Working memory enhancement using real-time phase-tuned transcranial alternating current stimulation.

BACKGROUND: Prior work has shown that transcranial alternating current stimulation (tACS) of parietooccipital alpha oscillations (8-14 Hz) can modulate working memory (WM) performance as a function of the phase lag to endogenous oscillations. However, leveraging this effect using real-time phase-tuned tACS has not been feasible so far due to stimulation artifacts preventing continuous phase tracking. OBJECTIVES AND HYPOTHESIS: We aimed to develop a system that tracks and adapts the phase lag between tACS and ongoing parietooccipital alpha oscillations in real-time. We hypothesized that such real-time phase-tuned tACS enhances working memory performance, depending on the phase lag. METHODS: We developed real-time phase-tuned closed-loop amplitude-modulated tACS (CLAM-tACS) targeting parietooccipital alpha oscillations. CLAM-tACS was applied at six different phase lags relative to ongoing alpha oscillations while participants (N = 21) performed a working memory task. To exclude that behavioral effects of CLAM-tACS were mediated by other factors such as sensory co-stimulation, a second group of participants (N = 25) received equivalent stimulation of the forehead. RESULTS: WM accuracy improved in a phase lag dependent manner (p = 0.0350) in the group receiving parietooccipital stimulation, with the strongest enhancement observed at 330° phase lag between tACS and ongoing alpha oscillations (p = 0.00273, d = 0.976). Moreover, across participants, modulation of frontoparietal alpha oscillations correlated both in amplitude (p = 0.0248) and phase (p = 0.0270) with the modulation of WM accuracy. No such effects were observed in the control group receiving frontal stimulation. CONCLUSIONS: Our results demonstrate the feasibility and efficacy of real-time phase-tuned CLAM-tACS in modulating both brain activity and behavior, thereby paving the way for further investigation into brain-behavior relationships and the exploration of innovative therapeutic applications.

Probing sustained attention and fatigue across the lifespan.

Trait fatigues reflects tiredness that persists throughout a prolonged period, whereas state fatigue is a short-term reaction to intense or prolonged effort. We investigated the impact of sustained attention (using the SART) on both trait and state fatigue levels in the general population. An online version of the SART was undertaken by 115 participants, stratified across the whole adult lifespan. While pre-task trait fatigue was a strong indicator of the initial state fatigue levels, undergoing the task itself induced an increase in reported subjective state fatigue, and an accompanying reduction in subjective energy rating. Consistent with this finding, greater subjective state fatigue levels were associated with reduced accuracy. In addition, age was the best predictor of inter-participant accuracy (the older the participants, the greater the accuracy), and learning (i.e., task duration reducing reaction times). Moreover, a ceiling effect occurred where participants with higher trait fatigue did not experience greater state fatigue changes relative to those with low trait scores. In summary, we found improved accuracy in older adults, as well as a tight coupling between state fatigue and SART performance decline (in an online environment). The findings warrant further investigation into fatigue as a dynamic, task-dependent state and into SART performance as an objective measure and inducer of fatigue.

Transcranial magnetic stimulation effects support an oscillatory model of ERP genesis.

Whether prestimulus oscillatory brain activity contributes to the generation of post-stimulus-evoked neural responses has long been debated, but findings remain inconclusive. We first investigated the hypothesized relationship via EEG recordings during a perceptual task with this correlational evidence causally probed subsequently by means of online rhythmic transcranial magnetic stimulation. Both approaches revealed a close link between prestimulus individual alpha frequency (IAF) and P1 latency, with faster IAF being related to shorter latencies, best explained via phase-reset mechanisms. Moreover, prestimulus alpha amplitude predicted P3 size, best explained via additive (correlational and causal evidence) and baseline shift mechanisms (correlational evidence), each with distinct prestimulus alpha contributors. Finally, in terms of performance, faster prestimulus IAF and shorter P1 latencies were both associated with higher task accuracy, while lower prestimulus alpha amplitudes and higher P3 amplitudes were associated with higher confidence ratings. Our results are in favor of the oscillatory model of ERP genesis and modulation, shedding new light on the mechanistic relationship between prestimulus oscillations and functionally relevant evoked components.

