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Abstract—Transcranial direct current stimulation (tDCS)
has been shown to modulate neural activity. Neural activity has
been shown to be closely related, spatially and temporally, to
cerebral blood flow (CBF) that supplies glucose via
neurovascular coupling. Therefore, noninvasive and continuous
monitoring of neural activity is possible with a measure of
cerebral hemoglobin oxygenation using near-infrared
spectroscopy (NIRS). In principal accordance, NIRS can
capture the hemodynamic response to tDCS but the challenge
remains in removing the systemic interference occurring in the
superficial layers of the head that are also affected by tDCS. An
approach may be to use short optode separations to measure
systemic hemodynamic fluctuations occurring in the superficial
layers which can then be used as regressors to remove the
systemic contamination. Here, we demonstrate that temporal
artery tap may be used to better identify systemic interference
using this short-separation NIRS. Moreover, NIRS-EEG joint-
imaging during anodal tDCS was used to measure changes in
mean cerebral haemoglobin oxygen saturation (rSO2) along
with changes in the log-transformed mean-power of EEG
within 0.5 Hz-11.25 Hz. We found that percent change in the
mean rSO2 better correlated with the corresponding percent
change in log-transformed mean-power of EEG within 0.5 Hz-
11.25 Hz frequency band after removing the systemic
contamination using the temporal artery tap method. Based on
our findings, we propose that anterior temporal artery tap
technique presented in this paper may be able to classify
carotid stenosis, external carotid artery stenosis, and internal
carotid artery stenosis patients using the laterality in the
hemodynamic response evoked by anodal tDCS both at the
brain as well as at the superficial layers. These findings may
have important implications for both prognosis and
rehabilitation of patients with intracranial stenosis.
I. I
NTRODUCTION
Transcranial direct current stimulation (tDCS) - an
electrically based intervention directed at the central nervous
*
Research supported by INRIA-DST Associate Team 2014-2017.
M. Sood is with the International Institute of Information Technology,
Hyderabad, India.
U. Jindal is with the International Institute of Information Technology,
Hyderabad, India.
S. Roy Chowdhury is with the International Institute of Information
Technology, Hyderabad, India.
A. Das is with the Institute of Neurosciences Kolkata, India.
D. Kondziella is with the Department of Neurology, Rigshospitalet,
Blegdamsvej 9, København Ø, Denmark 2100 and Institute of
Neuroscience, Norwegian University of Science and Technology,
Trondheim, Norway.
A. Dutta is with the Institut national de recherche en informatique et en
automatique (INRIA), Montpellier, France (e-mail: adutta@ieee.org).
system level - has been shown to modulate cortical neural
activity and is a promising tool to facilitate neuroplasticity
[1]. During neural activity, the electric currents from
excitable membranes of brain tissue superimpose at a given
location in the extracellular medium and generate a
potential, which is referred to as the electroencephalogram
(EEG) when recorded from the scalp [2]. Respective neural
activity has been shown to be closely related, spatially and
temporally, to cerebral blood flow (CBF) that supplies
glucose via neurovascular coupling [3]. The hemodynamic
response to neural activity can be captured by near-infrared
spectroscopy (NIRS), which enables continuous monitoring
of cerebral oxygenation and blood volume [4]. CBF is
increased in brain regions with enhanced neural activity via
metabolic coupling mechanisms [5]. We developed a
method for electroencephalography (EEG) - near-infrared
spectroscopy (NIRS) based assessment of neurovascular
coupling (NVC) during anodal tDCS [6]. Our preliminary
studies showed the feasibility of identifying the lesional
hemisphere in subacute stroke with a low-cost NIRS-tDCS
hardware [7]. A significant change in oxy-haemoglobin
(HbO2) post-tDCS from pre-tDCS baseline was found for
the contralesional (3.43 ± 0.86), but not the lesional side
(0.26 ± 0.28), p<0.01. Moreover, the results of the stroke
case series [6] showed that anodal tDCS induces a local
neurovascular response which may be used for assessing
regional NVC functionality. However, the challenge
remained in removing the systemic interference occurring in
the superficial layers of the head that are also affected by
tDCS where the importance of integrating short-separation
measurements both at the source and at the detector optode
has been shown [9].
