1
Focality Oriented Selection of Current Dose for Transcranial Direct Current
Stimulation
Rajan Kashyap
1*
, Sagarika Bhattacharjee
2
, Ramaswamy Arumugam
3
, Rose Dawn Bharath
4
,
Kaviraja Udupa
5
, Kenichi Oishi
6
, John E. Desmond
6†
, SH Annabel Chen
2,3,7,8#
,
Cuntai Guan
1*#
1
School of Computer Science and Engineering, Nanyang Technological University,
Singapore
2
Psychology, School of Social Sciences (SSS), Nanyang Technological University,
Singapore
3
Centre for Research and Development in Learning (CRADLE), Nanyang
Technological University, Singapore
4
Department of Neuroimaging and Interventional Radiology, National Institute of
Mental Health and Neurosciences, India
5
Department of Neurophysiology, National Institute of Mental Health and
Neurosciences, India
6
The Johns Hopkins University School of Medicine, Baltimore, United States
7
Lee Kong Chian School of Medicine (LKC Medicine), Nanyang Technological
University, Singapore
8
National Institute of Education, Nanyang Technological University, Singapore
# Equal contribution, †senior author
Address correspondence to:
Rajan Kashyap
School of Computer Science and Engineering
Nanyang Technological University, Singapore
Email: rajankashyap6@gmail.com
And
Cuntai Guan
School of Computer Science and Engineering
Nanyang Technological University, Singapore
Email: ctguan@ntu.edu.sg
Preprints (www.preprints.org) | NOT PEER-REVIEWED | Posted: 23 June 2021 doi:10.20944/preprints202106.0584.v1
© 2021 by the author(s). Distributed under a Creative Commons CC BY license.
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Abstract
Background: In Transcranial Direct Current Stimulation (tDCS) the injected current gets
distributed across the brain areas. The motive is to stimulate the target region-of-interest
(ROI), while minimizing the current in non-target ROIs. For this purpose, determining the
appropriate current-dose for an individual is difficult.
Aim: To introduce Dose-Target-Determination-Index (DTDI) to quantify the focality of tDCS
and examine the dose-focality relationship in three different populations.
Method: Here, we extended our previous toolbox i-SATA to the MNI reference space. After
a tDCS montage is simulated for a current-dose, the i-SATA(MNI) computes the average (over
voxels) current density for every region in the brain. DTDI is the ratio of average current
density at target ROI to the ROI with maximum value (peak region). Ideally target ROI should
be the peak region, so DTDI shall range from 0 to 1. Higher the value, the better the dose. We
estimated the variation of DTDI within and across individuals using T1-weighted brain images
of 45 males and females distributed equally across three age groups- (a) Young adults (20 ≥ x
˂ 40 years), (b) Mid adults (40 ≥ x ˂ 60 years), and (c) Older adults (60 ≥ x ˂ 80 years).
DTDI’s were evaluated for the frontal montage with electrodes at F3 and right supra-orbital for
three current doses 1mA, 2mA, and 3mA with the target ROI at left middle frontal gyrus.
Result: As the dose is incremented, DTDI may show (a) increase, (b) decrease, and (c) no
change across the individuals. The focality decreases with age and the decline is stronger in
males. Higher current dose at older age can enhance the focality of stimulation.
Conclusion: DTDI provides information on which tDCS current dose will optimize the focality
of stimulation. DTDI recommended dose should be prioritised based on the age (> 40 years)
and sex (especially males) of an individual. The toolbox i-SATA(MNI) is freely available.
Keywords: Transcranial direct current stimulation (tDCS), Realistic volumetric Approach-
based Simulator for Transcranial electric stimulation (ROAST), Systematic Approach for
tDCS Analysis (SATA), Current dose, Individualized tDCS, Age and Sex difference.
Preprints (www.preprints.org) | NOT PEER-REVIEWED | Posted: 23 June 2021 doi:10.20944/preprints202106.0584.v1
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Introduction
Transcranial Direct Current Stimulation (tDCS) is a noninvasive brain stimulation
technique that could alleviate symptoms of several neurological and psychiatric brain
disorders [1–3]. A conventional tDCS setup consists of anode and cathode placed over the
scalp (referred as montage) with low intensity of current (~ 1- 3mA) being injected to
stimulate the target region of interest (ROI) [4,5]. However, the injected current gets diffused
in the intermediary regions of the brain and might not essentially stimulate the target ROI
with desired intensity [6,7]. Computational models that predict the pattern of current flow
across the brain of an individual are used to optimize the tDCS stimulation parameters [8–
14]. The amount of injected current (referred as ‘current dose’) plays an important role in the
dispersal of stimulation intensity across the brain regions [15,16]. The distribution may vary
from person to person and within a person based on the quantity of the dose [17–19].
Therefore, selection of optimal current dose for an individual’s brain that could sufficiently
stimulate the target ROI while minimizing the current in non-target ROIs is important
[15,16].
