NeuroImage 87 (2014) 332–344

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NeuroImage
journal homepage: www.elsevier.com/locate/ynimg

A computational modelling study of transcranial direct current

stimulation montages used in depression
Siwei Bai a, Socrates Dokos a, Kerrie-Anne Ho b,d, Colleen Loo b,c,d,⁎
a
Graduate School of Biomedical Engineering, Faculty of Engineering, University of New South Wales (UNSW), NSW 2052, Australia
b
School of Psychiatry, UNSW, NSW 2052, Australia
c
Department of Psychiatry, St George Hospital, NSW 2217, Australia
d
Black Dog Institute, NSW 2031, Australia

a r t i c l e i n f o a b s t r a c t

Article history: Transcranial direct current stimulation (tDCS) is a neuromodulatory technique which involves passing a mild
Accepted 5 November 2013 electric current to the brain through electrodes placed on the scalp. Several clinical studies suggest that tDCS
Available online 15 November 2013 may have clinically meaningful efficacy in the treatment of depression. The objective of this study was to simulate
and compare the effects of several tDCS montages either used in clinical trials or proposed, for the treatment of
Keywords:
depression, in different high-resolution anatomically-accurate head models. Detailed segmented finite element
Transcranial direct current stimulation
Depression
head models of two subjects were presented, and a total of eleven tDCS electrode montages were simulated.
Computational model Sensitivity analysis on the effects of changing the size of the anode, rotating both electrodes and displacing the
anode was also conducted on selected montages. The F3–F8 and F3–F4 montages have been used in clinical trials
reporting significant antidepressant effects and both result in relatively high electric fields in dorsolateral
prefrontal cortices. Other montages using a fronto-extracephalic or fronto-occipital approach result in greater
stimulation of central structures (e.g. anterior cingulate cortex) which may be advantageous in treating depres-
sion, but their efficacy has yet to be tested in randomised controlled trials. Results from sensitivity analysis
suggest that electrode position and size may be adjusted slightly to accommodate other priorities, such as skin
discomfort and damage.
© 2013 Elsevier Inc. All rights reserved.

Introduction
Transcranial direct current stimulation (tDCS) is a neuromodulatory
technique which involves passing a mild electric current to the brain
through electrodes placed on the scalp. This direct constant flow of
current modulates underlying cortical activity with specific outcomes
related to anodal or cathodal stimulation (Nitsche and Paulus, 2000,
2001). The relative position (electrode montage) and size of the anode
and cathode determine the distribution of current density throughout
the brain (Bikson et al., 2010; Datta et al., 2011; Lee et al., 2012;
Miranda et al., 2009; Wagner et al., 2007). Thus there is potential for
stimulation to be focussed on specific cortical brain regions for thera-
peutic or investigative purposes or more diffuse effects can be produced
if widespread activation of brain regions is desired.
A key application of tDCS has been investigated in the treatment of
depression. Several recent open label and placebo-controlled trials,
and a meta-analysis of mean change in depression scores from
placebo-controlled studies suggest that tDCS may have clinically
⁎ Corresponding author at: Black Dog Institute, Hospital Road, Prince of Wales Hospital,
Randwick, NSW 2031, Australia. Fax: +61 2 9113 3734.
E-mail addresses: s.bai@unsw.edu.au (S. Bai), s.dokos@unsw.edu.au (S. Dokos),
kerrie-anne.ho@unsw.edu.au (K.-A. Ho), colleen.loo@unsw.edu.au (C. Loo).
meaningful efficacy (Boggio et al., 2008; Brunoni et al., 2011; Fregni
et al., 2006a, 2006b; Kalu et al., 2012; Loo et al., 2012; Martin et al.,
2011; Palm et al., 2011). These studies focused on anodal stimulation
of the left dorsolateral prefrontal cortex (DLPFC), based on observations
that this area has been associated with underactivity in depression
(Grimm et al., 2008). However, studies differed in the location of the
cathode, i.e. the return electrode — right supraorbital, right lateral
orbitofrontal, right DLPFC or in an extracephalic position. Though the
anodal left DLPFC electrode is often considered the “active” electrode,
the placement of the cathode is important for several reasons: shunting
of much of the current over the scalp may occur if the inter-electrode
distance is too close (Datta et al., 2008; Miranda et al., 2006; Weaver
et al., 1976), current density under the anode is affected by the place-
ment of the reference or “return” electrode (Bikson et al., 2010; Datta
et al., 2011), and the pattern of brain areas stimulated will be deter-
mined by the overall montage. All of these factors may have important
therapeutic implications.
Pathophysiological changes in depression are system-wide, involv-
ing a network of various cortical and limbic structures rather than a sol-
itary brain region such as the left DLPFC (Mayberg, 2007). Hypoactivity
in cortical regions and hyperactivity in subcortical and limbic regions is
often associated with symptoms of depression (Fitzgerald et al., 2008;
Mayberg, 1997). Meta-analyses have identified frontal and temporal

