Dynamic Stimulation of Visual Cortex Produces Form Vision in Sighted and Blind Humans.

A visual cortical prosthesis (VCP) has long been proposed as a strategy for restoring useful vision to the blind, under the assumption that visual percepts of small spots of light produced with electrical stimulation of visual cortex (phosphenes) will combine into coherent percepts of visual forms, like pixels on a video screen. We tested an alternative strategy in which shapes were traced on the surface of visual cortex by stimulating electrodes in dynamic sequence. In both sighted and blind participants, dynamic stimulation enabled accurate recognition of letter shapes predicted by the brain's spatial map of the visual world. Forms were presented and recognized rapidly by blind participants, up to 86 forms per minute. These findings demonstrate that a brain prosthetic can produce coherent percepts of visual forms.

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."

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.

Pre-processing visual scenes for retinal prosthesis systems: A comprehensive review.

BACKGROUND: Retinal prostheses offer hope for individuals with degenerative retinal diseases by stimulating the remaining retinal cells to partially restore their vision. This review delves into the current advancements in retinal prosthesis technology, with a special emphasis on the pivotal role that image processing and machine learning techniques play in this evolution. METHODS: We provide a comprehensive analysis of the existing implantable devices and optogenetic strategies, delineating their advantages, limitations, and challenges in addressing complex visual tasks. The review extends to various image processing algorithms and deep learning architectures that have been implemented to enhance the functionality of retinal prosthetic devices. We also illustrate the testing results by demonstrating the clinical trials or using Simulated Prosthetic Vision (SPV) through phosphene simulations, which is a critical aspect of simulating visual perception for retinal prosthesis users. RESULTS: Our review highlights the significant progress in retinal prosthesis technology, particularly its capacity to augment visual perception among the visually impaired. It discusses the integration between image processing and deep learning, illustrating their impact on individual interactions and navigations within the environment through applying clinical trials and also illustrating the limitations of some techniques to be used with current devices, as some approaches only use simulation even on sighted-normal individuals or rely on qualitative analysis, where some consider realistic perception models and others do not. CONCLUSION: This interdisciplinary field holds promise for the future of retinal prostheses, with the potential to significantly enhance the quality of life for individuals with retinal prostheses. Future research directions should pivot towards optimizing phosphene simulations for SPV approaches, considering the distorted and confusing nature of phosphene perception, thereby enriching the visual perception provided by these prosthetic devices. This endeavor will not only improve navigational independence but also facilitate a more immersive interaction with the environment.

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.

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.

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.

Real-world indoor mobility with simulated prosthetic vision: The benefits and feasibility of contour-based scene simplification at different phosphene resolutions.

Neuroprosthetic implants are a promising technology for restoring some form of vision in people with visual impairments via electrical neurostimulation in the visual pathway. Although an artificially generated prosthetic percept is relatively limited compared with normal vision, it may provide some elementary perception of the surroundings, re-enabling daily living functionality. For mobility in particular, various studies have investigated the benefits of visual neuroprosthetics in a simulated prosthetic vision paradigm with varying outcomes. The previous literature suggests that scene simplification via image processing, and particularly contour extraction, may potentially improve the mobility performance in a virtual environment. In the current simulation study with sighted participants, we explore both the theoretically attainable benefits of strict scene simplification in an indoor environment by controlling the environmental complexity, as well as the practically achieved improvement with a deep learning-based surface boundary detection implementation compared with traditional edge detection. A simulated electrode resolution of 26 × 26 was found to provide sufficient information for mobility in a simple environment. Our results suggest that, for a lower number of implanted electrodes, the removal of background textures and within-surface gradients may be beneficial in theory. However, the deep learning-based implementation for surface boundary detection did not improve mobility performance in the current study. Furthermore, our findings indicate that, for a greater number of electrodes, the removal of within-surface gradients and background textures may deteriorate, rather than improve, mobility. Therefore, finding a balanced amount of scene simplification requires a careful tradeoff between informativity and interpretability that may depend on the number of implanted electrodes.

End-to-end optimization of prosthetic vision.

