Understanding the effects of transcranial direct current stimulation on the neurovascular unit: a narrative review

Transcranial direct current stimulation (tDCS) is a non-invasive neuromodulation technique that has demonstrated promise both for treating diverse clinical conditions and for enhancing brain function in healthy adults. Despite increasing popularity, the precise physiological mechanisms underlying its effects remain poorly defined, contributing to inconsistent findings. This review synthesises current evidence for both acute and enduring effects of tDCS across the complete neurovascular unit, encompassing neurons, astrocytes, oligodendrocytes, microglia, the blood–brain barrier, metabolic pathways, and immune responses. We review recent transcriptomic, proteomic, and metabolomic studies which reveal that tDCS induces coordinated molecular changes, including modulation of genes involved in inflammation, neurogenesis, calcium signalling, mitochondrial metabolism, and synaptic plasticity proteins. We emphasise significant gaps in current literature, particularly the limited consideration given to astrocytes and oligodendrocytes, despite their known importance in activity-dependent plasticity. We conclude that the neurovascular unit represents an integrative and complex target of tDCS, suggesting that comprehensive modulation of these components may better explain observed changes in cognitive, behavioural, and neuropsychological outcomes. Future research should move beyond a neuron-centric perspective, embracing a more integrative framework that considers interactions amongst all elements of the neurovascular unit. Such a holistic approach will enhance our understanding of how tDCS exerts its effects, thereby improving its clinical utility.

1 Introduction

Transcranial direct current stimulation (tDCS) is a non-invasive brain stimulation technique that delivers a weak electrical current to the brain, modulating the function of brain cells and influencing behavioural outcomes (Nitsche and Paulus, 2000). tDCS has emerged as a tool for both enhancing human capabilities and treating various neurological disorders (Nitsche and Fregni, 2007; Pustovrh, 2014). Due to its affordability, ease of application, minimal side effects, and broad potential applications, the technique has accumulated significant interest from both popular media (McCarthy-Jones, 2017; Ruddick, 2019), and the research community (Day et al., 2022; Riggall et al., 2015). For example, over 8,000 peer-reviewed documents relating to tDCS have been published since 2000, with more than 4,000 of these articles published since 2020 (PubMed search, “transcranial direct current stimulation”). This “explosion” of research reflects the scientific community’s interest in its prospective benefits, resulting in a substantial body of literature exploring its uses.

Despite the excitement and promise surrounding tDCS, criticism regarding its validity and utility persists. Several scholarly critiques (Bestmann et al., 2015; Horvath et al., 2015), and meta-analyses suggest that tDCS has no reliable effects on behaviour (Müller et al., 2022; Saleh et al., 2023) due to irreproducible effects (Horvath et al., 2014) and heterogenous findings (Klees-Themens and Théoret, 2023). Indeed, the inconsistency and variability of tDCS limits its clinical application, with the technique currently approved by the Australian Therapeutic Goods Administration and European Union Medical Device Regulation only for unipolar depression, major depressive disorder, and chronic pain (Royal Australian and New Zealand College of Psychiatrists, 2022), despite a plethora of tDCS research in other psychological conditions including anxiety (Garcia et al., 2020), schizophrenia (Brunelin et al., 2012), attention deficit hyperactive disorder (Salehinejad et al., 2017), and autism (García-González et al., 2021). Contributing to the uncertainty, the mechanisms by which tDCS affects brain function remain poorly understood. There is limited understanding of how tDCS impacts neural functions at the level of individual neurons and local microcircuits, particularly in humans (Parkin et al., 2019). Arguments suggest that these knowledge gaps hinder hypothesis-driven research and the interpretation of findings: “The use of [tDCS] has thus outpaced the mechanistic rationales for its application. This is no trivial matter, because these gaps in our knowledge delay the development of more effective and ever-safer stimulation protocols, lead to wastefulness when applications are based on spurious rationales, and promote the proliferation of implausible mechanistic inferences” (Bestmann et al., 2015).

Despite two decades of intensive investigation, the physiological mechanisms of tDCS remain incompletely mapped, and the technique continues to yield heterogeneous results within and between participants (Chew et al., 2015). Closing this mechanistic knowledge-gap is now a critical pre-requisite for sound dose design, reproducible experimental work, and clinical translation. Earlier syntheses have advanced the field but left key questions open. Pelletier and Cicchetti (2015) mapped the intracellular pathways governing inflammation and neurogenesis after direct current stimulation, whereas Bikson et al. (2019) and Stagg et al. (2018) focused on shifts in neuronal excitability and network physiology. More recently, Bahr-Hosseini and Bikson (2021) broadened the lens by charting tDCS-evoked vascular responses along the arterial tree. Even so, existing syntheses remain predominantly neuron-centric, offering only cursory attention of the wider neurovascular unit—astrocytes, oligodendrocytes, pericytes, microglia, and the blood–brain barrier—as well as the emerging roles of cerebrospinal-fluid and glymphatic exchange.

Due to the heterogeneity of the literature that spans multiple species, models, and temporalities, we provide a narrative review to address the aforementioned shortfall. Here, the aim is to provide a deeper understanding of how tDCS impacts each element of the neurovascular unit and its implications for clinical translation. Drawing on the latest molecular, cellular, haemodynamic and immuno-metabolomic evidence, we present an integrated view of tDCS effects, spanning immediate effects on single cells to enduring adaptations across neuronal networks. We first discuss the immediate effects of stimulation, showing how electric-field orientation, montage geometry and tissue conductivity jointly impact responses in both neuronal and non-neuronal elements. We then discuss the enduring effects of stimulation that persist upon stimulation cessation, highlighting the drivers and modulators of plasticity, as well as emerging contributors of the neurovascular unit including astrocytes, microglia, and oligodendrocytes, all of which may explain the technique’s variable efficacy. It should be noted that the relative length of each section mirrors the current evidence base: the literature is dominated by studies on neuronal effects, with fewer investigations into the wider neurovascular unit. Figure 1 provides an overview of the neurovascular elements discussed in this review.

Figure 1

Figure 1. A visual depiction of the elements of the neurovascular unit. The neurovascular unit, blood brain barrier and its tight junctions have all been proposed to be impacted by tDCS. Created in BioRender. Lewis (2025) https://BioRender.com/4rg7khk.

Building on earlier syntheses, we incorporate the most recent evidence on elements of the neurovascular unit that have been largely overlooked. We extend and synthesise findings on how tDCS modulates gene expression, aiming to holistically explain how tDCS may exert its behavioural and cognitive effects. Our aim is to provide researchers with a comprehensive review of all known mechanisms of action of tDCS that spans molecular and cellular processes through to whole-brain dynamics. To respect the distinct timescales of tDCS action, we begin with its acute neuronal effects at multiple organisational levels, proceed to longer-lasting neuronal adaptations, before examining the non-neuronal effects of tDCS and how these may address the heterogeneity seen in the literature.

2 The neuronal mechanisms underlying tDCS

Observable changes in psychophysiological outcomes during or following tDCS administration are largely attributed to the effects of tDCS on neurons (Nitsche and Paulus, 2000). Neurons are electrically excitable cells, and their function depends critically on the generation of action potentials, which are elicited when the resting membrane reaches a certain potential threshold (usually −50 mV). The application of tDCS initiates the polarisation of the cell membranes (Bikson et al., 2004), but this change in cell membrane potential is subthreshold and does not elicit action potentials themselves. Indeed, tDCS delivers a current intensity between 1 and 2 mA which is too low to directly elicit action potentials (the peak current density at any point in the brain is roughly 0.05–0.5 A/m²). Despite being subthreshold, the polarisation of cell membranes has multifaceted consequences that extend beyond the resting potential of the cell itself, impacting various aspects of neuronal function, including action potential threshold and timing, whole brain oscillations, synaptic plasticity, and morphological and molecular changes (Bikson et al., 2004; Bindman et al., 1964; Marshall et al., 2016; Radman et al., 2009; Reato et al., 2014). These diverse neurophysiological effects can be viewed as being secondary to the primary consequences of tDCS for the polarisation of cell membranes. These neurophysiological effects will be discussed alongside their relationship to the behavioural, cognitive, and neuropsychological changes observed following tDCS administration.

2.1 Acute effects of tDCS on neurons

2.1.1 Membrane polarisation

tDCS stimulation produces electrical current flow across the brain (Datta et al., 2009; Huang et al., 2017; Miranda et al., 2006; Opitz et al., 2016), with current from the anode flowing into the brain and then exiting at the site of the cathode. This flow of current around neurons results in the polarisation of cell membranes. Flow into a specific membrane compartment (from outside the neuron into it) will result in local membrane hyperpolarisation, and flow out of another membrane compartment (from inside to out) will result in local membrane depolarization (Bikson et al., 2004; Andreasen and Nedergaard, 1996). At the single neuron level, the physics of electrical stimulation dictate that any neuron exposed to extracellular direct current (DC) stimulation will have some compartments that are depolarized while others are hyperpolarized (Bikson et al., 2004; Chan et al., 1988). Which compartments are polarised, and in which direction, depends on the neuronal morphology relative to the DC electric field. For a typical cortical pyramidal neuron, with a large apical dendrite pointed towards the cortical surface, a surface anode (positive electrode, generating a cortical inward current flow) will result in somatic depolarisation and apical dendrite hyperpolarisation (Radman et al., 2009). For this same neuron, a surface cathode (negative electrode, generating cortical outward current flow) will result in somatic hyperpolarisation and apical dendrite depolarisation. This pattern has motivated a term called the “somatic doctrine,” which holds that tDCS-evoked shifts in excitability arise chiefly from changes in somatic membrane potential (Bikson et al., 2019).

The soma is indeed central to action-potential initiation; yet mounting evidence indicates that the decision to fire also reflects the integrated activity of the entire neuronal architecture, including dendrites, axon, presynaptic terminals, and axon hillock (Bikson et al., 2004; Bindman et al., 1964; Radman et al., 2009; Purpura and McMurtry, 1965). Direct-current fields polarise these other compartments as well: afferent axons and their terminals experience morphology-dependent shifts in membrane potential during DC stimulation, sometimes with polarity opposite to that of the soma, thereby shaping synaptic transmission (Kabakov et al., 2012; Márquez-Ruiz et al., 2012; Ranck, 1975; Tranchina and Nicholson, 1986). DC fields can modulate the functionality of all these compartments, increasing the complexity of a purely “somatic doctrine” (Kabakov et al., 2012; Kronberg et al., 2017; Rahman et al., 2013). Despite the involvement of all compartments of the neuron, the somatic doctrine has predominantly and implicitly informed the rationale for most tDCS human trials – namely presumed excitation by the anode and inhibition by the cathode.

While the respective effects of anodal and cathodal tDCS on the soma have been extended to the whole neuron, they cannot generalise to the effects on the excitability of the whole brain. The neuronal morphology inside the brain is heterogenous. Current that is passed through tDCS electrodes takes a path through the head determined by individual anatomy and the resistivity of each tissue type (Neuling et al., 2012). A fraction of the current never crosses the resistive cranium, instead shunting across the relativity conducive (low resistivity) scalp (Paulus and Rothwell, 2016). Of the current fraction that crosses the skull, a further portion is shunted by the high conductivity cerebrospinal fluid (Neuling et al., 2012). The current component that reaches the brain crosses the grey and then white matter (Lee et al., 2015). As current crosses brain tissue, it generates an electric field on the local tissue, which neurons are then exposed to. However, due to the lack of uniformity across other tissue types (i.e., skull thickness, skin conductance) between participants, a resultant heterogeneity in electric field intensity distribution across the cortex occurs (Mosayebi-Samani et al., 2021). Considering this, the targeted application of tDCS is challenging given the inconsistent electric field delivered to the brain across individuals.

In addition to varied current intensity that crosses into the brain tissue, the direction of current flow resulting from tDCS is also varied. The direction of current flow across the grey matter can be radial inward (from the pial surface towards grey/white matter boundary), radial outward, or tangential (along the grey matter) (Rahman et al., 2013). The direction of current with respect to the orientation of the somato-dendritic axes of neurons being stimulated is a primary determinant of the physiological impact of tDCS (Bikson et al., 2004; Rahman et al., 2013; Farahani et al., 2021; Lafon et al., 2017; Rahman et al., 2015). Current flowing parallel to the somato-dendritic axis (radial orientation) can cause somatic depolarisation or hyperpolarisation: current flowing inward (radial inward) from dendrite to soma causes depolarisation, whereas current flowing outward (radial outward) from soma to dendrite causes hyperpolarisation. By contrast, current applied orthogonally to the somatodendritic axis – hereon referred to as “tangential” orientation (along the grey matter) – results in little to no somatic polarisation (Bikson et al., 2004; Rahman et al., 2013; Farahani et al., 2021; Lafon et al., 2017; Rahman et al., 2015). Although computational models often treat the electric field beneath each electrode as uniform in strength and orientation, individual differences in skull thickness, cortical folding, and other anatomical features generate appreciable field variability—even directly under the stimulating electrodes (Rahman et al., 2013; Lafon et al., 2017). These local disparities can drive neurons towards opposite polarisation states (depolarisation in some elements, hyperpolarisation in others; see Figure 2), perhaps explaining the diverse behavioural effects reported across studies. Such variability highlights the limits of one-compartment explanations and underscores the need for in vivo measures that capture the integrated response of entire pathways rather than isolated cells.

Figure 2

Figure 2. A visual representation of the impact of cortical folding and orientation of neurons on how tDCS-derived electric fields impact polarisation. Created in BioRender. Lewis (2025) https://BioRender.com/grakwub.

2.1.2 Motor evoked potentials

One method for quantifying online, pathway-level excitability effects of tDCS is the motor-evoked potential (MEP). Nitsche and Paulus (2000) first paired 4 s of 1 mA anodal tDCS with single-pulse TMS and recorded an immediate (online) increase in twitch amplitude of the contralateral hand, consistent with a transient boost in the number or synchrony of descending corticospinal volleys (Bestmann et al., 2015; Nitsche et al., 2003a; Tremblay et al., 2016). Follow-up work on online MEPs is sparse: a handful of reports have replicated the facilitation and even linked its size to stronger after-effects measured minutes later (Nitsche et al., 2003a; Bergmann et al., 2009; Liebetanz et al., 2002), yet a near-replication by Pillen et al. (2022) did not detect any change in online MEP size. Conversely, Santarnecchi et al. (2014) found no immediate effect but did see a post-stimulation increase, suggesting that the principal action of tDCS might occur only once current flow ceases. Such discrepancies highlight the multifaceted nature of the measurement itself. An MEP reflects not only the excitability of cortical pyramidal neurons, but also the state of inter-neuronal circuits, spinal motoneurons, as well as peripheral axons—all of which can be differentially influenced by the weak, spatially heterogeneous fields produced in vivo. MEPs also ignore glial partners in the neurovascular unit; astrocytes, oligodendrocytes and microglia can alter ion homeostasis, neurotransmitter clearance and microvascular tone (De Luca et al., 2020), shifting neuronal thresholds or synchrony without necessarily enlarging the evoked potential. With little research focused on the during-stimulation window—and most of the literature targeting post-stimulation outcomes—it is unsurprising that results remain heterogeneous. This unclear evidence points to the need for alternative approaches to understanding tDCS effects, from single-neuron measures of firing rate and spike timing to population-level markers such as oscillatory dynamics and neurovascular signals, which may offer a clearer understanding of the mechanisms of action of tDCS.