Developmental changes in individual alpha frequency: Recording EEG data during public engagement events.

Statistical power in cognitive neuroimaging experiments is often very low. Low sample size can reduce the likelihood of detecting real effects (false negatives) and increase the risk of detecting non-existing effects by chance (false positives). Here, we document our experience of leveraging a relatively unexplored method of collecting a large sample size for simple electroencephalography (EEG) studies: by recording EEG in the community during public engagement and outreach events. We collected data from 346 participants (189 females, age range 6-76 years) over 6 days, totalling 29 hours, at local science festivals. Alpha activity (6-15 Hz) was filtered from 30 seconds of signal, recorded from a single electrode placed between the occipital midline (Oz) and inion (Iz) while the participants rested with their eyes closed. A total of 289 good-quality datasets were obtained. Using this community-based approach, we were able to replicate controlled, lab-based findings: individual alpha frequency (IAF) increased during childhood, reaching a peak frequency of 10.28 Hz at 28.1 years old, and slowed again in middle and older age. Total alpha power decreased linearly, but the aperiodic-adjusted alpha power did not change over the lifespan. Aperiodic slopes and intercepts were highest in the youngest participants. There were no associations between these EEG indexes and self-reported fatigue, measured by the Multidimensional Fatigue Inventory. Finally, we present a set of important considerations for researchers who wish to collect EEG data within public engagement and outreach environments.

Distinct frequencies balance segregation with interaction between different memory types within a prefrontal circuit.

Once formed, the fate of memory is uncertain. Subsequent offline interactions between even different memory types (actions versus words) modify retention.1,2,3,4,5,6 These interactions may occur due to different oscillations functionally linking together different memory types within a circuit.7,8,9,10,11,12,13 With memory processing driving the circuit, it may become less susceptible to external influences.14 We tested this prediction by perturbing the human brain with single pulses of transcranial magnetic stimulation (TMS) and simultaneously measuring the brain activity changes with electroencephalography (EEG15,16,17). Stimulation was applied over brain areas that contribute to memory processing (dorsolateral prefrontal cortex, DLPFC; primary motor cortex, M1) at baseline and offline, after memory formation, when memory interactions are known to occur.1,4,6,10,18 The EEG response decreased offline (compared with baseline) within the alpha/beta frequency bands when stimulation was applied to the DLPFC, but not to M1. This decrease exclusively followed memory tasks that interact, revealing that it was due specifically to the interaction, not task performance. It remained even when the order of the memory tasks was changed and so was present, regardless of how the memory interaction was produced. Finally, the decrease within alpha power (but not beta) was correlated with impairment in motor memory, whereas the decrease in beta power (but not alpha) was correlated with impairment in word-list memory. Thus, different memory types are linked to different frequency bands within a DLPFC circuit, and the power of these bands shapes the balance between interaction and segregation between these memories.

Two Oscillatory Correlates of Attention Control in the Alpha-Band with Distinct Consequences on Perceptual Gain and Metacognition.

