Search

Phosphenes induced by transcranial magnetic stimulation (TMS) are sensations of light, whereas a missing region in the visual field induced by TMS is generally referred to as a scotoma. It is believed that phosphenes are caused by neural excitation, while scotomas are due to neural inhibition. In light of the recent literature it might, however, be surmised that both phenomena are the result of neural noise injected into the cortex by TMS and that the likelihood of perceiving the two kinds of percepts depends on the state of the cortex at the time of stimulation. In the present study, TMS was applied over the left occipital cortex under different background conditions (Experiments 1-2) and using different TMS intensities (Experiment 3). Behavioral responses indicate the visual system processes luminance in a standardized manner, as lighter percepts were reacted to faster than darker percepts; this effect, however, did not extend to percept size. Our results suggest that phenomenological characteristics of artificial visual percepts are in line with the proposed effects of TMS as the induction of random neural noise interfering with the neural dynamics (the state of the cortex) at the time of stimulation.

Phosphenes are illusory visual percepts produced by the application of transcranial magnetic stimulation to occipital cortex. Phosphene thresholds, the minimum stimulation intensity required to reliably produce phosphenes, are widely used as an index of cortical excitability. However, the neural basis of phosphene thresholds and their relationship to individual differences in visual cognition are poorly understood. Here, we investigated the neurochemical basis of phosphene perception by measuring basal GABA and glutamate levels in primary visual cortex using magnetic resonance spectroscopy. We further examined whether phosphene thresholds would relate to the visuospatial phenomenology of grapheme-color synesthesia, a condition characterized by atypical binding and involuntary color photisms. Phosphene thresholds negatively correlated with glutamate concentrations in visual cortex, with lower thresholds associated with elevated glutamate. This relationship was robust, present in both controls and synesthetes, and exhibited neurochemical, topographic, and threshold specificity. Projector synesthetes, who experience color photisms as spatially colocalized with inducing graphemes, displayed lower phosphene thresholds than associator synesthetes, who experience photisms as internal images, with both exhibiting lower thresholds than controls. These results suggest that phosphene perception is driven by interindividual variation in glutamatergic activity in primary visual cortex and relates to cortical processes underlying individual differences in visuospatial awareness., (© The Author 2015. Published by Oxford University Press.)

Astronauts in orbit reported phosphenes varying in shape and orientation across the visual field; incidence was correlated with the radiation flux. Patients with skull tumors treated by (12)C ions and volunteers whose posterior portion of the eye was exposed to highly ionizing particles in early studies reported comparable percepts. An origin in radiation activating the visual system is suggested. Bursts (∼ 4 ms) of (12)C ions evoked electrophysiological mass responses comparable to those to light in the retina of anesthetized wild-type mice at threshold flux intensities consistent with the incidence observed in humans. The retinal response amplitude increased in mice with ion intensity to a maximum at ∼ 2000 ions/burst, to decline at higher intensities; the inverted-U relationship suggests complex effects on retinal structures. Here, we show that bursts of (12)C ions presented simultaneously to white light stimuli reduced the presynaptic mass response to light in the mouse retina, while increasing the postsynaptic retinal and cortical responses amplitude and the phase-locking to stimulus of cortical low frequency and gamma (∼ 25-45 Hz) responses. These findings suggest (12)C ions to interfere with, rather than mimicking the light action on photoreceptors; a parallel action on other retinal structures/mechanisms resulting in cortical activation is conceivable. Electrophysiological visual testing appears applicable to monitor the radiation effects and in designing countermeasures to prevent functional visual impairment during operations in space., (Copyright © 2015. Published by Elsevier Ireland Ltd.)

Strong stimuli may capture attention automatically, suggesting that attentional selection is determined primarily by physical stimulus properties. The mechanisms underlying capture remain controversial, in particular, whether feedforward subcortical processes are its main source. Also, it remains unclear whether only physical stimulus properties determine capture strength. Here, we demonstrate strong capture in the absence of feedforward input to subcortical structures such as the superior colliculus, by using transcranial magnetic stimulation (TMS) over occipital visual cortex as an attention cue. This implies that the feedforward sweep through subcortex is not necessary for capture to occur but rather provides an additional source of capture. Furthermore, seen cues captured attention more strongly than (physically identical) unseen cues, suggesting that the momentary state of the nervous system modulates attentional selection. In summary, we demonstrate the existence of several sources of attentional capture, and that both physical stimulus properties and the state of the nervous system influence capture., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Transcranial magnetic stimulation (TMS) of the occipital cortex is known to induce visual sensations, i.e. phosphenes, which appear as flashes of light in the absence of an external stimulus. Recent studies have shown that TMS can produce phosphenes also when the intraparietal sulcus (IPS) is stimulated. The main question addressed in this paper is whether parietal phosphenes are generated directly by local mechanisms or emerge through indirect activation of other visual areas. Electroencephalographic (EEG) signals were recorded while stimulating left occipital or parietal cortices inducing phosphene perception in healthy participants and in a hemianopic patient who suffered from complete destruction of the early visual cortex of the left hemisphere. Results in healthy participants showed that the onset of phosphene perception induced by occipital TMS correlated with differential cortical activity in temporal sites while the onset of phosphene perception induced by parietal TMS correlated with differential cortical activity in the stimulated parietal site. Moreover, IPS-TMS of the lesioned hemisphere of the hemianopic patient with a complete lesion to V1 showed again that the onset of phosphene perception correlated with differential cortical activity in the stimulated parietal site. The present data seem thus to suggest that temporal and parietal cortices can serve as different local early gatekeepers of perceptual awareness and that activity in the occipital cortex, although being relevant for perception in general, is not part of the neural bases of the perceptual awareness of phosphenes., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Background: Classically, studies adopting non-invasive transcranial electrical stimulation have placed greater importance on the position of the primary "stimulating" electrode than the secondary "reference" electrode. However, recent current density modeling suggests that ascribing a neutral role to the reference electrode may prove an inappropriate oversimplification., Hypothesis: We set out to test the hypothesis that the behavioral effects of transcranial electrical stimulation are critically dependent on the position of the return ("reference") electrode., Methods: We examined the effect of transcranial alternating current stimulation (sinusoidal waveform with no direct current offset at a peak-to-peak amplitude of 2000 μA and a frequency matched to each participant's peak tremor frequency) on physiological tremor in a group of healthy volunteers (N = 12). We implemented a sham-controlled experimental protocol where the position of the stimulating electrode remained fixed, overlying primary motor cortex, whilst the position of the return electrode varied between two cephalic (fronto-orbital and contralateral primary motor cortex) and two extracephalic (ipsilateral and contralateral shoulder) locations. We additionally controlled for the role of phosphenes in influencing motor output by assessing the response of tremor to photic stimulation, through self-reported phosphene ratings., Results: Altering only the position of the return electrode had a profound behavioral effect: only the montage with extracephalic return contralateral to the primary stimulating electrode significantly entrained physiological tremor (15.9% ± 6.1% increase in phase stability, 1 S.E.M.). Photic stimulation also entrained tremor (11.7% ± 5.1% increase in phase stability). Furthermore, the effects of electrical stimulation are distinct from those produced from direct phosphene induction, in that the latter were only seen with the fronto-orbital montage that did not affect the tremor., Conclusion: The behavioral effects of transcranial alternating current stimulation appear to be critically dependent on the position of the reference electrode, highlighting the importance of electrode montage when designing experimental and therapeutic protocols., (Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective: Retinal prosthetic devices aim to restore sight in visually impaired people by means of electrical stimulation of surviving retinal ganglion cells (RGCs). This modelling study aims to demonstrate that RGC inhibition caused by high-intensity cathodic pulses greatly influences their responses to epiretinal electrical stimulation and to investigate the impact of this inhibition on spatial activation profiles as well as their implications for retinal prosthetic device design. Another aim is to take advantage of this inhibition to reduce axonal activation in the nerve fibre layer., Approach: A three-dimensional finite-element model of epiretinal electrical stimulation was utilized to obtain RGC activation and inhibition threshold profiles for a range of parameters., Main Results: RGC activation and inhibition thresholds were highly dependent on cell and stimulus parameters. Activation thresholds were 1.5, 3.4 and 11.3 μA for monopolar electrodes with 5, 20 and 50 μm radii, respectively. Inhibition to activation threshold ratios were mostly within the range 2-10. Inhibition significantly altered spatial patterns of RGC activation. With concentric electrodes and appropriately high levels of stimulus amplitudes, activation of passing axons was greatly reduced., Significance: RGC inhibition significantly impacts their spatial activation profiles, and therefore it most likely influences patterns of perceived phosphenes induced by retinal prosthetic devices. Thus this inhibition should be taken into account in future studies concerning retinal prosthesis development. It might be possible to utilize this inhibitory effect to bypass activation of passing axons and selectively stimulate RGCs near their somas and dendrites to achieve more localized phosphenes.