2.1.3 Action potential firing rate

Changes to individual neurons and whole brain excitability resulting from tDCS are important because they produce changes in action potential firing rate. Early animal studies using weak DCS showed a change in ongoing action potential discharge rate that shares a roughly linear relationship with electric field intensity (Bindman et al., 1964; Purpura and McMurtry, 1965; Creutzfeldt et al., 1962; Terzuolo and Bullock, 1956). Some of the earliest work by Terzuolo and Bullock (1956) reported a detectable change in neuronal firing rate at electric fields as small as 0.8 V/m, and Bindman et al. (1964) showed classic polarity-dependent effects—anodal currents raised, whereas cathodal currents lowered, cortical firing rates. Subsequent in-vivo recordings have refined that threshold. Tanaka et al. (2020) reported that both anodal and cathodal tDCS boosted single-unit firing beneath the electrode in anaesthetised rat cortex, while Farahani et al. (2024) demonstrated monotonic rate increases down to 0.35 V/m in mouse hippocampus – equivalent to 0.4 A/m² current densities delivered in standard human protocols and far below the 34.2 A/m² often used in earlier animal studies (Brunoni et al., 2011a). Together, these findings overturn the notion that only high-intensity laboratory fields influence neuronal output.

Increases in mean firing rate do not automatically translate into reliable behavioural or cognitive gains. Single neurons embedded in a complex circuit can polarise in opposite directions depending on cell type, morphology, and compartment, so population-level effects may cancel out. Further, tDCS alters much more than how often neurons fire; but also, when they fire, how they synchronise, and how synaptic inputs are weighted, all of which are factors that can dominate network function even when average firing rates shift only modestly. Indeed, Milighetti et al. (2020) caution that behavioural and cognitive effects reported in previous tDCS studies are likely driven by effects other than changes in spontaneous neuronal firing.

The evidence therefore points to a two-step conclusion: clinically relevant electric fields are indeed sufficient to modulate firing rate, but firing rate shifts alone are not enough to induce changes in behaviour. The next section builds on this by examining timing-based and network-level mechanisms that may better account for the variability of tDCS outcomes.

2.1.4 Action potential timing

Weak electric fields generated by tDCS affect not only how often neurons fire (action potential firing rate) but also when they fire. Spike timing—the precise millisecond at which an action potential occurs relative to the neuron’s own membrane trajectory or to ongoing network rhythms—can change synaptic integration and plasticity even when the average firing rate remains constant. Experimental work on hippocampal neurons illustrates this: Radman et al. (2007) applied a spatially uniform field to rat primary motor cortex during steady depolarisation and found that anodal stimulation advanced the moment a neuron crossed threshold, whereas cathodal stimulation delayed it, thereby shifting spike timing without altering spike count. Similar timing shifts appear at the population level: in cortical slices, Reato et al. (2010) observed that depolarising fields compressed, and hyperpolarising fields stretched, the intervals between peaks in local-field potentials of rat hippocampal slices, indicating advances or delays across many cells. Computational models reproduce the same pattern, showing cathodal DCS systematically advances and anodal DCS delays spikes relative to unstimulated controls (Lafon et al., 2017).

These millisecond adjustments, however, do not automatically translate into long-lasting synaptic change. Plasticity emerges only when tDCS acts on circuits that are already active; a network “at rest” shows weak polarisation but no enduring synaptic modification (Márquez-Ruiz et al., 2012; Fritsch et al., 2010). This qualifier is critical for interpreting behavioural outcomes: while tDCS instantaneously polarises membranes and alters both firing rate and spike timing, the behavioural and cognitive gains reported in humans likely stem from activity-dependent plasticity and broader network reorganisation, not from single-neuron effects alone. Moreover, because current density and field orientation vary markedly across the folded human cortex, spike-timing shifts will differ from one region or cell type to another. Such heterogeneity challenges the convenient—but overly simplistic—rule that “anodal depolarises” and “cathodal hyperpolarises,” and underscores the need to examine how tDCS reshapes activity in larger neural and neurovascular networks.

2.1.5 Oscillations

Neuronal oscillations emerge when large ensembles of neurons fire rhythmically; the frequency reflects how quickly successive population volleys occur, whereas the amplitude (power) scales with the proportion of cells that discharge in synchrony (Buzsáki and Draguhn, 2004). At the single-cell level, the firing-rate and spike-timing effects reviewed in Sections 2.1.2–2.1.3 form the foundation for these network rhythms: when many neurons shift their timing together, the power of the resulting population oscillation rises or falls. Oscillatory power therefore explains how micro-scale excitability changes lead to changes at the macro-scale network dynamics.

In humans, functional magnetic resonance imaging has shown that tDCS generally alters activity in regions near the anode, but also in distant brain structures that are functionally connected (Amadi et al., 2014; Hunter et al., 2015; Krishnamurthy et al., 2015). These findings indicate the possibility of tDCS to induce changes in large-scale oscillatory coupling. EEG and MEG studies have examined this possibility more directly, yet the pattern is inconsistent. For example, McDermott et al. (2019) reported that occipital anodal tDCS impaired visual working-memory accuracy, elevated resting theta power in prefrontal cortex, raised alpha power in occipital cortex, and suppressed task-related frontal theta—all effects that could reflect downstream propagation from the stimulated site. Over primary motor cortex, anodal stimulation has been found to boost alpha- and beta-band power during motor imagery and execution (Mondini et al., 2018; Wei et al., 2013), whereas cathodal currents reduce it (Baxter et al., 2017); however, several groups using comparable montages have observed no significant changes (Gordon et al., 2018; Luft et al., 2018). A recent meta-analysis pooling 39 experiments concluded that, on average, neither resting-state nor event-related oscillatory power differs reliably from sham stimulation (Chan et al., 2021). In short, tDCS can shift oscillatory dynamics, but the direction, size, and behavioural relevance of those shifts are highly context dependent. Moreover, since most behavioural improvements emerge after the current is switched off, we need to examine the stimulation’s lasting effects and the mechanisms by which its immediate actions consolidate into longer-term changes—topics addressed in the following section.

2.2 Enduring effects of tDCS on neurons

Beyond its immediate and online effects, tDCS can continue to shape neuronal excitability for minutes to hours after stimulation cessation (Kuo et al., 2013). In the human motor cortex, the polarity-dependent pattern seen during stimulation—anodal facilitation, cathodal suppression—often re-emerges immediately after current offset. For example, Nitsche and Paulus (2000) and Fricke et al. (2010) both recorded larger MEPs in the first seconds following anodal tDCS, an effect replicated in several subsequent studies (López-Alonso et al., 2015; Siebner et al., 2004). The duration of these after-effects scales with stimulation length. Stimulation between 5 and 7 min fade within ∼30 min, whereas ≥9 min of stimulation extend the effect to 60–90 min (Nitsche and Paulus, 2000). Longer follow-ups show still-prolonged excitability: Vaseghi et al. (2015) reported MEPs peaking ~30 min post-tDCS and remaining above baseline 24 h later; similar trajectories have been observed for oscillatory power (Romero Lauro et al., 2014) and for MEPs in other cohorts (Vaseghi et al., 2015; Jamil et al., 2017). These sustained changes are widely attributed to NMDA-dependent synaptic plasticity—long-term potentiation (LTP) and depression (LTD)—that alters the efficacy of neuronal firing (Malenka and Bear, 2004). LTP is a marked increase in synaptic strength that emerges when bursts of presynaptic spikes coincide with large and concurrent postsynaptic depolarisation (Hulme et al., 2014). This removes the Mg²⁺ block on NMDA receptors, allowing Ca²⁺ to flood the dendritic spine and activate kinase cascades that insert additional AMPA receptors and enlarge the spine head, thereby amplifying future transmissions (Kronberg et al., 2017). LTD, in contrast, is a sustained weakening that follows lower-frequency or poorly timed activity; the smaller Ca²⁺ rise favours phosphatase pathways that remove AMPA receptors and shrink the spine, diminishing synaptic efficacy (Lüscher and Malenka, 2012). Figure 3 illustrates this process. There are two main drivers of this neuronal plasticity (Arckens et al., 2000), as well as a range of modulators of neuronal plasticity (Pedrosa and Clopath, 2017), which may be targeted by tDCS. Understanding the underlying mechanisms of neuronal plasticity and how tDCS may impact its drivers and modulators is critical for understanding of how tDCS can influence behavioural outcomes.

Figure 3

Figure 3. (A) The proposed pathway from acute tDCS effects into the enduring changes at the synapse. (B) A visual representation of how tDCS induce LTD and LTP-like effects. Created in BioRender. Lewis (2025) https://BioRender.com/2ve210s.

2.2.1 Drivers of plasticity

2.2.1.1 Glutamate

NMDA-type glutamate receptors regulate the influx of calcium (Ca²⁺) ions in response to coincident pre- and postsynaptic activity, thereby determining whether synapses undergo LTP or LTD (Citri and Malenka, 2008). Pharmacological studies have clearly demonstrated that tDCS exerts its plasticity-modulating effects predominantly via these NMDA receptors. Specifically, administration of the NMDA receptor antagonist dextromethorphan in humans abolishes both LTP- and LTD-like effects typically induced by tDCS (Liebetanz et al., 2002; Nitsche et al., 2003b; Stefan et al., 2002; Wolters et al., 2003), whereas treatment with the partial NMDA receptor agonist d-cycloserine extends and enhances the LTP-like effects induced by anodal tDCS (Nitsche et al., 2004a). Recent experimental findings further highlight the pivotal role of glutamatergic NMDA receptor activity in tDCS-induced neuroplasticity. In a study involving eighteen healthy participants, modulation of glutamatergic plasticity via dopaminergic agents showed distinct interactions: activation of D1-like dopamine receptors amplified glutamatergic NMDA receptor-mediated LTP-like plasticity induced by anodal stimulation, while concurrently abolishing the LTD-like plasticity typically observed with cathodal stimulation (Ghanavati et al., 2025). Conversely, general dopaminergic activation and specific D2-like receptor stimulation appeared to diminish glutamatergic NMDA receptor-mediated LTP-like effects while facilitating LTD-like plasticity, indicating a complex relationship between dopamine receptor activity and NMDA receptor-mediated glutamatergic signalling (Ghanavati et al., 2025). Collectively, these studies highlight the importance of the NMDA receptor and the broader glutamatergic system as essential mediators of the enduring synaptic plasticity induced by tDCS.

2.2.1.2 GABAergic system

Recent evidence also indicates that tDCS can modulate neuronal excitability through interactions with the GABAergic system. Most research supports the view that anodal tDCS decreases GABA concentration or weakens GABAergic neurotransmission in the stimulated cortical region, thereby facilitating LTP-like neuroplastic effects (Antonenko et al., 2017; Heise et al., 2022; Patel et al., 2019; Stagg et al., 2014; Stagg et al., 2011; Tremblay et al., 2016). Nonetheless, findings have been inconsistent, with some studies reporting no significant changes in GABA concentration or GABA receptor activity following anodal tDCS (Nwaroh et al., 2020). In cats, Zhao et al. (2020) demonstrated a significant reduction in GABA concentration after anodal tDCS compared to sham stimulation, whereas cathodal tDCS primarily affected glutamatergic rather than GABAergic neurotransmission. A recent study by Ghanavati et al. (2025) supports the importance of both glutamatergic and GABAergic interactions in modulating cortical plasticity, highlighting that dopamine receptor subtypes (D1 and D2) significantly influence both GABA and glutamatergic neurotransmitter systems. This study suggests that dopaminergic modulation, via interactions with glutamatergic NMDA and GABAergic receptors, underlies the complex plasticity effects observed during tDCS, reinforcing the role of neurotransmitter-specific modulation as crucial to the variable outcomes reported across different tDCS protocols (Monte-Silva et al., 2010).

Together, these findings demonstrate that plasticity induced by tDCS is shaped by a delicate and dynamic balance between excitatory and inhibitory neurotransmission. Yet, while the glutamatergic and GABAergic systems form the neurochemical foundation of synaptic modulation, they do not fully explain the spectrum of plastic responses observed with tDCS. To capture the full complexity of tDCS-induced neuroplasticity, we must consider broader systems-level processes that extend beyond synaptic transmission. This includes the influence of additional neuromodulatory systems, as well as non-neuronal mechanisms such as glial function and cellular structural changes. The following sections explore these wider modulators of plasticity, beginning with the role of non-glutamatergic neurotransmitter systems and continuing through to cellular-level adaptations like proliferation and morphological remodelling.

2.2.2 Modulators of plasticity

2.2.2.1 Neurotransmitter systems

Beyond the primary excitatory and inhibitory systems, several additional neurotransmitter systems—including dopaminergic, cholinergic, serotonergic, and noradrenergic pathways—play modulatory roles in shaping neuroplasticity and may influence how tDCS-induced effects manifest. For instance, blockade of dopamine receptors has been shown to reliably abolish tDCS-induced plasticity, underscoring dopamine’s permissive role in facilitating plastic change in the motor cortex (Monte-Silva et al., 2013; Nitsche et al., 2009; Nitsche et al., 2006). However, this relationship is not linear: low and high doses of levodopa can suppress plasticity, while intermediate doses may enhance it (Monte-Silva et al., 2010). Similarly, cholinergic modulation appears to bias synaptic change towards potentiation, with receptor activation promoting LTP-like effects and antagonism blocking them (Auerbach and Segal, 1996; Blitzer et al., 1991; Hasselmo and Barkai, 1995). Adrenergic involvement is also evident; for example, monoamine reuptake inhibitors prolong the after-effects of anodal tDCS, whereas β-adrenergic receptor antagonism dampens both LTP- and LTD-like responses (Nitsche et al., 2004b). Importantly, these neuromodulatory systems are not universally required for tDCS-induced plasticity to occur. Rather, they influence the threshold, magnitude, and direction of plastic change in a context-dependent and often non-linear fashion (Nitsche et al., 2012). This suggests that tDCS-induced plasticity is contingent upon the state of these systems, but not necessarily dependent on their engagement. Their fluctuating activity levels, receptor distribution, and downstream signalling pathways can introduce considerable variability in outcomes, adding yet another layer of complexity to interpreting and predicting the effects of tDCS.

2.2.2.2 Cell proliferation

In addition to synaptic and neuromodulatory effects, tDCS may also be capable of inducing non-synaptic plasticity, particularly at the level of cellular development and regeneration. A growing body of evidence suggests that electrical stimulation influences cell proliferation, neurite outgrowth, and morphological remodelling. Endogenous electric fields are known to play significant roles in neural development and repair processes (McCaig et al., 2005), and tDCS may similarly harness these mechanisms. For instance, Rueger et al. (2012) demonstrated that 10 consecutive days of cathodal tDCS applied to the rat primary motor cortex increased the number of proliferating cells and neural stem cells in the stimulated region by 160%. Complementary in vitro findings have shown that direct current electric fields can rapidly promote neurite extension (Koppes et al., 2011; Wood and Willits, 2009), modulate their orientation, and influence axonal guidance. Depending on the cell type, developmental stage, or experimental context, neurites have been observed to orient towards the cathode (Wood and Willits, 2009; Erskine and McCaig, 1995; Patel and Poo, 1984; Rajnicek et al., 2006), the anode (Cork et al., 1994), or perpendicular to the electric field (Pan and Borgens, 2010). In vivo, prolonged tDCS following ischemic injury in rats has been associated with increased dendritic spine density in surviving neurons at the infarct site, accompanied by improvements in motor function (Jiang et al., 2012). These findings suggest that extended tDCS protocols may support neurorestorative processes by promoting cellular growth and regeneration. However, the behavioural significance of tDCS-induced cell proliferation remains unexplored. Whether these structural changes translate into functionally meaningful outcomes—particularly in human populations—remains an important avenue for future research. Future research needs to directly assess the regenerative capacity of tDCS on cell proliferation and quantify any restorative effects on altered behavioural outcomes.

2.2.3 Variability of tDCS effects

The effects of tDCS are often only interpreted through its impact on neurophysiological excitability—as reported above, predominately indexed by changes in TMS-evoked MEPs, TMS–EEG potentials, and metabolite changes (e.g., glutamate, GABA). The foundational research cited above establishes polarity-dependent after-effects on corticospinal excitability, whereby anodal tDCS increases cortical activity and producing LTP-like changes, whereas cathodal tDCS decreases cortical activity and producing LTD-like changes. However, contemporary evidence suggests a multitude of moderators—biological (age, sex, disease state, baseline excitability) and technical (stimulation parameters)—that shape both the magnitude and the direction of behavioural and neurophysiological outcomes. Indeed. umbrella and domain-specific meta-analyses increasingly emphasise these moderators when interpreting small-to-moderate average effects and occasional null results, emphasising the need to look beyond simple dichotomous and neuron-centric approaches to understanding the effects of tDCS (Ciechanski et al., 2018; Schroeder et al., 2020).

