Non-invasive brain stimulation (NIBS) enables the modulation of neural activity in targeted, superficial areas of the human brain. There are two primary NIBS techniques: transcranial magnetic stimulation (TMS) and transcranial electrical stimulation (tES).

Transcranial magnetic stimulation utilizes electromagnetic induction to generate brief electric currents within the stimulated brain area and can be delivered as either single pulses or a string of repetitive pulses. Single pulses of TMS can generate action potentials that induce a motor or perceptual response. For example, TMS delivered to the primary motor cortex can cause peripheral muscle contraction (Pascualleone et al., 1994) and TMS of the primary visual cortex can induce a phosphene percept (Bohotin et al., 2003). Repetitive pulses of TMS (rTMS) can increase or decrease cortical excitability within the stimulated brain region and alter the regional concentration of neurotransmitters such as gamma-aminobutyric acid (GABA) and glutamate (Michael et al., 2003). The effect of rTMS on cortical excitability and local neurochemistry depends on the structure of the pulse train (Hallett, 2000). Commonly used pulse trains include 1 and 10 Hz stimulation frequencies as well as continuous and intermittent theta burst protocols (cTBS and iTBS) (Huang et al., 2005).

Transcranial electrical stimulation involves the delivery of an electrical current to the brain using head-mounted electrodes. tES stimulation protocols include transcranial direct current stimulation (tDCS), transcranial random noise stimulation (tRNS) and transcranial alternating current stimulation (tACS). tES does not induce action potentials but may alter membrane potentials [tDCS (Nitsche and Paulus, 2001; Nitsche et al., 2003), tRNS (Terney et al., 2008)], induce regional changes in neurotransmitter concentration [tDCS (Stagg et al., 2009; Bachtiar et al., 2015; Hunter et al., 2015)], alter cortical excitability [tDCS (Nitsche and Paulus, 2000, 2001), tRNS (Terney et al., 2008; Moliadze et al., 2010)], entrain patterns of neural activity [tACS (Battleday et al., 2014)] and alter the signal to noise ratio within stimulated regions [tRNS, refer to Reed (Reed and Kadosh, 2018) for a review]. NIBS has been used in multiple research contexts including the study of fundamental neurological processes, cognition (Hoy et al., 2015; Grabner et al., 2018; Guleken et al., 2020), and the development of new therapeutic interventions [e.g., depression (Martin et al., 2018; Moreno et al., 2020), neurorehabilitation (Liew et al., 2014)].

Visual brain areas are attractive targets for NIBS research because regions such as the primary visual cortex and motion sensitive extrastriate area [middle temporal (MT)] are close to the cortical surface and techniques such as visual psychophysics, electroencephalography, and magnetic resonance imaging are available to measure the effects of the stimulation on neural activity and perception (Thompson et al., 2009, 2016; Miniussi et al., 2013). In addition, NIBS is emerging as a promising tool for vision rehabilitation (Pascual-Leone et al., 1998; Thompson et al., 2008). However, the literature on NIBS of visual brain areas is diverse with a wide range of different study designs, stimulation protocols, outcome measures and population samples. The aim of this structured review and meta-analysis was to assess whether visual cortex NIBS can enhance visual perception and/or modulate visual cortex activity (measured using visual evoked potentials). We did not include studies that used NIBS to induce “virtual lesions” or impair visual function to probe fundamental neurological processes. Our original plan was to review visual cortex NIBS studies involving either healthy or clinical populations [e.g., amblyopia (Spiegel et al., 2013; Ding et al., 2016) or hemianopia (Plow et al., 2012; Olma et al., 2013)]. However, our literature search revealed that studies of clinical populations did not employ common study designs and were relatively few. We therefore limited our review to studies examining the effect of NIBS on vision enhancement in healthy participants with normal vision.

This systematic review conforms to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020 (PRISMA-2020) guidelines (Page et al., 2021). We registered the review protocol with the International Prospective Register of Systematic Reviews (PROSPERO; Ref. No: CRD42021255882) in June 2021, prior to the initiation of the data extraction processes. We adopted the PICO (Participants, Intervention, Comparators and Outcome) format in generating the research question. The intervention was any form of NIBS (including tDCS, tACS, tRNS, and TMS), while the comparators included sham (placebo) NIBS. Outcomes of interest included psychophysical measures of contrast sensitivity, visual crowding, visual acuity, motion perception, visual evoked potentials (VEPs), and reaction time among others. The study conceptualization and development of the review protocol were undertaken by authors UMB, JYW, BT, and AMYC.