Objective: No cure currently exists for photoreceptor degenerative diseases, which cause partial or total blindness in millions of people worldwide. Electrical retinal prostheses have been developed by several groups with the goal of restoring vision lost to these diseases, but electrical stimulation has limitations. It excites both somas and axons, activating retinal pathways nonphysiologically, and limits spatial resolution because of current spread. Chemical stimulation of retinal ganglion cells (RGCs) using the neurotransmitter glutamate has been suggested as an alternative to electrical stimulation with some significant advantages. However, sufficient scientific data to support developing a chemical-based retinal prosthesis is lacking. The goal of this study was to investigate the feasibility of a neurotransmitter-based retinal prosthesis and determine therapeutic stimulation parameters., Approach: We injected controlled amounts of glutamate into rat retinas from the epiretinal side ex vivo via micropipettes using a pressure injection system and recorded RGC responses with a multielectrode array. Responsive units were identified using a spike rate threshold of 3 Hz., Main Results: We recorded both somal and axonal units and demonstrated successful glutamatergic stimulation across different RGC subtypes. Analyses show that exogenous glutamate acts on RGC synapses similar to endogenous glutamate and, unlike electrical prostheses, stimulates only RGC somata. The spatial spread of glutamate stimulation was ≈ 290 μm from the injection site, comparable to current electrical prostheses. Further, the glutamate injections produced spatially differential responses in OFF, ON, and ON-OFF RGC subtypes, suggesting that differential stimulation of the OFF and ON systems may be possible. A temporal resolution of 3.2 Hz was obtained, which is a rate suitable for spatial vision., Significance: We provide strong support for the feasibility of an epiretinal neurotransmitter-based retinal prosthesis. Our findings suggest that chemical stimulation of RGCs is a viable alternative to electrical stimulation and could offer distinct advantages such as the selective stimulation of RGC somata.

Objective: We evaluated a novel visual representation for current and near-term prosthetic vision. Augmented depth emphasizes ground obstacles and floor-wall boundaries in a depth-based visual representation. This is achieved by artificially increasing contrast between obstacles and the ground surface via a novel ground plane extraction algorithm specifically designed to preserve low-contrast ground-surface boundaries., Approach: The effectiveness of augmented depth was examined in human mobility trials compared against standard intensity-based (Intensity), depth-based (Depth) and random (Random) visual representations. Eight participants with normal vision used simulated prosthetic vision with 20 phosphenes and eight perceivable brightness levels to traverse a course with randomly placed small and low-contrast obstacles on the ground., Main Results: The number of collisions was significantly reduced using augmented depth, compared with intensity, depth and random representations (48%, 44% and 72% less collisions, respectively)., Significance: These results indicate that augmented depth may enable safe mobility in the presence of low-contrast obstacles with current and near-term implants. This is the first demonstration that an augmentation of the scene ensuring key objects are visible may provide better outcomes for prosthetic vision.

Objective. Stimulation strategies for retinal prostheses predominately seek to directly encode image brightness values rather than edge orientations. Recent work suggests that the generation of oriented elliptical phosphenes may be possible by controlling interactions between neighboring electrodes. Based on this, we propose a novel stimulation strategy for prosthetic vision that extracts edge orientation information from the intensity image and encodes it as oriented elliptical phosphenes. We test the hypothesis that encoding edge orientation via oriented elliptical phosphenes leads to better alphabetic letter recognition than standard intensity-based encoding. Approach. We conduct a psychophysical study with simulated phosphene vision with 12 normal-sighted volunteers. The two stimulation strategies were compared with variations of letter size, electrode drop-out and spatial offsets of phosphenes. Main results. Mean letter recognition accuracy was significantly better with the new proposed stimulation strategy (65%) compared to direct grayscale encoding (47%). All examined parameters-stimulus size, phosphene dropout, and location shift-were found to influence the performance, with significant two-way interactions between phosphene dropout and stimulus size as well as between phosphene dropout and phosphene location shift. The analysis delivers a model of perception performance. Significance. Displaying available directional information to an implant user may improve their visual performance. We present a model for designing a stimulation strategy under the constraints of existing retinal prostheses that can be exploited by retinal implant developers to strategically employ oriented phosphenes.

Background: Electrical brain stimulation can elicit neurosensory side effects that are unrelated to the intended stimulation effects. This presents a challenge when designing studies with blinded control conditions., Objective: The aim of this research was to investigate the role of different transcranial alternating current stimulation (tACS) parameters, i.e. intensity, frequency, and electrode montage, on the probability, duration and intensity of elicited neurosensory side effects., Methods: In a first study, we examined the influence of tACS on sensations of phosphenes, dizziness, pressure, and skin sensation in fifteen healthy subjects, during 8 s of stimulation with different amplitudes (1500 μA, 1000 μA, 500 μA, 250 μA), frequencies (2 Hz, 4 Hz, 8 Hz, 16 Hz, 32 Hz, 64 Hz), and montages (F3/F4, F3/C4, F3/P4, P3/F4, P3/C4, P3/P4). In a second study, ten healthy subjects were exposed to 60 s of tACS (1000 μA, 2 Hz versus 16 Hz, F3/F4 versus P3/P4) and were asked to rate the intensity of sensations every 12 s., Results: The first study showed that all stimulation parameters had an influence on the probability and intensity of sensations. Phosphenes were most likely and strongest for frontal montages and higher frequencies. Dizziness was most likely and strongest for parietal montages and at stimulation frequency of 4 Hz. Skin sensations and pressure was more likely when stimulation was performed across central regions and at posterior montages, respectively. The second study also revealed that the probability and the intensity of sensations were neither modified during more extended periods of stimulation nor affected by carry-over effects., Conclusion: We demonstrated that the strength and the likelihood of sensations elicited by tACS were specifically modulated by the stimulation parameters. The present work may therefore be instrumental in establishing effective blinding conditions for studies with tACS., (Copyright © 2014 Elsevier Inc. All rights reserved.)