2.2.3.1 Age

Head and brain anatomy change with ageing, including cortical atrophy and cerebrospinal fluid expansion (Fjell et al., 2010), altering the induced electric field and thereby moderating excitability responses (Indahlastari et al., 2020). Computational modelling in large ageing cohorts shows systematic age-related differences in electric field strength and distribution under conventional montages, implying that a fixed current dose can deliver different intracranial doses across the lifespan (Indahlastari et al., 2020; Ma et al., 2024). Indeed, experimental data in older adults show that anodal tDCS can reduce motor cortex GABA and alter sensorimotor network connectivity—physiological substrates that track excitability modulation—but with effects that differ from young adults, again consistent with age as a moderator (Antonenko et al., 2017). Collectively, these results argue for age-aware dose control and montage selection whenever excitability is the primary endpoint.

2.2.3.2 Sex

Beyond age-related variability in the effects of tDCS, there are also sex-related anatomical differences that have the capacity to shift electric field focality and magnitude and thus excitability outcomes (Rudroff et al., 2020). Indeed, modelling data in humans indicate that tDCS-induced electric fields are higher in female head models than male head models at the same stimulation site and dose, indicating gender-related differences. This difference in gender related electric field distribution appears to be related to observed gender differences in a wide range of behavioural outcomes. For example, Weller et al. (2023) report that, regardless of stimulation condition, performance gains in a cognitive training task between the sexes were higher in females compared to males. Sex differences are also evident in clinical populations. Recent evidence suggests that sex modulates functional connectivity changes in primary progressive aphasia, with women receiving active tDCS showing greater language network connectivity changes compared to those in the sham condition (Licata et al., 2023). Beyond anatomy, endocrine state can shift baseline cortical physiology: menstrual-cycle–related hormone fluctuations are associated with changes in cortical excitability measures and manual dexterity in women (Zoghi et al., 2015). For excitability-focused studies, reporting sex, menstrual phase/contraceptive use, and—where possible—controlling for these factors must be considered.

2.2.3.3 Disease state

The health of participants may also impact tDCS-induced effects, where many disorders and pathologies are characterised by altered baseline excitability and network physiology, which can shape tDCS after-effects (Chan and Han, 2020). For pathologies that impact the anatomy of the brain, this has a significant impact in electric fields and baseline excitability. For example, using current flow modelling in patients with stroke, van der Cruijsen et al. (2023) compared electric field variability when applying conventional anodal tDCS electrode configurations targeting the primary motor cortex in individualised MRI-based finite-element modelling in chronic stroke shows that a “standard” anodal M1 montage produces weaker, more variable, and sometimes polarity-inverted fields relative to healthy heads. These dose distortions mean that protocols validated in neurotypical samples often do not translate without individualised modelling and montage adjustment. Beyond anatomy, disease-specific network dynamics also impact tDCS-induced effects. An excitation–inhibition (E/I) imbalance is implicated across several neurodevelopmental conditions (Selten et al., 2018). In children with autism, active tDCS increased α power, narrowed α bandwidth, alongside gains on the Autism Behaviour Checklist and the Social Responsiveness Scale; with no comparable changes occurred after sham tDCS, consistent with a shift towards more balanced E/I dynamics (Kang et al., 2025). Taken together, pathology-specific anatomy and physiology should be treated as moderators of both dose (electric field strength) and response, and must be considered when interpreting cortical excitability endpoints and designing disease-appropriate stimulation parameters.

2.2.3.4 Baseline excitability and state-dependence

The effects of tDCS may also be heavily impacted by baseline excitability and momentary brain state. For example, in the motor cortex, baseline excitability predicts the magnitude and sometimes the direction of plasticity after anodal or cathodal tDCS (Fresnoza et al., 2014). Applying tDCS during an active task directs current into the networks engaged by that task (e.g., frontoparietal or dorsal attention systems), leading to stronger and more specific plastic changes than stimulation at rest—demonstrating state dependence (Iordan et al., 2022). Similarly, when the default mode network (DMN) is dominant during internally focused thought, the current engages DMN-related regions rather than task-positive networks. In this context, stimulating DMN nodes alters the content of mind wandering—what people think about—without necessarily changing its frequency. This illustrates how ongoing cognitive state can redirect which networks are recruited by tDCS, reinforcing state dependence as a critical determinant of outcome. Together, baseline excitability and ongoing cognition govern which circuits are recruited and how durable plasticity will be. This highlights that controlling state and baseline excitability is crucial in determining tDCS effects.

2.2.3.5 Stimulation parameters

tDCS variability is heavily shaped by how you stimulate: intensity, duration, polarity, and timing interact in non-linear ways, so the same montage can potentiate, null, or even reverse expected effects (Lewis et al., 2025a). For example, raising cathodal dose from 1 mA for 20 min to 2 mA for 20 min in the motor cortex can flip inhibition to facilitation, and prolonging anodal stimulation can likewise reverse LTP-like after-effects (Batsikadze et al., 2013). Montage choices then determine where and how current actually impacts the cortex: electrode placement of both the anode and cathode shapes the intracranial electric field through individual skull and CSF anatomy, while the electric field direction relative to cortical columns selects different corticospinal inputs (e.g., posterior–anterior vs. anterior–posterior), changing recruitment patterns and effect sizes (Opitz et al., 2015). Electrode size and arrangement add more variance: smaller, high-definition 4 × 1 arrays increase current density and focality compared with conventional pads (Kuo et al., 2013), but behavioural and physiological advantages over standard bipolar tDCS are mixed across tasks and samples (Mattavelli et al., 2025). Protocol timing also has an important role in tDCS outcome: pairing stimulation online with training versus applying it offline (Bikson and Rahman, 2013), and spacing repeated sessions to leverage metaplasticity, can amplify or mute outcomes (Besson et al., 2020; Lewis et al., 2025b). Therefore, tDCS dose is multidimensional, and accounting for how these variables interact is critical for interpreting and optimising its neurophysiological effects (Laakso et al., 2019).

Together, this section has discussed the immediate and enduring effects of tDCS on the neuronal components of the brain. Immediate changes in membrane potential and firing rate and timing cause larger, more enduring effects on the functional connectivity between brain regions and cortical excitability that can last for hours or days after stimulation cessation. These enduring effects and, indeed, the overall effects of stimulation are moderated by neuromodulatory systems including GABA, glutamate, and dopamine, and are differentially impacted by factors including age, sex, disease state, as well as stimulation parameters. Importantly, the effects of tDCS on neurons are only one layer of how electricity can impact the brain. Several of the moderators outlined above also act through non-neuronal targets—including astrocyte-mediated glutamatergic–GABAergic homeostasis, neurovascular coupling, and immune signalling—which can, in turn, modulate cortical excitability. The next section examines these non-neuronal effects of tDCS.

3 The non-neuronal mechanisms underlying tDCS

While the majority of tDCS research has focused on neuronal targets, there is growing recognition that tDCS-induced electric fields also influence non-neuronal elements within the brain, potentially contributing to the broader outcomes of neuromodulation. As our understanding of brain plasticity advances, it is increasingly important to account for the integrated function of the entire neurovascular unit—including neurons, glia, vasculature, and supporting cells—rather than isolating effects to neuronal activity alone. Building on the mechanisms described in the previous sections, following sections focus on how tDCS interacts with non-neuronal components. Specifically, we explore two broad domains of influence: the vascular structures that support cerebral blood flow and metabolic exchange, and the non-vascular elements that include microglia, astrocytes and oligodendrocytes.

3.1 The vascular mechanisms underlying tDCS

Given the tight link between neural firing and perfusion, early work treated any tDCS-related haemodynamic change as a downstream consequence of altered neuronal demand. Recent data, however, paint a more complex picture. Across preparation and imaging modality, polarity- and dose-dependent shifts have been recorded in blood vessels of every size—from pial arteries to endothelial tight-junctions in the BBB—suggesting that the vasculature itself is an active target of stimulation, not merely a passive consequence of it (Khadka and Bikson, 2022; Phillips et al., 2015; Shin et al., 2020). Building on the work of Bahr-Hosseini and Bikson (2021), we add the most recent findings on the effects of tDCS on the vasculature and extend the review to the extracellular space: anodal currents have now been shown to enlarge extracellular space and accelerate the glymphatic interchange of cerebrospinal and interstitial fluids (Wang and Monai, 2024).

3.1.1 tDCS-induced effects on brain vasculature

Animal and human studies converge on the finding that tDCS produces polarity- and dose-dependent effects across the entire vascular tree. In rats, direct current pulses (10–20 V, 5–10 Hz) delivered to the exposed dura induce dilation of the middle meningeal artery in an intensity- and frequency-sensitive manner. Because this vasodilatory response persists even when the dura is physically separated from the underlying cortex, perivascular nerves rather than cortical neuronal activity appear to mediate the effect (Gozalov et al., 2008; Petersen et al., 2004; Kurosawa et al., 1995). Preclinical work further demonstrates similar dose-dependent changes in vascular diameter within larger cerebral arteries such as those in the circle of Willis (Emerson and Segal, 2001; Harder and Madden, 1987). Human experiments align with these observations: anodal tDCS reliably causes skin reddening and warmth due to superficial vessel dilation (Brunoni et al., 2011b; Durand et al., 2002) and modulates vasomotor reactivity of the middle cerebral artery, with montage-dependent, bilateral effects (List et al., 2015; Vernieri et al., 2004).

The microvasculature also exhibits direct susceptibility to stimulation. For instance, 10 min of low-intensity (0.1–1.5 mA) anodal stimulation applied across cultured brain endothelial monolayers increased permeability via electro-osmotic mechanisms, independently of neuronal activation (Cancel et al., 2018). Complementary in vivo studies show that 20 min sessions of 0.1–1 mA anodal tDCS transiently enhance BBB permeability to small (Na-fluorescein) and large (Dextran-70 kDa) solutes in rats (Shin et al., 2020). Multiphoton microscopy further reveals that tDCS accelerates solute diffusion throughout the extracellular matrix (Xia et al., 2020). However, in healthy humans, a single 20 min session of 2 mA anodal stimulation over the primary motor cortex did not alter salivary levels of S100B, a marker of BBB integrity, although subsequent exhaustive exercise did raise S100B concentrations. This suggests that a single session at typical therapeutic intensities is unlikely to significantly disrupt a healthy human BBB (Lewis et al., 2025c). Collectively, these findings strongly support the notion that cerebrovascular structures represent direct targets of tDCS, rather than merely reflecting secondary changes driven by neuronal activation. Future research needs to continue to quantify tDCS-induced changes in the BBB in humans using larger samples and more sensitive markers for BBB quantification.

3.1.2 tDCS effects on cerebrospinal-interstitial fluid flux

Beyond the vasculature itself, low-intensity anodal stimulation may have an impact on the brain’s glymphatic system, the peri-arterial pathway that moves cerebrospinal fluid (CSF) into the interstitial space (ISF) to wash away metabolic waste (Mestre et al., 2020). This bulk flow is largely driven by aquaporin-4 (AQP4) water channels concentrated in the end-feet of perivascular astrocytes (Mestre et al., 2018). In mice, a single 10 min, 0.1 mA session enlarged the extracellular space, accelerated both CSF ingress and ISF efflux, and sped tracer wash-out through cervical lymph nodes (Wang and Monai, 2024). The effect hinged on astrocytic Ca²⁺ signalling and coincided with a transient increase in delta-band EEG power, yet AQP4 abundance was unchanged within the first 30 min (Wang and Monai, 2024). By contrast, when the same tDCS polarity was delivered for 30 min daily over 2 months in 3 × Tg-AD mice, AQP4 expression rose persistently and glymphatic tracer transit quickened (Luo et al., 2022). Together, these studies suggest that anodal currents can acutely hasten both CSF influx and solute-laden ISF efflux via astrocytic signalling, and—when applied repeatedly—induce structural AQP4 changes that maintain enhanced clearance. Whether a comparable glymphatic acceleration occurs in humans remains untested, but the rodent data place fluid-exchange pathways, alongside blood vessels, as polarity-sensitive targets that may underscore part of the therapeutic profile of tDCS. Future research is needed to better understand the role of glymphatic exchange and the removal of metabolic waste and its relationship to neuronal plasticity.

3.2 The non-vascular mechanisms underlying tDCS

In addition to its effects on brain vasculature, tDCS has been found to modulate other non-neuronal cells within the neurovascular unit, including astrocytes, microglia, and oligodendrocytes. Recent findings have indicated these cells provide their own essential role in neuronal functions, including plasticity, challenging the outdated notion of their passive role in neuronal function (Di Castro et al., 2011; Haydon and Carmignoto, 2006; Panatier et al., 2011) and neuromodulation.

3.2.1 Astrocytes

Astrocytes are essential glial cells that regulate synaptic transmission and plasticity (Takata et al., 2011; Yang et al., 2003) by maintaining the extracellular environment (Verkhratsky et al., 2015), mediating energy substrate transfer from the bloodstream to neurons, and secreting bioactive molecules, thus contributing to the concept of a “tripartite synapse” (Perea et al., 2009). Given their role in LTP-like plasticity, tDCS-induced changes in astrocytic function may explain the effect of tDCS on synaptic plasticity. Recent findings suggest that anodal tDCS of 0.1 mA for 10 min results in cortex-wide, astrocytic derived Ca²⁺ elevations in mice (Monai et al., 2016). In addition, Cancel et al. (2022) investigated the effects of tDCS on the gene expression by astrocytes in mice. BDNF and FOS were chosen as markers of interest, as BDNF responsiveness relates to sensitivity to tDCS (Podda et al., 2016), and FOS is a reported marker of astrocytic activation (Rubio, 1997). The authors report FOS and BDNF gene upregulation in astrocytes in response to tDCS, providing further evidence of the role of astrocytes in tDCS-induced long-term effects. Using a different assessment of astrocytic activation, Callai et al. (2022) assessed astrocytic activation, also in mice, after tDCS via the quantification of S100B; an astrocytic derived protein. The authors report a significant increase in S100B in mouse CSF after 30 min of active tDCS, potentially indicating astrocytic activation. These findings suggest that the modulation of astrocytes may explain the long-term synaptic effects induced by tDCS. Drawing on similar mechanisms, future research should aim to better understand the relationship between astrocytic Ca+ signalling and its influence on glymphatic exchange and their combined influence on neuronal plasticity.

3.2.2 Microglia

Microglia are a major glial cell element of the CNS and play a critical role as the resident macrophage in the CNS (Kreutzberg, 1996; Perry and Gordon, 1988). They serve as scavenger cells in the event of infection, inflammation, trauma, ischemia, and neurodegeneration in the CNS (González-Scarano and Baltuch, 1999; McGeer and McGeer, 1995). Research exploring the impact of tDCS on microglia has been driven by the opportunity to use tDCS to leverage the inflammatory response mediated by microglia. One study on rodents demonstrated that under both the anodal and cathodal electrodes, tDCS increased the density of microglia within the stimulated brain region, suggesting a shift of microglia towards their active state during tDCS (Rueger et al., 2012). When active, these microglial cells are implicated in immunomodulatory and neurogenesis effects (Pikhovych et al., 2016). Another study examining the effects of multi-session tDCS on microglia report that stimulation led to a polarity-dependent downregulation of the expression of Iba1, a marker of microglial activation (Pikhovych et al., 2016). Mishima et al. (2019) report that tDCS induces subtle, but significant, alterations in microglial motility in the cerebral cortex in awake mice. This was later confirmed and extended upon by Gellner et al. (2021), who report a wide spectrum of characteristic microglia features that are promoted by anodal DCS, including activation state dependent motility, to phagocytosis. Extending these findings to pathological contexts, Oishi et al. (2024) showed that direct current stimulation in mice with spinal cord injury facilitated motor function recovery by suppressing microglial hyperactivity in the damaged spinal cord. Similarly, Cherchi et al. (2022) demonstrated that cathodal tDCS improved outcomes following cerebral ischemia, with motor recovery associated with reduced microglial density, a shift towards more ramified and complex morphologies, and a corresponding attenuation of phagocytic, pro-inflammatory activity in perilesional regions. Together, these findings underscore that microglia are not only dynamically modulated by tDCS under physiological conditions but are also recruited in response to CNS damage, where their activity appears to mediate functional recovery.