1053-8119/$ – see front matter © 2013 Elsevier Inc. All rights reserved.
http://dx.doi.org/10.1016/j.neuroimage.2013.11.015
 S. Bai et al. / NeuroImage 87 (2014) 332–344
cortices, the insula and cerebellum as regions of hypoactivity while
subcortical and limbic regions tend to be hyperactive. This distributed
network of structures includes the DLPFC, medial prefrontal cortex
(MPFC), orbitofrontal cortex (OFC), as well as the anterior cingulate
cortex (ACC), insula and hippocampus (Fox et al., 2012; Mayberg,
2003). Most recently, functional connectivity studies have suggested
altered activity at a network level during the resting state (Carballedo
et al., 2011). In particular, there is increased functional connectivity in
the subgenual anterior cingulate (sgACC), thalamus and OFC in people
with depression (Greicius et al., 2007). Further, overactivity in the
sgACC has been shown to be strongly negatively correlated with resting
state underactivity in the left DLPFC (Fox et al., 2012).
Studies of deep brain stimulation (DBS) in depression have also
provided insight into the critical regions involved in depression. Consis-
tent with imaging studies, DBS interventions targeted at the sgACC have
demonstrated efficacy in reducing symptoms of depression (Lozano
et al., 2012; Mayberg et al., 2005). DBS to specific regions of the basal
ganglia such as the nucleus accumbens (NAcc) and the ventral
capsule/ventral striatum (VC/VS) have also been found to have signifi-
cant antidepressant effects (Anderson et al., 2012; Bewernick et al.,
2010, 2012; Malone et al., 2009).
As the therapeutic potential of tDCS in psychiatric disorders is
further explored, information on how different electrode arrangements
determine current density in key brain regions, is essential. This study
compared the effects of several DCS montages, with realistic head
models reconstructed from MRI head scans, by investigating the brain
electric field (E-field) distribution and the average E-field in various
brain regions. tDCS montages modelled were those used in recent
tDCS depression studies: the F3–supraorbital (F3–SO) montage first
used when interest was rekindled in tDCS from 2006 onwards (Boggio
et al., 2008; Fregni et al., 2006a, 2006b; Loo et al., 2010; Palm et al.,
2011), and modified approaches in which the cathode was moved
more laterally to reduce shunting, F3–F8 (Loo et al., 2012), to the right
DLPFC, F3–F4 (Brunoni et al., 2011, 2013; Dell'Osso et al., 2012;
Ferrucci et al., 2009a, 2009b), or to an extracephalic position to achieve
a more widespread pattern of brain activation, F3–extracephalic
(F3–EC, brain sites based on the 10–20 EEG system; Martin et al.,
2011). The bilateral supraorbital–extracephalic (SO–EC) montage
most commonly used in earlier, pre-2000 studies, involving two
small anodes at the frontal poles and an extracephalic cathode was
also modelled (Arul-Anandam and Loo, 2009; Lippold and Redfearn,
1964; Redfearn et al., 1964). In addition, several hypothetical
montages were modelled: supraorbital–occipital (SO–OCC), pre-
mised on maximal stimulation of the sgACC and other central and
midline subcortical structures; temporal–extracephalic (TMP–EC),
prioritising temporal lobe stimulation as neurotrophic changes in
this region may have a key role in the pathophysiology of depression
(Pittenger and Duman, 2007), and supraorbital–cerebellum (SO–
CB), as abnormal cerebellar modulation of the cerebello-thalamo-
cortical pathway has been implicated in the mood and cognitive
symptoms associated with several psychiatric disorders, including
bipolar disorder and depression (Hoppenbrouwers et al., 2008).
The montages were modelled in two subjects — one male and one
female — to examine the extent to which inter-individual differences
in head anatomy affect variation in electric field with different
montages. Finally, a sensitivity analysis was performed to examine the
effects of displacing the anodal electrode by ~ 1 cm, to inform on
the likely importance of accuracy in electrode placement in clinical
applications.
Methods
Image segmentation and mesh generation
Two different high-resolution computational head models were
reconstructed from human subjects. One subject was a 35-year-old
333
Asian male whose MRI head scan, labelled “Msub” (short for male
subject), was truncated at the level of cervical vertebra 6. The other
was a 42-year-old Caucasian female, labelled “Fsub” (female subject,
Fig. 1S in Supplementary data): her scan was truncated at the level
of the atlas-axis, i.e., cervical vertebrae 1–2. T1-weighted MRI
scans of both subjects were obtained from Neuroscience Research
Australia. The scans were sagittally-oriented with voxel resolution
of 1 mm × 1 mm × 1 mm. The images of Msub were later down-
sampled to 1.5 mm in every dimension.
Head tissue masks were obtained using a combination of automated
and manual segmentation softwares. Automated mask generation was
performed using BrainSuite, an open-source package from the Laborato-
ry of NeuroImaging at the University of California (Shattuck and Leahy,
2002). Thus, tissue compartments including skin, skull, cerebrospinal
fluid (CSF), grey matter (GM) and white matter (WM) were generated
from the MRI data. The segmented masks were exported from
BrainSuite as grayscale images, and imported into ScanIP (Simpleware
Ltd., UK) for manual correction and further processing. The five original
masks were hence divided into more compartments:
• masks representing eyes, paranasal sinuses, larynx and cervical verte-
brae were separated from the skin and skull, as shown in Fig. 1a. In
addition, the major foramina of the skull were included in the skull
mask, including the superior orbital fissure, optic canal, foramen
ovale and foramen magnum;
• the skull was divided into the cranium and jaw. The cranium was then
subdivided into three layers, with spongy bone tissue as the middle
layer, and compact bone tissue as the outermost and innermost layers.
The jaw was considered compact. These skull compartments are
shown in Fig. 1b;
• the brain masks consisted of GM, WM, cerebellum (CB, with
brainstem) and the cervical spinal cord (SC), as well as the ventricular
system which was later assigned to the CSF mask;
• several brain regions of interest (ROIs), considered important in tDCS
therapeutic effects, were further segmented from the GM mask as
shown in Fig. 1c — anterior cingulate cortices (ACCs), amygdalae, hip-
pocampi, dorsolateral prefrontal cortices (DLPFCs) and orbitofrontal
cortices (OFCs).
In the head models, fat and muscle were included in the skin com-
partment, due to the fact that their conductivities are of the same
order of magnitude as skin conductivity (Gabriel et al., 1996). Similarly,
the venous sinuses and cranial arteries were included in the cerebrospi-
nal fluid compartment. Finally, any remaining blank voxels were manu-
ally assigned to the most appropriate neighbouring mask.
To examine the effect of an extracephalic clinical electrode montage
used in some tDCS studies (Martin et al., 2011; Moliadze et al., 2010), a
synthetic upper torso attached to the segmented head was manually
painted in ScanIP up to the level above the axilla based on anthropomet-
ric measurements (Dreyfuss and Tilley, 1993), as shown in Fig. 1d. A
similar approach was used in other studies (Borckardt et al., 2012;
Datta et al., 2011, 2012; Mendonca et al., 2011).
The + FE Free meshing algorithm in the + FE module of ScanIP
(v4.3) was selected to generate the tetrahedral mesh elements for the
high-resolution head models, with a compound coarseness of -30.
The meshes were then imported into the COMSOL Multiphysics FE
solver (v4.2).
Tissue conductivities
Most compartments of the head models were considered to be elec-
trically homogeneous and isotropic. The electrical conductivity of
paranasal sinuses (and larynx) was set to zero. Conductivities of the
scalp, compact and spongy bones of the skull, CSF, GM and WM, were
assigned mean values from multiple studies (Akhtari et al., 2000,
2002; Baumann et al., 1997; Geddes and Baker, 1967; Gonçalves et al.,
2003; Gutierrez et al., 2004; Lai et al., 2005; Oostendorp et al., 2000).
334 S. Bai et al. / NeuroImage 87 (2014) 332–344

