Effects of Anodal High-Definition Transcranial Direct Current Stimulation on Bilateral Sensorimotor Cortex Activation During Sequential Finger Movements: An fNIRS Study.

Abstract

Transcranial direct current stimulation (tDCS) is a non-invasive electrical brain stimulation technique that can modulate cortical neuronal excitability and activity. This study utilized functional near infrared spectroscopy (fNIRS) neuroimaging to determine the effects of anodal high-definition (HD)-tDCS on bilateral sensorimotor cortex (SMC) activation. Before (Pre), during (Online), and after (Offline) anodal HD-tDCS (2 mA, 20 min) targeting the left SMC, eight healthy subjects performed a simple finger sequence (SFS) task with their right or left hand in an alternating blocked design (30-s rest and 30-s SFS task, repeated five times). In order to determine the level of bilateral SMC activation during the SFS task, an Oxymon MkIII fNIRS system was used to measure from the left and right SMC, changes in oxygenated (O2Hb) and deoxygenated (HHb) haemoglobin concentration values. The fNIRS data suggests a finding that compared to the Pre condition both the "Online" and "Offline" anodal HD-tDCS conditions induced a significant reduction in bilateral SMC activation (i.e., smaller decrease in HHb) for a similar motor output (i.e., SFS tap rate). These findings could be related to anodal HD-tDCS inducing a greater efficiency of neuronal transmission in the bilateral SMC to perform the same SFS task.

Full text

Chapter 44
Effects of Anodal High-Definition
Transcranial Direct Current Stimulation
on Bilateral Sensorimotor Cortex Activation
During Sequential Finger Movements: An
fNIRS Study
Makii Muthalib, Pierre Besson, John Rothwell, Tomas Ward,
and Stephane Perrey
Abstract Transcranial direct current stimulation (tDCS) is a non-invasive electri-
cal brain stimulation technique that can modulate cortical neuronal excitability and
activity. This study utilized functional near infrared spectroscopy (fNIRS) neuro-
imaging to determine the effects of anodal high-definition (HD)-tDCS on bilateral
sensorimotor cortex (SMC) activation. Before (Pre), during (Online), and after
(Offline) anodal HD-tDCS (2 mA, 20 min) targeting the left SMC, eight healthy
subjects performed a simple finger sequence (SFS) task with their right or left hand
in an alternating blocked design (30-s rest and 30-s SFS task, repeated five times).
In order to determine the level of bilateral SMC activation during the SFS task, an
Oxymon MkIII fNIRS system was used to measure from the left and right SMC,
changes in oxygenated (O
2
Hb) and deoxygenated (HHb) haemoglobin concentra-
tion values. The fNIRS data suggests a finding that compared to the Pre condition
both the “Online” and “Offline” anodal HD-tDCS conditions induced a significant
reduction in bilateral SMC activation (i.e., smaller decrease in HHb) for a similar
motor output (i.e., SFS tap rate). These findings could be related to anodal
HD-tDCS inducing a greater efficiency of neuronal transmission in the bilateral
SMC to perform the same SFS task.
Keywords Functional near-infrared spectroscopy • tDCS • Neuroplasticity •
Neuromodulation • Sensorimotor cortex
M. Muthalib (*) • P. Besson • S. Perrey
Movement to Health (M2H) Laboratory, EuroMov, University of Montpellier, Montpellier,
France
e-mail: makii.muthalib@gmail.com;makii.muthalib@univ-montp1.fr
J. Rothwell
Institute of Neurology, University College London, London, UK
T. Ward
Department of Electronic Engineering, National University of Ireland, Maynooth, Ireland
©Springer Science+Business Media, New York 2016
C.E. Elwell et al. (eds.), Oxygen Transport to Tissue XXXVII, Advances in
Experimental Medicine and Biology 876, DOI 10.1007/978-1-4939-3023-4_44
351

