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Beta EEG increased during tDCS
- 1. Cognitive neuroscience and neuropsychology 1433
Beta-frequency EEG activity increased during transcranial
direct current stimulation
Myeongseop Songa,b, Yungjae Shinb and Kyongsik Yunb,c
Transcranial direct current stimulation (tDCS) is a technique
for noninvasively stimulating specific cortical regions of the
brain with small (<2 mA) and constant direct current on the
scalp. tDCS has been widely applied, not only for medical
treatment, but also for cognitive and somatosensory
function enhancement, motor learning improvement, and
social behavioral change. However, the mechanism that
underlies the effect of tDCS is unclear. In this study, we
performed simultaneous electroencephalogram (EEG)
monitoring during tDCS to understand the dynamic
electrophysiological changes throughout the stimulation.
A total of 10 healthy individuals participated in this
experiment. We recorded EEGs with direct current
stimulation, as well as during a 5-min resting state before
and after the stimulation. All participants kept their eyes
closed during the experiment. Anode and cathode patches
of tDCS were placed on the left and the right dorsolateral
prefrontal cortex, respectively. In addition, an EEG electrode
was placed on the medial prefrontal cortex. The beta-frequency
power increased promptly after starting the
stimulation. The significant beta-power increase was
maintained during the stimulation. Other frequency bands
did not show any significant changes. The results indicate
that tDCS of the left dorsolateral prefrontal cortex changed
the brain to a ready state for efficient cognitive functioning
by increasing the beta-frequency power. This is the first
attempt to simultaneously stimulate the cortex and record
the EEG and then systematically analyze the prestimulation,
during-stimulation, and poststimulation
EEG data. NeuroReport 25:1433–1436 © 2014
Wolters Kluwer Health | Lippincott Williams & Wilkins.
NeuroReport 2014, 25:1433–1436
Keywords: electroencephalogram, resting state,
transcranial direct current stimulation
aDepartment of Bio and Brain Engineering, Korea Advanced Institute of Science
and Technology (KAIST), Daejeon, bYbrain Research Institute, Seoul, South Korea
and cComputation and Neural Systems, California Institute of Technology,
Pasadena, California, USA
Correspondence to Kyongsik Yun, PhD, Computation and Neural Systems,
California Institute of Technology, 1200 E. California Blvd. MC139-74, Pasadena,
CA 91125, USA
Tel: + 1 626 415 7556; fax: +1 626 792 8583; e-mail: yunks@caltech.edu
Received 1 September 2014 accepted 23 September 2014
Introduction
Transcranial direct current stimulation (tDCS) is a method
that can noninvasively stimulate specific cortical regions of
the brain with weak and constant direct current (DC) on
the scalp [1]. tDCS has been used for the treatment of
various brain disorders, including Alzheimer’s disease [2],
depression [3], attention deficit hyperactivity disorder [4],
and different kinds of addictions, including alcohol and
substance abuse [5]. tDCS has also been applied for cog-nitive
enhancement, including that of working memory [6]
and motor learning [7]. Recent advances in tDCS studies
include cortical–subcortical network stimulation and [8]
application to social behavioral change [9].
However, the underlying mechanisms of tDCS have
rarely been investigated. A previous study found that DC
stimulation increased brain-derived neurotrophic factor
levels, which induces synaptic plasticity [10]. The most
accepted theory so far is that tDCS induces polarity-driven
alterations in resting membrane potentials, which
can result in spontaneous depolarization (anode) or
hyperpolarization (cathode) [11].
Moreover, we have no clue about what is happening in the
brain while stimulating it. There is one study that showed
that the number of epileptiform electroencephalogram
(EEG) discharges reduced while patients with focal
refractory epilepsy were stimulated with DC [12]. This
study is, as far as we know, the first to analyze the EEG
signal with concomitant DC stimulation. They used mul-tichannel
EEG to observe the interaction between current
stimulation and the neural network. However, they just
counted the number of epileptiform EEG discharges with
raw EEG data, without analyzing detailed EEG dynamics,
such as EEG power spectra and frequency coupling. They
collected EEG data from just two patients requiring further
study [12].
In this study, we concomitantly recorded EEG changes
with tDCS in the prefrontal cortex. We hypothesize that
the beta-frequency EEG activity would be enhanced
during and after stimulation. Beta rhythms have been
known to operate cognitive functions [13], and the cog-nitive
performance enhancement is one of the main
tDCS effects [6].