brain

cerebrospinal
fluid
a)
skull
eye
sinuses
& pharynx

skin vertebrae

spongy bone tissue GM

WM
ACC

DLPFC
b) c) OFC

AH CB
compact bone tissue
& the jaw SC

d)

Fig. 1. a): Segmentation of the head model “Msub”: skin, eyes, paranasal sinuses (with larynx), skull (including compact bone tissue and spongy bone tissue), vertebrae, CSF and brain.
b): Segmentation of skull: compact bone tissue and spongy bone tissue. c): Detailed segmentation of the brain, including defined regions for white matter (WM), grey matter (GM),
anterior cingulate cortex, (ACC), dorsolateral prefrontal cortex (DLPFC), orbitofrontal cortex (OFC), amygdala and hippocampus (AH), cerebellum (CB, with brainstem), and cervical spinal
cord (SC). d): Frontal view of the model with extended shoulder. To respect the subject's privacy, the eyes of the model are hidden.

All conductivity values are listed in Table 1. The conductivities of the

eyes and the synthetic torso were assigned to the scalp conductivity.

White matter conductivity anisotropy Table 1

Tissue conductivities.
Modelling studies dedicated to the comparison between isotropic Compartment Electrical conductivity (S/m)
and anisotropic conductivities (Lee et al., 2012; Shahid et al., 2013;
Scalp 0.41
Suh et al., 2012), have shown that the presence of WM anisotropy
Eyes 0.41
resulted in a significant difference in regional E-fields, especially in the Sinus 0
deep brain structures. Hence, the WM anisotropic conductivity was CSF 1.79
also adopted in this study. GM 0.31
WM 0.14
DT-MRI was performed only on Msub in 61 gradient directions, with
WM (longitudinal) 0.65
voxel resolution of 2.5 mm × 2.5 mm × 2.5 mm. After being registered WM (transverse) 0.065
to the T1 structural scan in Amira (Visage Imaging GmbH, Germany), Vertebrae 0.013
diffusion tensor calculation was performed in FSL, an open source soft- Synthetic torso 0.41
ware developed by the FMRIB Analysis Group of University of Oxford Skull (compact bone) 0.006
Skull (spongy bone) 0.028
(Behrens et al., 2003a, 2003b, 2007). Eigenvectors and fractional
 S. Bai et al. / NeuroImage 87 (2014) 332–344 335

anisotropy (FA) were then calculated, with the latter being widely used Anode Cathode
to denote the degree of anisotropy: typically greater than 0.45 for WM
(Johansen-Berg and Behrens, 2009).
The conductivity tensor of WM, σ, was calculated from:
⊤
σ ¼ Sdiagðσ l ; σ t ; σ t ÞS ; ð1Þ
F3-SO

where S is the orthogonal matrix of unit eigenvectors obtained from the

WM diffusion tensor, and σl and σt are the assigned conductivities lon-
gitudinal and transverse to the fibre directions respectively, with
σl : σt = 10 : 1 (Nicholson, 1965). σl and σt were calculated using the
volume-constraint method (Wolters et al., 2006). This resulted in the
values of WM longitudinal and transverse conductivities being 0.65
and 0.065 S/m respectively. F3-F8
Following the diffusion tensor calculation, the calculated conduc-
tivity tensors of data points in the DT-MRI scans were then linked
to their individual coordinates in the Msub model. This process
was performed using MATLAB software (The Mathworks, USA).
Only fibre conductivity data having a strong anisotropy signal
(FA ≥ 0.45) were exported.