Neural prosthetics may provide a promising solution to restore visual perception in some forms of blindness. The restored prosthetic percept is rudimentary compared to normal vision and can be optimized with a variety of image preprocessing techniques to maximize relevant information transfer. Extracting the most useful features from a visual scene is a nontrivial task and optimal preprocessing choices strongly depend on the context. Despite rapid advancements in deep learning, research currently faces a difficult challenge in finding a general and automated preprocessing strategy that can be tailored to specific tasks or user requirements. In this paper, we present a novel deep learning approach that explicitly addresses this issue by optimizing the entire process of phosphene generation in an end-to-end fashion. The proposed model is based on a deep auto-encoder architecture and includes a highly adjustable simulation module of prosthetic vision. In computational validation experiments, we show that such an approach is able to automatically find a task-specific stimulation protocol. The results of these proof-of-principle experiments illustrate the potential of end-to-end optimization for prosthetic vision. The presented approach is highly modular and our approach could be extended to automated dynamic optimization of prosthetic vision for everyday tasks, given any specific constraints, accommodating individual requirements of the end-user.

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.

Occipital alpha-TMS causally modulates temporal order judgements: Evidence for discrete temporal windows in vision.

Recent advances in neuroscience have challenged the view of conscious visual perception as a continuous process. Behavioral performance, reaction times and some visual illusions all undergo periodic fluctuations that can be traced back to oscillatory activity in the brain. These findings have given rise to the idea of a discrete sampling mechanism in the visual system. In this study we seek to investigate the causal relationship between occipital alpha oscillations and Temporal Order Judgements using neural entrainment via rhythmic TMS in 18 human subjects (9 females). We find that certain phases of the entrained oscillation facilitate temporal order perception of two visual stimuli, whereas others hinder it. Our findings support the idea that the visual system periodically compresses information into discrete packages within which temporal order information is lost. SIGNIFICANCE STATEMENT: Neural entrainment via TMS serves as a valuable tool to interfere with cortical rhythms and observe changes in perception. Here, using α-rhythmic TMS-pulses, we demonstrate the effect of the phase of entrained oscillations on performance in a temporal order judgment task. In extension of previous work, we 1. causally influenced brain rhythms far more directly using TMS, and 2. showed that previous results on discrete perception cannot simply be explained by rhythmic fluctuations in visibility. Our findings support the idea that the temporal organization of visual processing is discrete rather than continuous, and is causally modulated by cortical rhythms. To our knowledge, this is the first study providing causal evidence via TMS for an endogenous periodic modulation of time perception.

Restoring Color Perception to the Blind: An Electrical Stimulation Strategy of Retina in Patients with End-stage Retinitis Pigmentosa.

PURPOSE: Bioelectronic retinal prostheses that stimulate the remaining inner retinal neurons, bypassing degenerated photoreceptors, have been demonstrated to restore some vision in patients blinded by retinitis pigmentosa (RP). These implants encode luminance of the visual scene into electrical stimulation, however, leaving out chromatic information. Yet color plays an important role in visual processing when it comes to recognizing objects and orienting to the environment, especially at low spatial resolution as generated by current retinal prostheses. In this study, we tested the feasibility of partially restoring color perception in blind RP patients, with the aim to provide chromatic information as an extra visual cue. DESIGN: Case series. PARTICIPANTS: Seven subjects blinded by advanced RP and monocularly fitted with an epiretinal prosthesis. METHODS: Frequency-modulated electrical stimulation of retina was tested. Phosphene brightness was controlled by amplitude tuning, and color perception was acquired using the Red, Yellow, Green, and Blue (RYGB) hue and saturation scaling model. MAIN OUTCOME MEASURES: Brightness and color of the electrically elicited visual perception reported by the subjects. RESULTS: Within the tested parameter space, 5 of 7 subjects perceived chromatic colors along or nearby the blue-yellow axis in color space. Aggregate data obtained from 20 electrodes of the 5 subjects show that an increase of the stimulation frequency from 6 to 120 Hz shifted color perception toward blue/purple despite a significant inter-subject variation in the transition frequency. The correlation between frequency and blue-yellow perception exhibited a good level of consistency over time and spatially matched multi-color perception was possible with simultaneous stimulation of paired electrodes. No obvious correlation was found between blue sensations and array placement or status of visual impairment. CONCLUSIONS: These findings present a strategy for the generation and control of color perception along the blue-yellow axis in blind patients with RP by electrically stimulating the retina. It could transform the current prosthetic vision landscape by leading in a new direction beyond the efforts to improve the visual acuity. This study also offers new insights into the response of our visual system to electrical stimuli in the photoreceptor-less retina that warrant further mechanistic investigation.