In this paper, we present a temporal artery tap technique
to identify systemic interference using short-separation
NIRS measurements. We use NIRS-EEG joint-imaging to
measure the changes due to anodal tDCS in the mean
cerebral haemoglobin oxygen saturation (rSO2) along with
the changes in log-transformed mean-power of EEG within
0.5 Hz-11.25 Hz frequency band. We show that the percent
change in the mean rSO2 better correlated with the
corresponding percent change in log-transformed mean-
power of EEG within 0.5 Hz-11.25 Hz frequency band after
removing the systemic contamination using the proposed
temporal artery tap method.
Anterior temporal artery tap to identify systemic interference using
short-separation NIRS measurements: a NIRS/EEG-tDCS study
Mehak Sood, Utkarsh Jindal, Shubhajit Roy Chowdhury, Abhijit Das, Daniel Kondziella, Anirban
Dutta, Member, IEEE
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II. M
ETHODS
A. NIRS-EEG/tDCS joint-imaging
Simultaneous recording of NIRS and EEG [6] for
evaluation of NVC (see Figure 1a) was conducted on five
chronic (>6 months, see Table 1) ischemic stroke survivors
after obtaining informed consent. The patients had no
contraindications to non-invasive brain stimulation. All
experiments were conducted in accordance with the
Declaration of Helsinki. The NIRS-EEG/tDCS joint-imaging
protocol was similar to that of our prior NIRS-tDCS study
[7]. Participants were seated in a quiet room and their eyes
were open and fixed on a point on the wall in front of them
during the entire experiment. PISTIM (Neuroelectrics,
Spain) electrodes were placed over F3 (corresponding to left
hemisphere) and F4 (right hemisphere) of the international
10-20 EEG system, and SPONSTIM-25 (Neuroelectrics,
Spain) electrodes were placed over Cz. This F3 (F4 when
monitoring right hemisphere) anodal and Cz cathodal tDCS
montage was selected based on computational modeling
(using StimViewer, Neuroelectrics, Spain)[6] in order to
target primarily the outer convex brain territory (superficial
divisions) of the middle cerebral artery (MCA). MCA is one
of the three major paired arteries that supply blood to the
cerebrum and is the most commonly occluded vessel in
ischemic stroke. The tDCS at a current density of 0.526
A/m
2
was turned ON for 30 sec with 10 sec ramp-up and
ramp-down (see Figure 1b), which was repeated 15 times in
random order with 30 sec OFF periods in between for both
the lesional and contralesional hemispheres (ischemic stroke
was restricted to a single hemisphere). Eyes-open block-
averaged resting-state NIRS oximeter measurements were
conducted using our own custom-built hardware [7] just
above each eyebrow at the F3 and F4 sites using a custom-
built NIRS sensor (see Figure c) that was similar in design to
SomaSensor (SAFB-SM, INVOS, USA). The custom-built
NIRS sensor consisted of two LED sources (770 nm and 850
nm) and two photodiode detectors at a distance of 3 cm and
4 cm so that the short separation NIRS signal can be
regressed out from the longer separation NIRS signal in
order to diminish the systemic interference [10]. Also, eyes-
open resting state EEG (StarStim, Neuroelectrics, Spain)
was recorded at 500 Hz from the nearby electrodes F1, FC3,
F5, F2, FC4, F6 (international 10-20 system).
B. Temporal artery tap technique to identify systemic
interference using short separation NIRS measurements
The frontal branch of the superficial temporal artery
(anterior temporal) runs forward to the forehead and can be
manually tapped lightly to create fluctuations in the blood
supply to the forehead (see Figure 1c). These fluctuations
should be registered primarily by the short-separation NIRS
signal where the long-separation NIRS signal was
considered contaminated [10] with a filtered version of the
short-separation NIRS signal. This filter was estimated in the
resting-state (without tDCS) by least-square fitting the
recorded fluctuations in the short-separation NIRS signal
during temporal artery tap to the long-separation NIRS
signal. The temporal artery tap produced large (compared to
baseline NIRS signals) impulse-like fluctuations which
made the least-square fitting easier for the impulse response.