Boundary conditions for volume conductor model sF3-F8

All head compartments in the tDCS simulations were formulated as
passive volume conductors using Laplace's equation:

∇  ð−σ∇φÞ ¼ 0; ð2Þ

where φ is the electric potential, and σ is the conductivity tensor.

For scalp boundaries at the electrodes, two types of boundary condi-
tions were modelled separately: F3-F4-1
• normal component of inward current density set to Jn for anode, and
− Jn for cathode, where J n ¼ area of I electrode, with Is defined as the applied
s

stimulus current fixed at a DC level of 1 mA;

• constant voltage set to V for anode, and − V for cathode, with V satis-
fying ∫ J n dS ¼ I s , where S was the electrode area.
S
These two types of boundary conditions represented two extreme
cases for the electrode. In clinical reality, typical use of a saline-soaked
sponge between the skin and electrode pads suggests that neither
constant current, or constant voltage conditions are likely to precisely
hold at the scalp–electrode interface. Nonetheless, our simulation
results suggested that E-field distributions remained generally the
same regardless of the choice of electrode boundary condition, even
though absolute E-field values were slightly different between the two
cases. As a result, we report only results adopting constant current
electrode boundaries. Results using fixed voltage electrode boundaries
are supplied in the Supplementary data (Fig. 2S).
The rest of the boundary conditions were:
• ground (zero electric potential) at the lower boundary of the synthetic
(extended) torso;
• all other external boundaries were assigned as electric insulators
(zero normal component of current density);
• continuous current density (i.e., flux continuity) across all interior
boundaries.
Electrode placements
Electrodes located on the scalp surface were defined mathematical-
ly, which enabled their size, location and orientation to be readily
adjusted. A total of eleven tDCS electrode montages were simulated,
as shown in Figs. 2 and 3. For most montages, standard 7 cm × 5 cm
electrodes were used. For montages with the return electrode placed
in an EC position, focal stimulation of the extracephalic region was not
required and a 10 cm × 10 cm electrode was used for reasons of
comfort. Similarly, a 10 cm × 10 cm return electrode was placed over
F3-F4-2
Fig. 2. tDCS electrode placement — part 1: F3-supraorbital (F3–SO), F3–F8, sF3–F8, F3–F4-
1 and F3–F4-2. The red and blue electrodes represent the anode and cathode, respectively.
To respect the subject's privacy, the eyes of the model are hidden.
the occiput for the SO–OCC montage, as the aim was to tailor current
pathways to broadly target the medial subcortical structures described
above (sgACC, basal ganglia) rather than deliver occipital stimula-
tion. The electrode placements for these montages are described as
follows:
• F3–SO: both electrodes were 7 cm × 5 cm rectangular pads. The
anode was placed over the F3 electrode site on a standard 10–20
EEG cap system, with the long axis of the pad pointing towards
the vertex. The cathode was placed above the arcus superciliaris
on the right, with the long axis of the pad parallel to the horizontal
plane.
• F3–F8: both electrodes were 7 cm × 5 cm rectangular pads. The
anode was placed at the same location as in F3–SO. The cathode
was placed over the F8 EEG cap electrode site, with the lower
edge of the pad 4–5 mm below the eye socket, and the long axis
perpendicular to the horizontal plane.
336 S. Bai et al. / NeuroImage 87 (2014) 332–344

Anode Cathode • F3–F4-2: both electrodes were 7 cm × 5 cm rectangular pads, and

were placed at the same sites as the F3–F4-1 configuration, but the
orientations of both electrodes were perpendicular to those in F3–
F4-1.
• F3–EC: the 7 cm × 5 cm anode was placed at the same location as
F3-EC
in F3–SO, and the cathode was a 10 cm × 10 cm rectangular pad
placed on the right shoulder.
• sF3–EC: the anode was placed at the same location as that of F3–EC,
but the size of the pad was 4 cm × 4 cm. The 10 cm × 10 cm cath-
ode was placed in the same location as the F3–EC configuration.
• TMP–EC: the anode was a 7 cm × 5 cm rectangular pad placed
between the F3 and T3 EEG positions, with the long axis of the
pad parallel to the line connecting F3 and T3. The 10 cm × 10 cm
sF3-EC cathode was placed on the right shoulder.
• SO–OCC: the anode was a 7 cm × 5 cm rectangular pad, placed
above the arcus superciliaris on the left, with the long axis of
the pad parallel to the horizontal plane. The cathode was a
10 cm × 10 cm square pad centred over the inion, with the larger
electrode size used to diffuse cathodal effects.
• SO–CB: the anode was a 7 cm × 5 cm rectangular pad, placed at
the same position as the SO–OCC configuration. The cathode was
TMP-EC a 10 cm × 5 cm rectangular pad, with the top edge centred at the
inion, and the long axis parallel to the horizontal plane, to achieve
bilateral cerebellar stimulation.
• SO–EC: two circular anodes with a diameter of 0.5 in. (1.27 cm)
were placed above the arcus superciliaris on both sides, with the
cathode located as in the F3–EC configuration.

