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conventional tDCS, thereby further augmenting interest in this technology [12, 13].
However, the focal nature of the stimulation leads to an increase in interindividual
variability in electric elds, which presents a signicant challenge for the practical
implementation of HD-tDCS [13].
2.1.2 Common Parameters oftDCS
Despite its limited current clinical application, extensive research conducted abroad
over the past decade has demonstrated the efcacy of tDCS in stimulating the
human cerebral cortex and established its optimal stimulation patterns. Key parameters for tDCS include the delivered current intensity (in mA), stimulation duration
(in min), and electrode size and placement [7]. By calculating the current density at
the electrode, which is obtained by dividing the delivered current by the size of the
electrode, one can determine it based on the electrode size and applied current [7,
10]. Typically used for tDCS are current intensities ranging from 0.5 to 2mA with
corresponding current densities between 0.029 and 0.08mA/cm2. In standard tDCS
protocols in humans, a current density of approximately 0.05mA/cm2 is typically
generated [9]. The duration of the stimulation commonly ranges between 20 and
40min [7]. In addition to the key parameters mentioned above, the parameters of
tDCS also include stimulation charge (in coulombs, C), stimulation charge density
(A×t/m2=C/m2), stimulation power (in watts, W=V×A), and stimulation energy
(in joules, J=V×A×t). Stimulation charge is determined by multiplying current
by duration. Stimulation charge density is charge divided by electrode area, and is
also an average metric. Stimulation power is voltage multiplied by current.
Stimulation energy is power multiplied by duration [10].
2.2 Treatment Procedures andPrecautions
As a noninvasive and well-established intervention, tDCS has been extensively
investigated for its therapeutic potential in various conditions, including chronic
pain and neuropsychiatric disorders such as stroke, Alzheimer’s disease, refractory
epilepsy, Parkinson’s disease, major depressive disorder, substance addiction, and
bromyalgia [7, 16].
In terms of safety and tolerability, numerous systematic reviews and metaanalyses have consistently demonstrated that the application of tDCS to both motor
and non-motor areas, in accordance with current tDCS safety guidelines, is associated with minimal adverse effects in healthy individuals as well as patients with
various neurological disorders [14, 17–19]. In the subsample reporting AEs, the
most common were, for active vs. sham tDCS group, itching, tingling, headache,
burning sensation, and discomfort [18]. Several empirical studies have also corroborated the safety of tDCS, for example, Prateek C.Gandiga and colleagues evaluated the effects of tDCS and sham stimulation (SHAM) on healthy subjects and
stroke patients’ self-report measures of attention, fatigue, duration of elicited
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J. Fu et al.
sensations, and discomfort, they found that tDCS and SHAM elicited comparably
minimal discomfort and duration of sensations [20]. The study conducted by
M.A.Nitsche and colleagues demonstrated that the application of anodal and cathodal tDCS protocols to the human brain did not elicit any structural changes in brain
tissue or induce alterations in the blood–brain barrier, as conrmed by magnetic
resonance imaging (MRI) [21].
The treatment procedures of tDCS includes the following seven points:
1. Physical examination: Prior to commencing tDCS treatment, it is imperative for
the physician to conduct a comprehensive safety screening in order to ascertain
the patient’s suitability for undergoing tDCS therapy.
2. Patient history and assessment: Gather comprehensive patient history, including
clinical presentation and current medication regimen.
3. Informed consent: Obtain informed consent from the patient before initiating
treatment.
4. Electrode placement: Typically, electrode placement is determined using the
International 10–20 System [7]. Precise localization can be achieved using standardized positioning electrode caps compatible with the tDCS device, or alternative methods such as neuro-navigation systems (e.g., magnetic resonance
imaging-guided localization) or physiologically-based methods (e.g., transcranial magnetic stimulation-induced motor evoked potentials) [8, 22].