To recapitulate, the aim of this structured review and meta-analysis was to assess whether visual cortex NIBS could enhance visual function and/or modulate visual cortex activity. Both tES and TMS have been used as rehabilitation tools to enhance a variety of neural functions including cognition (Hara et al., 2021) and motor control (Liew et al., 2014). Unexpectedly, our literature review identified only five studies that investigated the use of TMS to enhance a specific visual function. Because these five studies used different stimulation protocols and/or different outcome measures, they could not be meta-analyzed (see Supplementary material for details). Although TMS has been widely used in vision research, it appears to have been used primarily to explore the function of targeted cortical areas or neural networks rather than a tool to enhance specific visual functions. However, it is clear that TMS does exert an effect on brain areas involved in visual processing and the five studies identified by our review reported improvements or alterations in the targeted visual function post stimulation. These effects were associated with changes in cortical excitability, neurotransmitter concentrations and signal to noise within the stimulated area. Furthermore, studies involving clinical populations have reported improvements in a variety of visual functions following visual cortex TMS (Thompson et al., 2008; Clavagnier et al., 2013). Therefore, it is likely that TMS will play a larger role in vison enhancement studies as the field continues to grow.

For the reasons described above, our meta-analysis involved only tES studies. Studies exploring the use of tES to enhance normal vision have employed a diverse range of experimental designs with time scales that range from the acute effects of a single tES session to multi-session studies that combine tES with perceptual learning. This diversity resulted in limited opportunities for meta-analyses. However, by pooling across different tES stimulation protocols and differing methodologies for assessing a common outcome measure, we were able to assess the effects of a single tES session vs. sham stimulation on contrast sensitivity, VEP amplitude, visual crowding, visual acuity, motion perception, and reaction time.

Both contrast sensitivity (Kraft et al., 2010; Ding et al., 2016; Behrens et al., 2017; He et al., 2019; Battaglini et al., 2020a; Nakazono et al., 2020) and visual crowding (Contemori et al., 2019; Raveendran et al., 2020; Chen et al., 2021) were significantly enhanced by visual cortex tES relative to sham within our meta-analyses, and were examined at different timescales relative to stimulation. Results from our meta-analyses showed beneficial acute effects of tES in enhancing contrast sensitivity (Figure 2) and reduced crowding (Figure 6). The sub-analysis of studies that only employed a-tDCS revealed improvements in crowding following stimulation (Figure 7), but not for contrast sensitivity (Figure 3). Our meta-analyses looking at later time points (i.e., aftereffects) could only be performed for contrast sensitivity as there was only one study investigating the effect of NIBS on crowding. We observed that tES was effective in modulating contrast sensitivity at a fixed time point after stimulation (Figure 4), indicating that the effects of stimulation on improving contrast sensitivity persisted beyond the stimulation period. Despite only one study measuring the aftereffects of a-tDCS on crowding (Raveendran et al., 2020) (in this case lateral-inhibition, a low-level mechanism that may contribute to crowding), the study reported a larger effect at 30 min vs. 5 min after stimulation, which is in line with the time-scale of the effects observed in the contrast sensitivity meta-analysis.

From a mechanistic perspective, the meta-analysis of changes in VEP amplitude (Ding et al., 2016; Dong et al., 2020; Nakazono et al., 2020; Lau et al., 2021) following visual cortex tES vs. sham revealed enhanced cortical excitability (i.e., larger VEP amplitudes) following tES (Figure 5). Increased cortical excitability may enhance neural sensitivity to contrast and weaken lateral inhibition mechanisms that contribute to crowding. The connection between tES and increased cortical excitability may be mediated by the relative concentration of the inhibitory neurotransmitter GABA and the excitatory neurotransmitter glutamate within the stimulated area. Reduced GABA concentration within motor cortex following a-tDCS has been reported by multiple studies (Stagg et al., 2011; Bachtiar et al., 2018) and it is possible that tES may have a similar effect when applied to the visual cortex. Within this framework, the delayed effects of tES on contrast sensitivity (Ding et al., 2016; Nakazono et al., 2020) [and perhaps crowding (Raveendran et al., 2020)] could reflect a gradual change in GABA concentration that continues for a period after the stimulation session. However, the time course of tES effects on GABA concentration remains unclear and it is also unknown whether the effects of tES on GABA concentration are the same for the motor and visual cortices. It is worth noting that indirect evidence exists suggesting that visual cortex tES does not influence GABA (Abuleil et al., 2021). Therefore, while the effects of visual cortex tES on contrast sensitivity, crowding, and VEP amplitude are supported by our meta-analyses, the underlying mechanisms require investigation.