Behavioral consequences and neural underpinnings of visuospatial attention have long been investigated. Classical studies using the Posner paradigm have found that visual perception systematically benefits from the use of a spatially informative cue pointing to the to-be-attended spatial location, compared with a noninformative cue. Lateralized α amplitude modulation during visuospatial attention shifts has been suggested to account for such perceptual gain. However, recent studies on spontaneous fluctuations of prestimulus α amplitude have challenged this notion. These studies showed that spontaneous fluctuations of prestimulus α amplitude were associated with the subjective appreciation of stimulus occurrence, while objective accuracy was instead best predicted by the frequency of α oscillations, with faster prestimulus α frequency accounting for better perceptual performance. Here, in male and female humans, by using an informative cue in anticipation of lateralized stimulus presentation, we found that the predictive cue not only modulates preparatory α amplitude but also α frequency in a retinotopic manner. Behaviorally, the cue significantly impacted subjective performance measures (metacognitive abilities [meta-d']) and objective performance gain (d'). Importantly, α amplitude directly accounted for confidence levels, with ipsilateral synchronization and contralateral desynchronization coding for high-confidence responses. Crucially, the contralateral α amplitude selectively predicted interindividual differences in metacognitive abilities (meta-d'), thus anticipating decision strategy and not perceptual sensitivity, probably via excitability modulations. Instead, higher perceptual accuracy both within and across participants (d') was associated with faster contralateral α frequency, likely by implementing higher sampling at the attended location. These findings provide critical new insights into the neural mechanisms of attention control and its perceptual consequences.SIGNIFICANCE STATEMENT Prior knowledge serves the anticipation of sensory input to reduce sensory ambiguity. The growing interest in the neural mechanisms governing the integration of sensory input into our internal representations has highlighted a pivotal role of brain oscillations. Here we show that distinct but interacting oscillatory mechanisms are engaged during attentional deployment: one relying on α amplitude modulations and reflecting internal decision processes, associated with subjective perceptual experience and metacognitive abilities; the other relying on α frequency modulations and enabling mechanistic sampling of the sensory input at the attended location to influence objective performance. These insights are crucial for understanding how we reduce sensory ambiguity to maximize the efficiency of our conscious experience, but also in interpreting the mechanisms of atypical perceptual experiences.

TMS combined with EEG: Recommendations and open issues for data collection and analysis.

Transcranial magnetic stimulation (TMS) evokes neuronal activity in the targeted cortex and connected brain regions. The evoked brain response can be measured with electroencephalography (EEG). TMS combined with simultaneous EEG (TMS-EEG) is widely used for studying cortical reactivity and connectivity at high spatiotemporal resolution. Methodologically, the combination of TMS with EEG is challenging, and there are many open questions in the field. Different TMS-EEG equipment and approaches for data collection and analysis are used. The lack of standardization may affect reproducibility and limit the comparability of results produced in different research laboratories. In addition, there is controversy about the extent to which auditory and somatosensory inputs contribute to transcranially evoked EEG. This review provides a guide for researchers who wish to use TMS-EEG to study the reactivity of the human cortex. A worldwide panel of experts working on TMS-EEG covered all aspects that should be considered in TMS-EEG experiments, providing methodological recommendations (when possible) for effective TMS-EEG recordings and analysis. The panel identified and discussed the challenges of the technique, particularly regarding recording procedures, artifact correction, analysis, and interpretation of the transcranial evoked potentials (TEPs). Therefore, this work offers an extensive overview of TMS-EEG methodology and thus may promote standardization of experimental and computational procedures across groups.

The timing of cortical activation in associator grapheme-colour synaesthetes using MEG.

Grapheme-colour synaesthetes experience an anomalous form of perception in which graphemes systematically induce specific colour concurrents in their mind's eye ("associator" type). Although grapheme-colour synaesthesia has been well characterised behaviourally, its neural mechanisms remain largely unresolved. There are currently several competing models, which can primarily be distinguished according to the anatomical and temporal predictions of synaesthesia-inducing neural activity. The first main model (Cross-Activation/Cascaded Cross-Tuning and its variants) posits early recruitment of occipital colour areas in the initial feed-forward sweep of brain activity. The second (Disinhibited Feedback) posits: (i) later involvement of a multisensory convergence zone (for example, in parietal cortices) after graphemes have been processed in their entirety; and (ii) subsequent feedback to early visual areas (i.e., occipital colour areas). In this study, we examine both the timing and anatomical correlates of associator grapheme-colour synaesthetes (n = 6) using MEG. Using innovative and unbiased analysis methods with little a priori assumptions, we applied Independent Component Analysis (ICA) on a single-subject level to identify the dominant patterns of activity corresponding to the induced, synaesthetic percept. We observed evoked activity that significantly dissociates between synaesthesia-inducing and non-inducing graphemes at approximately 190 ms following grapheme presentation. This effect is present in grapheme-colour synaesthetes, but not in matched controls, and exhibits an occipito-parietal topology localised consistently within individuals to extrastriate visual cortices and superior parietal lobes. Due to the observed timing of this evoked activity and its localization, our results support a model predicting relatively late synaesthesia-inducing activity, more akin to the Disinhibited Feedback model.