5. Stimulation parameter determination: Currently, most clinical tDCS studies uti-
lize a continuous stimulation mode, where a constant current (typically 1–2mA)
is applied for a set duration (typically 20–30min). The current can be ramped up
and down gradually. Parameters requiring control include current amplitude and
stimulation duration. Medical technicians can titrate individual treatment parameters for different patients based on their needs [23–25]. In clinical practice, it is
recommended to start with the minimum stimulation current and duration recommended by consensus guidelines, and adjust these parameters based on
patient response and the severity of adverse events. Ultimately, the optimal therapeutic stimulation parameters should be determined. Twenty minutes of 2.0mA
tDCS is a typical starting point to assess tolerability and efcacy of the dose [6].
6. Treatment administration: Initiate tDCS treatment according to the established
parameters.
7. Posttreatment monitoring and adverse event reporting: Monitor the patient after
treatment and document any adverse reactions.
The precautions of tDCS includes the following seven points:
1. Training and qualication: Prior to treating patients with tDCS, medical person-
nel should undergo training and pass competency assessments in a qualied
facility where this technology is implemented [5]. A treatment team comprised
of licensed physicians, nurses, and technicians should be involved, with a
licensed physician responsible for prescribing tDCS therapy. Other trained personnel can administer tDCS under the physician’s supervision. Training should
encompass, but is not limited to, safety protocols, treatment principles, equip-
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ment operation, and implementation of commonly used evidence-based
prescriptions.
2. Safety screening: Ensure that patients do not have any skull defects or fractures,
and are not wearing metal implants, pacemakers, or other devices that could
increase local current density and pose safety risks [5].
3. Electrical safety: Maintain electrical safety during treatment. As tDCS devices
are electrical equipment, caution must be exercised to prevent safety hazards.
4. Electrode xation: Utilize nonconductive headwear, such as elastic bands, to
secure electrodes in their designated positions. Improper xation can alter current distribution [5].
5. Patient monitoring and response assessment: If the patient experiences discom-
fort, excessive distraction, pain, or any other adverse reaction, reduce the stimulation intensity and duration as necessary. Continuously and objectively assess
patient response and any adverse events to determine if parameter optimization
or cessation of tDCS treatment is required [6].
6. Stimulation dosage limits: Daily tDCS sessions should not exceed the maximum
stimulation dosage (total duration of 60min at a stimulation intensity of 4mA,
with electrodes ranging from 1 to 100cm2) [26].
7. Posttreatment observation: Following treatment, the patient should be moni-
tored for a period of time to ensure no adverse reactions occur before discharge.
2.3 Principle andMechanism
The prevailing perspective on the fundamental mechanisms of tDCS is that it initially modies neuronal activity by altering membrane potentials, thereby inducing
changes in action potential rate, while exerting no signicant impact on synaptic
plasticity. Longer-lasting effects of tDCS may arise from alterations in neurotransmitter release, modications in the functioning of membrane-bound receptors and
ion channels, or other neurobiological and neurochemical changes [27]. Despite the
absence of a fully elucidated mechanism for tDCS, signicant advancements have
been made in comprehending its underlying mechanisms over the past two decades
through the integration of techniques such as transcranial magnetic stimulation
(TMS), pharmacological investigations, and neuroimaging.
2.3.1 Alteration ofMembrane Potential andCortical Excitability
The application of tDCS has demonstrated its reliability as a cortical excitability
modulation technique [7]. During tDCS, low-amplitude direct currents permeate
the skull and enter the brain to modify the transmembrane neuronal potential,
thereby inuencing excitability levels and modulating individual neuron ring
rates [4]. Priori and colleagues investigated the functional effects of scalp direct
current (DC) stimulation with very weak intensity (<0.5mA, 7s) on the human
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J. Fu et al.
motor cortex by evaluating alterations in motor potentials elicited through transcranial magnetic brain stimulation. Their ndings demonstrate that such lowintensity anodal scalp DC, combined with cathodal DC, signicantly reduces the
excitability of the human motor cortex [28]. Nitsche and Paulus have demonstrated that the application of weak direct current through the human scalp can
modulate motor cortex excitability, with effects lasting for several minutes after
stimulation cessation [1]. Furthermore, they have shown that transcranial direct
current stimulation in humans is capable of inducing sustained elevations in cortical excitability. The application of transcranial magnetic stimulation revealed a
signicant increase in motor cortical excitability, reaching approximately 150%
above baseline levels for up to 90min following the cessation of stimulation [29].