The systemic interference was then found by convolving
short-separation NIRS signal with the impulse response, and
then subtracting that from the respective long-separation
NIRS signal.
C. NIRS-EEG/tDCS joint-imaging data analysis with and
without temporal artery tap technique
EEG artifacts related to tDCS are possible due to issues
with electrical (e.g. unknown electrode impedance changes
during stimulation) and mechanical compatibility (saline
from sponges shunting neighboring electrodes) where
concurrent recording is possible with an optimized device
(Starstim; Neuroelectrics, Spain) and rational experimental
design (using PISTIM electrodes; Neuroelectrics, Spain)
[11]. The raw EEG was pre-processed using EEGLAB
functions (specifically, Artifact Subspace Reconstruction
method) [12] where artefactual epochs were also removed
following subsequent visual inspection of the data. Then, log-
transformed mean-power of EEG within the 0.5 Hz-11.25 Hz
range (selected based on our prior work [6]) from F3, F1,
FC3, F5 sites were averaged for left hemisphere and from the
F4, F2, FC4, F6 sites were averaged for the right hemisphere.
The percent change in log-transformed mean-power of EEG
within 0.5 Hz-11.25 Hz frequency band was computed for
the first 10 sec of ON periods (called "initial dip" in our prior
work [6]) relative to the first 10 sec of OFF periods. The
percent change in log-transformed mean-power of EEG
within 0.5 Hz-11.25 Hz frequency band was analyzed for
both the lesional and contralesional hemispheres. Eyes-open
block-averaged resting-state percent change in the mean
a)
b)
F3 anode or
F4 anode
OFF
10s 30s 10s 30s
30 times
tDCS at 0.526A/m
2
30s
OFF
F3 anode or
F4 anode
OFF
10s 30s 10s 30s
30 times
tDCS at 0.526A/m
2
30s
OFF
c)
Fig. 1. a) NIRS-EEG/tDCS joint-imaging montage, b) tDCS protocol,
c) digital tapping of anterior temporal artery.
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regional cerebral haemoglobin oxygen saturation (rSO2) in
the first 10 sec of ON periods relative to the first 10 sec of
OFF periods was measured from the NIRS signals where the
Baseline was set at the start of the experiment. In one case
(rSO2
subtract
), the short separation NIRS signal was subtracted
from the longer separation NIRS signal while in the other
case (rSO2
filter
), the short separation NIRS signal was
convolved with the impulse response and then subtracted
from the respective longer separation NIRS signal.
Table 1: Subject summary (M: male, F: female, MCA: middle cerebral
artery)
III. R
ESULTS
There was an increase in log-transformed mean-power of
EEG within 0.5 Hz-11.25 Hz frequency band in the first 10
sec of ON periods relative to the first 10 sec of OFF periods
for the contralesional hemisphere stimulation/recording.
This increase was primarily in the Theta (4–8 Hz) frequency
band in agreement to our prior results [6]. Also, there was a
corresponding decrease in the mean rSO2
subtract
in the first 10
sec of ON periods (called "initial dip" in our prior work [6])
relative to the first 10 sec of OFF periods where the
individual Baseline for rSO2
subtract
measurements was set at
the beginning of the session. The "initial dip" was greater for
the lesional hemisphere stimulation/recording where the
percent change in the mean rSO2
subtract
mostly correlated
with the corresponding percent change in the log-
transformed mean-power of EEG within 0.5 Hz-11.25 Hz
frequency band. Here, the percent change in the mean
rSO2
filter
for the lesional hemisphere better correlated with
the log-transformed mean-power of EEG within 0.5 Hz-
11.25 Hz frequency band as shown in Table 2.
Table 2: Summary of the results from the case series.
IV. D
ISCUSSION
In this study, we found that the percent change in the
mean rSO2 typically correlated with the corresponding
percent change in log-transformed mean-power of EEG
within 0.5 Hz-11.25 Hz frequency band. We also found in the
contralesional hemisphere of the stroke survivors that there
was an immediate increase in the 0.5Hz-11.25Hz frequency
band during anodal tDCS [6]; however, there was also
significant inter-subject variability after tDCS. Here, the
percent change in the mean rSO2
filter
for the lesional
hemisphere better correlated with the log-transformed mean-
power of EEG within 0.5 Hz-11.25 Hz frequency band than
the percent change in the mean rSO2
subtract
.