Effects of Rhythmic Transcranial Magnetic Stimulation in the Alpha-Band on Visual Perception Depend on Deviation From Alpha-Peak Frequency: Faster Relative Transcranial Magnetic Stimulation Alpha-Pace Improves Performance.

Alpha-band oscillatory activity over occipito-parietal areas is involved in shaping perceptual and cognitive processes, with a growing body of electroencephalographic (EEG) evidence indicating that pre-stimulus alpha-band amplitude relates to the subjective perceptual experience, but not to objective measures of visual task performance (discrimination accuracy). The primary aim of the present transcranial magnetic stimulation (TMS) study was to investigate whether causality can be established for this relationship, using rhythmic (alpha-band) TMS entrainment protocols. It was anticipated that pre-stimulus 10 Hz-TMS would induce changes in subjective awareness ratings but not accuracy, in the visual hemifield contralateral to TMS. To test this, we administered 10 Hz-TMS over the right intraparietal sulcus prior to visual stimulus presentation in 17 participants, while measuring their objective performance and subjective awareness in a visual discrimination task. Arrhythmic and 10 Hz sham-TMS served as control conditions (within-participant design). Resting EEG was used to record individual alpha frequency (IAF). A study conducted in parallel to ours with a similar design but reported after we completed data collection informed further, secondary analyses for a causal relationship between pre-stimulus alpha-frequency and discrimination accuracy. This was explored through a regression analysis between rhythmic-TMS alpha-pace relative to IAF and performance measures. Our results revealed that contrary to our primary expectation, pre-stimulus 10 Hz-TMS did not affect subjective measures of performance, nor accuracy, relative to control-TMS. This null result is in accord with a recent finding showing that for influencing subjective measures of performance, alpha-TMS needs to be applied post-stimulus. In addition, our secondary analysis showed that IAF was positively correlated with task accuracy across participants, and that 10 Hz-TMS effects on accuracy-but not awareness ratings-depended on IAF: The slower (or faster) the IAF, relative to the fixed 10 Hz TMS frequency, the stronger the TMS-induced performance improvement (or worsening), indicating that 10 Hz-TMS produced a gain (or a loss) in individual performance, directly depending on TMS-pace relative to IAF. In support of recent reports, this is evidence for alpha-frequency playing a causal role in perceptual sensitivity likely through regulating the speed of sensory sampling.

A TMS/EEG protocol for the causal assessment of the functions of the oscillatory brain rhythms in perceptual and cognitive processes.

The combined use of transcranial magnetic stimulation (TMS), electroencephalogram (EEG), and behavioral performance allows investigation of causal relationships between neural markers and their functional relevance across a number of perceptual and cognitive processes. Here, we present a protocol for combining and applying these techniques on human subjects. We describe correlation approach and causal approach to disentangle the role of different oscillatory parameters, namely alpha frequency and amplitude that control for accuracy and metacognitive abilities, respectively, in a visual detection task. For complete details on the use and execution of this protocol, please refer to Di Gregorio et al. (2022).

Non-invasive brain stimulation and neuroenhancement.