In summary, current evidence establishes that tDCS can influence microglial density, motility, and morphology, with effects that vary according to polarity and experimental context. While studies in both healthy and damaged tissue converge on the capacity of tDCS to modulate microglial activation states, the precise mechanisms governing these responses, and their downstream contribution to neuroprotection or maladaptive inflammation, remain uncertain. Future research should prioritise delineating polarity- and region-specific effects of tDCS on microglia, clarifying whether these changes represent causal drivers of behavioural recovery, and systematically testing their relevance in translational models of CNS injury and disease.

3.2.3 Oligodendrocytes

Oligodendrocytes play a vital role in myelinating axons in the CNS, enabling rapid electrical transmission through saltatory conduction of action potentials (Simons and Nave, 2016). The process of myelination and myelin repair relies in part on oligodendrogenesis, involving the migration, maturation, and differentiation of oligodendrocyte precursor cells into mature oligodendrocytes (Bradl and Lassmann, 2010). Currently, there is limited information regarding the effects of tDCS on oligodendrocytes, myelination, and remyelination of diseased cells. One in vivo study in rodents found an increase in oligodendrocyte-specific progenitor cells in the pyramidal tract after multiple days of tDCS stimulation, suggesting a potential avenue for investigating tDCS effects on oligodendrocyte production (Li et al., 2010). A single study has explored the potential of tDCS to enhance remyelination. In a mouse model using cuprizone-induced demyelination, researchers observed that tDCS treatment resulted in a greater degree of remyelination compared to the control group (Mojaverrostami et al., 2022). Furthermore, the combination of tDCS with mesenchymal stem cell transplantation further enhanced remyelination. Collectively, these findings indicate that tDCS may promote oligodendrocyte activation and remyelination processes, though the evidence remains preliminary. While existing evidence then appears to indicate oligodendrocyte activation following tDCS, additional research, including human trials, is needed. Future research in animal models that investigate the influence of tDCS-induced remyelination and its clinical utility for neurodegenerative diseases should be conducted before we can explore potential consequences for human behaviour.

In summary, available studies establish that tDCS can increase oligodendrocyte precursor cell proliferation and, under demyelinating conditions, facilitate remyelination, particularly when combined with adjunctive therapies. However, the evidence is sparse, limited to animal models, and the underlying mechanisms—whether through direct modulation of oligodendrocyte precursor cell differentiation, altered neuroinflammation, or secondary effects on neuronal activity—remain unresolved. Future research should aim to clarify the cellular pathways through which tDCS influences oligodendrogenesis and remyelination, and to determine whether these effects can be replicated in humans and leveraged for therapeutic benefit in demyelinating and neurodegenerative diseases.

3.2.4 Immuno-metabolic responses to tDCS

Recent transcriptomic, proteomic, and metabolomic studies have begun to clarify how low-intensity tDCS initiates coordinated molecular adaptations extending far beyond acute membrane polarisation (Lee et al., 2022). Early RNA sequencing experiments in healthy rats demonstrated that even a single anodal session, depending on intensity, altered the expression of approximately one thousand cortical transcripts, notably influencing genes involved in inflammation, calcium-binding, and multiple neurotransmitter-receptor signalling pathways (Holmes et al., 2016). Chronic applications of tDCS further refine this picture, revealing a distinct neurotrophic profile linked to enhanced neurogenesis: genes promoting growth and survival (SOS, Raf, PI3K, Rac1, IRAK, and Bax) are consistently upregulated, while negative regulators of these processes (CHK, Crk, Rap1, p38, Ras, and NF-κB) are downregulated (Lee et al., 2022). Complementary metabolomic analyses have shown that tDCS influences metabolic pathways critical to mitochondria and bioenergetics, notably glycolysis and the tricarboxylic acid (TCA) cycle, speculated via calcium signalling pathways (Agrawal et al., 2024).

Immune genes display polarity-specific and time-sensitive responses. Within hours, anodal stimulation applied to rat brain upregulates major histocompatibility complex-I (MHC-I) transcripts, potentially enhancing neuronal tagging for microglial surveillance, thus limiting excessive sprouting. Conversely, cathodal currents elevate osteopontin, a protein associated with microglial polarisation towards a neuroprotective phenotype and promoting stem-cell proliferation (Rabenstein et al., 2019). Such polarity-dependent immune modulation is reflected functionally in disease models. For example, Liu et al. (2025) demonstrated that repeated anodal tDCS treatments shifted pro-inflammatory M1 microglia and neurotoxic A1 astrocytes towards anti-inflammatory M2 and protective A2 phenotypes, respectively. This shift suppressed the NF-κB → NLRP3 → IL-18 signalling axis, alleviating chronic pain symptoms in a rat osteoarthritis model. Proteomic analyses further enrich these transcriptomic findings by highlighting molecular changes directly at the synaptic level. Jung et al. (2019) reported that anodal tDCS administered prior to memory acquisition improved long-term memory performance and significantly altered the abundance of 184 hippocampal synaptoneurosome proteins, particularly those linked to glutamate receptors, ion-channel dynamics, and long-term potentiation scaffolds such as SHANK, GRIN, and GRIA. Extending these insights into disease models, Magri et al. (2021) found that tDCS selectively remodelled the blood transcriptome in 3 × Tg-AD mice but not in wild-type animals, suggesting potential peripheral biomarkers to track therapeutic responses in neurodegenerative conditions.

These studies highlight tDCS as a potent, context-dependent modulator of immunometabolic gene expression. By modulating neurogenic and metabolic gene networks, tDCS induces neuronal growth, plasticity, and improved energetic efficiency. Its ability to modulate immune pathways can either heighten microglial surveillance or establish a reparative microenvironment, contingent upon polarity and dose. At the synapse, tDCS adjusts protein expression to support sustained plasticity and memory formation. However, it must be noted that much of the research on immune-metabolic responses to tDCS have been conducted in vivo. Therefore, future research should extend beyond animal models and continue to use transcriptomics and proteomics in humans to better understand the genetic adaptations that occur after acute and chronic applications of tDCS. This is crucial for developing targeted stimulation protocols that maximise therapeutic plasticity while avoiding maladaptive immune or metabolic responses.

4 Clinical implications

The evidence that tDCS impacts the whole neurovascular unit has direct implications for approaches to how stimulation should be applied in clinical settings. One immediate implication relates to electrode placement. Current modelling studies and experimental data both highlight that electric fields are not uniformly distributed but instead interact with elements of the neurovascular unit, including astrocytes and capillary beds (Khadka and Bikson, 2022; Cancel et al., 2022). Placement strategies that account for these components of the neurovascular unit—beyond conventional EEG 10–20 coordinates—may yield more predictable modulation of target pathways, or prove to be more effective targets for therapeutic outcomes. For instance, positioning electrodes relative to denser vascular networks or ischemic areas could influence local changes in blood flow, BBB permeability, or extracellular ion clearance, thereby amplifying or constraining a broad range of behavioural outcomes.

A second consideration is polarity selection. While anodal stimulation has traditionally been associated with excitatory effects and cathodal with inhibitory effects, the evidence reviewed here indicates that polarity also governs non-neuronal processes. Anodal tDCS has been shown to promote BDNF expression, Ca²⁺-dependent signalling cascades, and oligodendrocyte progenitor differentiation (Monai et al., 2016; Mojaverrostami et al., 2022), processes potentially beneficial in pathological state recovery and remyelination contexts. Conversely, cathodal stimulation may attenuate hyperexcitability and reduce pro-inflammatory responses by modulating microglial motility and astrocytic activity (Monai et al., 2016). These polarity-specific pathways suggest that beyond traditional approaches to increase or decrease cortical excitability, researchers may also be able to shape molecular and cellular environments in line with therapeutic objectives.

Finally, insights into the broader patient phenotype underscore the importance of individualised approaches. Patients with altered BBB integrity, chronic inflammation, or demyelinating conditions may show distinct responsiveness to stimulation (Rossi et al., 2024; Shen et al., 2024). For example, tDCS-induced increases in BBB permeability could pose additional risks in acute injury contexts but may conversely facilitate drug delivery in carefully controlled scenarios (Petrovskaya et al., 2023). Similarly, in individuals with compromised vascular health, tDCS-evoked modulation of arterioles and capillaries may interact with baseline perfusion status in ways that alter efficacy (Peruzzotti-Jametti et al., 2013). These findings suggest that incorporating a broader understanding of the neurovascular unit profile should guide candidate selection and stimulation parameters to achieve more appropriate and effective therapeutic outcomes.

Taken together, these clinical implications show that translation of mechanistic findings requires moving beyond a neuron-centric model. Because tDCS acts on the neurovascular unit as a whole (see Table 1 for summary), choices regarding optimising clinical outcomes including electrode placement, polarity, and patient selection should be guided by cellular and systems-level interactions. Accounting for these dynamics offers a route to more targeted and effective therapeutic outcomes.

Table 1

Table 1. Summary of the effects of direct current stimulation on elements of the neurovascular unit.

5 Conclusion

This narrative review has highlighted the diverse and complex neurophysiological effects of tDCS across multiple components of the neurovascular unit. While neuronal outcomes remain the most extensively studied aspect of tDCS physiology, findings of acute effects at both single-neuron and network levels remain notably inconsistent, likely due to variability in current flow, directionality, and methodological limitations. Although more consistent evidence exists regarding the long-term influences of tDCS, including effects on synaptic plasticity mechanisms such as LTP and LTD, the direct relationships between these physiological changes and meaningful behavioural or cognitive outcomes remain underexplored.

Importantly, emerging evidence indicates that tDCS effects extend beyond neurons alone, significantly modulating vascular function, BBB permeability, astrocytes, microglia, and oligodendrocytes. Recent studies employing transcriptomic, proteomic, and metabolomic techniques demonstrate that tDCS initiates molecular adaptations affecting inflammatory pathways, neurotrophic signalling, calcium-dependent processes, mitochondrial function, and synaptic proteins critical to long-term potentiation. The neurovascular unit thus represents an integrative and complex target of tDCS, suggesting that comprehensive modulation of these components collectively may better explain observed changes in cognitive, behavioural, and neuropsychological outcomes. Future research should move beyond a neuron-centric perspective to fully embrace a more integrative framework that considers interactions amongst all elements of the neurovascular unit. Such a holistic approach will enhance our understanding of how tDCS exerts its effects, thereby improving its therapeutic and cognitive-enhancement potential.

Author contributions

AL: Conceptualization, Writing – review & editing, Writing – original draft. BR: Supervision, Writing – original draft, Writing – review & editing. AF: Supervision, Writing – original draft, Writing – review & editing.

Funding

The author(s) declare that financial support was received for the research and/or publication of this article. This work was supported by research block grant funding allocated to the Research Training Program and Research Support Program at the University of Canberra. This work was partly funded by the dtec.bw—Digitalization and Technology Research Center of the Bundeswehr (MEXT project) and the University of the Bundeswehr Munich. The dtec.bw was funded by the European Union—NextGenerationEU.

Conflict of interest

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision.

Generative AI statement

The authors declare that no Gen AI was used in the creation of this manuscript.

Any alternative text (alt text) provided alongside figures in this article has been generated by Frontiers with the support of artificial intelligence and reasonable efforts have been made to ensure accuracy, including review by the authors wherever possible. If you identify any issues, please contact us.

Publisher’s note

All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.

References

Agrawal, B., Boulos, S., Khatib, S., Feuermann, Y., Panov, J., and Kaphzan, H. (2024). Molecular insights into transcranial direct current stimulation effects: metabolomics and transcriptomics analyses. Cells Internet 13:205. doi: 10.3390/cells13030205

PubMed Abstract | Crossref Full Text | Google Scholar

Amadi, U., Ilie, A., Johansen-Berg, H., and Stagg, C. J. (2014). Polarity-specific effects of motor transcranial direct current stimulation on fMRI resting state networks. NeuroImage 88, 155–161. doi: 10.1016/j.neuroimage.2013.11.037

PubMed Abstract | Crossref Full Text | Google Scholar

Andreasen, M., and Nedergaard, S. (1996). Dendritic electrogenesis in rat hippocampal CA1 pyramidal neurons: functional aspects of Na+ and Ca2+ currents in apical dendrites. Hippocampus 6, 79–95. doi: 10.1002/(SICI)1098-1063(1996)6:1<79::AID-HIPO13>3.0.CO;2-H

PubMed Abstract | Crossref Full Text | Google Scholar

Antonenko, D., Schubert, F., Bohm, F., Ittermann, B., Aydin, S., Hayek, D., et al. (2017). tDCS-induced modulation of GABA levels and resting-state functional connectivity in older adults. J. Neurosci. 37, 4065–4073. doi: 10.1523/JNEUROSCI.0079-17.2017

PubMed Abstract | Crossref Full Text | Google Scholar

Arckens, L., Schweigart, G., Qu, Y., Wouters, G., Pow, D. V., Vandesande, F., et al. (2000). Cooperative changes in GABA, glutamate and activity levels: the missing link in cortical plasticity. Eur. J. Neurosci. 12, 4222–4232. doi: 10.1046/j.0953-816X.2000.01328.x

PubMed Abstract | Crossref Full Text | Google Scholar

Auerbach, J. M., and Segal, M. (1996). Muscarinic receptors mediating depression and long-term potentiation in rat hippocampus. J. Physiol. 492, 479–493. doi: 10.1113/jphysiol.1996.sp021323

PubMed Abstract | Crossref Full Text | Google Scholar

Bahr-Hosseini, M., and Bikson, M. (2021). Neurovascular-modulation: A review of primary vascular responses to transcranial electrical stimulation as a mechanism of action. Brain Stimul. 14, 837–847. doi: 10.1016/j.brs.2021.04.015

PubMed Abstract | Crossref Full Text | Google Scholar

Batsikadze, G., Moliadze, V., Paulus, W., Kuo, M. F., and Nitsche, M. A. (2013). Partially non-linear stimulation intensity-dependent effects of direct current stimulation on motor cortex excitability in humans. J. Physiol. 591, 1987–2000. doi: 10.1113/jphysiol.2012.249730

PubMed Abstract | Crossref Full Text | Google Scholar

Baxter, B. S., Edelman, B. J., Sohrabpour, A., and He, B. (2017). Anodal transcranial direct current stimulation increases bilateral directed brain connectivity during motor-imagery based brain-computer interface control. Front. Neurosci. 11:691. doi: 10.3389/fnins.2017.00691

PubMed Abstract | Crossref Full Text | Google Scholar

Bergmann, T. O., Groppa, S., Seeger, M., Mölle, M., Marshall, L., and Siebner, H. R. (2009). Acute changes in motor cortical excitability during slow oscillatory and constant anodal transcranial direct current stimulation. J. Neurophysiol. 102, 2303–2311. doi: 10.1152/jn.00437.2009

PubMed Abstract | Crossref Full Text | Google Scholar

Besson, P., Muthalib, M., De Vassoigne, C., Rothwell, J., and Perrey, S. (2020). Effects of multiple sessions of cathodal priming and anodal HD-tDCS on visuo motor task plateau learning and retention. Brain Sci. 10:875. doi: 10.3390/brainsci10110875

PubMed Abstract | Crossref Full Text | Google Scholar

Bestmann, S., de Berker, A. O., and Bonaiuto, J. (2015). Understanding the behavioural consequences of noninvasive brain stimulation. Trends Cogn. Sci. 19, 13–20. doi: 10.1016/j.tics.2014.10.003

PubMed Abstract | Crossref Full Text | Google Scholar

Bikson, M., Inoue, M., Akiyama, H., Deans, J. K., Fox, J. E., Miyakawa, H., et al. (2004). Effects of uniform extracellular DC electric fields on excitability in rat hippocampal slices in vitro. J. Physiol. 557, 175–190. doi: 10.1113/jphysiol.2003.055772

PubMed Abstract | Crossref Full Text | Google Scholar

Bikson, M., Paulus, W., Esmaeilpour, Z., Kronberg, G., and Nitsche, M. A. (2019). “Mechanisms of acute and after effects of transcranial direct current stimulation” in Practical guide to transcranial direct current stimulation: Principles, procedures and applications. eds. H. Knotkova, M. A. Nitsche, M. Bikson, and A. J. Woods (Cham: Springer International Publishing), 81–113.