One way to study the neural correlates of visual consciousness is to localize the cortical areas whose stimulation generates subjective visual sensations, called phosphenes. While there is support for the view that the stimulation of several different visual areas in the occipital lobe may produce phosphenes, it is not clear what the contribution of each area is. Here, we studied the roles of the primary visual cortex (V1) and the adjacent area V2 in eliciting phosphenes by using functional magnetic resonance imaging-guided transcranial magnetic stimulation (TMS) combined with spherical modeling of the TMS-induced electric field. Reports of the subjective visual features of phosphenes were systematically collected and analyzed. We found that selective stimulation of V1 and V2 are equally capable of generating phosphenes, as demonstrated by comparable phosphene thresholds and similar characteristics of phosphene shape, color, and texture. However, the phosphenes induced by V1 stimulation were systematically perceived as brighter than the phosphenes induced by the stimulation of V2. Thus, these results suggest that V1 and V2 have a similar capability to produce conscious percepts. Nevertheless, V1 and V2 contribute differently to brightness: neural activation originating in V1 generates a more intense sensation of brightness than similar activation originating in V2., (© The Author 2013. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)

Objective: High-frequency repetitive transcranial magnetic stimulation (rTMS) modulates cortical excitability. We investigated its effect on visual evoked potentials (VEPs) in migraine., Methods: Thirty-two headache-free controls (CO), 25 interictal (MINT) and 7 preictal migraineurs (MPRE) remained after exclusions. VEPs to 8' and 65' checks were averaged in six blocks of 100 single responses. VEPs were recorded before, directly after and 25min after 10Hz rTMS. The study was blinded for diagnosis during recording and for diagnosis and block number during analysis. First block amplitudes and habituation (linear amplitude change over blocks) were analysed with repeated measures ANOVA., Results: With 65' checks, N70-P100 habituation was reduced in MINT compared to CO after rTMS (p=0.013). With 8' checks, habituation was reduced in MPRE compared to MINT and CO after rTMS (p<0.016). No effects of rTMS on first block amplitudes were found., Conclusion: RTMS reduced habituation only in migraineurs, indicating increased responsivity to rTMS. The magnocellular visual subsystem may be affected interictally, while the parvocellular system may only be affected preictally., Significance: Migraineurs may have increased responsiveness to rTMS because of a cortical dysfunction that changes before a migraine attack., (Copyright © 2014 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.)

Transcranial magnetic stimulation (TMS) applied over the occipital lobe approximately 100 ms after the onset of a stimulus decreases its visibility if it appears in the location of the phosphene. Because phosphenes can also be elicited by stimulation of the parietal regions, we asked if the same procedure that is used to reduce visibility of stimuli with occipital TMS will lead to decreased stimulus visibility when TMS is applied to parietal regions. TMS was randomly applied at 0-130 ms after the onset of the stimulus in steps of 10 ms in occipital and parietal regions. Participants responded to the orientation of the line stimulus and rated its visibility. We replicate previous reports of phosphenes from both occipital and parietal TMS. As previously reported, we also observed visual suppression around the classical 100 ms window both in the objective line orientation and subjective visibility responses with occipital TMS. Parietal stimulation, on the other hand, did not consistently reduce stimulus visibility in any time window.

Objectives: Behavioural observations provided by the waterfall illusion suggest that motion perception is mediated by a comparison of responsiveness of directional selective neurones. These are proposed to be optimally tuned for motion detection in different directions. Critically however, despite the behavioural observations, direct evidence of this relationship at a cortical level in humans is lacking. By utilising the state dependant properties of transcranial magnetic stimulation (TMS), one can probe the excitability of specific neuronal populations using the perceptual phenomenon of phosphenes., Method: We exposed subjects to unidirectional visual motion adaptation and subsequently simultaneously measured early visual cortex (V1) excitability whilst viewing motion in the adapted and non-adapted direction., Result: Following adaptation, the probability of perceiving a phosphene whilst viewing motion in the adapted direction was diminished reflecting a reduction in V1 excitability. Conversely, V1 excitability was enhanced whilst viewing motion in the opposite direction to that used for adaptation., Conclusion: Our results provide support that in humans a process of reciprocal inhibition between oppositely tuned directionally selective neurones in V1 facilitates motion perception., Significance: This paradigm affords a unique opportunity to investigate changes in cortical excitability following peripheral vestibular disorders., (Copyright © 2013 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.)

Objective: To demonstrate that benign transient focal neurological symptoms represent equivalents of migraine auras without headache., Background: Benign focal neurological symptoms suggesting cerebral dysfunction are common and usually prompt an extensive diagnostic workup, but their etiology is often not elucidated. We hypothesized that benign transient focal neurological symptoms represent equivalents of migraine auras without headache, even in subjects who have never experienced migraine headaches., Methods: We led a cross-sectional study and identified individuals who presented at least 1 episode of unexplained transient focal neurological symptoms suggestive of cerebral dysfunction, but no history of migraine headache, among physicians and inpatients of an academic hospital. Cortical hyperexcitability, assessed by occipital transcranial magnetic stimulation (oTMS), was used as a marker of possible migraine auras without headache., Results: Frequency of transient focal neurological symptoms suggestive of cerebral dysfunction among the physicians who responded was 9% (21/233), vs 0.09% (6/690) of inpatients. Most episodes resembled typical visual migrainous auras. Motor, sensory, and language dysfunction were more common among inpatients than among physicians. oTMS induced phosphenes in 12/16 (75%) subjects and in none of 10 controls., Conclusion: Benign focal neurological symptoms were common in our population and likely represent migraine aura without headache. Non-visual symptoms are less common and lead to medical consultation. oTMS is abnormal in most cases, supporting the diagnosis of migraine aura without headache and helping separate this benign condition from transient ischemic attacks.

A phenomenon characterized by the experience of seeing light without any light actually entering the eye is called phosphenes or photopsias. Phosphenes can occur spontaneously or via induction by external stimuli. Previous reports regarding phosphenes have primarily focused on externally induced phosphenes such as by applying alternating or direct current to the cortex. A few of these reports used functional magnetic resonance (fMRI) to study activations induced by cortical phosphenes. However, there are no fMRI reports on spontaneous phosphenes originating from the retina and the resulting pattern of cortical activations. We performed fMRI during a reversing checkerboard paradigm in three LCA patients who underwent unilateral gene therapy and reported experiencing frequent phosphene on a daily basis. We observed bilateral cortical activation covering the entire visual cortices when patients reported experiencing phosphenes. In contrast, in the absence of phosphenes, activation was regulated by patient's visual ability and demonstrated improved cortical activation due to gene therapy. These fMRI results illustrate the potential impact of phosphene perception on visual function and they may explain some of the variability that clinicians find in visual function testing in retinal degeneration. Although we did not perform correlations between visual function and phosphenes, we hope data presented here raises awareness of this phenomenon and its potential effect on visual function and the implications for clinical testing. We recommend a thorough history for phosphene experiences be taken in patients with retinal disease who are candidates for gene or molecular therapy. Lastly, these data illustrate the potential power of fMRI as an outcome measure of gene therapy and the negative impact phosphenes may have on vision testing. fMRI has proven to be a sensitive, non-invasive, and reproducible test paradigm for these purposes and can complement standard visual function testing.