Patient-detectable responsive neurostimulation as a seizure warning system.

Many people with epilepsy are not aware of their seizures or do not have reliable auras. The responsive neurostimulation system (RNS) delivers stimulation triggered by intracranial epileptiform activity. If an epileptiform pattern continues, the RNS repeats stimulation up to five times per event. The RNS can cause acute stimulation-related symptoms that can be avoided by reducing stimulation. Because each of the five therapies can be programmed independently, it may be possible to program the latter therapies to induce a seizure warning. The goal of this study was to determine what proportion of patients could have tolerable symptoms safely elicited by stimulation, ultimately for the purpose of subjective seizure recognition. Of 18 patients, 12 (67%) had induced symptoms, which were tolerable in 11. Phosphenes were most common. We also present one patient in whom the fifth therapy was set to induce a symptom for early recognition and treatment of clusters of focal impaired awareness seizures, which were previously unrecognized and had led to days of disabling cognitive impairment. This protocol prevented disabling clusters successfully for several years. The findings suggest the RNS can provide a seizure warning, potentially improving safety and quality of life, and leading to prevention of clinical seizures or clusters in select patients.

Retinal and Cortical Contributions to Phosphenes During Transcranial Electrical Current Stimulation.

It is generally believed that the phosphenes induced by transcranial electric current stimulation (tECS) are a product of retinal activation, even when electrode placement is directly over the primary visual cortex. However, the origins of these tECS-induced phosphenes have not yet been conclusively determined. In this study, phosphene detection thresholds using an FPz-Oz montage were compared with those from (i) an Oz-Cz montage to determine whether prefrontal regions, such as the retina, contribute to phosphenes and (ii) an FPz-Cz montage to determine whether the visual cortex in the occipital lobe contributes to phosphenes. Twenty-two participants received transcranial current stimulation with each of these montages (as well as a T3-T4 montage included for exploratory purposes) at 6, 10, 16, 20, 24, 28, and 32 Hz. To estimate differences in current density at the retina and occipital lobe across montages, modeling of current density at phosphene thresholds was measured across 20 head models. Consistent with the proposal that tECS-induced phosphenes are generated in the retina, increasing current density near the retina (FPz-Oz relative to Oz-Cz montage) reduced phosphene thresholds. However, increasing current density near the occipital cortex (FPz-Oz relative to FPz-Cz montage) also reduced phosphene thresholds while also requiring less current density at the retina according to the modeling estimates. This suggests that tECS of this occipital cortex also contributed to phosphene perception. © 2020 Bioelectromagnetics Society.

Radiation Force as a Physical Mechanism for Ultrasonic Neurostimulation of the Ex Vivo Retina.

Focused ultrasound has been shown to be effective at stimulating neurons in many animal models, both in vivo and ex vivo Ultrasonic neuromodulation is the only noninvasive method of stimulation that could reach deep in the brain with high spatial-temporal resolution, and thus has potential for use in clinical applications and basic studies of the nervous system. Understanding the physical mechanism by which energy in a high acoustic frequency wave is delivered to stimulate neurons will be important to optimize this technology. We imaged the isolated salamander retina of either sex during ultrasonic stimuli that drive ganglion cell activity and observed micron scale displacements, consistent with radiation force, the nonlinear delivery of momentum by a propagating wave. We recorded ganglion cell spiking activity and changed the acoustic carrier frequency across a broad range (0.5-43 MHz), finding that increased stimulation occurs at higher acoustic frequencies, ruling out cavitation as an alternative possible mechanism. A quantitative radiation force model can explain retinal responses and could potentially explain previous in vivo results in the mouse, suggesting a new hypothesis to be tested in vivo Finally, we found that neural activity was strongly modulated by the distance between the transducer and the electrode array showing the influence of standing waves on the response. We conclude that radiation force is the dominant physical mechanism underlying ultrasonic neurostimulation in the ex vivo retina and propose that the control of standing waves is a new potential method to modulate these effects.SIGNIFICANCE STATEMENT Ultrasonic neurostimulation is a promising noninvasive technology that has potential for both basic research and clinical applications. The mechanisms of ultrasonic neurostimulation are unknown, making it difficult to optimize in any given application. We studied the physical mechanism by which ultrasound is converted into an effective energy form to cause neurostimulation in the retina and find that ultrasound acts via radiation force leading to a mechanical displacement of tissue. We further show that standing waves have a strong modulatory effect on activity. Our quantitative model by which ultrasound generates radiation force and leads to neural activity will be important in optimizing ultrasonic neurostimulation across a wide range of applications.