Google Scholar

Bikson, M., and Rahman, A. (2013). Origins of specificity during tDCS: anatomical, activity-selective, and input-bias mechanisms. Front. Hum. Neurosci. 7:688. doi: 10.3389/fnhum.2013.00688

PubMed Abstract | Crossref Full Text | Google Scholar

Bindman, L. J., Lippold, O. C., and Redfearn, J. W. (1964). The action of brief polarizing currents on the cerebral cortex of the rat (1) during current flow and (2) in the production of long-lasting after-effects. J. Physiol. 172, 369–382. doi: 10.1113/jphysiol.1964.sp007425

PubMed Abstract | Crossref Full Text | Google Scholar

Blitzer, R. D., Gil, O., Omri, G., and Landau, E. M. (1991). Nifedipine blocks calcium-dependent cholinergic depolarization in the guinea pig hippocampus. Brain Res. 542, 293–299. doi: 10.1016/0006-8993(91)91581-K

PubMed Abstract | Crossref Full Text | Google Scholar

Bradl, M., and Lassmann, H. (2010). Oligodendrocytes: biology and pathology. Acta Neuropathol. 119, 37–53. doi: 10.1007/s00401-009-0601-5

PubMed Abstract | Crossref Full Text | Google Scholar

Brunelin, J., Mondino, M., Gassab, L., Haesebaert, F., Gaha, L., Suaud-Chagny, M.-F., et al. (2012). Examining transcranial direct-current stimulation (tDCS) as a treatment for hallucinations in schizophrenia. Am. J. Psychiatry 169, 719–724. doi: 10.1176/appi.ajp.2012.11071091

PubMed Abstract | Crossref Full Text | Google Scholar

Brunoni, A. R., Amadera, J., Berbel, B., Volz, M. S., Rizzerio, B. G., and Fregni, F. (2011b). A systematic review on reporting and assessment of adverse effects associated with transcranial direct current stimulation. Int. J. Neuropsychopharmacol. 14, 1133–1145. doi: 10.1017/S1461145710001690

PubMed Abstract | Crossref Full Text | Google Scholar

Brunoni, A. R., Fregni, F., and Pagano, R. L. (2011a). Translational research in transcranial direct current stimulation (tDCS): a systematic review of studies in animals. Rev. Neurosci. 22, 471–481. doi: 10.1515/rns.2011.042

PubMed Abstract | Crossref Full Text | Google Scholar

Buzsáki, G., and Draguhn, A. (2004). Neuronal oscillations in cortical networks. Science 304, 1926–1929. doi: 10.1126/science.1099745

PubMed Abstract | Crossref Full Text | Google Scholar

Callai, E. M. M., Zin, L. E. F., Catarina, L. S., Ponzoni, D., Gonçalves, C. A. S., Vizuete, A. F. K., et al. (2022). Evaluation of the immediate effects of a single transcranial direct current stimulation session on astrocyte activation, inflammatory response, and pain threshold in naïve rats. Behav. Brain Res. 428:113880. doi: 10.1016/j.bbr.2022.113880

PubMed Abstract | Crossref Full Text | Google Scholar

Cancel, L. M., Arias, K., Bikson, M., and Tarbell, J. M. (2018). Direct current stimulation of endothelial monolayers induces a transient and reversible increase in transport due to the electroosmotic effect. Sci. Rep. 8, 1–13. doi: 10.1038/s41598-018-27524-9

PubMed Abstract | Crossref Full Text | Google Scholar

Cancel, L. M., Silas, D., Bikson, M., and Tarbell, J. M. (2022). Direct current stimulation modulates gene expression in isolated astrocytes with implications for glia-mediated plasticity. Sci. Rep. 12:17964. doi: 10.1038/s41598-022-22394-8

PubMed Abstract | Crossref Full Text | Google Scholar

Chan, M. M. Y., and Han, Y. M. Y. (2020). The effect of transcranial direct current stimulation in changing resting-state functional connectivity in patients with neurological disorders: a systematic review. J. Cent. Nerv. Syst. Dis. 12:1179573520976832. doi: 10.1177/1179573520976832

PubMed Abstract | Crossref Full Text | Google Scholar

Chan, C. Y., Hounsgaard, J., and Nicholson, C. (1988). Effects of electric fields on transmembrane potential and excitability of turtle cerebellar Purkinje cells in vitro. J. Physiol. 402, 751–771. doi: 10.1113/jphysiol.1988.sp017232

PubMed Abstract | Crossref Full Text | Google Scholar

Chan, M. M. Y., Yau, S. S. Y., and Han, Y. M. Y. (2021). The neurobiology of prefrontal transcranial direct current stimulation (tDCS) in promoting brain plasticity: a systematic review and meta-analyses of human and rodent studies. Neurosci. Biobehav. Rev. 125, 392–416. doi: 10.1016/j.neubiorev.2021.02.035

PubMed Abstract | Crossref Full Text | Google Scholar

Cherchi, L., Anni, D., Buffelli, M., and Cambiaghi, M. (2022). Early application of ipsilateral cathodal-tDCS in a mouse model of brain ischemia results in functional improvement and perilesional microglia modulation. Biomolecules 12:588. doi: 10.3390/biom12040588

PubMed Abstract | Crossref Full Text | Google Scholar

Chew, T., Ho, K.-A., and Loo, C. K. (2015). Inter- and intra-individual variability in response to transcranial direct current stimulation (tDCS) at varying current intensities. Brain Stimul. 8, 1130–1137. doi: 10.1016/j.brs.2015.07.031

PubMed Abstract | Crossref Full Text | Google Scholar

Ciechanski, P., Carlson, H. L., Yu, S. S., and Kirton, A. (2018). Modeling transcranial direct-current stimulation-induced electric fields in children and adults. Front. Hum. Neurosci. 12:268. doi: 10.3389/fnhum.2018.00268

Crossref Full Text | Google Scholar

Citri, A., and Malenka, R. C. (2008). Synaptic plasticity: multiple forms, functions, and mechanisms. Neuropsychopharmacology 33, 18–41. doi: 10.1038/sj.npp.1301559

PubMed Abstract | Crossref Full Text | Google Scholar

Cork, R. J., McGinnis, M. E., Tsai, J., and Robinson, K. R. (1994). The growth of PC-12 neurites is biased towards the anode of an applied electrical field. J. Neurobiol. 25, 1509–1516. doi: 10.1002/neu.480251204

PubMed Abstract | Crossref Full Text | Google Scholar

Creutzfeldt, O. D., Fromm, G. H., and Kapp, H. (1962). Influence of transcortical d-c currents on cortical neuronal activity. Exp. Neurol. 5, 436–452. doi: 10.1016/0014-4886(62)90056-0

Crossref Full Text | Google Scholar

Datta, A., Bansal, V., Diaz, J., Patel, J., Reato, D., and Bikson, M. (2009). Gyri-precise head model of transcranial direct current stimulation: improved spatial focality using a ring electrode versus conventional rectangular pad. Brain Stimul. 2, 201–207.e1. doi: 10.1016/j.brs.2009.03.005

PubMed Abstract | Crossref Full Text | Google Scholar

Day, P., Twiddy, J., and Dubljević, V. (2022). Present and emerging ethical issues with tDCS use: a summary and review. Neuroethics 16:1. doi: 10.1007/s12152-022-09508-9

Crossref Full Text | Google Scholar

De Luca, C., Colangelo, A. M., Virtuoso, A., Alberghina, L., and Papa, M. (2020). Neurons, glia, extracellular matrix and neurovascular unit: a systems biology approach to the complexity of synaptic plasticity in health and disease. Int. J. Mol. Sci. 21:1539. doi: 10.3390/ijms21041539

PubMed Abstract | Crossref Full Text | Google Scholar

Di Castro, M. A., Chuquet, J., Liaudet, N., Bhaukaurally, K., Santello, M., Bouvier, D., et al. (2011). Local Ca2+ detection and modulation of synaptic release by astrocytes. Nat. Neurosci. 14, 1276–1284. doi: 10.1038/nn.2929

PubMed Abstract | Crossref Full Text | Google Scholar

Durand, S., Fromy, B., Bouyé, P., Saumet, J. L., and Abraham, P. (2002). Vasodilatation in response to repeated anodal current application in the human skin relies on aspirin-sensitive mechanisms. J. Physiol. 540, 261–269. doi: 10.1113/jphysiol.2001.013364

PubMed Abstract | Crossref Full Text | Google Scholar

Emerson, G. G., and Segal, S. S. (2001). Electrical activation of endothelium evokes vasodilation and hyperpolarization along hamster feed arteries. Am. J. Phys. Heart Circ. Phys. 280, H160–H167. doi: 10.1152/ajpheart.2001.280.1.H160

PubMed Abstract | Crossref Full Text | Google Scholar

Erskine, L., and McCaig, C. D. (1995). Growth cone neurotransmitter receptor activation modulates electric field-guided nerve growth. Dev. Biol. 171, 330–339. doi: 10.1006/dbio.1995.1285

PubMed Abstract | Crossref Full Text | Google Scholar

Farahani, F., Khadka, N., Parra, L. C., Bikson, M., and Vöröslakos, M. (2024). Transcranial electric stimulation modulates firing rate at clinically relevant intensities. Brain Stimul. 17, 561–571. doi: 10.1016/j.brs.2024.04.007

PubMed Abstract | Crossref Full Text | Google Scholar

Farahani, F., Kronberg, G., FallahRad, M., Oviedo, H. V., and Parra, L. C. (2021). Effects of direct current stimulation on synaptic plasticity in a single neuron. Brain Stimul. 14, 588–597. doi: 10.1016/j.brs.2021.03.001

PubMed Abstract | Crossref Full Text | Google Scholar

Fjell, A. M., Walhovd, K. B., Fennema-Notestine, C., McEvoy, L. K., Hagler, D. J., Holland, D., et al. (2010). Brain atrophy in healthy aging is related to CSF levels of Aβ1-42. Cereb. Cortex 20, 2069–2079. doi: 10.1093/cercor/bhp279

Crossref Full Text | Google Scholar

Fresnoza, S., Kuo, M. F., Paulus, W., and Nitsche, M. A. (2014). Impact of baseline excitability on tDCS-induced plasticity. Brain Stimul. 7:e12. doi: 10.1016/j.brs.2014.01.043

Crossref Full Text | Google Scholar

Fricke, K., Seeber, A. A., Thirugnanasambandam, N., Paulus, W., Nitsche, M. A., and Rothwell, J. C. (2010). Time course of the induction of homeostatic plasticity generated by repeated transcranial direct current stimulation of the human motor cortex. J. Neurophysiol. 105, 1141–1149. doi: 10.1152/jn.00608.2009

Crossref Full Text | Google Scholar

Fritsch, B., Reis, J., Martinowich, K., Schambra, H. M., Ji, Y., Cohen, L. G., et al. (2010). Direct current stimulation promotes BDNF-dependent synaptic plasticity: potential implications for motor learning. Neuron 66, 198–204. doi: 10.1016/j.neuron.2010.03.035

PubMed Abstract | Crossref Full Text | Google Scholar

Garcia, S., Nalven, M., Ault, A., and Eskenazi, M. A. (2020). tDCS as a treatment for anxiety and related cognitive deficits. Int. J. Psychophysiol. 158, 172–177. doi: 10.1016/j.ijpsycho.2020.10.006

PubMed Abstract | Crossref Full Text | Google Scholar

García-González, S., Lugo-Marín, J., Setien-Ramos, I., Gisbert-Gustemps, L., Arteaga-Henríquez, G., Díez-Villoria, E., et al. (2021). Transcranial direct current stimulation in autism Spectrum disorder: A systematic review and meta-analysis. Eur. Neuropsychopharmacol. 48, 89–109. doi: 10.1016/j.euroneuro.2021.02.017

PubMed Abstract | Crossref Full Text | Google Scholar

Gellner, A.-K., Reis, J., Fiebich, B. L., and Fritsch, B. (2021). Electrified microglia: impact of direct current stimulation on diverse properties of the most versatile brain cell. Brain Stimul. 14, 1248–1258. doi: 10.1016/j.brs.2021.08.007

PubMed Abstract | Crossref Full Text | Google Scholar

Ghanavati, E., Salehinejad, M. A., Beaupain, M. C., Melo, L., Frese, A., Kuo, M.-F., et al. (2025). Contribution of glutamatergic and GABAergic mechanisms to the plasticity-modulating effects of dopamine in the human motor cortex. Hum. Brain Mapp. 46:e70162. doi: 10.1002/hbm.70162

PubMed Abstract | Crossref Full Text | Google Scholar

González-Scarano, F., and Baltuch, G. (1999). Microglia as mediators of inflammatory and degenerative diseases. Annu. Rev. Neurosci. 22, 219–240. doi: 10.1146/annurev.neuro.22.1.219

Crossref Full Text | Google Scholar

Gordon, P. C., Zrenner, C., Desideri, D., Belardinelli, P., Zrenner, B., Brunoni, A. R., et al. (2018). Modulation of cortical responses by transcranial direct current stimulation of dorsolateral prefrontal cortex: A resting-state EEG and TMS-EEG study. Brain Stimul. 11, 1024–1032. doi: 10.1016/j.brs.2018.06.004

PubMed Abstract | Crossref Full Text | Google Scholar

Gozalov, A., Jansen-Olesen, I., Klaerke, D., and Olesen, J. (2008). Role of KATP channels in cephalic vasodilatation induced by calcitonin gene-related peptide, nitric oxide, and transcranial electrical stimulation in the rat. Headache 48, 1202–1213. doi: 10.1111/j.1526-4610.2008.01205.x

PubMed Abstract | Crossref Full Text | Google Scholar

Harder, D. R., and Madden, J. A. (1987). Electrical stimulation of the endothelial surface of pressurized cat middle cerebral artery results in TTX-sensitive vasoconstriction. Circ. Res. 60, 831–836. doi: 10.1161/01.RES.60.6.831

PubMed Abstract | Crossref Full Text | Google Scholar

Hasselmo, M. E., and Barkai, E. (1995). Cholinergic modulation of activity-dependent synaptic plasticity in the piriform cortex and associative memory function in a network biophysical simulation. J. Neurosci. 15, 6592–6604. doi: 10.1523/JNEUROSCI.15-10-06592.1995

PubMed Abstract | Crossref Full Text | Google Scholar

Haydon, P. G., and Carmignoto, G. (2006). Astrocyte control of synaptic transmission and neurovascular coupling. Physiol. Rev. 86, 1009–1031. doi: 10.1152/physrev.00049.2005

PubMed Abstract | Crossref Full Text | Google Scholar

Heise, K.-F., Rueda-Delgado, L., Chalavi, S., King, B. R., Monteiro, T. S., Edden, R. A. E., et al. (2022). The interaction between endogenous GABA, functional connectivity, and behavioral flexibility is critically altered with advanced age. Commun. Biol. 5:426. doi: 10.1038/s42003-022-03378-w