1 Introduction
Transcranial direct current stimulation (tDCS) is a non-invasive electrical brain
stimulation technique that applies mild (1–2 mA) direct currents over time (10–
20 min) via the scalp to increase (anodal tDCS) or decrease (cathodal tDCS)
cortical neuronal excitability [1]. The subsequent increase in spontaneous neuronal
firing rates (during “Online” tDCS), coupled with synaptic neuroplasticity
(“Online” and after “Offline” tDCS), contribute to anodal tDCS effects of increas-
ing cortical excitability [1].
In order to increase sensorimotor cortex (SMC) excitability, tDCS is conven-
tionally applied using two large (~35 cm
2
) rubber-sponge electrodes with the anode
electrode placed on a target region (i.e., SMC) and return electrode on the contra-
lateral supraorbital region or non-cephalic region [2]. High-definition (HD)-tDCS is
a recent approach that uses arrays of small EEG size (~3 cm
2
) electrodes whose
configuration can be optimized for more focal targeting of cortical regions deter-
mined using computational modeling of current flows between the electrodes
[3]. Recently, anodal HD-tDCS (2 mA, 20 min) targeting the SMC (via a 4 !1
electrode montage) was shown to induce Offline increases in resting corticospinal
excitability assessed using transcranial magnetic stimulation [3]. However, it is not
clear how Online and Offline anodal HD-tDCS modulates SMC activation during
performance of a motor task.
An indirect marker of motor task-related SMC activation is the subsequent
increase in the regional cortical blood flow and oxygenation (i.e., neurovascular
coupling), which can be assessed using functional near infrared spectroscopy
(fNIRS) neuroimaging [4]. fNIRS measures several physiological parameters
related to cortical blood flow and oxygenation including measurements of changes
in oxygenated (O
2
Hb) and deoxygenated (HHb) haemoglobin concentration values
[5]. Therefore, the aim of this study was to utilize fNIRS neuroimaging to measure
bilateral SMC activation during a simple finger sequence (SFS) task in order to
determine the Online and Offline effects of anodal HD-tDCS targeting the
left SMC.
2 Methods
2.1 Subjects
Eight healthy subjects 30.4 "10.6 years (mean "SD) participated in the study. All
subjects were right handed as determined by the Edinburgh handedness question-
naire [6]. All subjects had no known health problems (e.g. metabolic or neuromus-
cular disorders) or any upper extremity muscle or joint injuries. The study
conformed to the recommendations of the local Human Research Ethics Committee
in accordance with the Declaration of Helsinki.
352 M. Muthalib et al.

2.2 Protocol
Before (Pre), at 10 min during (Online), and 3 min after (Offline) anodal HD-tDCS
(2 mA, 20 min) targeting the left SMC, subjects performed a self-paced SFS task
(i.e., sequential tapping of the index, middle, ring and fourth finger against the
thumb) with their right or left hand in an alternating blocked design (30-s rest and
30-s SFS task, repeated five times for each hand). Prior to the start of the experi-
ment, subjects were familiarised with the SFS task in order to maintain a consistent
rate of finger sequence taps (between 2 and 3 Hz), which was confirmed prior to the
start of the Pre condition. The number of finger sequence taps was counted by the
experimenter during each of the experimental SFS task blocks.
2.3 Experimental Setup
tDCS A Startim
®
tDCS system (Neuroelectrics, Spain) was used to deliver con-
stant direct currents to the left SMC via a 4 !1 anodal HD-tDCS electrode montage
(active anode electrode at the centre surrounded by four return electrodes each at a
distance of ~3.5 cm from the active electrode) [3]. The five electrodes (3.14 cm
2
AgCl electrodes) were secured on the scalp in the adjacent 10-10 EEG electrode
system positions (anode: C3, and 4 return electrodes: FC1, FC5, CP1, CP5) using
conductive paste (Ten20
®
, Weaver and Company, USA) and held in place using a
specially designed synthetic cap to hold the HD-tDCS electrodes and fNIRS probes
on the head (see Fig. 44.1 for layout).
fNIRS A continuous wave multi-channel Oxymon MkIII fNIRS system (Artinis
Medical Systems, The Netherlands) was used to measure changes in bilateral SMC
O
2
Hb and HHb concentration values during the SFS task. Four receiver (avalanche
photodiode) and 12 transmitter (pulsed laser diode) probes were placed in the
synthetic cap to obtain 16 channels (each channel represented by a receiver-
transmitter combination separated by ~3 cm) primarily covering the left (eight
channels) and right (eight channels) SMC regions (see Fig. 44.1 for locations of the
16 channels). Two wavelengths (856 and 781 nm) per channel were used at a
sampling rate of 10 Hz.
The changes in O
2
Hb and HHb concentration values (expressed in μM), calculated
according to a modified Beer-Lambert Law and including an age-dependent con-
stant differential pathlength factor (4.99 + 0.067*Age
0.814
)[7], were transferred
from the fNIRS system to a personal computer. During the data collection proce-
dure, the time course of changes in O
2
Hb and HHb concentration values were
displayed in real time, and the signal quality and absence of movement artefacts
were verified.
44 Effects of Anodal High-Definition Transcranial Direct Current Stimulation on... 353