Theta Phase-dependent Modulation of Perception by Concurrent Transcranial Alternating Current Stimulation and Periodic Visual Stimulation.

Sensory perception can be modulated by the phase of neural oscillations, especially in the theta and alpha ranges. Oscillatory activity in the visual cortex can be entrained by transcranial alternating current stimulation (tACS) as well as periodic visual stimulation (i.e., flicker). Combined tACS and visual flicker stimulation modulates BOLD response, and concurrent 4-Hz auditory click train, and tACS modulate auditory perception in a phase-dependent way. In this study, we investigated whether phase synchrony between concurrent tACS and periodic visual stimulation (i.e., flicker) can modulate performance on a visual matching task. Participants completed a visual matching task on a flickering visual stimulus while receiving either in-phase (0°) or asynchronous (180°, 90°, or 270°) tACS at alpha or theta frequency. Stimulation was applied over either occipital cortex or dorsolateral pFC. Visual performance was significantly better during theta frequency tACS over the visual cortex when it was in-phase (0°) with visual stimulus flicker, compared with antiphase (180°). This effect did not appear with alpha frequency flicker or with dorsolateral pFC stimulation. Furthermore, a control sham group showed no effect. There were no significant performance differences among the asynchronous (180°, 90°, and 270°) phase conditions. Extending previous studies on visual and auditory perception, our results support a crucial role of oscillatory phase in sensory perception and demonstrate a behaviorally relevant combination of visual flicker and tACS. The spatial and frequency specificity of our results have implications for research on the functional organization of perception.

The Clinical Characteristics and Neurophysiological Assessments of the Occipital Cortex in Visual Snow Syndrome With or Without Migraine.

OBJECTIVE: Visual snow syndrome (VS) is mainly characterized by flickering, little dots in both visual fields. The recognition of the clinical entity of VS has been increasing recently. Diagnosis is based on patient reports and not better accounted for by another diagnosis. BACKGROUND: The exact pathophysiology of this syndrome is still unknown. In this study, our aim was to investigate the role of neurophysiological assessments of the occipital cortex in VS patients with (VSm ) or without migraine (VSwom ) and the healthy control (HC). METHODS: To assess the occipital cortex hyperexcitability, we conducted a prospective, observational study to investigate the habituation/potentiation response by repetitive pattern reversal visual evoked potentials (rVEP) and examined the phosphene thresholds (PT) by transcranial magnetic stimulation in VS patients with or without migraine who were admitted to our tertiary headache clinic and the healthy control. RESULTS: Twenty-nine volunteers were recruited. The VSm (n = 10), the VSwom (n = 7), and the HC group (n = 12) did not differ demographically. Flickering and floaters were reported in all VS patients and flickering in the dark was the most distressing symptomatology in both VS groups. Higher VAS scores for palinopsia (trailing), photophobia, and concentration difficulty were more frequently self-reported by VSm patients. The HC demonstrated habituation; however, there was loss of habituation response and decreased PTs in both groups of VS patients. The N1P1 VEP amplitude ratios of the 10th/1st block from right and left eye stimulation disclosed higher values (lack of habituation) in VSm (1.04 ± 0.2 and 1.06 ± 0.2) and the VSwom (1.05 ± 0.2 and 0.96 ± 0.08) patients compared to the healthy control (0.75 ± 0.1 and 0.79 ± 0.1), P = .002 from right eye and P = .003 from left eye. In the post hoc analysis the VS patients did not differ according to the presence of migraine from right or left eye stimulations (both P > .999). The left occipital cortex PTs were lower in VSm (58.00 ± 6.60) and VSwom (62.14 ± 11.53) and higher in the HC (71.33 ± 5.56) P = .009. In the post hoc analysis the VS patients did not differ according to the presence of migraine (P > .999). The right occipital cortex PTs were lower in VSm (60.30 ± 8.15) and VSwom (62.00 ± 10.95), higher in the HC (69.67 ± 8.04); however, statistically, groups did not differ (P = .087). CONCLUSIONS: The loss of habituation and lower threshold for occipital cortex excitability were demonstrated electrophysiologically in VS patients. While statistically significant loss of habituation was seen in both VS patients (with or without migraine) in the right eye, statistically significant loss of habituation in the left eye and decreased threshold of left occipital cortex excitability was seen in visual snow with migraine patients. These findings may provide new insights on "visual snow" pathophysiology and serve as an objective and quantitative assessment tool in VS patients.