PubMed Abstract | Crossref Full Text | Google Scholar

Holmes, B., Jung, S. H., Lu, J., Wagner, J. A., Rubbi, L., Pellegrini, M., et al. (2016). Transcriptomic modification in the cerebral cortex following noninvasive brain stimulation: RNA-sequencing approach. Neural Plast. 2016, 1–15. doi: 10.1155/2016/5942980

PubMed Abstract | Crossref Full Text | Google Scholar

Horvath, J. C., Carter, O., and Forte, J. D. (2014). Transcranial direct current stimulation: five important issues we aren't discussing (but probably should be). Front. Syst. Neurosci. 8:8. doi: 10.3389/fnsys.2014.00002

PubMed Abstract | Crossref Full Text | Google Scholar

Horvath, J. C., Forte, J. D., and Carter, O. (2015). Evidence that transcranial direct current stimulation (tDCS) generates little-to-no reliable neurophysiologic effect beyond MEP amplitude modulation in healthy human subjects: A systematic review. Neuropsychologia 66, 213–236. doi: 10.1016/j.neuropsychologia.2014.11.021

PubMed Abstract | Crossref Full Text | Google Scholar

Huang, Y., Liu, A. A., Lafon, B., Friedman, D., Dayan, M., Wang, X., et al. (2017). Measurements and models of electric fields in the in vivo human brain during transcranial electric stimulation. eLife 6:e18834. doi: 10.7554/eLife.18834

PubMed Abstract | Crossref Full Text | Google Scholar

Hulme, S. R., Jones, O. D., Raymond, C. R., Sah, P., and Abraham, W. C. (2014). Mechanisms of heterosynaptic metaplasticity. Philos. Trans. R. Soc. Lond. B Biol. Sci. 369:20130148. doi: 10.1098/rstb.2013.0148

PubMed Abstract | Crossref Full Text | Google Scholar

Hunter, M. A., Coffman, B. A., Gasparovic, C., Calhoun, V. D., Trumbo, M. C., and Clark, V. P. (2015). Baseline effects of transcranial direct current stimulation on glutamatergic neurotransmission and large-scale network connectivity. Brain Res. 1594, 92–107. doi: 10.1016/j.brainres.2014.09.066

PubMed Abstract | Crossref Full Text | Google Scholar

Indahlastari, A., Albizu, A., O’Shea, A., Forbes, M. A., Nissim, N. R., Kraft, J. N., et al. (2020). Modeling transcranial electrical stimulation in the aging brain. Brain Stimul. 13, 664–674. doi: 10.1016/j.brs.2020.02.007

Crossref Full Text | Google Scholar

Iordan, A. D., Ryan, S., Tyszkowski, T., Peltier, S. J., Rahman-Filipiak, A., and Hampstead, B. M. (2022). High-definition transcranial direct current stimulation enhances network segregation during spatial navigation in mild cognitive impairment. Cereb. Cortex 32, 5230–5241. doi: 10.1093/cercor/bhac010

PubMed Abstract | Crossref Full Text | Google Scholar

Jamil, A., Batsikadze, G., Kuo, H.-I., Labruna, L., Hasan, A., Paulus, W., et al. (2017). Systematic evaluation of the impact of stimulation intensity on neuroplastic after-effects induced by transcranial direct current stimulation. J. Physiol. 595, 1273–1288. doi: 10.1113/JP272738

PubMed Abstract | Crossref Full Text | Google Scholar

Jiang, T., Xu, R. X., Zhang, A. W., Di, W., Xiao, Z. J., Miao, J. Y., et al. (2012). Effects of transcranial direct current stimulation on hemichannel pannexin-1 and neural plasticity in rat model of cerebral infarction. Neuroscience 226, 421–426. doi: 10.1016/j.neuroscience.2012.09.035

PubMed Abstract | Crossref Full Text | Google Scholar

Jung, S. H., Hatcher-Solis, C., Moore, R., Bechmann, N., Harshman, S., Martin, J., et al. (2019). Noninvasive brain stimulation enhances memory acquisition and is associated with synaptoneurosome modification in the rat hippocampus. eNeuro 6:ENEURO.0311-19.2019. doi: 10.1523/ENEURO.0311-19.2019

Crossref Full Text | Google Scholar

Kabakov, A. Y., Muller, P. A., Pascual-Leone, A., Jensen, F. E., and Rotenberg, A. (2012). Contribution of axonal orientation to pathway-dependent modulation of excitatory transmission by direct current stimulation in isolated rat hippocampus. J. Neurophysiol. 107, 1881–1889. doi: 10.1152/jn.00715.2011

PubMed Abstract | Crossref Full Text | Google Scholar

Kang, C., Li, Y., Mao, W., Wu, J., and Li, X. (2025). Effects of transcranial direct current stimulation on excitatory/inhibitory balance and behavior in children with autism—a randomized controlled study. Alpha Psychiatry 26:46111. doi: 10.31083/AP46111

Crossref Full Text | Google Scholar

Khadka, N., and Bikson, M. (2022). Neurocapillary-modulation. Neuromodulation Technol. Neural Interface 25, 1299–1311. doi: 10.1111/ner.13338

PubMed Abstract | Crossref Full Text | Google Scholar

Klees-Themens, G., and Théoret, H. (2023). The effects of transcranial direct current stimulation on corticospinal excitability: A systematic review of nonsignificant findings. Eur. J. Neurosci. 58, 3074–3097. doi: 10.1111/ejn.16073

PubMed Abstract | Crossref Full Text | Google Scholar

Koppes, A. N., Seggio, A. M., and Thompson, D. M. (2011). Neurite outgrowth is significantly increased by the simultaneous presentation of Schwann cells and moderate exogenous electric fields. J. Neural Eng. 8:046023. doi: 10.1088/1741-2560/8/4/046023

PubMed Abstract | Crossref Full Text | Google Scholar

Kreutzberg, G. W. (1996). Microglia: a sensor for pathological events in the CNS. Trends Neurosci. 19, 312–318. doi: 10.1016/0166-2236(96)10049-7

PubMed Abstract | Crossref Full Text | Google Scholar

Krishnamurthy, V., Gopinath, K., Brown, G. S., and Hampstead, B. M. (2015). Resting-state fMRI reveals enhanced functional connectivity in spatial navigation networks after transcranial direct current stimulation. Neurosci. Lett. 604, 80–85. doi: 10.1016/j.neulet.2015.07.042

PubMed Abstract | Crossref Full Text | Google Scholar

Kronberg, G., Bridi, M., Abel, T., Bikson, M., and Parra, L. C. (2017). Direct current stimulation modulates LTP and LTD: activity dependence and dendritic effects. Brain Stimul. 10, 51–58. doi: 10.1016/j.brs.2016.10.001

PubMed Abstract | Crossref Full Text | Google Scholar

Kuo, H., Bikson, M., Datta, A., Minhas, P., Paulus, W., Kuo, M.-F., et al. (2013). Comparing cortical plasticity induced by conventional and high-definition 4 x 1 ring tDCS: a neurophysiological study. Brain Stimul. 6, 644–648. doi: 10.1016/j.brs.2012.09.010

Crossref Full Text | Google Scholar

Kurosawa, M., Messlinger, K., Pawlak, M., and Schmidt, R. F. (1995). Increase of meningeal blood flow after electrical stimulation of rat dura mater encephali_ mediation by calcitonin gene-related peptide. Br. J. Pharmacol. 114, 1397–1402. doi: 10.1111/j.1476-5381.1995.tb13361.x

PubMed Abstract | Crossref Full Text | Google Scholar

Laakso, I., Mikkonen, M., Koyama, S., Hirata, A., and Tanaka, S. (2019). Can electric fields explain inter-individual variability in transcranial direct current stimulation of the motor cortex? Sci. Rep. 9:626. doi: 10.1038/s41598-018-37226-x

PubMed Abstract | Crossref Full Text | Google Scholar

Lafon, B., Rahman, A., Bikson, M., and Parra, L. C. (2017). Direct current stimulation alters neuronal input/output function. Brain Stimul. 10, 36–45. doi: 10.1016/j.brs.2016.08.014

PubMed Abstract | Crossref Full Text | Google Scholar

Lee, J.-W., Jeong, W.-H., Kim, E.-J., Choi, I., and Song, M.-K. (2022). Regulation of genes related to cognition after tDCS in an intermittent hypoxic brain injury rat model. Genes 13:1824. doi: 10.3390/genes13101824

PubMed Abstract | Crossref Full Text | Google Scholar

Lee, W. H., Lisanby, S. H., Laine, A. F., and Peterchev, A. V. (2015). Electric field model of transcranial electric stimulation in nonhuman Primates: correspondence to individual motor threshold. I.E.E.E. Trans. Biomed. Eng. 62, 2095–2105. doi: 10.1109/TBME.2015.2425406

PubMed Abstract | Crossref Full Text | Google Scholar

Lewis, A. (2025). A visual depiction of the elements of the neurovascular unit. Available at: https://BioRender.com/4rg7khk

Google Scholar

Lewis, A., Rattray, B., and Flood, A. (2025a). Optimising transcranial direct current stimulation application for the enhancement of exercise performance: a review. Front. Physiol. 16:1672603. doi: 10.3389/fphys.2025.1672603

Crossref Full Text | Google Scholar

Lewis, A., Rattray, B., and Flood, A. (2025b). Does cathodal preconditioning enhance the effects of subsequent anodal transcranial direct current stimulation on corticospinal excitability and grip strength? J. Strength Cond. Res. 39, e1–e12. doi: 10.1519/JSC.0000000000004954

PubMed Abstract | Crossref Full Text | Google Scholar

Lewis, A., Toufexis, C., Goldsmith, C., Robinson, R., Howie, G., Rattray, B., et al. (2025c). The effects of transcranial direct current stimulation and exercise on salivary s100b protein indicated blood-brain barrier permeability: A pilot study. Neuromod. Technol. Neu. Inter. 28, 76–85. doi: 10.1016/j.neurom.2023.11.006

Crossref Full Text | Google Scholar

Li, Q., Brus-Ramer, M., Martin, J. H., and McDonald, J. W. (2010). Electrical stimulation of the medullary pyramid promotes proliferation and differentiation of oligodendrocyte progenitor cells in the corticospinal tract of the adult rat. Neurosci. Lett. 479, 128–133. doi: 10.1016/j.neulet.2010.05.043

PubMed Abstract | Crossref Full Text | Google Scholar

Licata, A. E., Zhao, Y., Herrmann, O., Hillis, A. E., Desmond, J., Onyike, C., et al. (2023). Sex differences in effects of tDCS and language treatments on brain functional connectivity in primary progressive aphasia. Neuroimage Clin. 37:103329. doi: 10.1016/j.nicl.2023.103329

PubMed Abstract | Crossref Full Text | Google Scholar

Liebetanz, D., Nitsche, M. A., Tergau, F., and Paulus, W. (2002). Pharmacological approach to the mechanisms of transcranial DC-stimulation-induced after-effects of human motor cortex excitability. Brain 125, 2238–2247. doi: 10.1093/brain/awf238

PubMed Abstract | Crossref Full Text | Google Scholar

List, J., Lesemann, A., Kübke, J. C., Külzow, N., Schreiber, S. J., and Flöel, A. (2015). Impact of tDCS on cerebral autoregulation in aging and in patients with cerebrovascular diseases. Neurology 84, 626–628. doi: 10.1212/WNL.0000000000001230

PubMed Abstract | Crossref Full Text | Google Scholar

Liu, R., Zhu, T., Chu, X., Xu, Y., Wang, L., Wan, Q., et al. (2025). Transcranial direct current stimulation alleviates chronic pain in knee osteoarthritis by modulating microglial and astrocytic polarization and neuroinflammation. Life Sci. 376:123753. doi: 10.1016/j.lfs.2025.123753

PubMed Abstract | Crossref Full Text | Google Scholar

López-Alonso, V., Fernández-del-Olmo, M., Costantini, A., Gonzalez-Henriquez, J. J., and Cheeran, B. (2015). Intra-individual variability in the response to anodal transcranial direct current stimulation. Clin. Neurophysiol. 126, 2342–2347. doi: 10.1016/j.clinph.2015.03.022

PubMed Abstract | Crossref Full Text | Google Scholar

Luft, C. D. B., Zioga, I., and Bhattacharya, J. (2018). Anodal transcranial direct current stimulation (tDCS) boosts dominant brain oscillations. Brain Stimul. 11, 660–662. doi: 10.1016/j.brs.2018.02.019

PubMed Abstract | Crossref Full Text | Google Scholar

Luo, Y., Yang, H., Yan, X., Wu, Y., Wei, G., Wu, X., et al. (2022). Transcranial direct current stimulation alleviates neurovascular unit dysfunction in mice with preclinical Alzheimer’s disease. Front. Aging Neurosci. 14:857415. doi: 10.3389/fnagi.2022.857415

Crossref Full Text | Google Scholar

Lüscher, C., and Malenka, R. C. (2012). NMDA receptor-dependent long-term potentiation and long-term depression (LTP/LTD). Cold Spring Harb. Perspect. Biol. 4:a005710. doi: 10.1101/cshperspect.a005710

PubMed Abstract | Crossref Full Text | Google Scholar

Ma, W., Wang, F., Yi, Y., Huang, Y., Li, X., Liu, Y., et al. (2024). Mapping the electric field of high-definition transcranial electrical stimulation across the lifespan. Sci. Bull. 69, 3876–3888. doi: 10.1016/j.scib.2024.10.001

PubMed Abstract | Crossref Full Text | Google Scholar

Magri, C., Vitali, E., Cocco, S., Giacopuzzi, E., Rinaudo, M., Martini, P., et al. (2021). Whole blood transcriptome characterization of 3xTg-AD mouse and its modulation by transcranial direct current stimulation (tDCS). Int. J. Mol. Sci. 22:7629. doi: 10.3390/ijms22147629

Crossref Full Text | Google Scholar

Malenka, R. C., and Bear, M. F. (2004). LTP and LTD: an embarrassment of riches. Neuron 44, 5–21. doi: 10.1016/j.neuron.2004.09.012

PubMed Abstract | Crossref Full Text | Google Scholar

Márquez-Ruiz, J., Leal-Campanario, R., Sánchez-Campusano, R., Molaee-Ardekani, B., Wendling, F., Miranda, P. C., et al. (2012). Transcranial direct-current stimulation modulates synaptic mechanisms involved in associative learning in behaving rabbits. Proc. Natl. Acad. Sci. 109, 6710–6715. doi: 10.1073/pnas.1121147109

PubMed Abstract | Crossref Full Text | Google Scholar

Marshall, T. R., Esterer, S., Herring, J. D., Bergmann, T. O., and Jensen, O. (2016). On the relationship between cortical excitability and visual oscillatory responses — a concurrent tDCS–MEG study. NeuroImage 140, 41–49. doi: 10.1016/j.neuroimage.2015.09.069

PubMed Abstract | Crossref Full Text | Google Scholar

Mattavelli, G., Pirone, R., Gianelli, C., and Canessa, N. (2025). Comparing the effects of high-definition and conventional tDCS montages on inhibitory control via the stop signal task: a pre-registered study. Brain Stimul. 18:551. doi: 10.1016/j.brs.2024.12.979

Crossref Full Text | Google Scholar

McCaig, C. D., Rajnicek, A. M., Song, B., and Zhao, M. (2005). Controlling cell behavior electrically: current views and future potential. Physiol. Rev. 85, 943–978. doi: 10.1152/physrev.00020.2004

PubMed Abstract | Crossref Full Text | Google Scholar

McCarthy-Jones, S. Brain stimulation can boost creativity – but could it also help you hear inspirational voices? (2017).