Attempts to enhance human memory and learning ability have a long tradition in science. This topic has recently gained substantial attention because of the increasing percentage of older individuals worldwide and the predicted rise of age-associated cognitive decline in brain functions. Transcranial brain stimulation methods, such as transcranial magnetic (TMS) and transcranial electric (tES) stimulation, have been extensively used in an effort to improve cognitive functions in humans. Here we summarize the available data on low-intensity tES for this purpose, in comparison to repetitive TMS and some pharmacological agents, such as caffeine and nicotine. There is no single area in the brain stimulation field in which only positive outcomes have been reported. For self-directed tES devices, how to restrict variability with regard to efficacy is an essential aspect of device design and function. As with any technique, reproducible outcomes depend on the equipment and how well this is matched to the experience and skill of the operator. For self-administered non-invasive brain stimulation, this requires device designs that rigorously incorporate human operator factors. The wide parameter space of non-invasive brain stimulation, including dose (e.g., duration, intensity (current density), number of repetitions), inclusion/exclusion (e.g., subject's age), and homeostatic effects, administration of tasks before and during stimulation, and, most importantly, placebo or nocebo effects, have to be taken into account. The outcomes of stimulation are expected to depend on these parameters and should be strictly controlled. The consensus among experts is that low-intensity tES is safe as long as tested and accepted protocols (including, for example, dose, inclusion/exclusion) are followed and devices are used which follow established engineering risk-management procedures. Devices and protocols that allow stimulation outside these parameters cannot claim to be "safe" where they are applying stimulation beyond that examined in published studies that also investigated potential side effects. Brain stimulation devices marketed for consumer use are distinct from medical devices because they do not make medical claims and are therefore not necessarily subject to the same level of regulation as medical devices (i.e., by government agencies tasked with regulating medical devices). Manufacturers must follow ethical and best practices in marketing tES stimulators, including not misleading users by referencing effects from human trials using devices and protocols not similar to theirs.

EEG alpha power predicts the temporal sensitivity of multisensory perception.

Pre-stimulus electroencephalogram (EEG) oscillations, especially in the alpha range (8-13 Hz), can affect the sensitivity to temporal lags between modalities in multisensory perception. The effects of alpha power are often explained in terms of alpha's inhibitory functions, whereas effects of alpha frequency have bolstered theories of discrete perceptual cycles, where the length of a cycle, or window of integration, is determined by alpha frequency. Such studies typically employ visual detection paradigms with near-threshold or even illusory stimuli. It is unclear whether such results generalize to above-threshold stimuli. Here, we recorded EEG, while measuring temporal discrimination sensitivity in a temporal-order judgement task using above-threshold auditory and visual stimuli. We tested whether the power and instantaneous frequency of pre-stimulus oscillations predict audiovisual temporal discrimination sensitivity on a trial-by-trial basis. By applying a jackknife procedure to link single-trial pre-stimulus oscillatory power and instantaneous frequency to psychometric measures, we identified a posterior cluster where lower alpha power was associated with higher temporal sensitivity of audiovisual discrimination. No statistically significant relationship between instantaneous alpha frequency and temporal sensitivity was found. These results suggest that temporal sensitivity for above-threshold multisensory stimuli fluctuates from moment to moment and is indexed by modulations in alpha power.

Coupling of pupil- and neuronal population dynamics reveals diverse influences of arousal on cortical processing.

Fluctuations in arousal, controlled by subcortical neuromodulatory systems, continuously shape cortical state, with profound consequences for information processing. Yet, how arousal signals influence cortical population activity in detail has so far only been characterized for a few selected brain regions. Traditional accounts conceptualize arousal as a homogeneous modulator of neural population activity across the cerebral cortex. Recent insights, however, point to a higher specificity of arousal effects on different components of neural activity and across cortical regions. Here, we provide a comprehensive account of the relationships between fluctuations in arousal and neuronal population activity across the human brain. Exploiting the established link between pupil size and central arousal systems, we performed concurrent magnetoencephalographic (MEG) and pupillographic recordings in a large number of participants, pooled across three laboratories. We found a cascade of effects relative to the peak timing of spontaneous pupil dilations: Decreases in low-frequency (2-8 Hz) activity in temporal and lateral frontal cortex, followed by increased high-frequency (>64 Hz) activity in mid-frontal regions, followed by monotonic and inverted U relationships with intermediate frequency-range activity (8-32 Hz) in occipito-parietal regions. Pupil-linked arousal also coincided with widespread changes in the structure of the aperiodic component of cortical population activity, indicative of changes in the excitation-inhibition balance in underlying microcircuits. Our results provide a novel basis for studying the arousal modulation of cognitive computations in cortical circuits.