In this study, we used a simulation of upcoming low-resolution visual neuroprostheses to evaluate the benefit of embedded computer vision techniques in a wayfinding task. We showed that augmenting the classical phosphene rendering with the basic structure of the environment - displaying the ground plane with a different level of brightness - increased both wayfinding performance and cognitive mapping. In spite of the low resolution of current and upcoming visual implants, the improvement of these cognitive functions may already be possible with embedded artificial vision algorithms.

Crossmodal illusions clearly show how perception, rather than being a modular and self-contained function, can be dramatically altered by interactions between senses. Here, we provide evidence for a novel crossmodal "physiological" illusion, showing that sounds can boost visual cortical responses in such a way to give rise to a striking illusory visual percept. In healthy participants, a single-pulse transcranial magnetic stimulation (sTMS) delivered to the occipital cortex evoked a visual percept, i.e., a phosphene. When sTMS is accompanied by two auditory beeps, the second beep induces in neurologically unimpaired participants the perception of an illusory second phosphene, namely the sound-induced phosphene illusion. This perceptual "fission" of a single phosphene, due to multiple beeps, is not matched by a "fusion" of double phosphenes due to a single beep, and it is characterized by an early auditory modulation of the TMS-induced visual responses (~80 ms). Multiple beeps also induce an illusory feeling of multiple TMS pulses on the participants' scalp, consistent with an audio-tactile fission illusion. In conclusion, an auditory stimulation may bring about a phenomenological change in the conscious visual experience produced by the transcranial stimulation of the occipital cortex, which reveals crossmodal binding mechanisms within early stages of visual processing.

Multisensory interactions have been documented within low-level, even primary, cortices and at early post-stimulus latencies. These effects are in turn linked to behavioral and perceptual modulations. In humans, visual cortex excitability, as measured by transcranial magnetic stimulation (TMS) induced phosphenes, can be reliably enhanced by the co-presentation of sounds. This enhancement occurs at pre-perceptual stages and is selective for different types of complex sounds. However, the source(s) of auditory inputs effectuating these excitability changes in primary visual cortex remain disputed. The present study sought to determine if direct connections between low-level auditory cortices and primary visual cortex are mediating these kinds of effects by varying the pitch and bandwidth of the sounds co-presented with single-pulse TMS over the occipital pole. Our results from 10 healthy young adults indicate that both the central frequency and bandwidth of a sound independently affect the excitability of visual cortex during processing stages as early as 30 msec post-sound onset. Such findings are consistent with direct connections mediating early-latency, low-level multisensory interactions within visual cortices., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Objective: Transcranial alternating current stimulation (tACS), which is a novel technique for the manipulation of cortical oscillations, can generate subjective visual sensations (phosphenes). In this work, we computationally investigate the current that reaches the eyes from tACS electrodes in order to show that phosphenes induced by tACS are retinal in origin., Approach: The finite-element method is used for modelling the path of the current in an anatomically realistic model of the head for various electrode montages. The computational results are used for analysing previous experimental data to investigate the sensitivity of the eye to electrical stimulation., Main Results: Depending on the locations of both the stimulating and reference electrodes, a small portion of the stimulation current chooses a path that goes through the eyes. Due to the sensitivity of the retina to electrical stimulation, even distant electrodes can produce a sufficiently strong current at the eyes for inducing retinal phosphenes., Significance: The interference from retinal phosphenes needs to be considered in the design of tACS experiments. The occurrence of phosphenes can be reduced by optimizing the locations of the electrodes, or potentially increasing the number of reference electrodes to two or more. Computational modelling is an effective tool for guiding the electrode positioning.

Approaching or looming sounds (L-sounds) have been shown to selectively increase visual cortex excitability [Romei, V., Murray, M. M., Cappe, C., & Thut, G. Preperceptual and stimulus-selective enhancement of low-level human visual cortex excitability by sounds. Current Biology, 19, 1799-1805, 2009]. These cross-modal effects start at an early, preperceptual stage of sound processing and persist with increasing sound duration. Here, we identified individual factors contributing to cross-modal effects on visual cortex excitability and studied the persistence of effects after sound offset. To this end, we probed the impact of different L-sound velocities on phosphene perception postsound as a function of individual auditory versus visual preference/dominance using single-pulse TMS over the occipital pole. We found that the boosting of phosphene perception by L-sounds continued for several tens of milliseconds after the end of the L-sound and was temporally sensitive to different L-sound profiles (velocities). In addition, we found that this depended on an individual's preferred sensory modality (auditory vs. visual) as determined through a divided attention task (attentional preference), but not on their simple threshold detection level per sensory modality. Whereas individuals with "visual preference" showed enhanced phosphene perception irrespective of L-sound velocity, those with "auditory preference" showed differential peaks in phosphene perception whose delays after sound-offset followed the different L-sound velocity profiles. These novel findings suggest that looming signals modulate visual cortex excitability beyond sound duration possibly to support prompt identification and reaction to potentially dangerous approaching objects. The observed interindividual differences favor the idea that unlike early effects this late L-sound impact on visual cortex excitability is influenced by cross-modal attentional mechanisms rather than low-level sensory processes.

Purpose: We characterized electrically elicited visual evoked potentials (eVEPs) in Argus II retinal implant wearers., Methods: eVEPs were recorded in four subjects, and analyzed by determining amplitude and latency of the first two positive peaks (P1 and P2). Subjects provided subjective feedback by rating the brightness and size of the phosphenes. We established eVEP input-output relationships, eVEP variability between and within subjects, the effect of stimulating different areas of the retina, and the maximal pulse rate to record eVEPs reliably., Results: eVEP waveforms had low signal-to-noise ratios, requiring long recording times and substantial signal processing. Waveforms varied between subjects, but showed good reproducibility and consistent parameter dependence within subjects. P2 amplitude overall was the most robust outcome measure and proved an accurate indicator of subjective threshold. Peak latencies showed small within-subject variability, yet their correlation with stimulus level and subjective rating were more variable than that of peak amplitudes. Pulse rates of up to (2)/3 Hz resulted in reliable eVEP recordings. Perceived phosphene brightness declined over time, as reflected in P1 amplitude, but not in P2 amplitude or peak latencies. Stimulating-electrode location significantly affected P1 and P2 amplitude and latency, but not subjective percepts., Conclusions: While recording times and signal processing are more demanding than for standard visually evoked potential (VEP) recordings, the eVEP has proven to be a reliable tool to verify retinal implant functionality. eVEPs correlated with various stimulus parameters and with perceptual ratings. In view of these findings, eVEPs may become an important tool in functional investigations of retinal prostheses. (ClinicalTrials.gov number NCT00407602.) Dutch Abstract.