2.4 Data Analysis
The time course of changes in O
2
Hb and HHb concentration values for each of the
16 channels were first low-pass filtered at 0.1 Hz to attenuate cardiac signal,
respiration, and Mayer-wave systemic oscillations [5]. The time course of changes
in O
2
Hb and HHb concentration values for each SFS task block (30-s duration)
were then normalized using the mean of the O
2
Hb and HHb values measured during
the last 5 s of the 30-s rest period preceding each SFS task block. These were then
sample-to-sample averaged (i.e., 10 samples/s) the O
2
Hb and HHb time course
values over the 5 SFS task blocks, yielding one average O
2
Hb and HHb time course
for each subject.
In order to locate the channel to represent the level of SMC activation during the
SFS task period for each subject, we first selected in the Pre condition one channel
Fig. 44.1 Locations of the HD-tDCS electrodes and fNIRS probes on a 10-10 EEG electrode
system layout. Each of the 16 fNIRS channels are represented by a receiver-transmitter
combination
354 M. Muthalib et al.

on the left and right SMC (i.e., the channel corresponding to one of the four
channels located adjacent to the C3 and C4 electrode positions; see Fig. 44.1)
showing peak and consistent SFS task-related haemodynamic responses (i.e.,
increase in O
2
Hb and decrease in HHb), and then used the same channels for
analysis in the Online and Offline conditions. Following the selection of the left
and right SMC channel, we computed first the individual subject O
2
Hb maximum
(O
2
Hb
max
) and the HHb minimum (HHb
min
) values from the left and right SMC and
then group averaged these values for the Pre, Online and Offline conditions.
2.5 Statistical Analysis
For statistical analysis of the fNIRS dependent variables (O
2
Hb
max
and HHb
min
), a
Condition (Pre, Online, Offline) x Hemisphere (Left SMC, Right SMC) x Hand
(Left, Right) repeated measures ANOVA was used. If a significant main or inter-
action effect was evident, then post-hoc Tukey’s HSD (honestly significant differ-
ence) tests were performed. For statistical analysis of the behavioural dependent
variable (SFS tap rate), a Condition (Pre, Online, Offline) !Hand (Left and Right)
repeated measures ANOVA was used. Significance was set at P #0.05. Data are
presented as mean "SD.
3 Results
The behavioural results indicated that subjects were able to perform the SFS task at
a consistent rate (2.51 "0.32 Hz) with their right and left hand with no significant
difference over the three conditions.
Figure 44.2 shows a typical time course of changes in O
2
Hb and HHb from the
left and right SMC during the right hand SFS task. Before anodal HD-tDCS (i.e.,
Pre condition), the right and left hand SFS task induced a cortical haemodynamic
response (i.e., increase in O
2
Hb and decrease in HHb) in the bilateral SMC, with
a greater response in the contralateral hemisphere to the hand performing the task
(see Fig. 44.2 for right hand SFS task).
Table 44.1 shows the group average O
2
Hb
max
and HHb
min
values from the left
and right SMC during the SFS task for the Pre, Online and Offline conditions. The
ANOVA showed no significant Condition x Hemisphere x Hand interaction, but a
significant (p <0.001) Condition x Hemisphere interaction effect for both O
2
Hb
max
and HHb
min
. The post-hoc showed that for the right SMC (i.e., unstimulated
hemisphere), although there was no significant difference in O
2
Hb
max
over the
three conditions, there was a significantly (p <0.001) smaller HHb
min
in both the
Online and Offline conditions compared to Pre. For the left SMC (i.e., stimulated
hemisphere), O
2
Hb
max
significantly (p <0.001) increased in the Online condition
compared to Pre, but returned to Pre levels in the Offline condition. In contrast,
44 Effects of Anodal High-Definition Transcranial Direct Current Stimulation on... 355