Importantly, it should be noted that the subthreshold current employed in tDCS
does not elicit action potentials; rather, it modulates cortical excitability levels in
a polarity-dependent manner. In general, anodal stimulation typically enhances
excitability while cathodal stimulation generally diminishes excitability; however,
the polarization direction is strictly contingent upon the orientation of axons and
dendrites within the induced electrical eld [1, 4, 5, 7, 8, 30]. The effects of tDCS
on cortical excitability, both anodal and cathodal, are believed to be attributed to
alterations in the resting membrane potential (depolarization and hyperpolarization) [30]. Anodal stimulation enhances spontaneous neuronal ring and depolarizes the resting membrane potential, thereby augmenting neuronal excitability;
conversely, cathodal stimulation hyperpolarizes the resting membrane potential,
suppressing neuronal excitability. Additionally, while the nominal targets of tDCS
are often positioned beneath the electrodes, the resulting current ow generated
by conventional tDCS extends across all cortical regions between and surrounding
the electrodes, thereby not being conned solely to the localized area underneath
[7]. Consequently, the effects of tDCS can directly or indirectly modulate remote
neural networks [4, 8]. EEG studies provide further support for these ndings by
demonstrating that stimulation of a specic region (e.g., frontal cortex) elicits
synchronous changes in oscillatory activity across the entire brain [4]. In terms
of cellular mechanisms, the application of tDCS induces alterations inlocal pH
levels (dependent on changes in electrolytic hydrogen ion concentration) and ion
concentrations (e.g., intracellular calcium ion concentration) [31]. A prolonged
and constant electric eld can induce migration of transmembrane proteins, leading to changes in their steric and conformational properties as well as the local
alteration of tissue acid–base balance. This, in turn, directly and indirectly affects
membrane function outside the synapse by locally modifying ionic concentrations and properties of ion channels [4, 31]. In summary, a potential mechanism
of action for tDCS involves modulating the membrane potential of supercial
excitatory interneurons in the human motor cortex [5, 30]. By manipulating ion
channels or altering electrical gradients that affect the balance of ions inside and
outside neural membranes [28, 32], tDCS can induce enduring changes in cortical
excitability and neural cell membrane potential.
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2.3.2 Altering Synaptic Plasticity andCortical
Functional Connectivity
The mechanisms underlying changes in cortical excitability induced by tDCS differ
between the effects observed during stimulation and those occurring poststimulation, despite similar neurophysiological effects [9]. Prolonged effects of tDCS can
be attributed to modications in the efcacy of N-methyl-D-aspartate (NMDA)
receptors, alterations in gamma-aminobutyric acid-ergic activity, and modulation of
interneurons, resulting in enduring changes in synaptic efcacy [7, 30, 31]. Longterm potentiation (LTP) and long-term depression (LTD) have been proposed as the
likely mechanisms underlying the persistent effects of tDCS [28, 32–35]. These
effects are contingent upon the levels of postsynaptic calcium and involve N-methylD-aspartate (NMDA) and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid
(AMPA) receptors, metabotropic glutamate receptors, as well as gammaaminobutyric acid GABA-A and GABA-B receptors [8, 9]. They exert persistent
facilitatory/inhibitory modulation on synaptic connections. The modulation of neocortical LTP-like and LTD-like plasticity involves the inuence of various neuromodulators, including noradrenaline (NA), dopamine (DA), and serotonin. These
neuromodulators possess the capacity to facilitate both LTP and LTD at synaptic
levels [9]. Therefore, it has been proposed that tDCS could potentially modulate
neurotransmitter concentrations, thereby modifying the balance between excitatory
and inhibitory (E/I) neurotransmitters and subsequently eliciting long-term potentiation/depression (LTP/LTD) processes that may facilitate cortical reorganization.