The objective is to update and extend previous results of a systematic review of the literature with meta-analysis performed to determine the prevalence of phosphenes and the phosphene threshold (PT) values obtained during single-pulse transcranial magnetic stimulation (TMS) in adults with migraine. Both published and unpublished controlled studies measuring PT by single-pulse TMS in adults with migraine with or without aura (MA, MwA) were systematically reviewed. Prevalence of phosphenes and PT values were assessed calculating mean difference (MD) and odds ratio (OR) with 95 % confidence intervals (CI). Fifteen trials (369 migraine patients and 269 controls), were included. Patients with MA had a statistically significant lower PT compared with controls when a circular coil was used (MD: -22.27, 95 % CI -33.44 to -11.10); with a figure-of-eight coil the difference was not statistically significant. There was a significant higher phosphene prevalence in MA compared with controls (OR: 3.57, 95 % CI 1.16-10.94). No significant differences were found either in phosphene reporting between patients with MwA and controls, or in PT values obtained by figure-of-eight coil in subjects with MwA versus controls. In general, these results slightly support the hypothesis of a primary visual cortex hyper-excitability in MA, providing not enough evidence for MwA. A significant heterogeneity across studies probably reflects relevant clinical and methodological heterogeneity.

Objective: Epiretinal stimulation, which uses an array of electrodes implanted on the inner retinal surface to relay a representation of the visual scene to the neuronal elements of the retina, has seen considerable success. The objective of the present study was to quantify the effects of multi-electrode stimulation on the patterns of neural excitation in a computational model of epiretinal stimulation., Approach: A computational model of retinal ganglion cells was modified to represent the morphology of human retinal ganglion cells and validated against published experimental data. The ganglion cell model was then combined with a model of an axon of the nerve fiber layer to produce a population model of the inner retina. The response of the population of model neurons to epiretinal stimulation with a multi-electrode array was quantified across a range of electrode geometries using a novel means to quantify the model response-the minimum radius circle bounding the activated model neurons as a proxy for the evoked phosphene., Main Results: Multi-electrode stimulation created unique phosphenes, uch that the number of potential phosphenes can far exceed the number of electrode contacts., Significance: The ability to exploit the spatial and temporal interactions of stimulation may be critical to improvements in the performance of epiretinal prostheses.

Objective: Visual prostheses currently in development aim to restore some form of vision to patients suffering from diseases such as age-related macular degeneration and retinitis pigmentosa. Most rely on electrically stimulating inner retinal cells via electrodes implanted on or near the retina, resulting in percepts of light termed 'phosphenes'. Activation of spatially distinct populations of cells in the retina is key for pattern vision to be produced. To achieve this, the electrical stimulation must be localized, activating cells only in the direct vicinity of the stimulating electrode(s). With this goal in mind, a hexagonal return (hexapolar) configuration has been proposed as an alternative to the traditional monopolar or bipolar return configurations for electrically stimulating the retina. This study investigated the efficacy of the hexapolar configuration in localizing the activation of retinal ganglion cells (RGCs), compared to a monopolar configuration., Approach: Patch-clamp electrophysiology was used to measure the activation thresholds of RGCs in whole-mount rabbit retina to monopolar and hexapolar electrical stimulation, applied subretinally., Main Results: Hexapolar activation thresholds for RGCs located outside the hex guard were found to be significantly (>2 fold) higher than those located inside the area of tissue bounded by the hex guard. The hexapolar configuration localized the activation of RGCs more effectively than its monopolar counterpart. Furthermore, no difference in hexapolar thresholds or localization was observed when using cathodic-first versus anodic-first stimulation., Significance: The hexapolar configuration may provide an improved method for electrically stimulating spatially distinct populations of cells in retinal tissue.

Objective: A visual prosthesis based on penetrating electrode stimulation within the optic nerve (ON) is a potential way to restore partial functional vision for blind patients. We investigated the retinotopic organization of ON stimulation and its spatial resolution., Approach: A five-electrode array was inserted perpendicularly into the ON or a single electrode was advanced to different depths within the ON (~1-2 mm behind the eyeball, 13 cats). A sparse noise method was used to map ON electrode position and the visual cortex. Cortical responses were recorded by a 5 × 6 array. The visuotopic correspondence between the retinotopic position of the ON electrode was compared with the visual evoked cortical map and the electrical evoked potentials elicited in response to ON stimulation., Main Results: Electrical stimulation with penetrating ON electrodes elicited cortical responses in visuotopographically corresponding areas of the cortex. Stimulation of the temporal side of the ON elicited cortical responses corresponding to the central visual field. The visual field position shifted from the lower to central visual field as the electrode penetrated through the depth of the ON. A spatial resolution of ~ 2° to 3° within a limited cortical visuotopic representation could be obtained by this approach., Significance: Visuotopic electrical stimulation with a relatively fine spatial resolution can be accomplished using penetrating electrodes implanted at multiple sites and at different depths within the ON just behind the globe. This study also provides useful experimental data for the design of electrode density and the distribution of penetrating ON electrodes for a visual prosthesis.

Background: The current understanding of the mechanisms underlying photosensitivity is still limited, although most studies point to a hyperexcitability of the visual cortex., Methods: Using transcranial magnetic stimulation, we determined the resting motor threshold (rMT) and the phosphene threshold (PT) in 33 patients with IGEs (8 with photosensitivity) compared with 12 healthy controls., Results: Eleven controls (92%) reported phosphenes compared with fifteen (46%) patients with idiopathic generalized epilepsy (p=0.015). Phosphenes were reported more frequently among patients with epilepsy with photosensitivity (87.5%) than in patients with active epilepsy without photosensitivity (30.8%) (p=0.038) and patients with epilepsy in remission without photosensitivity (33.3%) (p=0.054); no differences were found between patients with epilepsy with photosensitivity and controls (p=0.648). Resting motor threshold and phosphene threshold were significantly higher among patients with epilepsy (active epilepsy or epilepsy in remission without photosensitivity) compared to healthy controls (p<0.01). Conversely, patients with active epilepsy and photosensitivity had significantly lower values than controls (p=0.03)., Conclusions: The marked decrease in PT and the high phosphene prevalence in patients with IGE with photosensitivity indicate a regional hyperexcitability of the primary visual cortex. Results of this study also suggest that the PT may serve as a biomarker for excitability in patients with IGE and photosensitivity., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Purpose: The main aim of the study was to determine whether intravenous sedation with midazolam reduces the ability of patients to see during cataract surgery performed under topical anaesthesia. We also sought to determine the effects of sedation on patient's level of disturbance to the microscope light and visualization of surgical instruments and on the overall of experience of the patients during surgery., Methods: A total of 78 patients, aged 40-75 years, were randomly divided into two groups: Group S, (sedation) who received intravenous midazolam 0.015 mg/kg, and Group NS, (no sedation) who did not receive midazolam. Patients with history of anxiety, those with history of intraocular surgery and those with severe chronic obstructive pulmonary disease were excluded. Topical anaesthesia was achieved by the application of 2% xylocaine gel over the conjunctiva. A blinded observer interviewed all the patients 30 min after the surgery using a standard questionnaire., Results: Significant number of patients (25.6%) in Group NS was disturbed a lot because of the microscope light compared to Group S (5.1%), p = 0.021. Also, statistically significant number of patients in Group S (48.7%) compared to Group NS (20.5%) was not sure about the images perceived during surgery and were unable to recollect them after the surgery, p = 0.008, and 12.8% of the patients in Group NS reported the visual experience as frightening compared to 2.6% of patients in Group S, p = 0.239., Conclusion: Our study confirms that intravenous midazolam reduces both the ability to see and recall intraoperative visual images in patients undergoing cataract surgery under topical anaesthesia., (© 2011 The Authors. Acta Ophthalmologica © 2011 Acta Ophthalmologica Scandinavica Foundation.)