Data analysis
SO-OCC
Three types of head models were investigated in this study —
“Msub-aniso” (referring to the Msub model with WM anisotropy),
“Msub” (referring to the Msub model without WM anisotropy) and
“Fsub” (without WM anisotropy). The models were solved using the
segregated numerical solver in COMSOL (v4.2) on a Windows 64-bit
workstation with 24 GB RAM utilising 4 processors. To solve the station-
ary equations, a direct linear solver was utilised with an absolute error
tolerance set to 10−5. It took ~20 min to solve for each simulation, for
SO-CB approximately 1.4 × 106 degrees of freedom.
Simulation results were analysed by comparing the difference in
brain E-field distribution among the various electrode montages and
different head models. The analysis also focused on comparing the
average E-field magnitude E in several ROIs in the brain. E was calculated
using:

Z
SO-EC jEj dV

E¼ Z V
; ð3Þ
dV
V

Fig. 3. tDCS electrode placement — part 2: F3-extracephalic (F3–EC), sF3–EC, temporal–
extracephalic (TMP–EC), supraorbital–occipital (SO–OCC), supraorbital–cerebellum (SO–
CB) and supraorbital–extracephalic (SO–EC). The red and blue electrodes represent the
anode and cathode, respectively. To respect the subject's privacy, the eyes of the model
are hidden.
• sF3–F8: the anode was placed at the same F3–F8 location, but the
size of the anode pad was 4 cm × 4 cm. The cathode was the
same as in F3–F8.
• F3–F4-1: both electrodes were 7 cm × 5 cm rectangular pads. The
anode was placed at the same location as in F3–SO, and the cathode
was placed over the F4 electrode site on the 10–20 EEG cap system,
with the long axis pointing towards the vertex of the head.
where |E| is the E-field magnitude in the ROI in question, and ∫
is a volume integral over this region. Note that the denominator V
is simply the volume of the ROI. The mean of E and its standard
error (SE) were then determined across all three head models.
The difference in the E-field was considered significant, if the
E-field range (mean ± SE) between any two montages did not
overlap.
In addition, a sensitivity analysis on E-fields in the ROIs to electrode
displacement from the original position was conducted on the Msub-
aniso. Three montages were included in this analysis: F3–F4-1, F3–F8
and F3–EC. For each montage, the anode F3 was perturbed from its
original position anteriorly, posteriorly, laterally or medially (note: the
antero-posterior displacement was on a sagittal plane, whereas the
medio-lateral displacement was on a horizontal plane). The displace-
ment was set to 1 cm, which is the likely margin of error in clinical trials.
 S. Bai et al. / NeuroImage 87 (2014) 332–344 337

The absolute differences in average E-fields from the original place-
ments were calculated.
Results
Fig. 4 shows the E-field magnitude and direction on the cortical
surface of the brain for six selected tDCS electrode montages with
Msub-aniso. Fig. 5 shows the E-field profile with the same head model
in cross-sectional slices of the brain for the selected tDCS electrode
montages. The montages which utilised the F3 anode and a contralateral
frontal cephalic cathode (F3–SO, F3–F8, F3–F4-1 as shown in Fig. 4)
exhibited higher current density predominately in the frontal lobes of
the brain. F3–F8 and F3–F4-1 shared a similar E-field magnitude profile,
but the E-field directions were quite distinctive, due to the different
positions of the cathodes. As for F3–EC, a more uniform and widely
distributed current density was present in the whole brain, especially
in the ventral part, owing to current predominantly flowing inferiorly
and posteriorly. Compared to the other F3 montages, the E-field magni-
tude was weaker in the frontal lobe with F3–EC. SO–OCC and TMP–EC
had E-field characteristics similar to F3–EC, except that the predomi-
nant E-field direction with SO–OCC was anterior–posterior, and the
E-field magnitude was large in the left temporal lobe with TMP–EC.
The mean and standard error of spatially-averaged E-field magni-
tude E for the three head models were shown in Fig. 6, with separate
data of E in individual head models shown in the Supplementary data
(Figs. 3S–5S). In comparison to the F3–SO montage, the modified mon-
tages with the anode on F3 but cathode placed at a greater distance from
the anode (F3–F8, F3–F4, F3–EC) all resulted in less shunting, i.e. more
current entered the brain, with F3–SO significantly different from F3–
F8 and F3–EC. The F3–EC montage resulted in the least shunting, with

F3-SO

F3-F8
V/m
≥ 0.25

F3-F4-1

0.15

F3-EC

0.05

SO-OCC

TMP-EC

Fig. 4. E-field magnitude distribution and direction in the whole brain for Msub-aniso model for six selected tDCS montages. The leftmost and two middle columns feature the lateral view
from the left, the frontal view and the top view, respectively. The black box specifies the location of the enlarged region shown in the rightmost column. The black arrows represent the
direction of E-field vectors, whereas the red arrows indicate the global electrode vector direction — from the anode to the cathode.
338 S. Bai et al. / NeuroImage 87 (2014) 332–344

