses.

Visual prostheses, used to assist in restoring functional vision to the visually impaired, convert captured external images into corresponding electrical stimulation patterns that are stimulated by implanted microelectrodes to induce phosphenes and eventually visual perception. Detecting and providing useful visual information to the prosthesis wearer under limited artificial vision has been an important concern in the field of visual prosthesis. Along with the development of prosthetic device design and stimulus encoding methods, researchers have explored the possibility of the application of computer vision by simulating visual perception under prosthetic vision. Effective image processing in computer vision is performed to optimize artificial visual information and improve the ability to restore various important visual functions in implant recipients, allowing them to better achieve their daily demands. This paper first reviews the recent clinical implantation of different types of visual prostheses, summarizes the artificial visual perception of implant recipients, and especially focuses on its irregularities, such as dropout and distorted phosphenes. Then, the important aspects of computer vision in the optimization of visual information processing are reviewed, and the possibilities and shortcomings of these solutions are discussed. Ultimately, the development direction and emphasis issues for improving the performance of visual prosthesis devices are summarized.

PVGAN: a generative adversarial network for object simplification in prosthetic vision.

Objective.By means of electrical stimulation of the visual system, visual prostheses provide promising solution for blind patients through partial restoration of their vision. Despite the great success achieved so far in this field, the limited resolution of the perceived vision using these devices hinders the ability of visual prostheses users to correctly recognize viewed objects. Accordingly, we propose a deep learning approach based on generative adversarial networks (GANs), termed prosthetic vision GAN (PVGAN), to enhance object recognition for the implanted patients by representing objects in the field of view based on a corresponding simplified clip art version.Approach.To assess the performance, an axon map model was used to simulate prosthetic vision in experiments involving normally-sighted participants. In these experiments, four types of image representation were examined. The first and second types comprised presenting phosphene simulation of real images containing the actual high-resolution object, and presenting phosphene simulation of the real image followed by the clip art image, respectively. The other two types were utilized to evaluate the performance in the case of electrode dropout, where the third type comprised presenting phosphene simulation of only clip art images without electrode dropout, while the fourth type involved clip art images with electrode dropout.Main results.The performance was measured through three evaluation metrics which are the accuracy of the participants in recognizing the objects, the time taken by the participants to correctly recognize the object, and the confidence level of the participants in the recognition process. Results demonstrate that representing the objects using clip art images generated by the PVGAN model results in a significant enhancement in the speed and confidence of the subjects in recognizing the objects.Significance.These results demonstrate the utility of using GANs in enhancing the quality of images perceived using prosthetic vision.

Percepts evoked by multi-electrode stimulation of human visual cortex.

BACKGROUND: Direct electrical stimulation of early visual cortex evokes the perception of small spots of light known as phosphenes. Previous studies have examined the location, size, and brightness of phosphenes evoked by stimulation of single electrodes. While it has been envisioned that concurrent stimulation of many electrodes could be used as the basis for a visual cortical prosthesis, the percepts resulting from multi-electrode stimulation have not been fully characterized. OBJECTIVE: To understand the rules governing perception of phosphenes evoked by multi-electrode stimulation of visual cortex. METHODS: Multi-electrode stimulation was conducted in human epilepsy patients. We examined the number and spatial arrangement of phosphenes evoked by stimulation of individual multi-electrode groups (n = 8), and the ability of subjects to discriminate between the pattern of phosphenes generated by stimulation of different multi-electrode groups (n = 7). RESULTS: Simultaneous stimulation of pairs of electrodes separated by greater than 4 mm tended to produce perception of two distinct phosphenes. Simultaneous stimulation of three electrodes gave rise to a consistent spatial pattern of phosphenes, but with significant variation in the absolute location, size, and orientation of that pattern perceived on each trial. Although multi-electrode stimulation did not produce perception of recognizable forms, subjects could use the pattern of phosphenes evoked by stimulation to perform simple discriminations. CONCLUSIONS: The number of phosphenes produced by multi-electrode stimulation can be predicted using a model for spread of activity in early visual cortex, but there are additional subtle effects that must be accounted for.