Previous studies have demonstrated that anodal tDCS applied over the primary
motor cortex (M1) results in a reduction of GABA levels, whereas cathodal stimulation leads to a signicant decrease in both glutamate and GABA concentrations.
This nding is consistent with the notion that tDCS-induced plasticity resembling
LTP in the neocortex, which is believed to be modulated by GABA, critically
depends on GABA modulation [35]. Vincent P Clark and colleagues employed proton magnetic resonance spectroscopy (1H MRS) to quantitatively assess changes in
brain metabolite concentrations following tDCS stimulation.
The right parietal cortex, beneath the stimulating electrode, exhibited signicantly elevated levels of combined glutamate and glutamine, indicating a disruption
in the Glutamine (Gln)—Glutamate (Glu) cycle with tDCS.Nonsignicant increases
were also observed in corresponding regions of the contralateral hemisphere. The
application of tDCS resulted in alterations in levels of Glu and Gln, which can reasonably be inferred to indicate changes in glutamatergic neurotransmission, thereby
affecting neural activation and metabolism. Furthermore, tDCS signicantly
increased N-acetylaspartate (tNAA) in the right parietal cortex beneath the stimulating electrode, while showing a trend toward the opposite direction in the corresponding region of the left hemisphere [27].
The advancement of brain imaging technologies, such as PET, EEG, and fMRI,
has facilitated a paradigm shift in our understanding of the brain from a simplistic
and isolated structure–function relationship to the domain of functional connectivity networks. The application of tDCS stimulation, which modulates synaptic
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J. Fu et al.
connections, holds promise for enhancing the functional connectivity between distinct cortical regions. Rafael Polania and colleagues investigate the impact of tDCS
on cortical network function, revealing that tDCS applied to the primary motor cortex enhances connectivity activity within the cortico-cortical and cortico- subcortical
motor neural network [36] components, including premotor cortex, parietal lobe,
thalamus, and caudate nucleus. In another study conducted by the researchers, EEG
recordings were utilized to investigate alterations in functional cortical networks
induced by excitatory anodal tDCS over the primary motor cortex during voluntary
hand movements. The ndings revealed a signicant increase in functional connectivity patterns within premotor, motor, and sensorimotor areas of the stimulated
hemisphere in the 60–90Hz frequency range, which were specically associated
with changes in the topological functional organization of the entire brain. The
functional connectivity in the entire dynamic brain is shifted and modulated by the
combined effects of motor activity and excitatory transcranial stimulation [37].
Furthermore, Charlotte J.Stagg and colleagues employed whole-brain arterial spin
labeling (ASL) to investigate alterations in brain perfusion and observed an increase
in perfusion within regions anatomically connected to the DLPFC during anodal
tDCS.Additionally, they found a decrease in functional coupling between the left
dorsolateral prefrontal cortex (DLPFC) and bilateral thalami, suggesting that tDCS
may play a role in modulating the functional connectivity between the DLPFC and
thalamus [16]. In addition to its direct effects, tDCS can also induce changes in
distal cortical and subcortical brain regions through functional connectivity between
different areas of the brain. Specically, prefrontal stimulation with tDCS has been
shown to modulate resting-state functional connectivity [7]. Keeser and colleagues
investigated the impact of tDCS on resting-state network (RSN) connectivity, as
measured by fMRI, and observed signicant alterations in regional brain connectivity within the default mode network (DMN) and frontoparietal networks (FPNs).
These changes were observed both near the primary stimulation site and in interconnected brain regions following real tDCS [38]. Furthermore, tDCS elicited polarityspecic modications in cerebral blood ow (CBF).