F3-SO

F3-F8 V/m
≥ 0.25

F3-F4-1
0.15

F3-EC
0.05

SO-OCC

TMP-EC

Fig. 5. E-field brain magnitude distribution in Msub-aniso in cross-sections through the DLPFC (coronal), ACC (sagittal) and OFC (horizontal) with these structures outlined. Dashed lines
indicate locations of slice planes.

more current reaching brain areas compared to the other F3 montages. electrode size at the F3 site (sF3–F8, sF3–EC) and rotation of electrodes
For F3–EC, the E-field in the DLPFCs was reduced compared to other F3 by 90° (F3–F4-2) only made a small difference to modulation patterns.
montages, but this montage more strongly modulated the ACCs and The SO–OCC montage was similar to the F3–EC montage in less
cerebellum/brainstem than the other F3 montages. Variation of shunting and a higher E-field in the ACCs than other frontal montages,
 S. Bai et al. / NeuroImage 87 (2014) 332–344 339

V/m F3-SO
F3-F8
0.1 sF3-F8
F3-F4-1
F3-F4-2
F3-EC
sF3-EC
TMP-EC
0 SO-OCC
Whole brain L hemisphere R hemisphere
SO-CB
SO-EC

0.1

0
CB L DLPFC R DLPFC

0.1

0
L OFC R OFC L ACC

0.1

0
R ACC L hippocampus R hippocampus

Fig. 6. Mean and standard error of spatially-averaged E-field magnitude E in various brain regions of interest across the three head models — Msub-aniso, Msub and Fsub.