Of note, we found in some stroke subjects inter-
hemispheric laterality in the systemic interference as well as
rSO2
filter
evoked by anodal tDCS. Indeed, Large Artery
Atherothrombosis leads commonly to stenosis at the
bifurcation of the carotid artery (carotid stenosis). At the
bifurcation of the carotid artery arises the internal carotid
artery (ICA) that supplies blood to the brain as well as the
external carotid artery (ECA) that supplies blood to the head
and neck, such as face, scalp, etc. Inter-hemispheric laterality
of carotid stenosis may lead to laterality in the hemodynamic
response to tDCS both at the brain (due to ICA) as well as the
superficial layers (due to ECA). Since ischemic stroke
secondary to carotid stenosis is common in older people so
our preliminary studies showed the feasibility of identifying
the lesional hemisphere in subacute ischemic stroke with a
low-cost NIRS-tDCS hardware [7]. Nevertheless, it cannot be
excluded that in certain stroke survivors the lesioned
hemisphere may not respond to anodal tDCS with an increase
in neural activity. This may result in an absent change in the
cerebral metabolic rate of oxygen, CMRO2 (i.e., oxygen
consumption [13] that is defined as the difference of oxygen
flow into and out of the tissue) in the lesioned hemisphere as
compared to the non-lesioned hemisphere. To avoid this
potential problem, the effects of tDCS on neural activity can
be elucidated with simultaneous EEG, which provides an
independent measure to supplement NIRS recordings. Based
on prior work [14] that found an association of individual
resting state EEG alpha frequency and cerebral blood flow,
we hypothesize that if the changes in EEG during tDCS are
correlated with the changes in NIRS, then this may enable us
to measure the state of neurovascular coupling.
Indeed, prior cross-sectional studies suggested that
impaired cerebral haemodynamics precedes stroke where
cerebrovascular reactivity (CVR) reflects the capacity of
blood vessels to dilate, and is an important marker for brain
vascular reserve [15]. CVR provides an useful addition to the
traditional baseline blood flow measurement where severely
reduced CVR predicts the risk of ipsilateral ischemic stroke
and TIA [15] as well as mild cognitive impairment [3] and
vascular dementia [16]. A meta-analysis summarizing the
association between CVR impairment with stroke risk
demonstrated an ≈4-fold higher stroke risk in asymptomatic
patients with impaired cerebral blood flow [17]. However,
the cost, access, and availability of trained technicians and
physicians to perform the Transcranial Doppler (TCD) blood
flow velocity measurements of CVR in a community setting
is one of the main limitations [18]. Therefore, a low-cost
NIRS-tDCS hardware [7] for point-of-care-testing of CVR is
relevant. Moreover, with the anterior temporal artery tap
Case
Age/gender
Diagnosis Year of stroke
1 68/M Right MCA stroke 2010
2 74/F Left MCA stroke 2011
3 76/M Left MCA stroke 2011
4 72/M Right MCA stroke 2012
5 75/M Right MCA stroke 2012
Case
Post-tDCS
(mean±1 std. dev.)
Correlation
Coefficient with
rSO2
subtract
Correlation
Coefficient with
rSO2
filter
1 0.42±0.18 0.54±0.12
2 0.49±0.14 0.58±0.14
3 0.54±0.17 0.61±0.12
4 0.48±0.14 0.57±0.15
5 0.53±0.18 0.59±0.13
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technique presented in this paper, we may be able to classify
carotid stenosis, ECA stenosis, and ICA stenosis patients
based on the laterality in the hemodynamic response evoked
by anodal tDCS both at the brain (due to ICA) as well as at
the superficial layers (due to ECA). For example, ICA
stenosis vs. ECA stenosis may be classified based on the
laterality in the rSO2
filter
vs. laterality in the systemic
interference. If verified by future prospective multicenter
trials, these findings may have important implications for
both prognosis and rehabilitation of patients with intracranial
stenosis.
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