2.3.3 Nonneuronal Mechanisms
In fact, tDCS not only modulates neuronal activity but also exerts an inuence on
nonneuronal cells, such as vascular endothelial cells to induce changes in blood vessel diameter or impact nonneuronal cell types like microglia and astrocytes [39]. For
instance, tDCS has been shown to directly alter blood vessel diameter, resulting
inlocalized vasodilation at the stimulation site and subsequent skin reddening. This
effect can also be observed within the cerebrovascular system [40, 41]. These
responses can be quantied by assessing CBF and vasomotor reactivity (VMR).
Studies have demonstrated widespread increases and decreases in regional CBF
within cortical and subcortical areas following anodal and cathodal tDCS interventions [42–44]. Bragina and colleagues reported that the application of 0.1 mA
anodal tDCS over the right barrel cortex or motor cortex, using epicranial electrodes
2 Transcranial Direct Current Stimulation
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with a contact area of 3.5mm2, resulted in vasodilation under the anode, signicantly enhancing CBF, along with elevated levels of blood oxygenation [44]. In an
experimental rat model, tDCS has been demonstrated to induce polarity-specic
and long-lasting changes in CBF.Specically, anodal tDCS leads to increased CBF
while cathodal tDCS results in decreased CBF [43]. Moreover, Shinde and colleagues found that a current intensity of 4mA during anodal tDCS produced a larger
increase in CBF compared to 2mA, and Jamil and colleagues showed that both
2mA anodal and cathodal tDCS induced greater polarity-specic changes in CBF
compared to intensities of 0.5 and 1mA [39, 44, 45]. These studies, conducted on
both animal models and human subjects, suggest that the impact of tDCS on CBF is
contingent upon the polarity and dosage of the stimulation. However, since CBF
measurements were limited to the cortical area targeted by tDCS, it remains unclear
whether tDCS-induced changes in CBF are conned to the ECA or if they extend
beyond this site [39]. The impact of tDCS on the VMR is characterized by a complex and intricate mechanism involving the autonomic nervous system. Anodal
tDCS has been shown to decrease VMR in a clinical experiment, whereas cathodal
tDCS has been found to increase it [40]. However, another clinical study reported
that anodal tDCS did not induce any signicant alterations in VMR among both
healthy controls and patients [46].
In addition to the aforementioned factors, studies in mouse models have revealed
the potential effects of this technique on glial cell function [47–49]. Cathodal tDCS
applied over the motor cortex has been found to downregulate astrocyte activity,
while anodal tDCS administered via epicranial electrodes over the visual and
somatosensory cortices enhances intracellular calcium ion (Ca2+) concentration
within astrocytes and activates microglia in these regions. However, the electric
eld intensities employed in these investigations typically exceed the standard dosages utilized in human tDCS treatments. Furthermore, the impact of tDCS on glial
cells may arise from their pivotal roles in neuronal cell polarization and signal propagation. In combination, these effects are somewhat distinct from its impact on
neuronal mechanisms.
2.3.4 Others
Recently conducted studies have also indicated that the mechanisms underlying
tDCS are intricately linked to immune and inammatory processes. Notably, in rats,
anodal tDCS administered at a current density of 14.29mA/cm2 has been demonstrated to upregulate the gene expression of major histocompatibility complex I
(MHC I), while cathodal tDCS at the same current density enhances the expression
of osteopontin [39], an immunomodulatory protein. In mouse/rat brain disease
models, cathodal tDCS using skull electrodes at a current intensity ranging from
200 to 500μA and a current density between 14.29 and 57.14mA/cm2 promotes the
migration of oligodendrocyte precursors toward the lesion site [50]. The administration of this treatment leads to a signicant reduction in pro-inammatory factors,
promotes white matter myelination, mitigates autophagy [51], and suppresses
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J. Fu et al.
phagocytic anti-inammatory activity at the site of stimulation [49, 52]. However,
in human tDCS studies, a relatively low current density is typically employed
(approximately 0.03–0.08mA/cm2) [53]. Animal models have shown no long-term
effects of tDCS on inammatory markers beyond 30min [54] when the current
density is as low as 0.3mA/cm2.