though the E-field in the DLPFC was reduced. When a smaller cathode
was used and centred over the cerebellum (SO–CB), the main effect
compared to SO–OCC was an E-field increase in more ventral structures
(hippocampus, OFC and CB), but not to a significant level. Compared
with more recent frontal montages, the (bilateral) SO–EC resulted in
less left DLPFC modulation, but greater OFC and ACC modulation
particularly in the left hemisphere. The TMP–EC montage most strongly
modulated the marked E-field reduction in frontal structures with
TMP–EC.
The pattern revealed by the average E-field (E) magnitude with
Msub mostly agreed with the anisotropic model. Similarly, the ROI
E-field data from Fsub was largely consistent with that from both
Msub and Msub-aniso, albeit with minor variations. Namely, Fsub
indicated more significant current-shunting in montages with closer
inter-electrode scalp distances (E of whole brain, left hemisphere and CB
with F3–SO and F3–F4 in Figs. 3S–5S), smaller inter-montage differ-
ences in E for left DLPFC, as well as increased E magnitude for right
DLPFC with both F3–F8 montages. These discrepancies are likely due
to the variation in head geometry, especially in skull size and thickness.
Regardless, the ROI E-field magnitude distribution with Fsub was quite
similar to that of the corresponding Msub regions (F3–F4-1 in Fig. 7),
and there were local hot-spots evident on the cortical surface, but
these were in slightly different locations in each head, due to the varia-
tion in cortical foldings.
Fig. 8 demonstrates the sensitivity analysis of E-fields (in Msub-aniso)
with respect to displacements of the anode in the anterior, posterior,
lateral and medial directions. Moving the electrode by 1 cm did
not make a substantive difference. Reduction in the inter-electrode
distance, such as medial displacement with F3–F4-1 and F3–F8, tended
to result in more shunting and less current entering the brain. More
significant changes (i.e., close to 10% of the original), were (ROIs): left
OFC in F3–F4-1 with antero-posterior displacement, left and right
ACCs in F3–F8 with antero-posterior displacement, and left and right
ACCs in F3–EC with antero-posterior displacement.
Discussion
Clinical implications of electrode montages
A number of recent tDCS studies have reported positive antidepres-
sant effects in depressed patients (Boggio et al., 2008; Brunoni et al.,
2011, 2013; Fregni et al., 2006a, 2006b; Kalu et al., 2012; Loo et al.,
2012; Martin et al., 2011; Palm et al., 2011). The rationale guiding the
choice of electrode montage in these trials is up-regulation of the left
340 S. Bai et al. / NeuroImage 87 (2014) 332–344
Msub
Fig. 7. Brain E-field magnitude distribution for the Msub and Fsub models using the F3–F4-1 montage. The rectangles specify the location of the enlarged cortical regions in the bottom row.
DLPFC, with the anode placed on F3 (Boggio et al., 2008; Brunoni et al.,
2011, 2013; Dell'Osso et al., 2012; Ferrucci et al., 2009a, 2009b; Fregni
et al., 2006a, 2006b; Loo et al., 2010, 2012; Martin et al., 2011; Palm
et al., 2011). This is based on the general premise that in depressed pa-
tients, the left DLPFC is hypoactive while the right DLPFC is hyperactive
(Grimm et al., 2008). The results from the present study showed that all
montages with the anode placed at F3 achieved this aim.
Findings from the present study also indicate the importance of
cathodal placement as it determines the relative current distribution
in other brain regions, as well as the intensity of stimulation at the left
DLPFC. In comparison to the F3–SO montage where the electrodes are
positioned close together, montages with wider spacing between the
electrodes result in less shunting and more current entering the brain.
However, E-field levels in the DLPFC also decreased as the inter-
electrode distance increased, in line with Moliadze et al. (2010) which
reported a significant decline in motor evoked potentials when they
compared left M1-contralateral EC with left M1-contralateral forehead
simulations. It is not known whether such a difference is of clinical
significance, though a pilot study of the F3–EC montage suggests it may
have more rapid antidepressant effects than the F3–F8 montage. This is
presumably due to more effective stimulation of other brain regions
(Martin et al., 2011), though the relative efficacy of these approaches
has yet to be tested in an adequately powered randomised controlled
Fsub
V/m
≥ 0.25
0.15
0.05
trial. It is useful to note that use of a smaller electrode at F3 increased
the E-field at the left DLPFC. This may be a useful strategy to compensate
for loss of intensity associated with moving the cathode further away.
The F3–F8 and F3–F4 montages produced similar patterns of the
E-field in the brain, resulting in strong stimulation of the left and
right DLPFC and clinical trials of these montages have demonstrated
antidepressant effects (Brunoni et al., 2011, 2013; Dell'Osso et al.,
2012; Ferrucci et al., 2009a; Loo et al., 2012). The role of cathodal stim-
ulation of ventral right frontal regions, particularly achieved with the
F3–F8 montage, in antidepressant efficacy is unclear. The F3–F8 mon-
tage resulted in a significantly greater E-field in the right OFC compared
to the F3–F4 and other montages examined. A recent trial of the F3–F8
montage reported clear antidepressant results, with a 50% response rate
after six weeks of tDCS (Loo et al. 2012). However, the independent ef-
fects of right frontal cathodal stimulation have not been adequately
studied. Boggio et al. (2008) found that the OCC–F8 montage (i.e. cath-
odal stimulation at F8, used as an active control group) was still able to
induce a larger effect than sham tDCS, but results from this trial were in-
conclusive due to the possible confounding effects of concurrent anodal
occipital stimulation and a small sample size.
Brain regions other than the DLPFC have also been implicated in
depression. These include bilateral sgACC, NAcc, VS/VC, and other
central structures, with evidence to suggest that specific aspects of
 S. Bai et al. / NeuroImage 87 (2014) 332–344
Whole brain
L hemisphere
R hemisphere
CB
L DLPFC
R DLPFC
L OFC
R OFC
L ACC
R ACC
L hippocampus
R hippocampus
0 0.04
Fig. 8. The sensitivity of average E-field magnitude E in brain regions of interest using Msub-aniso, with displacements of F3 electrode with F3–F4-1, F3–F8 and F3–EC. The bar charts on the
left represent the average E-field magnitude when F3 is at the original position. The data points on the right represent the absolute differences in average E-fields from the original
placement.
depressive symptomatology may be linked to particular brain regions
(Anderson et al., 2012). For example, cognitive aspects (pathological
guilt, impaired concentration, suicidal ideation) may be linked to ACC,
OFC and PFC dysfunction, whereas anhedonia, depressed mood and
anxiety may be mediated by the NAcc, sgACC and OFC. Central struc-
tures including the hypothalamus, locus coeruleus and dorsal raphe
nuclei may be responsible for neurovegetative symptoms such as
sleep and appetite disturbances. At present, the relative importance of
stimulating such regions remains unclear and it is also unknown wheth-
er frontal montages adopted since 2000 are more advantageous in
treating depression than the prevailing bilateral SO–EC montage used
in earlier decades, which results in strong ACC and OFC activation. The
diffuse nature of tDCS may be therapeutically advantageous, given the
widespread anatomy of areas involved in depression, as all of the afore-
mentioned areas are stimulated to some extent. This is particularly the
case for montages with an extracephalic or posterior electrode, which
have been shown to lead to more widespread brain current distribution
than montages with a contralateral cephalic cathode.
341
F3-F4-1
F3-F8
F3-EC
Post
Ant
Lat
Med
Unit: V/m
0.08 0.12 -0.01 0 0.01
Theoretically, it is possible for electrode montages to be tailored to
an individual patient's depressive symptoms. For example, montages
that result in greater stimulation of deep central structures (F3–EC,