In recent years there has been a growing interest towards individualization of current
dose [15,16,20]. It has been reported that varying the current intensity at scalp for each
individual can reduce the interindividual variability in the electric field intensity at the target
ROI [20]. The current dose calculated through inverse modelling of tDCS induced electric
field at the target ROI correlates with the motor thresholds generated by transcranial
magnetic stimulation [15,16]. In a recent tDCS experiment using frontal montage and 2mA
(fixed) current dose, individuals with high simulated current density at the target ROI (left
dorsolateral prefrontal cortex) were found to have stronger improvements in working
memory compared to those with low current density [21]. They also showed that
individualizing the current dose by fixing the current density desired at the target region can
Preprints (www.preprints.org) | NOT PEER-REVIEWED | Posted: 23 June 2021 doi:10.20944/preprints202106.0584.v1
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maximize the benefits of tDCS [21]. Though the models are a step towards individualizing
the current dose, they do not consider the spread of the field to intermediary (non-target)
regions. The current flow in the intermediary regions have a vital role to play in determining
the outcome of tDCS [6,12,22–25]. It has been found that some brain regions may act as
conduit clustering most of the current to a specific location that can deter the stimulation
intensity expected at the target ROI [6,26]. Increasing the focality of stimulation in
conventional tDCS setup has been an area of investigation [27–30]. Therefore, the
approaches to individualize the current dose should consider the focality of stimulation in
order to recommend the optimal intensity of input current.
In our previous work, we developed individual-Systematic-Approach-for-tDCS-
Analysis (i-SATA) toolbox [31] that estimates the average current density received by target
ROI and intermediary regions of an individual's brain after a montage has been simulated in
Realistic-volumetric-Approach-based-Simulator-for-Transcranial-electric-stimulation
(ROAST) toolbox [10]. We demonstrated the ease with which i-SATA toolbox can be
applied on an individual brain to reverse calculate the current dose that can stimulate the
target ROI with desired intensity [31]. This was done based on the assumption that electric
field intensity at target ROI increases linearly with current dose by following the procedure
laid down by Evans and colleagues [20] . Since we will be using it throughout the study, it
will be helpful to familiarize our readers with an example. Suppose the calculated stimulation
intensity at the target ROI is 0.25 mA/m
2
when 1 mA of current is applied on the scalp. To
achieve an intensity of 0.5 mA/m
2
desired at the target ROI, the required dosage
(individualized) can be reverse calculated as 𝐼𝑛𝑑𝑖𝑣𝑖𝑑𝑢𝑎𝑙𝑖𝑠𝑒𝑑 𝑑𝑜𝑠𝑒 =
×
𝐹𝑖𝑥𝑒𝑑 𝑑𝑜𝑠𝑒 [𝑖.𝑒.,
.
.
× 1 = 2 mA].
In i-SATA, we used the Talairach client toolbox [32] to map an individual brain to the
Talairach atlas space [33]. In this respect, another widely used brain template that provides
Preprints (www.preprints.org) | NOT PEER-REVIEWED | Posted: 23 June 2021 doi:10.20944/preprints202106.0584.v1
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detailed stereotaxic information on the location and variability of cortical areas is provided by
the Montreal Neurological Institute (MNI) reference space [34–38]. Simon and colleagues
[39–41] had developed the SPM anatomy toolbox that integrates the cytoarchitectonic maps
in the MNI space. Here we leveraged on the potential of SPM anatomy toolbox to extend i-
SATA to the MNI space. The extended toolbox i-SATA(MNI) that integrates the SPM
anatomy toolbox with i-SATA will enable researchers to visualize the comprehensive
overview of the current density distribution across the cortex (target and intermediary
regions) in the MNI space.
With i-SATA(MNI), we introduce the Dose-Target-Determination-Index (DTDI), a
simple estimate that will quantify the focality of stimulation and facilitate the selection of
optimal current dose required to stimulate the target ROI in an individual’s brain. The index
provides a comprehensive overview of the intensity of stimulation received by the target ROI
and intermediary regions after a montage has been postprocessed in i-SATA(MNI). To
explain DTDI, we will use the montage with anode positioned at F3 and cathode at right
supra-orbital (RSO) (referred to as F3-RSO, Figure 1A). The montage has been shown to
stimulate the left middle frontal gyrus [22,25] and is effective for depression [3,22,42] and
working memory [43]. To make it easy for our readers to interpret how DTDI facilitates
selection of the current dose, we will show the inter-individual as well as the intra-individual
variation in the index by uniformly increasing the current dose. Finally, we will evaluate the
variation in DTDI with age and sex of individuals. The purpose will be to explore if dose
selection should be prioritised for any category (age and sex) of individuals.
Preprints (www.preprints.org) | NOT PEER-REVIEWED | Posted: 23 June 2021 doi:10.20944/preprints202106.0584.v1