Perceptual and Physiological Consequences of Dark Adaptation: A TMS-EEG Study.

Existing literature on sensory deprivation suggests that short-lasting periods of dark adaptation (DA) can cause changes in visual cortex excitability. DA cortical effects have previously been assessed through phosphene perception, i.e., the ability to report visual sensations when a transcranial magnetic stimulation (TMS) pulse is delivered over the visual cortex. However, phosphenes represent an indirect measure of visual cortical excitability which relies on a subjective report. Here, we aimed at overcoming this limitation by assessing visual cortical excitability by combining subjective (i.e., TMS-induced phosphenes) and objective (i.e., TMS-evoked potentials - TEPs) measurements in a TMS-EEG protocol after 30 min of DA. DA effects were compared to a control condition, entailing 30 min of controlled light exposure. TMS was applied at 11 intensities in order to estimate the psychometric function of phosphene report and explore the relationship between TEPs and TMS intensity. Compared to light adaptation, after DA the slope of the psychometric function was significantly steeper, and the amplitude of a TEP component (P60) was lower, only for high TMS intensities. The perceptual threshold was not affected by DA. These results support the idea that DA leads to a change in the excitability of the visual cortex, accompanied by a behavioral modification of visual perception. Furthermore, this study provides a first valuable description of the relationship between TMS intensity and visual TEPs.

Frequency-dependent and montage-based differences in phosphene perception thresholds via transcranial alternating current stimulation.

It is well known that applying transcranial alternating current stimulation (tACS) to the scalp can generate artefactual visual perceptions of flashing or shimmering light known as phosphenes. The thresholds for generating these phosphenes have been used by international standards bodies to provide conservative estimates of the field strength required to interfere with human neural functioning and set safety limits accordingly. However, the precise relationship between electric currents and phosphene perception thresholds remains uncertain. The present study used tACS to systematically investigate the effects of the location and the frequency of stimulation on phosphene perception thresholds. These thresholds were obtained from 24 participants using a within-subject design as a function of scalp stimulation sites (FPz-Cz versus Oz-Cz) and stimulation frequency (2-30 Hz in steps of 2 Hz). Phosphene perception thresholds were consistently lower for FPz-Cz stimulation, and regardless of tACS location were lowest for 16 Hz stimulation. Threshold variation between participants was very small, which is meaningful when setting standards based on phosphenes. Bioelectromagnetics. 2019;40:365-374. © 2019 Bioelectromagnetics Society.

Migraine-linked characteristics of transcranial magnetic stimulation-induced phosphenes.

Transcranial magnetic stimulation is used to explore visual cortex hyperexcitability in migraine. We hypothesized that the phosphene threshold in subjects suffering from migraines with and without aura would be lower than in controls, and this phenomenon could be linked to higher pain and disability levels. We also implied that subjects with lower phosphene threshold could see more phosphenes of different colors and shapes. Our primary objective was to compare the phosphene threshold between migraine without aura, migraine with aura, and control groups and investigate which factors contribute to different phosphene parameters in migraineurs. Secondary objectives were to compare color, shape, and number of phosphenes between groups and assess pain and disability level correlation with the phosphene characteristics. Phosphene threshold in migraine without aura, migraine with aura, and control groups were 68 ± 9.5% vs. 75 ± 12%, vs. 80 ± 11%, respectively. Other phosphene parameters (number, color and shape) did not differ between groups. Average pain level during the attack did not correlate with phosphene threshold significantly, though the non-significant trend for negative correlation of migraine disability assessment scale score and a phosphene threshold has been found the higher was migraine disability assessment scale value, the lower was phosphene threshold (ß = -0.255; P = 0.139). Other variables: gender, age, migraine subtype, migraine duration and use of hormone contraceptives - were not related to the phosphene threshold value. Our study provides additional data on visual cortex hyperexcitability in migraineurs, regarding transcranial magnetic stimulation with a figure-of-eight coil. Visual cortex excitability might be linked to higher disability.