Light flashes (phosphenes) are reported by most of the astronauts during spaceflight and patients treated with radiotherapy for brain tumors. They are induced by cosmic ray traversals, but the target area is unknown. With a correlation analysis of the visual sensation and the position of the beam in patients treated with energetic carbon ions for skull base tumors, we demonstrate here that light flashes are elicited only when the energetic particles hit the retina., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Purpose: A visual prosthesis may elicit an irregular phosphene map relative to a regular electrode array. This study used simulated irregular phosphene maps as a way of optimizing the display methods of Chinese characters (CCs) to improve recognition and reading performance., Methods: TWENTY SUBJECTS WITH NORMAL OR CORRECTED SIGHT PARTICIPATED IN TWO EXPERIMENTS (9 FEMALES, 11 MALES, 2030 YEARS OF AGE). EXPERIMENT 1: two character display methods were proposed: selecting phosphenes covered by character strokes on a simulated phosphene array (projection method) and finding the phosphene closest to the expected location in some range of an irregular phosphene array as a substitute (nearest neighbor search [NNS] method). The recognition accuracy of CCs was investigated using six levels for the coverage ratio of stroke and phosphene area and for search range, respectively, for two methods, for several irregularity levels. Experiment 2: reading accuracy (RA) and reading efficiency (RE) were measured using the regular array correspondence and NNS methods., Results: EXPERIMENT 1: projection and NNS methods were significantly affected by coverage ratio or search range. NNS significantly improved CC recognition accuracy to the highest at 81.3 ± 2.7% and 59.1 ± 5.2%, respectively, for different irregularity levels, compared with the projection method. Experiment 2: RA and RE significantly decreased as the distortion level increased; NNS significantly improved RA (from approximately 40% to >80%) and RE (from approximately 13 char/min to >40 char/min) when reading more irregular paragraphs., Conclusions: The performance of CC recognition and paragraph reading when using an irregular phosphene array can be improved through optimizing the display method.

Retinal implants offer prospects of vision restoration for some blind patients by eliciting visual percepts of spots of light called 'phosphenes'. Recently, a mathematical model has been developed that predicts patients' perception of phosphene brightness for current-driven electrical stimulation of the retina. This model is explored for different stimulation parameters on a single electrode, including safety and hardware limitations, to produce phosphenes of specified brightness. We describe a procedure to derive stimulation parameters to account for such constraints, and describe methods to construct optimal stimuli in terms of producing maximal perceived brightness and efficient generation of phosphenes of a given brightness by employing minimal energy. In both cases, it is found that the resulting optimized stimulation waveforms consist of a long stimulation period, and interphase delays between initial and charge-balancing phases.

Purpose: Transcranial alternating current stimulation (tACS) is a non-invasive stimulation technique for shaping neuroplastic processes and possibly entraining ongoing neural oscillations in humans. Despite the growing number of studies using tACS, we know little about the procedural sensations caused by stimulation. In order to fill this gap, we explored the cutaneous sensation and phosphene perception during tACS., Methods: Twenty healthy participants took part in a randomized, single-blinded, sham-controlled study, where volunteers received short duration stimulation at 1.0 mA intensity between 2 to 250 Hz using the standard left motor cortex-contralateral supraorbital montage. We recorded the perception onset latency and the strength of the sensations assessed by visual rating scale as dependent variables., Results: We found that tACS evoked both cutaneous sensation and phosphene perception in a frequency-dependent manner. Our results show that the most perceptible procedural sensations were induced in the beta and gamma frequency range, especially at 20 Hz, whereas minimal procedural sensations were indicated in the ripple range (140 and 250 Hz)., Conclusions: We believe that our results provide a relevant insight into the procedural sensations caused by oscillatory currents, and will offer a basis for developing more sophisticated stimulation protocols and study designs for future investigations.

Efficient visual exploration requires the ability to select possible target locations via spatial attention and to deselect previously inspected locations via inhibition of return (IOR). Although a great deal is known about the effects of spatial attention on processing in visual cortex, much less is known about the effects of IOR on early visual areas. One possibility is that IOR acts in an opposite way to spatial attention, such that, whereas spatial attention enhances target related neural signals in visual cortex, IOR suppress target-related signals. Using a novel dual-coil TMS protocol, we found that IOR reduced the probability of detecting a TMS-induced phosphene in extrastriate cortex (V5). Specifically, a nonpredictive spatial precue presented 500 or 800 msec before stimulation significantly reduced the probability of detecting a phosphene when the precue appeared contralaterally to the site of stimulation (i.e., ipsilaterally to the potential location of the phosphene), compared with ipsilaterally or centrally presented cues. This result demonstrates that IOR facilitates visual exploration by directly affecting the strength of target-related signals in extrastriate visual cortex. This result is consistent with neurophysiological models of attention, which postulate that IOR modulates perception by biasing competition between sensory representations.

Purpose: To evaluate electrically evoked phosphene thresholds (EPTs) in healthy subjects and in patients with retinal disease and to assess repeatability and possible correlations with common ophthalmologic tests., Methods: In all, 117 individuals participated: healthy subjects (n = 20) and patients with retinitis pigmentosa (RP, n = 30), Stargardt's disease (STG, n = 14), retinal artery occlusion (RAO, n = 20), nonarteritic anterior ischemic optic neuropathy (NAION, n = 16), and primary open-angle glaucoma (POAG, n = 17). EPTs were determined at 3, 6, 9, 20, 40, 60, and 80 Hz with 5 + 5-ms biphasic current pulses using DTL electrodes. Subjects were examined twice (test-retest range: 1-6 weeks). An empirical model was developed to describe the current-frequency relationship of EPTs. Visual acuity, visual field (kinetic + static), electrophysiology (RP, RAO, STG: Ganzfeld-electroretinography [ERG]/multifocal-ERG; POAG: pattern-ERG; NAION: VEP), slit-lamp biomicroscopy, fundus examination, and tonometry were assessed., Results: EPTS varied between disease groups (20 HZ: healthy subjects: 0.062 ± 0.038 mA; STG: 0.102 ± 0.097 mA; POAG: 0.127 ± 0.09 mA; NAION: 0.244 ± 0.126 mA; RP: 0.371 ± 0.223 mA; RAO: 0.988 ± 1.142 mA). In all groups EPTs were lowest at 20 Hz. In patients with retinal diseases and across all frequencies EPTs were significantly higher than those in healthy subjects, except in STG at 20 Hz (P = 0.09) and 40 Hz (P = 0.17). Test-retest difference at 20 Hz was 0.006 mA in the healthy group and 0.003-0.04 mA in disease groups., Conclusions: Considering the fast, safe, and reliable practicability of EPT testing, this test might be used more often under clinical circumstances. Determination of EPTs could be potentially useful in elucidation of the progress of ophthalmologic diseases, either in addition to standard clinical assessment or under conditions in which these standard tests cannot be used meaningfully. (ClinicalTrials.gov number, NCT00804102.).