Tuning alpha rhythms to shape conscious visual perception.

It is commonly held that what we see and what we believe we see are overlapping phenomena. However, dissociations between sensory events and their subjective interpretation occur in the general population and in clinical disorders, raising the question as to whether perceptual accuracy and its subjective interpretation represent mechanistically dissociable events. Here, we uncover the role that alpha oscillations play in shaping these two indices of human conscious experience. We used electroencephalography (EEG) to measure occipital alpha oscillations during a visual detection task, which were then entrained using rhythmic-TMS. We found that controlling prestimulus alpha frequency by rhythmic-TMS modulated perceptual accuracy, but not subjective confidence in it, whereas controlling poststimulus (but not prestimulus) alpha amplitude modulated how well subjective confidence judgments can distinguish between correct and incorrect decision, but not accuracy. These findings provide the first causal evidence of a double dissociation between alpha speed and alpha amplitude, linking alpha frequency to spatiotemporal sampling resources and alpha amplitude to the internal, subjective representation and interpretation of sensory events.

Low pre-stimulus EEG alpha power amplifies visual awareness but not visual sensitivity.

Pre-stimulus oscillatory neural activity has been linked to the level of awareness of sensory stimuli. More specifically, the power of low-frequency oscillations (primarily in the alpha-band, i.e., 8-14 Hz) prior to stimulus onset is inversely related to measures of subjective performance in visual tasks, such as confidence and visual awareness. Intriguingly, the same EEG signature does not seem to influence objective measures of task performance (i.e., accuracy). We here examined whether this dissociation holds when stringent accuracy measures are used. Previous EEG-studies have employed 2-alternative forced choice (2-AFC) discrimination tasks to link pre-stimulus oscillatory activity to correct/incorrect responses as an index of accuracy/objective performance at the single-trial level. However, 2-AFC tasks do not provide a good estimate of single-trial accuracy, as many of the responses classified as correct will be contaminated by guesses (with the chance correct response rate being 50%). Here instead, we employed a 19-AFC letter identification task to measure accuracy and the subjectively reported level of perceptual awareness on each trial. As the correct guess rate is negligible (~5%), this task provides a purer measure of accuracy. Our results replicate the inverse relationship between pre-stimulus alpha/beta-band power and perceptual awareness ratings in the absence of a link to discrimination accuracy. Pre-stimulus oscillatory phase did not predict either subjective awareness or accuracy. Our results hence confirm a dissociation of the pre-stimulus EEG power-task performance link for subjective versus objective measures of performance, and further substantiate pre-stimulus alpha power as a neural predictor of visual awareness.

Parietal alpha tACS shows inconsistent effects on visuospatial attention.

Transcranial alternating current stimulation (tACS) is a popular technique that has been used for manipulating brain oscillations and inferring causality regarding the brain-behaviour relationship. Although it is a promising tool, the variability of tACS results has raised questions regarding the robustness and reproducibility of its effects. Building on recent research using tACS to modulate visuospatial attention, we here attempted to replicate findings of lateralized parietal tACS at alpha frequency to induce a change in attention bias away from the contra- towards the ipsilateral visual hemifield. 40 healthy participants underwent tACS in two separate sessions where either 10 Hz tACS or sham was applied via a high-density montage over the left parietal cortex at 1.5 mA for 20 min, while performance was assessed in an endogenous attention task. Task and tACS parameters were chosen to match those of previous studies reporting positive effects. Unlike these studies, we did not observe lateralized parietal alpha tACS to affect attention deployment or visual processing across the hemifields as compared to sham. Likewise, additional resting electroencephalography immediately offline to tACS did not reveal any notable effects on individual alpha power or frequency. Our study emphasizes the need for more replication studies and systematic investigations of the factors that drive tACS effects.