SO–OCC, SO–CB, SO–EC) may be effective for treating melancholic
depression. However, stimulation of the same central structures may
increase the risk of a manic episode in bipolar depression (Gálvez
et al., 2011). In addition to montages used in clinical practice, several hy-
pothetical montages were also modelled. Though the SO–OCC montage
was designed for maximal stimulation of ACC and central structures
(thalamus, striatum), our modelling results suggest that ACC modula-
tion is achieved as readily with the F3–EC montage. The mean E-fields
in the DLPFC are also similar for the two montages. Given the promising
results in an open label depression trial of the F3–EC montage (Martin
et al., 2011), a similar antidepressant efficacy is also expected from the
SO–OCC montage. High E-fields were found in the cerebellum and hip-
pocampus with the SO–CB and TMP–EC montages respectively, and
these montages may be useful where modulation of these brain regions
is particularly desired. Both cerebellar and temporal lobe changes have
342 S. Bai et al. / NeuroImage 87 (2014) 332–344
been reported in depression (Fitzgerald et al., 2008; Hoppenbrouwers
et al., 2008), and it is possible that neuromodulation targeted at these
areas may be beneficial in treating depression.
The E-field directions provide a preliminary understanding of the
current pathways within the brain, since the current density vector in
a conductive medium is in the same direction as the E-field vector.
Local E-field vectors generally follow the dominant directionality of
the E-field in the entire model, which is from anode to cathode. Howev-
er, the E-field vectors may not all be in parallel with the main E-field
direction, depending on the location of the ROI relative to the elec-
trodes, and on the local electrical properties. For instance, WM fibres
provide a preferential pathway for current flow along the fibres when
the flow is partially aligned with the fibre orientation, whereas higher
E-field magnitudes are generated when current flow is transverse to
the fibre orientation (Bai et al., 2013; Lee et al., 2012). Since the modu-
lation of neurons may also be dependent on directionality of the E-field
(Basser and Roth, 2000; Creutzfeldt et al., 1962; Molaee-Ardekani et al.,
2012), including directionality in analysis may provide more compre-
hensive information on brain activation, though the clinical implications
are as yet unclear.
While changes in the electrode size or orientation resulted in differ-
ences in the E-field magnitude, the differences were not large. This was
perhaps due to a relatively small difference in electrode sizes (35 cm2
vs. 16 cm2), indeed previous studies have shown that large differences
in E-field magnitude are only found when there is a considerable change
in electrode size (Miranda et al., 2009; Parazzini et al., 2011). Similarly,
displacing the electrode by 1 cm around the actual position did not
result in a large difference. These results suggest that electrodes may
be adjusted slightly to accommodate other priorities, such as skin dis-
comfort and damage. For example, rotation of an electrode to avoid
stimulation over a skin lesion such as a mole, may not substantially
affect neuronal outcomes.
An interesting finding from our results is that current density was
not evenly spread over the cerebral cortex, but that local hot spots
were evident. This phenomenon has been previously reported in
modelling studies (Datta et al., 2009; Salvador et al., 2010) and indicate
that these localised areas of intense activation may be of clinical impor-
tance for both efficacy and safety. It appears that the location of the hot
spot is determined by individual anatomical variations in cerebral folds,
thickness of the CSF layer, skull and scalp, and may contribute to inter-
individual differences in efficacy.
Model validation and limitations
The novelty of this study is that the anatomically-accurate head
models from two different subjects were employed, each with three-
layered skull structure and one also with WM anisotropy, in order to
investigate several tDCS montages specifically targeted at depression
treatment. This was achieved by comparing E-fields in several brain
ROIs. Even though some of the above modelling features have appeared
in other studies, they have not been combined together in a single study
as has been done in this work. In addition, there has been no modelling
study dedicated to examining tDCS electrode montages which may be
useful in the treatment of depression.
As noted by Lee et al. (2012), validation of computer simulations of
brain E-field distribution against experimental data remains a chal-
lenge. As our head model was only comprised of a limited number of
tissues, errors may arise from the exclusion of the dielectric properties
of other tissues, even though their electrical conductivities were of the
same order as that of the substitute compartment. The conductivities
were chosen as an average across different experimental studies,
which suggested that they were not measured with the same experi-
mental setup. This, together with the artificial approximation of the
torso, may contribute to computational errors. As DTI was not per-
formed on Fsub, Msub also served as a transition model. However, in
order to provide a more generalised conclusion for clinical investigation
regarding the effects of these montages, simulations using head models
from more subjects with the same electrical properties may be neces-
sary as to further substantiate our results.
Nevertheless, the simulation results presented in this study are in
line with other modelling studies. Parazzini et al. (2011) reported a
median E-field magnitude of 0.33 V/m in the cortex using the left M1–
right SO configuration, about five times the average E-field value
found here. This is probably due to the variation in head geometry, as
well as the adoption of a three-layer skull in our head model, and the
difference in the tissue conductivities chosen, which likely resulted in
the disparities in the brain E-field magnitude. In addition, Bikson et al.
(2010) found a peak cortical E-field value of 0.44 V/m in simulations
of a healthy subject with left M1–contralateral forehead tDCS. Datta
et al. (2011) simulated the head of a stroke patient, and found a peak
value at 0.36 V/m with the left M1–contralateral shoulder montage.
Those studies, however, assumed a higher value of skull conductivity
than the three-layer skull used in this study.
Conclusion
With the aid of computational modelling, this study presented a
systematic analysis of various tDCS electrode montages that have been
used in clinical trials, as well as hypothetical montages specifically for
the treatment of depression. The overall profile of E-field magnitude
and direction, as well as the average E-field magnitudes in key brain
regions were presented. While the clinical significance of these
outcomes is not as yet well understood, these results may form a useful
reference for researchers seeking to optimise the therapeutic potential
of tDCS by manipulation of electrode montage. Sensitivity analysis on
the effects of changing the size of the anode, rotating both electrodes
and displacing the anode was also conducted on selected montages.
This is the first computational study dedicated to this type of analysis.
This approach could equally inform the use of tDCS to treat other neuro-
psychiatric disorders, or the design of montages for neuropsychological
experiments.
Acknowledgment
The authors would like to thank Prof. Caroline Rae and Dr. John Geng
from Neuroscience Research Australia for their support in acquiring and
processing the structural MRI and DT-MRI data, Dr. Elizabeth Tancred
from the University of New South Wales for her expertise in the head
anatomy, and Dr. Angelo Alonzo from the Black Dog Institute for his
help in determining the accurate position of scalp electrodes.
Appendix A. Supplementary data
Supplementary data to this article can be found online at http://dx.
doi.org/10.1016/j.neuroimage.2013.11.015.
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