Google Scholar

McDermott, T. J., Wiesman, A. I., Mills, M. S., Spooner, R. K., Coolidge, N. M., Proskovec, A. L., et al. (2019). Tdcs modulates behavioral performance and the neural oscillatory dynamics serving visual selective attention. Hum. Brain Mapp. 40, 729–740. doi: 10.1002/hbm.24405

Crossref Full Text | Google Scholar

McGeer, P. L., and McGeer, E. G. (1995). The inflammatory response system of brain: implications for therapy of Alzheimer and other neurodegenerative diseases. Brain Res. Rev. 21, 195–218. doi: 10.1016/0165-0173(95)00011-9

PubMed Abstract | Crossref Full Text | Google Scholar

Mestre, H., Hablitz, L. M., Xavier, A. L. R., Feng, W., Zou, W., Pu, T., et al. (2018). Aquaporin-4-dependent glymphatic solute transport in the rodent brain. eLife 7:e40070. doi: 10.7554/eLife.40070

PubMed Abstract | Crossref Full Text | Google Scholar

Mestre, H., Mori, Y., and Nedergaard, M. (2020). The brain's Glymphatic system: current controversies. Trends Neurosci. 43, 458–466. doi: 10.1016/j.tins.2020.04.003

PubMed Abstract | Crossref Full Text | Google Scholar

Milighetti, S., Sterzi, S., Fregni, F., Hanlon, C. A., Hayley, P., Murphy, M. D., et al. (2020). Effects of tDCS on spontaneous spike activity in a healthy ambulatory rat model. Brain Stimul. 13, 1566–1576. doi: 10.1016/j.brs.2020.08.016

PubMed Abstract | Crossref Full Text | Google Scholar

Miranda, P. C., Lomarev, M., and Hallett, M. (2006). Modeling the current distribution during transcranial direct current stimulation. Clin. Neurophysiol. 117, 1623–1629. doi: 10.1016/j.clinph.2006.04.009

PubMed Abstract | Crossref Full Text | Google Scholar

Mishima, T., Nagai, T., Yahagi, K., Akther, S., Oe, Y., Monai, H., et al. (2019). Transcranial direct current stimulation (tDCS) induces adrenergic receptor-dependent microglial morphological changes in mice. eNeuro 6:ENEURO.0204-19.2019. doi: 10.1523/ENEURO.0204-19.2019

Crossref Full Text | Google Scholar

Mojaverrostami, S., Khadivi, F., Zarini, D., and Mohammadi, A. (2022). Combination effects of mesenchymal stem cells transplantation and anodal transcranial direct current stimulation on a cuprizone-induced mouse model of multiple sclerosis. J. Mol. Histol. 53, 817–831. doi: 10.1007/s10735-022-10092-8

PubMed Abstract | Crossref Full Text | Google Scholar

Monai, H., Ohkura, M., Tanaka, M., Oe, Y., Konno, A., Hirai, H., et al. (2016). Calcium imaging reveals glial involvement in transcranial direct current stimulation-induced plasticity in mouse brain. Nat. Commun. 7:11100. doi: 10.1038/ncomms11100

PubMed Abstract | Crossref Full Text | Google Scholar

Mondini, V., Mangia, A. L., and Cappello, A. (2018). Single-session tDCS over the dominant hemisphere affects contralateral spectral EEG power, but does not enhance neurofeedback-guided event-related desynchronization of the non-dominant hemisphere's sensorimotor rhythm. PLoS One 13:e0193004. doi: 10.1371/journal.pone.0193004

PubMed Abstract | Crossref Full Text | Google Scholar

Monte-Silva, K., Kuo, M.-F., Hessenthaler, S., Fresnoza, S., Liebetanz, D., Paulus, W., et al. (2013). Induction of late LTP-like plasticity in the human motor cortex by repeated non-invasive brain stimulation. Brain Stimul. 6, 424–432. doi: 10.1016/j.brs.2012.04.011

PubMed Abstract | Crossref Full Text | Google Scholar

Monte-Silva, K., Liebetanz, D., Grundey, J., Paulus, W., and Nitsche, M. A. (2010). Dosage-dependent non-linear effect of l-dopa on human motor cortex plasticity. J. Physiol. 588, 3415–3424. doi: 10.1113/jphysiol.2010.190181

PubMed Abstract | Crossref Full Text | Google Scholar

Mosayebi-Samani, M., Jamil, A., Salvador, R., Ruffini, G., Haueisen, J., and Nitsche, M. A. (2021). The impact of individual electrical fields and anatomical factors on the neurophysiological outcomes of tDCS: A TMS-MEP and MRI study. Brain Stimul. 14, 316–326. doi: 10.1016/j.brs.2021.01.016

PubMed Abstract | Crossref Full Text | Google Scholar

Müller, D., Habel, U., Brodkin, E. S., and Weidler, C. (2022). High-definition transcranial direct current stimulation (HD-tDCS) for the enhancement of working memory – A systematic review and meta-analysis of healthy adults. Brain Stimul. 15, 1475–1485. doi: 10.1016/j.brs.2022.11.001

PubMed Abstract | Crossref Full Text | Google Scholar

Neuling, T., Wagner, S., Wolters, C. H., Zaehle, T., and Herrmann, C. S. (2012). Finite-element model predicts current density distribution for clinical applications of tDCS and tACS. Front. Psych. 3:83. doi: 10.3389/fpsyt.2012.00083

PubMed Abstract | Crossref Full Text | Google Scholar

Nitsche, M. A., and Fregni, F. (2007). Transcranial direct current stimulation - an adjuvant tool for the treatment of neuropsychiatric diseases? Curr. Psychiatr. Rev. 3, 222–232. doi: 10.2174/157340007781369649

Crossref Full Text | Google Scholar

Nitsche, M. A., Fricke, K., Henschke, U., Schlitterlau, A., Liebetanz, D., Lang, N., et al. (2003b). Pharmacological modulation of cortical excitability shifts induced by transcranial direct current stimulation in humans. J. Physiol. 553, 293–301. doi: 10.1113/jphysiol.2003.049916

PubMed Abstract | Crossref Full Text | Google Scholar

Nitsche, M. A., Grundey, J., Liebetanz, D., Lang, N., Tergau, F., and Paulus, W. (2004b). Catecholaminergic consolidation of motor cortical neuroplasticity in humans. Cereb. Cortex 14, 1240–1245. doi: 10.1093/cercor/bhh085

PubMed Abstract | Crossref Full Text | Google Scholar

Nitsche, M. A., Jaussi, W., Liebetanz, D., Lang, N., Tergau, F., and Paulus, W. (2004a). Consolidation of human motor cortical neuroplasticity by D-Cycloserine. Neuropsychopharmacology 29, 1573–1578. doi: 10.1038/sj.npp.1300517

PubMed Abstract | Crossref Full Text | Google Scholar

Nitsche, M. A., Kuo, M.-F., Karrasch, R., Wächter, B., Liebetanz, D., and Paulus, W. (2009). Serotonin affects transcranial direct current–induced neuroplasticity in humans. Biol. Psychiatry 66, 503–508. doi: 10.1016/j.biopsych.2009.03.022

PubMed Abstract | Crossref Full Text | Google Scholar

Nitsche, M. A., Lampe, C., Antal, A., Liebetanz, D., Lang, N., Tergau, F., et al. (2006). Dopaminergic modulation of long-lasting direct current-induced cortical excitability changes in the human motor cortex. Eur. J. Neurosci. 23, 1651–1657. doi: 10.1111/j.1460-9568.2006.04676.x

PubMed Abstract | Crossref Full Text | Google Scholar

Nitsche, M. A., Müller-Dahlhaus, F., Paulus, W., and Ziemann, U. (2012). The pharmacology of neuroplasticity induced by non-invasive brain stimulation: building models for the clinical use of CNS active drugs. J. Physiol. 590, 4641–4662. doi: 10.1113/jphysiol.2012.232975

PubMed Abstract | Crossref Full Text | Google Scholar

Nitsche, M. A., and Paulus, W. (2000). Excitability changes induced in the human motor cortex by weak transcranial direct current stimulation. J. Physiol. 527, 633–639. doi: 10.1111/j.1469-7793.2000.t01-1-00633.x

PubMed Abstract | Crossref Full Text | Google Scholar

Nitsche, M. A., Schauenburg, A., Lang, N., Liebetanz, D., Exner, C., Paulus, W., et al. (2003a). Facilitation of implicit motor learning by weak transcranial direct current stimulation of the primary motor cortex in the human. J. Cogn. Neurosci. 15, 619–626. doi: 10.1162/089892903321662994

PubMed Abstract | Crossref Full Text | Google Scholar

Nwaroh, C., Giuffre, A., Cole, L., Bell, T., Carlson, H. L., MacMaster, F. P., et al. (2020). Effects of transcranial direct current stimulation on GABA and Glx in children: a pilot study. PLoS One 15:e0222620. doi: 10.1371/journal.pone.0222620

Crossref Full Text | Google Scholar

Oishi, R., Takeda, I., Ode, Y., Okada, Y., Kato, D., Nakashima, H., et al. (2024). Neuromodulation with transcranial direct current stimulation contributes to motor function recovery via microglia in spinal cord injury. Sci. Rep. 14:18031. doi: 10.1038/s41598-024-69127-7

PubMed Abstract | Crossref Full Text | Google Scholar

Opitz, A., Falchier, A., Yan, C.-G., Yeagle, E. M., Linn, G. S., Megevand, P., et al. (2016). Spatiotemporal structure of intracranial electric fields induced by transcranial electric stimulation in humans and nonhuman primates. Sci. Rep. 6:31236. doi: 10.1038/srep31236

PubMed Abstract | Crossref Full Text | Google Scholar

Opitz, A., Paulus, W., Will, S., Antunes, A., and Thielscher, A. (2015). Determinants of the electric field during transcranial direct current stimulation. NeuroImage 109, 140–150. doi: 10.1016/j.neuroimage.2015.01.033

PubMed Abstract | Crossref Full Text | Google Scholar

Pan, L., and Borgens, R. B. (2010). Perpendicular organization of sympathetic neurons within a required physiological voltage. Exp. Neurol. 222, 161–164. doi: 10.1016/j.expneurol.2009.12.002

PubMed Abstract | Crossref Full Text | Google Scholar

Panatier, A., Vallée, J., Haber, M., Murai Keith, K., Lacaille, J.-C., and Robitaille, R. (2011). Astrocytes are endogenous regulators of basal transmission at central synapses. Cell 146, 785–798. doi: 10.1016/j.cell.2011.07.022

Crossref Full Text | Google Scholar

Parkin, B. L., Bhandari, M., Glen, J. C., and Walsh, V. (2019). The physiological effects of transcranial electrical stimulation do not apply to parameters commonly used in studies of cognitive neuromodulation. Neuropsychologia 128, 332–339. doi: 10.1016/j.neuropsychologia.2018.03.030

PubMed Abstract | Crossref Full Text | Google Scholar

Patel, N. B., and Poo, M. M. (1984). Perturbation of the direction of neurite growth by pulsed and focal electric fields. J. Neurosci. 4, 2939–2947. doi: 10.1523/JNEUROSCI.04-12-02939.1984

PubMed Abstract | Crossref Full Text | Google Scholar

Patel, H. J., Romanzetti, S., Pellicano, A., Nitsche, M. A., Reetz, K., and Binkofski, F. (2019). Proton magnetic resonance spectroscopy of the motor cortex reveals long term GABA change following anodal transcranial direct current stimulation. Sci. Rep. 9:2807. doi: 10.1038/s41598-019-39262-7

PubMed Abstract | Crossref Full Text | Google Scholar

Paulus, W., and Rothwell, J. C. (2016). Membrane resistance and shunting inhibition: where biophysics meets state-dependent human neurophysiology. J. Physiol. 594, 2719–2728. doi: 10.1113/JP271452

PubMed Abstract | Crossref Full Text | Google Scholar

Pedrosa, V., and Clopath, C. (2017). The role of neuromodulators in cortical plasticity. A computational perspective. Front. Synaptic Neurosci. 8:38. doi: 10.3389/fnsyn.2016.00038

Crossref Full Text | Google Scholar

Pelletier, S. J., and Cicchetti, F. (2015). Cellular and molecular mechanisms of action of transcranial direct current stimulation: evidence from in vitro and in vivo models. Int. J. Neuropsychopharmacol. 18:pyu047. doi: 10.1093/ijnp/pyu047

PubMed Abstract | Crossref Full Text | Google Scholar

Perea, G., Navarrete, M., and Araque, A. (2009). Tripartite synapses: astrocytes process and control synaptic information. Trends Neurosci. 32, 421–431. doi: 10.1016/j.tins.2009.05.001

PubMed Abstract | Crossref Full Text | Google Scholar

Perry, V. H., and Gordon, S. (1988). Macrophages and microglia in the nervous system. Trends Neurosci. 11, 273–277. doi: 10.1016/0166-2236(88)90110-5

PubMed Abstract | Crossref Full Text | Google Scholar

Peruzzotti-Jametti, L., Cambiaghi, M., Bacigaluppi, M., Gallizioli, M., Gaude, E., Mari, S., et al. (2013). Safety and efficacy of transcranial direct current stimulation in acute experimental ischemic stroke. Stroke 44, 3166–3174. doi: 10.1161/STROKEAHA.113.001687

PubMed Abstract | Crossref Full Text | Google Scholar

Petersen, K. A., Birk, S., Doods, H., Edvinsson, L., and Olesen, J. (2004). Inhibitory effect of BIBN4096BS on cephalic vasodilatation induced by CGRP or transcranial electrical stimulation in the rat. Br. J. Pharmacol. 143, 697–704. doi: 10.1038/sj.bjp.0705966

PubMed Abstract | Crossref Full Text | Google Scholar

Petrovskaya, A., Tverskoi, A., Medvedeva, A., and Nazarova, M. (2023). Is blood-brain barrier a probable mediator of non-invasive brain stimulation effects on Alzheimer’s disease? Commun. Biol. 6:416. doi: 10.1038/s42003-023-04717-1

PubMed Abstract | Crossref Full Text | Google Scholar

Phillips, A. A., Chan, F. H. N., Zheng, M. M. Z., Krassioukov, A. V., and Ainslie, P. N. (2015). Neurovascular coupling in humans: physiology, methodological advances and clinical implications. J. Cereb. Blood Flow Metab. 36, 647–664. doi: 10.1177/0271678X15617954

PubMed Abstract | Crossref Full Text | Google Scholar

Pikhovych, A., Stolberg, N. P., Jessica Flitsch, L., Walter, H. L., Graf, R., Fink, G. R., et al. (2016). Transcranial direct current stimulation modulates neurogenesis and microglia activation in the mouse brain. Stem Cells Int. 2016:2715196. doi: 10.1155/2016/2715196

PubMed Abstract | Crossref Full Text | Google Scholar

Pillen, S., Knodel, N., Hermle, D., Hanke, M., Ziemann, U., and Bergmann, T. O. (2022). No robust online effects of transcranial direct current stimulation on corticospinal excitability. Brain Stimul. 15, 1254–1268. doi: 10.1016/j.brs.2022.08.024

PubMed Abstract | Crossref Full Text | Google Scholar

Podda, M. V., Cocco, S., Mastrodonato, A., Fusco, S., Leone, L., Barbati, S. A., et al. (2016). Anodal transcranial direct current stimulation boosts synaptic plasticity and memory in mice via epigenetic regulation of Bdnf expression. Sci. Rep. 6:22180. doi: 10.1038/srep22180

PubMed Abstract | Crossref Full Text | Google Scholar

Purpura, D. P., and McMurtry, J. G. (1965). Intracellular activities and evoked potential changes during polarization of motor cortex. J. Neurophysiol. 28, 166–185. doi: 10.1152/jn.1965.28.1.166

Crossref Full Text | Google Scholar

Pustovrh, T. (2014). The Neuroenhancement of healthy individuals using tDCS: some ethical, legal and societal aspects. Interdiscip. Descr. Complex Syst. 12, 270–279. doi: 10.7906/indecs.12.4.1

PubMed Abstract | Crossref Full Text | Google Scholar

Rabenstein, M., Unverricht-Yeboah, M., Keuters, M. H., Pikhovych, A., Hucklenbroich, J., Vay, S. U., et al. (2019). Transcranial current stimulation alters the expression of immune-mediating genes. Front. Cell. Neurosci. 13:461. doi: 10.3389/fncel.2019.00461