Meta-analyses revealed no evidence for the effectiveness of tES on visual acuity, motion perception or reaction time. The visual acuity and motion perception meta-analyses included the fewest individual experiments [two for visual acuity (Reinhart et al., 2016; Bonder et al., 2018) and three for motion perception (Zito et al., 2015; Battaglini et al., 2017; Wu et al., 2020)] with considerable variations in the visual stimuli used to measure the outcomes. The small sample combined with significant protocol differences may have limited our power to detect an effect. It is possible that measures of visual acuity and motion perception differ from contrast sensitivity and crowding in their response to tES. For motion perception, it is also possible that area MT responds to tES in a way that is distinct from that of the primary visual cortex. However, additional studies are required to fully address these questions.

The reaction time meta-analysis included seven experiments and revealed high variability across studies with two reporting longer reaction times following tES (Barbieri et al., 2016; Bonder et al., 2018), three reporting no effect (Fertonani et al., 2011; Zito et al., 2015) and two reporting shorter reaction times (Reinhart et al., 2016; van Koningsbruggen et al., 2016); one with a moderate effect size (Reinhart et al., 2016) and the other with a Hedge’s G greater than five (van Koningsbruggen et al., 2016). Reaction times can be affected by multiple variables including attention, task complexity, participant instructions, and speed accuracy trade-off. The studies included in the reaction time meta-analysis differed considerably in the types of visual stimuli and tasks employed and therefore it is perhaps not surprising that tES of cortical regions responsible for early, low-level visual processing did not produce consistent effects across studies.

Our search criteria included studies involving low and high level visual functions, however, the studies eligible for meta-analysis all focused on relatively low-level visual functions. This may be because the identified studies tended to target the primary visual cortex and therefore selected outcomes measures targeting early-stages of visual processing. However, studies not included in the meta-analysis did report NIBSs effects on face perception (Barbieri et al., 2016), visuo-motor coordination (Antal et al., 2004b,c), and attention (Laczo et al., 2012). Higher level processed such as attentive search, multisensory integration and sensory decision making are potential targets for studies exploring the potential beneficial effects of NIBS on higher level sensory function and perception.

The diverse nature of the NIBS and vision literature forced us to pool across different tES protocols, visual stimuli, and experimental designs in our meta-analyses. Therefore, our results should be interpreted with caution. In particular, a non-significant meta-analysis may reflect important variations in experimental parameters rather than no effect of the stimulation itself. The tES studies included in this review varied in terms of the stimulation devices employed and specific stimulation parameters. Unfortunately, this variation combined with the different outcome measures used across studies prevented us from conducting analyses to identify optimal visual cortex stimulation protocols. However, Table 1 does provide details of device-independent parameters such as electrode size and properties of the stimulating current to enable future analyses when a pool of more uniform studies becomes available. In addition, our inclusion of multiple independent experiments from a single publication may have amplified study-specific sources of bias. As the literature on NIBS and vision continues to develop, future meta-analyses may be able to adopt more stringent analyses criteria.

Our review revealed that most vision enhancement studies involving healthy populations have employed tES rather than TMS. Meta-analyses provided evidence for the effectiveness of visual cortex tES compared to sham stimulation on modulating contrast sensitivity and crowding. These effects were accompanied by evidence for a significant increase in visual cortex excitability indexed by VEP amplitude following tES. Despite the diversity of study designs in the current tES and vision literature, the results of this review indicate that tES can enhance at least some visual functions and strengthen the foundation for the application of tES in studies of vision rehabilitation. The TMS studies identified by this review also suggest that the use of TMS to enhance visual function warrants further investigation.

UMB: accessing and verifying the data, conceptualization, articles’ electronic search, articles screening, meta-analysis, and draft of manuscript. JYW: accessing and verifying the data, articles screening, conceptualization, and draft of manuscript. ASYP: conceptualization, quality rating, and draft of manuscript. KWST: quality rating and draft of manuscript. BWSC: accessing and verifying the data, and data extraction. BT and AMYC: conceptualization, draft of manuscript, and project supervision. All authors had full access to the data in the study and had final responsibility for the decision to submit for publication.