Similarly, recent animal model studies have investigated the direct effects of
tDCS on the blood–brain barrier. In these cases, invivo rat brain studies have demonstrated that the application of 1mA tDCS through skull electrodes with a current
density of 8mA/cm2 enhances the blood–brain barrier permeability and facilitates
the transport of large molecules into the extracellular matrix of brain tissue [54].
Additionally, it reduces the density of the extracellular matrix, thereby promoting
increased diffusion of solutes through the extracellular space irrespective of their
charge [54]. However, when a current of 1mA tDCS (with a current density of
approximately 0.03mA/cm2) was administered over the motor cortex in healthy
volunteers, magnetic resonance imaging (MRI) revealed no evidence of lesions or
disruption to the blood–brain barrier following 13min of anodal stimulation and
9min of cathodal stimulation [21].
In general, lower current densities may not be adequate to elicit immune and
inammatory responses; however, higher current densities in tDCS exhibit a modulatory inuence on these processes, thereby potentially paving the way for novel
nonneuronal mechanisms in future research.
2.4 Effect Factors
The effects of tDCS critically depend on the specic parameters of stimulation
employed. While these parameters may vary, it has been demonstrated that polarity,
duration, current density (i.e., intensity relative to electrode size), and stimulation
location signicantly inuence the neuromodulatory outcomes of tDCS [4, 8–10,
16, 30]. Subsequent sections will provide a comprehensive discussion on the factors
that impact tDCS efcacy.
2.4.1 Stimulus Polarity
The effects of tDCS on cortical excitability are polarity specic [9, 30]. Anodal
stimulation enhances cortical excitability during and after stimulation, provided that
the duration of stimulation is sufcient. Conversely, cathodal stimulation decreases
excitability within the cortex [5, 8, 30]. Nitsche and colleagues reported that opposite effects were observed in individual cortical layers, highlighting the dependence
of DC stimulation effects on the interplay between electric ow direction and neuronal geometry [1]. The impact of anodal tDCS during stimulation appears to be
exclusively reliant on alterations in membrane potential. The effects of anodal stimulation were reduced by the Ca2+ channel blocker unarizine (FLU) and abolished
by the Na+ channel blocker carbamazepine (CBZ). Neither dextromethorphan
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(DMO), an NMDA receptor antagonist, nor Lorazepam (LOR), a GABA-A receptor
agonist, exerted any modulatory effect on the intrastimulation response. In contrast
to anodal stimulation, blockade of voltage-dependent Ca2+ or Na+ channels did not
inuence excitability shifts during cathodal stimulation. Moreover, the effects of
intrastimulation cathodal tDCS were not modulated by either NMDA or GABA
blockade [9]. Additionally, a study investigated the impact of tDCS pretreatment on
repetitive transcranial magnetic stimulation (rTMS) action and revealed that preconditioning with cathodal tDCS could reverse the suppressive effect typically
observed with 1Hz rTMS, leading to a seemingly paradoxical facilitation in the
human corticospinal motor system [55]. Conversely, anodal tDCS exerted opposite
effects on subsequent conditioning rTMS trains.
2.4.2 Duration
The duration of tDCS after-effects is contingent upon the stimulation duration [21];
if the stimulation duration is sufciently prolonged, the modied cortical excitability can persist for up to 1h poststimulation. Nitsche reported that by varying the
current intensity and duration, one can regulate both the strength and duration of
these after-effects [1]. Notably, acute excitability alterations induced by tDCS for
4s do not result in subsequent after-effects (at an intensity of 1mA with an electrode size of 35cm2) [5]. Short-lasting after-effects lasting up to 10min can be
achieved with 5 and 7-min stimulation, while stimulation for 9min under the cathode electrode on the motor cortex and for 13min under the anode electrode result in
after-effects lasting approximately 1h (using electrodes measuring 5×7cm and a
motor cortex-contralateral supraorbital ridge electrode arrangement) [5]. However,
several studies have indicated that prolonged duration of stimulation does not necessarily correspond to improved therapeutic outcomes. Katia Monte-Silva reported
that applying anodal tDCS at 1mA for 26min with a surface area of 35cm2 resulted
in decreased excitability compared to a shorter stimulation period of 13min, suggesting the presence of a nonlinear relationship between stimulation parameters and
excitability [56].