Transcranial electrical stimulation (tES) is a promising therapeutic tool for a range of neurological diseases. Understanding how the small currents used in tES spread across the scalp and penetrate the brain will be important for the rational design of tES therapies. Alternating currents applied transcranially above visual cortex induce the perception of flashes of light (phosphenes). This makes the visual system a useful model to study tES. One hypothesis is that tES generates phosphenes by direct stimulation of the cortex underneath the transcranial electrode. Here, we provide evidence for the alternative hypothesis that phosphenes are generated in the retina by current spread from the occipital electrode. Building on the existing literature, we first confirm that phosphenes are induced at lower currents when electrodes are placed farther away from visual cortex and closer to the eye. Second, we explain the temporal frequency tuning of phosphenes based on the well-known response properties of primate retinal ganglion cells. Third, we show that there is no difference in the time it takes to evoke phosphenes in the retina or by stimulation above visual cortex. Together, these findings suggest that phosphenes induced by tES over visual cortex originate in the retina. From this, we infer that tES currents spread well beyond the area of stimulation and are unlikely to lead to focal neural activation. Novel stimulation protocols that optimize current distributions are needed to overcome these limitations of tES.

An extraordinary variety of experimental (e.g., flicker, magnetic fields) and clinical (epilepsy, migraine) conditions give rise to a surprisingly common set of elementary hallucinations, including spots, geometric patterns, and jagged lines, some of which also have color, depth, motion, and texture. Many of these simple hallucinations fall into a small number of perceptual geometries-the Klüver forms-that (via a nonlinear mapping from retina to cortex) correspond to even simpler sets of oriented stripes of cortical activity (and their superpositions). Other simple hallucinations (phosphenes and fortification auras) are linked to the Klüver forms and to pattern-forming cortical mechanisms by their spatial and temporal scales. The Klüver cortical activity patterns are examples of self-organized pattern formation that arise from nonlinear dynamic interactions between excitatory and inhibitory cortical neurons; with reasonable modifications, this model accounts for a wide range of hallucinated patterns. The Klüver cortical activity patterns are a subset of autonomous spatiotemporal cortical patterns, some of which have been studied with functional imaging techniques. Understanding the interaction of these intrinsic patterns with stimulus-driven cortical activity is an important problem in neuroscience. In line with this, hallucinatory pattern formation interacts with physical stimuli, and many conditions that induce hallucinations show interesting interactions with one another. Both types of interactions are predictable from neural and psychophysical principles such as localized processing, excitatory-inhibitory neural circuits, lateral inhibition, simultaneous and sequential contrast, saccadic suppression, and perceptual opponency. Elementary hallucinations arise from familiar mechanisms stimulated in unusual ways.

Purpose: To investigate the elementary temporal properties of electrically evoked percepts in blind patients chronically implanted with an epiretinal prosthesis., Methods: Nine subjects were presented with isolated stimuli of variable duration and pulse rate. Stimulation amplitude was set to the upper comfortable level and a group of 2 × 2 adjacent electrodes was simultaneously activated. First, subjects were asked to verbally describe their visual perception paying particular attention to the time-course of brightness. Then, in subsequent trials, they described the brightness time dependence using a joystick while auditory feedback of joystick position was provided., Results: All subjects described a bright, well-localized percept at stimulus onset. Only one subject reported such a bright, well-localized visual sensation during an entire 10-second stimulation trial. For the remaining eight subjects, it faded more or less rapidly (in four cases <0.5 second) and was often followed by a percept described as less bright, poorly localized, and having different color. Only initial percepts at stimulation onset seemed bright and localized enough to reconstruct a patterned image. Changing stimulation pulse rate influenced the time course of perception only in some cases but the effect was not systematic., Conclusions: Percepts differed considerably across subjects, probably because of the considerable variations in the progression and remodeling processes associated with the disease. Appropriate coding of a patterned image under such conditions appears challenging. Further research of the underlying mechanisms of visual perception upon electrical stimulation of the retina is required to optimize stimulation paradigms and to better establish patient selection criteria.

The primary visual cortex (V1) has been the target of stimulation in a number of transcranial magnetic stimulation (TMS) studies. In this study, we estimated the actual sites of stimulation by modeling the cortical location of the TMS-induced electric field when participants reported visual phosphenes or scotomas. First, individual retinotopic areas were identified by multifocal functional magnetic resonance imaging (mffMRI). Second, during the TMS stimulation, the cortical stimulation sites were derived from electric field modeling. When an external anatomical landmark for V1 was used (2 cm above inion), the cortical stimulation landed in various functional areas in different individuals, the dorsal V2 being the most affected area at the group level. When V1 was specifically targeted based on the individual mffMRI data, V1 could be selectively stimulated in half of the participants. In the rest, the selective stimulation of V1 was obstructed by the intermediate position of the dorsal V2. We conclude that the selective stimulation of V1 is possible only if V1 happens to be favorably located in the individual anatomy. Selective and successful targeting of TMS pulses to V1 requires MRI-navigated stimulation, selection of participants and coil positions based on detailed retinotopic maps of individual functional anatomy, and computational modeling of the TMS-induced electric field distribution in the visual cortex. It remains to be resolved whether even more selective stimulation of V1 could be achieved by adjusting the coil orientation according to sulcal orientation of the target site., (Copyright © 2011 Wiley Periodicals, Inc.)

Clinical trials have successfully shown that a visual prosthesis can elicit visual perception (phosphenes) in the visual field. Psychophysical studies based on simulated prosthetic vision offer an effective means to evaluate and refine prosthetic vision. We designed three experiments to examine the effect of phosphene luminance, flicker rate, and eccentricity on the ability to estimate simulated phosphene sizes using tactile perception. Thirty subjects participated in the three experiments. There was a linear increase in reported size as visual stimulus size increased. Judgment was significantly affected by stimulus luminance and eccentricity (P < 0.05) but not by flicker rates. Brighter stimuli were perceived as being larger, and the more eccentric the position, the larger the estimated size. These simulation studies, although idealized, suggested that tactile perception is a potential way to estimate phosphene sizes., (© 2011, Copyright the Authors. Artificial Organs © 2011, International Center for Artificial Organs and Transplantation and Wiley Periodicals, Inc.)

Retinal diseases are leading causes of severe vision loss and blindness throughout the world. Visual prosthetics has been demonstrated to be an effective therapy to partially restore vision. Reading is one of the most important functional abilities derived from vision. Therefore, we propose a text image processing strategy for visual prostheses. Text information is firstly detected and recognized from images acquired from a camera, and then recognized text is represented by simplified characters so as to be displayed in low-resolution phosphene vision. In this paper, a BP neural network is created to recognize text information in the images acquired from a high-resolution camera. The recognized text is represented using simplified characters with the resolution of 5×7 pixels. In order to mimic the visual percepts and to evaluate potential benefits of this proposed text processing strategy, a simulation model of prosthetic vision is created based on the reported visual characteristics of elicited phosphenes. Simulated prosthetic vision using 25×25 distorted phosphene array covering four letters shows phosphene letters that can be read readily. Compared to the displayed phosphene letters without this strategy, the contours of all the phosphene letters processed by this strategy were more intact and clearer. These results demonstrate benefits of this proposed strategy which is aimed to provide better reading experience for blind patients using prosthetic vision.