Crossref Full Text | Google Scholar

Radman, T., Ramos, R. L., Brumberg, J. C., and Bikson, M. (2009). Role of cortical cell type and morphology in subthreshold and suprathreshold uniform electric field stimulation in vitro. Brain Stimul. 2, 215–28.e3. doi: 10.1016/j.brs.2009.03.007

PubMed Abstract | Crossref Full Text | Google Scholar

Radman, T., Su, Y., An, J. H., Parra, L. C., and Bikson, M. (2007). Spike timing amplifies the effect of electric fields on neurons: implications for endogenous field effects. J. Neurosci. 27, 3030–3036. doi: 10.1523/JNEUROSCI.0095-07.2007

PubMed Abstract | Crossref Full Text | Google Scholar

Rahman, A., Lafon, B., and Bikson, M. (2015). Chapter 2 - multilevel computational models for predicting the cellular effects of noninvasive brain stimulation. Prog. Brain Res. 222, 25–40. doi: 10.1016/bs.pbr.2015.09.003

Crossref Full Text | Google Scholar

Rahman, A., Reato, D., Arlotti, M., Gasca, F., Datta, A., Parra, L. C., et al. (2013). Cellular effects of acute direct current stimulation: somatic and synaptic terminal effects. J. Physiol. 591, 2563–2578. doi: 10.1113/jphysiol.2012.247171

PubMed Abstract | Crossref Full Text | Google Scholar

Rajnicek, A. M., Foubister, L. E., and McCaig, C. D. (2006). Temporally and spatially coordinated roles for rho, Rac, Cdc42 and their effectors in growth cone guidance by a physiological electric field. J. Cell Sci. 119, 1723–1735. doi: 10.1242/jcs.02896

PubMed Abstract | Crossref Full Text | Google Scholar

Ranck, J. B. (1975). Which elements are excited in electrical stimulation of mammalian central nervous system: a review. Brain Res. 98, 417–440. doi: 10.1016/0006-8993(75)90364-9

PubMed Abstract | Crossref Full Text | Google Scholar

Reato, D., Bikson, M., and Parra, L. C. (2014). Lasting modulation of in vitro oscillatory activity with weak direct current stimulation. J. Neurophysiol. 113, 1334–1341. doi: 10.1152/jn.00208.2014

Crossref Full Text | Google Scholar

Reato, D., Rahman, A., Bikson, M., and Parra, L. C. (2010). Low-intensity electrical stimulation affects network dynamics by modulating population rate and spike timing. J. Neurosci. 30, 15067–15079. doi: 10.1523/JNEUROSCI.2059-10.2010

PubMed Abstract | Crossref Full Text | Google Scholar

Riggall, K., Forlini, C., Carter, A., Hall, W., Weier, M., Partridge, B., et al. (2015). Researchers’ perspectives on scientific and ethical issues with transcranial direct current stimulation: An international survey. Sci. Rep. 5:10618. doi: 10.1038/srep10618

PubMed Abstract | Crossref Full Text | Google Scholar

Romero Lauro, L. J., Rosanova, M., Mattavelli, G., Convento, S., Pisoni, A., Opitz, A., et al. (2014). TDCS increases cortical excitability: direct evidence from TMS–EEG. Cortex 58, 99–111. doi: 10.1016/j.cortex.2014.05.003

PubMed Abstract | Crossref Full Text | Google Scholar

Rossi, E., Marenna, S., Castoldi, V., Comi, G., and Leocani, L. (2024). Transcranial direct current stimulation as a potential remyelinating therapy: visual evoked potentials recovery in cuprizone demyelination. Exp. Neurol. 382:114972. doi: 10.1016/j.expneurol.2024.114972

PubMed Abstract | Crossref Full Text | Google Scholar

Royal Australian and New Zealand College of Psychiatrists (2022). Clinical Memorandum: Transcranial direct current stimulation (tDCS). Melbourne, Australia: Royal Australian and New Zealand College of Psychiatrists.

Google Scholar

Rubio, N. (1997). Interferon-γ induces the expression of immediate early genes c-fos and c-Jun in astrocytes. Immunology 91, 560–564. doi: 10.1046/j.1365-2567.1997.00305.x

PubMed Abstract | Crossref Full Text | Google Scholar

Ruddick, B. Portable neurostimulation device trial for remote sufferers of depression. (2019).

Google Scholar

Rudroff, T., Workman, C. D., Fietsam, A. C., and Kamholz, J. (2020). Response variability in transcranial direct current stimulation: why sex matters. Front. Psych. 11:585. doi: 10.3389/fpsyt.2020.00585

Crossref Full Text | Google Scholar

Rueger, M. A., Keuters, M. H., Walberer, M., Braun, R., Klein, R., Sparing, R., et al. (2012). Multi-session transcranial direct current stimulation (tDCS) elicits inflammatory and regenerative processes in the rat brain. PLoS One 7:e43776. doi: 10.1371/journal.pone.0043776

PubMed Abstract | Crossref Full Text | Google Scholar

Saleh, O., Assaf, M., Alzoubi, A., Anshase, A., Tarkhan, H., Ayoub, M., et al. (2023). The effects of transcranial direct current stimulation on cognitive function for mild cognitive impairment: a systematic review and meta-analysis of randomized controlled trials. Aging Clin. Exp. Res. 35, 2293–2306. doi: 10.1007/s40520-023-02528-2

PubMed Abstract | Crossref Full Text | Google Scholar

Salehinejad, M. A., Ghanavai, E., Rostami, R., and Nejati, V. (2017). Cognitive control dysfunction in emotion dysregulation and psychopathology of major depression (MD): evidence from transcranial brain stimulation of the dorsolateral prefrontal cortex (DLPFC). J. Affect. Disord. 210, 241–248. doi: 10.1016/j.jad.2016.12.036

PubMed Abstract | Crossref Full Text | Google Scholar

Santarnecchi, E., Feurra, M., Barneschi, F., Acampa, M., Bianco, G., Cioncoloni, D., et al. (2014). Time course of corticospinal excitability and autonomic function interplay during and following monopolar tDCS. Front. Psych. 5:86. doi: 10.3389/fpsyt.2014.00086

Crossref Full Text | Google Scholar

Schroeder, P. A., Schwippel, T., Wolz, I., and Svaldi, J. (2020). Meta-analysis of the effects of transcranial direct current stimulation on inhibitory control. Brain Stimul. 13, 1159–1167. doi: 10.1016/j.brs.2020.05.006

PubMed Abstract | Crossref Full Text | Google Scholar

Selten, M., van Bokhoven, H., and Nadif Kasri, N. (2018). Inhibitory control of the excitatory/inhibitory balance in psychiatric disorders. F1000Res 7:23. doi: 10.12688/f1000research.12155.1

PubMed Abstract | Crossref Full Text | Google Scholar

Shen, Y., Lin, Z., Wen, L., Cheng, R., and Shang, P. (2024). The potential of noninvasive brain stimulation techniques for the treatment of central nervous system demyelinating diseases: a narrative review. Adv. Technol. Neurosci. 1, 211–228. doi: 10.4103/ATN.ATN-D-24-00020

Crossref Full Text | Google Scholar

Shin, D. W., Fan, J., Luu, E., Khalid, W., Xia, Y., Khadka, N., et al. (2020). In vivo modulation of the blood–brain barrier permeability by transcranial direct current stimulation (tDCS). Ann. Biomed. Eng. 48, 1256–1270. doi: 10.1007/s10439-020-02447-7

PubMed Abstract | Crossref Full Text | Google Scholar

Siebner, H. R., Lang, N., Rizzo, V., Nitsche, M. A., Paulus, W., Lemon, R. N., et al. (2004). Preconditioning of low-frequency repetitive transcranial magnetic stimulation with transcranial direct current stimulation: evidence for homeostatic plasticity in the human motor cortex. J. Neurosci. 24, 3379–3385. doi: 10.1523/JNEUROSCI.5316-03.2004

PubMed Abstract | Crossref Full Text | Google Scholar

Simons, M., and Nave, K.-A. (2016). Oligodendrocytes: myelination and axonal support. Cold Spring Harb. Perspect. Biol. 8:a020479. doi: 10.1101/cshperspect.a020479

PubMed Abstract | Crossref Full Text | Google Scholar

Stagg, C. J., Antal, A., and Nitsche, M. A. (2018). Physiology of transcranial direct current stimulation. J. ECT 34, 144–152. doi: 10.1097/YCT.0000000000000510

PubMed Abstract | Crossref Full Text | Google Scholar

Stagg, C. J., Bachtiar, V., Amadi, U., Gudberg, C. A., Ilie, A. S., Sampaio-Baptista, C., et al. (2014). Local GABA concentration is related to network-level resting functional connectivity. eLife 3:e01465. doi: 10.7554/eLife.01465

PubMed Abstract | Crossref Full Text | Google Scholar

Stagg, C. J., Bestmann, S., Constantinescu, A. O., Moreno Moreno, L., Allman, C., Mekle, R., et al. (2011). Relationship between physiological measures of excitability and levels of glutamate and GABA in the human motor cortex. J. Physiol. 589, 5845–5855. doi: 10.1113/jphysiol.2011.216978

PubMed Abstract | Crossref Full Text | Google Scholar

Stefan, K., Kunesch, E., Benecke, R., Cohen, L. G., and Classen, J. (2002). Mechanisms of enhancement of human motor cortex excitability induced by interventional paired associative stimulation. J. Physiol. 543, 699–708. doi: 10.1113/jphysiol.2002.023317

PubMed Abstract | Crossref Full Text | Google Scholar

Takata, N., Mishima, T., Hisatsune, C., Nagai, T., Ebisui, E., Mikoshiba, K., et al. (2011). Astrocyte calcium signaling transforms cholinergic modulation to cortical plasticity in vivo. J. Neurosci. 31:18155. doi: 10.1523/JNEUROSCI.5289-11.2011

Crossref Full Text | Google Scholar

Tanaka, T., Isomura, Y., Kobayashi, K., Hanakawa, T., Tanaka, S., and Honda, M. (2020). Electrophysiological effects of transcranial direct current stimulation on neural activity in the rat motor cortex. Front. Neurosci. 14:495. doi: 10.3389/fnins.2020.00495

PubMed Abstract | Crossref Full Text | Google Scholar

Terzuolo, C. A., and Bullock, T. H. (1956). Measurement of imposed voltage gradient adequate to modulate neuronal firing. Proc. Natl. Acad. Sci. 42, 687–694. doi: 10.1073/pnas.42.9.687

PubMed Abstract | Crossref Full Text | Google Scholar

Tranchina, D., and Nicholson, C. (1986). A model for the polarization of neurons by extrinsically applied electric fields. Biophys. J. 50, 1139–1156. doi: 10.1016/S0006-3495(86)83558-5

PubMed Abstract | Crossref Full Text | Google Scholar

Tremblay, S., Larochelle-Brunet, F., Lafleur, L.-P., El Mouderrib, S., Lepage, J.-F., and Théoret, H. (2016). Systematic assessment of duration and intensity of anodal transcranial direct current stimulation on primary motor cortex excitability. Eur. J. Neurosci. 44, 2184–2190. doi: 10.1111/ejn.13321

PubMed Abstract | Crossref Full Text | Google Scholar

Tremblay, R., Lee, S., and Rudy, B. (2016). GABAergic interneurons in the neocortex: from cellular properties to circuits. Neuron 91, 260–292. doi: 10.1016/j.neuron.2016.06.033

PubMed Abstract | Crossref Full Text | Google Scholar

van der Cruijsen, J., Dooren, R., Schouten, A., Oostendorp, T., Frens, M., Ribbers, G., et al. (2023). Modelling patient-tailored tDCS to reduce electric field variability in patients with chronic stroke. Brain Stimul. 16:195. doi: 10.1016/j.brs.2023.01.241

Crossref Full Text | Google Scholar

Vaseghi, B., Zoghi, M., and Jaberzadeh, S. (2015). The effects of anodal-tDCS on corticospinal excitability enhancement and its after-effects: conventional vs. unihemispheric concurrent dual-site stimulation. Front. Hum. Neurosci. 9:533. doi: 10.3389/fnhum.2015.00533

PubMed Abstract | Crossref Full Text | Google Scholar

Verkhratsky, A., Nedergaard, M., and Hertz, L. (2015). Why are astrocytes important? Neurochem. Res. 40, 389–401. doi: 10.1007/s11064-014-1403-2

PubMed Abstract | Crossref Full Text | Google Scholar

Vernieri, F., Tibuzzi, F., Pasqualetti, P., Rosato, N., Passarelli, F., Rossini, P. M., et al. (2004). Transcranial Doppler and Near-infrared spectroscopy can evaluate the hemodynamic effect of carotid artery occlusion. Stroke 35, 64–70. doi: 10.1161/01.STR.0000106486.26626.E2

PubMed Abstract | Crossref Full Text | Google Scholar

Wang, Y., and Monai, H. (2024). Transcranial direct current stimulation alters cerebrospinal fluid-interstitial fluid exchange in mouse brain. Brain Stimul. 17, 620–632. doi: 10.1016/j.brs.2024.04.009

PubMed Abstract | Crossref Full Text | Google Scholar

Wei, P., He, W., Zhou, Y., and Wang, L. (2013). Performance of motor imagery brain-computer Interface based on anodal transcranial direct current stimulation modulation. IEEE Trans. Neural Syst. Rehabil. Eng. 21, 404–415. doi: 10.1109/TNSRE.2013.2249111

PubMed Abstract | Crossref Full Text | Google Scholar

Weller, S., Derntl, B., and Plewnia, C. (2023). Sex matters for the enhancement of cognitive training with transcranial direct current stimulation (tDCS). Biol. Sex Differ. 14:78. doi: 10.1186/s13293-023-00561-4

PubMed Abstract | Crossref Full Text | Google Scholar

Wolters, A., Sandbrink, F., Schlottmann, A., Kunesch, E., Stefan, K., Cohen, L. G., et al. (2003). A temporally asymmetric Hebbian rule governing plasticity in the human motor cortex. J. Neurophysiol. 89, 2339–2345. doi: 10.1152/jn.00900.2002

PubMed Abstract | Crossref Full Text | Google Scholar

Wood, M. D., and Willits, R. K. (2009). Applied electric field enhances DRG neurite growth: influence of stimulation media, surface coating and growth supplements. J. Neural Eng. 6:046003. doi: 10.1088/1741-2560/6/4/046003

PubMed Abstract | Crossref Full Text | Google Scholar

Xia, Y., Khalid, W., Yin, Z., Huang, G., Bikson, M., and Fu, B. M. (2020). Modulation of solute diffusivity in brain tissue as a novel mechanism of transcranial direct current stimulation (tDCS). Sci. Rep. 10:18488. doi: 10.1038/s41598-020-75460-4

Crossref Full Text | Google Scholar

Yang, Y., Ge, W., Chen, Y., Zhang, Z., Shen, W., Wu, C., et al. (2003). Contribution of astrocytes to hippocampal long-term potentiation through release of d-serine. Proc. Natl. Acad. Sci. 100, 15194–15199. doi: 10.1073/pnas.2431073100

PubMed Abstract | Crossref Full Text | Google Scholar

Zhao, X., Ding, J., Pan, H., Zhang, S., Pan, D., Yu, H., et al. (2020). Anodal and cathodal tDCS modulate neural activity and selectively affect GABA and glutamate syntheses in the visual cortex of cats. J. Physiol. 598, 3727–3745. doi: 10.1113/JP279340

PubMed Abstract | Crossref Full Text | Google Scholar

Zoghi, M., Vaseghi, B., Bastani, A., Jaberzadeh, S., and Galea, M. P. (2015). The effects of sex hormonal fluctuations during menstrual cycle on cortical excitability and manual dexterity (a pilot study). PLoS One 10:e0136081. doi: 10.1371/journal.pone.0136081

PubMed Abstract | Crossref Full Text | Google Scholar