2.4.3 Current Intensity
Similarly, there is not a strictly linear relationship between the intensity of stimulation and the effects of tDCS.In a study conducted by Koen Cuypers and colleagues,
three groups of right-handed subjects received 20min of anodal, cathodal, or sham
tDCS applied to the left prefrontal cortex. The results showed that at 1mA tDCS,
there were no signicant effects on subjects’ performance. However, when the
intensity was increased to 2mA, verbal uency signicantly improved with anodal
tDCS while mildly decreased with cathodal tDCS [24]. Vincent P Clark conducted
a study to investigate the impact of tDCS on learning and performance for a challenging visual perceptual task. The results showed that anodal tDCS over parietal
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J. Fu et al.
cortex led to signicant improvements, with the amount of learning being proportional to current strength. Subjects who received 2.0mA of anodal tDCS current
over right inferior frontal or right parietal cortex demonstrated more than twice the
performance improvement compared to those who received 0.1mA sham tDCS
current [27]. Furthermore, in a tDCS study conducted by Koen Cuypers and colleagues, a signicant enhancement in motor performance at retention was observed
for 1.5mA tDCS compared to sham tDCS, while no statistically signicant differences were reported between 1mA tDCS and sham tDCS.Conversely, other studies
have also documented more pronounced effects with lower current densities.
Andisheh Bastani and colleagues [57] reported that a current density of 0.013mA/
cm2 elicited greater cortical excitability compared to the commonly employed
0.029mA/cm2, with no statistically signicant distinctions observed between this
density and higher densities of 0.058 and 0.083mA/cm2.
2.4.4 Others
In addition to the aforementioned stimulation parameters, there exist other factors that
exert an inuence on the efcacy of tDCS.Primarily, a crucial aspect in tDCS lies in
determining the optimal placement of electrodes on the cranium. The neurochemical
response to tDCS may exhibit variations based on anatomical location, thereby accounting for divergent outcomes observed across different studies [27]. The amount of current
that reaches neuronal tissue, however, is contingent upon several uncontrollable factors,
encompassing the resistance posed by various cephalic structures such as the integumentary system, cranium, vasculature, and cerebral matter [30]. Accurately quantifying
the trajectory of current ow across the human subjects’ cerebral cortex presents inherent challenges, necessitating our reliance on indirect observations from human and animal studies as well as mathematical models to ascertain the path and density of current
within specic cortical regions [9]. Studies investigating physiological changes following tDCS and computational modeling studies of predicted current ow have demonstrated that the relative positioning of electrodes signicantly inuences both the spatial
distribution and magnitude of delivered current to the brain [5]. Additionally, the effects
of tDCS can be inuenced by the placement of electrodes. Caroline Paquette and colleagues employed positron emission tomography (PET) to quantify the impact on activation-induced changes in regional cerebral blood ow (ΔrCBF) during bilateral
tDCS.The study revealed that the implementation of bilateral tDCS electrode mount
can effectively induce alterations in brain activation during movement, with the cathode
exhibiting stronger effects compared to the anodal effect observed in unilateral stimulation [58].
Accumulating evidence suggests that the effects of transcranial direct current stimulation (tDCS) exhibit a cumulative pattern, necessitating consecutive daily applications
to achieve clinically meaningful outcomes [6]. However, it is noteworthy that the behavioral effects of single tDCS sessions are relatively transient, lasting for a maximum duration of a few tens of minutes. Conversely, employing multiple spaced sessions may
extend the duration of these behavioral effects up to several weeks [9]. The time interval