Top-down control of visual cortex by the frontal eye fields through oscillatory realignment.

Voluntary allocation of visual attention is controlled by top-down signals generated within the Frontal Eye Fields (FEFs) that can change the excitability of lower-level visual areas. However, the mechanism through which this control is achieved remains elusive. Here, we emulated the generation of an attentional signal using single-pulse transcranial magnetic stimulation to activate the FEFs and tracked its consequences over the visual cortex. First, we documented changes to brain oscillations using electroencephalography and found evidence for a phase reset over occipital sites at beta frequency. We then probed for perceptual consequences of this top-down triggered phase reset and assessed its anatomical specificity. We show that FEF activation leads to cyclic modulation of visual perception and extrastriate but not primary visual cortex excitability, again at beta frequency. We conclude that top-down signals originating in FEF causally shape visual cortex activity and perception through mechanisms of oscillatory realignment.

Training in the practice of noninvasive brain stimulation: Recommendations from an IFCN committee.

As the field of noninvasive brain stimulation (NIBS) expands, there is a growing need for comprehensive guidelines on training practitioners in the safe and effective administration of NIBS techniques in their various research and clinical applications. This article provides recommendations on the structure and content of this training. Three different types of practitioners are considered (Technicians, Clinicians, and Scientists), to attempt to cover the range of education and responsibilities of practitioners in NIBS from the laboratory to the clinic. Basic or core competencies and more advanced knowledge and skills are discussed, and recommendations offered regarding didactic and practical curricular components. We encourage individual licensing and governing bodies to implement these guidelines.

Vision modulation, plasticity and restoration using non-invasive brain stimulation - An IFCN-sponsored review.

The visual system has one of the most complex structures of all sensory systems and is perhaps the most important sense for everyday life. Its functional organization was extensively studied for decades in animal and humans, for example by correlating circumscribed anatomical lesions in patients with the resulting visual dysfunction. During the past two decades, significant achievements were accomplished in characterizing and modulating visual information processing using non-invasive stimulation techniques of the normal and damaged human eye and brain. Techniques include transcranial magnetic stimulation (TMS) and low intensity electric stimulation using either direct or alternating currents applied transcranially (tDCS or tACS) near or above the visual cortex, or alternating currents applied transorbitally (trACS). In the case of transorbital stimulation of the visual system the electrodes are attached near the eye, to the eyelids (transpalpebral electrical stimulation - TPES) or the cornea (tanscorneal electrical stimulation TcES). Here, we summarize the state-of-the-art of visual system magnetic and electric stimulation as a method to modulate normal vision, induce brain plasticity, and to restore visual functions in patients. We review this field's history, models of current flow paths in the eye and brain, neurophysiological principles (e.g. entrainment and after-effects), the effects on vision in normal subjects and the clinical impact on plasticity and vision restoration in patients with low vision, with a particular focus on "off-line" or "after-effects". With regard to the therapeutic possibilities, ACS was demonstrated to be effective in patients affected by glaucoma and optic neuropathy, while tDCS and random noise stimulation (tRNS) are most promising for the treatment of amblyopia, hemianopia and myopia. In addition, rTMS applied above the occipital area is a promising approach to treat migraine, neglect and hemianopia. Although the response to these treatment options is better than to sham stimulation in double blinded clinical studies, the clinical efficacy is still rather variable and a proportion of patients do not respond. It is therefore imperative to better understand the mechanisms of action to be able to optimize treatment protocols possibly through personalization of brain stimulation protocols. By identifying the current opportunities and challenges in the field, we hope to provide insights to help improve neuromodulation protocols to restore visual function in patients with visual system damage.