Synesthesia is an unusual condition characterized by the over-binding of two or more features and the concomitant automatic and conscious experience of atypical, ancillary images or perceptions. Previous research suggests that synesthetes display enhanced modality-specific perceptual processing, but it remains unclear whether enhanced processing contributes to conscious awareness of color photisms. In three experiments, we investigated whether grapheme-color synesthesia is characterized by enhanced cortical excitability in primary visual cortex and the role played by this hyperexcitability in the expression of synesthesia. Using transcranial magnetic stimulation, we show that synesthetes display 3-fold lower phosphene thresholds than controls during stimulation of the primary visual cortex. We next used transcranial direct current stimulation to discriminate between two competing hypotheses of the role of hyperexcitability in the expression of synesthesia. We demonstrate that synesthesia can be selectively augmented with cathodal stimulation and attenuated with anodal stimulation of primary visual cortex. A control task revealed that the effect of the brain stimulation was specific to the experience of synesthesia. These results indicate that hyperexcitability acts as a source of noise in visual cortex that influences the availability of the neuronal signals underlying conscious awareness of synesthetic photisms., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Background: The aetiology of visual hallucinations is poorly understood in dementia with Lewy bodies. Pathological alterations in visual cortical excitability may be one contributory mechanism., Aims: To determine visual cortical excitability in people with dementia with Lewy bodies compared with aged-matched controls and also the relationship between visual cortical excitability and visual hallucinations in dementia with Lewy bodies., Method: Visual cortical excitability was determined by using transcranial magnetic stimulation (TMS) applied to the occiput to elicit phosphenes (transient subjective visual responses) in 21 patients with dementia with Lewy bodies and 19 age-matched controls., Results: Phosphene parameters were similar between both groups. However, in the patients with dementia with Lewy bodies, TMS measures of visual cortical excitability correlated strongly with the severity of visual hallucinations (P = 0.005). Six patients with dementia with Lewy bodies experienced visual hallucination-like phosphenes (for example, seeing people or figures on stimulation) compared with none of the controls (P = 0.02)., Conclusions: Increased visual cortical excitability in dementia with Lewy bodies does not appear to explain visual hallucinations but it may be a marker for their severity.

Objective: To investigate test-retest reliability of visual cortical excitatory and inhibitory phenomena., Methods: Transcranial magnetic stimulation (TMS) was applied over occipital cortex twice in 22 healthy young adults with at least a one-month interval between both measurements. The test-retest reliability of the phosphenes and TMS-induced suppression of visual perception was assessed using correlation and calculation of the repeatability coefficient., Results: Both analyses revealed a high reliability for phosphenes but not for the suppression of visual perception., Conclusions: It seems likely that the phosphenes may be better used than the TMS-induced suppression of visual perception in experiments which need repeated measurements (e.g., longitudinal studies or studies with pharmacological and non-pharmacological interventions)., Significance: The study demonstrates a rather limited value of the TMS-induced suppression of visual perception for studies with repeated measurements., (Copyright © 2011 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.)

The adult visual cortex maintains a substantial potential for plasticity in response to a change in visual input. For instance, transcranial magnetic stimulation (TMS) studies have shown that binocular deprivation (BD) increases the cortical excitability for inducing phosphenes with TMS. Here, we employed TMS to trace plastic changes in adult visual cortex before, during, and after 48 h of monocular deprivation (MD) of the right dominant eye. In healthy adult volunteers, MD-induced changes in visual cortex excitability were probed with paired-pulse TMS applied to the left and right occipital cortex. Stimulus-response curves were constructed by recording the intensity of the reported phosphenes evoked in the contralateral visual field at range of TMS intensities. Phosphene measurements revealed that MD produced a rapid and robust decrease in cortical excitability relative to a control condition without MD. The cortical excitability returned to preinterventional baseline levels within 3 h after the end of MD. The results show that in contrast to the excitability increase in response to BD, MD acutely triggers a reversible decrease in visual cortical excitability. This shows that the pattern of visual deprivation has a substantial impact on experience-dependent plasticity of the human visual cortex.

Objectives: The effects of visual cortical transcranial magnetic stimulation (TMS) depends upon the initial state of the stimulated region. Thus TMS perceptually facilitates the attributes encoded by adapted neuronal populations. These reports however, relied upon subjects' description of phosphene qualia and were not quantified. We aimed to: (1) quantify the effect of visual motion adaptation on cortical excitability; (2) assess whether the effect on neuronal excitability was limited to the neuronal population undergoing adaptation or whether there was a generalised modulation of visual cortical excitability., Methods: Visual motion adaptation was induced using a random dot kinematogram display. The frequency of induced phosphenes, using baseline threshold TMS intensity, was used to probe visual cortical excitability., Results: Adaptation to visual motion increased the frequency of V5/MT-stimulated phosphene reports. The effect was only observed when the adapting stimulus and the phosphene spatially overlapped., Conclusions: Neuronal adaptation increases the susceptibility to threshold intensity TMS-induced facilitation of neuronal activation., Significance: Our data imply that the process of neuronal adaption is not synonymous with down-modulation of neuronal excitability depends upon the relative intensity of the stimulus probing neuronal function., (Copyright © 2011 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.)

We present a model for flicker phosphenes, the spontaneous appearance of geometric patterns in the visual field when a subject is exposed to diffuse flickering light. We suggest that the phenomenon results from interaction of cortical lateral inhibition with resonant periodic stimuli. We find that the best temporal frequency for eliciting phosphenes is a multiple of intrinsic (damped) oscillatory rhythms in the cortex. We show how both the quantitative and qualitative aspects of the patterns change with frequency of stimulation and provide an explanation for these differences. We use Floquet theory combined with the theory of pattern formation to derive the parameter regimes where the phosphenes occur. We use symmetric bifurcation theory to show why low frequency flicker should produce hexagonal patterns while high frequency produces pinwheels, targets, and spirals.

The response to stimulating the visual cortex with transcranial magnetic stimulation (TMS) depends on its initial activation state, for example, visual motion adaptation biases perceived TMS-induced phosphene characteristics (e.g., color). We quantified this state dependence by assessing the probability of reporting a phosphene (P(λ) ) with "threshold" TMS (i.e., the TMS intensity producing P(λ) = 0.5 at baseline) following visual motion adaptation to a random dot motion display. Postadaptation, P(λ) was increased, and this effect was confined to the adapted neuronal population. We then adapted subjects using a population of moving dots of fixed average motion direction with standard deviations (SD) ranging from 1° to 128° (SD fixed for a given trial). P(λ) was significantly increased at all dot motion SDs except SD = 1°. Neuronal adaptation increases the susceptibility of the neuronal population to activation by threshold intensity TMS. Thus the process of neuronal adaption is not necessarily synonymous with a downmodulation of neuronal excitability., (© 2011 New York Academy of Sciences.)