there was a significantly (p <0.001) smaller HHb
min
during both the Online and
Offline conditions compared to Pre.
4 Discussion
The main new finding of this study was of a significant reduction in bilateral SMC
activation (based on smaller HHb
min
) for a similar motor behaviour (i.e., SFS tap
rate) in the Online and Offline conditions compared to the Pre condition.
Although O
2
Hb
max
increased significantly only in the Online condition for the
stimulated left SMC, we consider that changes in O
2
Hb were likely contaminated
by anodal HD-tDCS induced local skin blood flow changes in the vicinity of the
HD-tDCS electrodes. In contrast, changes in HHb are considered less affected by
skin blood flow changes [8] and we found less variability in HHb responses during
the five blocks of the SFS task than with O
2
Hb responses. Therefore, we suggest
that HHb may be a more reliable marker of HD-tDCS induced effects on task-
related cortical activation.
The present study findings of smaller bilateral SMC HHb
min
values during the
SFS task in the Online and Offline conditions compared to Pre could be related to a
greater efficiency of neuronal transmission [9] in the bilateral SMC (i.e., less
synaptic input for the same neuronal output) that reduced SFS task-induced
regional blood flow and thus produced smaller changes in fNIRS-derived HHb in
the bilateral SMC. Furthermore, since the effect of anodal HD-tDCS on SFS task-
related SMC activation was similar for both the Online and Offline conditions, it
seems that synaptic neuroplastic modifications are necessary to induce these motor
task-related reductions in SMC activation.
Fig. 44.2 Typical task-related changes in oxygenated (O
2
Hb) and deoxygenated (HHb)
haemoglobin concentrations in the left (Left SMC) and right (Right SMC) sensorimotor cortex
during the right hand simple finger sequence task in the Pre condition. Dashed vertical lines denote
the start and end of the 30-s SFS task period
356 M. Muthalib et al.

Table 44.1 Group mean ("SD) oxygenated haemoglobin maximum (O
2
Hb
max
) and deoxygenated haemoglobin minimum (HHb
min
) concentration values
from the left (Left SMC) and right (Right SMC) sensorimotor cortex during the simple finger sequence task performed before (Pre), during (Online) and after
(Offline) anodal HD-tDCS
Left SMC Right SMC
Pre Online Offline Pre Online Offline
O
2
Hb
max
(ΔμM) 0.83 "0.28 0.99 "0.29* 0.83 "0.26 0.78 "0.38 0.76 "0.49 0.77 "0.40
HHb
min
(ΔμM) $0.38 "0.14 $0.33 "0.11* $0.27 "0.09* $0.34 "0.14 $0.29 "0.17* $0.28 "0.11*
*:p <0.001; significantly different from Pre
44 Effects of Anodal High-Definition Transcranial Direct Current Stimulation on... 357

In the present study, despite the attempt at focal stimulation to the left SMC
by anodal 4 !1 HD-tDCS, the effects on motor task-related cortical activation
were bilateral, probably because intervening in one part of a distributed neural
network system has effects on many nodes in the system [10]. It should also be
noted that we found the same effect on bilateral SMC activation during SFS
movements with the left and right hand. Although it would have been more
expected to have observed a difference in ipsilateral and contralateral SMC acti-
vation between the left and right hand, evidence exists from recent studies which
demonstrate that unilateral tDCS of the SMC can have bilateral effects [11,12]. For
example, Hendy et al. [12] have found bilateral changes in activation and muscle
strength after anodal unilateral tDCS, and Roy et al. [12] found wide bihemispheric
effects on EEG of unilateral HD-tDCS.
5 Conclusion
This preliminary study has shown for the first time that both Online and Offline
anodal HD-tDCS reduced bilateral SMC activation to perform a sequential finger
movement task. These positive initial results justify further research efforts to
optimize the effects and enhance our understanding of the neurophysiological
mechanisms of HD-tDCS-induced neuroplastic modifications.
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