Methods
Ethics statement
All participants submitted written informed consent after
receiving a detailed explanation of the experimental
procedures. This study was approved by the Institutional
Review Board of the Ybrain Research Institute.
0959-4965 © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins DOI: 10.1097/WNR.0000000000000283
Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
- 2. 1434 NeuroReport 2014, Vol 25 No 18
Participants
A total of 10 healthy participants (five women, mean age
of 23.6 ± 2.5 years) were recruited through an online
advertisement in Seoul, South Korea. Participants had at
least 14 years of education (16.6 ± 2.5 years). All partici-pants
were medication free and psychiatric illness free
and did not take any medication on the day of the
experiment.
Experiment protocol
Each participant was seated on a comfortable chair and
was fitted with tDCS and one-channel EEG equipment
(Fig. 1a). After installation, we recorded resting state
EEG with the eyes closed for 10 min. Next, we stimu-lated
the brain by tDCS while simultaneously recording
EEG for 10 min. Finally, we again recorded resting state
EEG with the eyes closed for 10 min.
After the experiment, the participants were interviewed
about their feelings, such as discomfort and pain during
and after the stimulation.
Transcranial direct current stimulation and
electroencephalogram recording
DC stimulation was applied through hydrogel patches
(rectangular shape: 5 cm × 5 cm= 25 cm2). Scalp pre-paration
included investigation of skin condition and
reduction of skin impedance. When investigating skin
condition, we checked for rashes or pre-existing lesions
to avoid skin burns by DC stimulation. Second, we used
wet tissue to reduce impedance of the skin to under
40 kΩ (during tDCS, impedance was maintained under
20 kΩ), resulting in pain reduction on tDCS and
decreased noise for cleaner EEG recording [14]. After
skin preparation, anode and cathode hydrogel patches
were placed on the left (F3) and right (F4) dorsolateral
prefrontal cortices (DLPFCs), respectively (EEG 10–20
system), whereas an EEG recording electrode was posi-tioned
on the medial prefrontal cortex (MPFC) in
between Fp1 and Fp2 (EEG 10–20 system; Fig. 1a). We
placed the reference and ground electrodes on the right
mastoid. In this experiment, the current intensity of 1mA
was maintained for 10 min; the current was slowly
increased up to 1mA for 15 s at first and was slowly
decreased for 15 s and turned off at the end of the sti-mulation.
EEGs of the participants were recorded for a
total of 30 min, separated by three periods. For the first
10 min, EEGs were recorded at the resting state. For the
next 10 min, EEGs were measured during DC stimula-tion.
Finally, the resting state EEGs were recorded for
10 min. During every period, participants kept their eyes
closed. EEGs were recorded in 500 Hz, and the recording
impedance was kept under 10 kΩ. We used OpenViBE
software (Campus de Beaulieu, Rennes Cedex, France)
for EEG data acquisition [15].
Data analysis
We divided the spectrum of EEG signals into six fre-quency
bands: delta (1–4 Hz), theta (4–8 Hz), slow alpha
(8–10 Hz), fast alpha (10–13.5 Hz), beta (13.5–30 Hz), and
gamma (30–80 Hz). We obtained the power spectrum of
the EEG data by short-time Fourier transform with
250-ms Hamming windows and a nonoverlap. After the
short-time Fourier transform of each participant’s EEG
data, we took the log of the frequency bands’ power, and
these log values were divided by the max value of each
frequency band to see the trend of each frequency band’s
Fig. 1
Cathode Anode
EEG
tDCS
∗ ∗∗ ∗
1.3
1.2
1.1
1
0.9
0.8
0.7
Beta power (dB)
−4 −2 0 2 4 6 8 10 12 14
Time (min)
∗
∗∗
P <0.1
P <0.05
(a) (b)
(a) tDCS and EEG electrode locations; (b) beta-power time series before, during, and after stimulation. Shaded box indicates stimulation period.
EEG, electroencephalogram; tDCS, transcranial direct current stimulation.
Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
- 3. power change by lapse of time. EEG was analyzed for
25min (5min before tDCS+10min during tDCS+10 min
after tDCS). We used smoothing for the moving average of
5000 data points for visualization (Fig. 1b).
We separated each frequency band for each participant
into 14 parts (2-min duration) and averaged the power of
each frequency band in each section. We performed the
analysis of variance (ANOVA) test using these sections as
conditions. After the ANOVA test, we compared the
power of adjacent time blocks and the power of baseline
prestimulation (−2 to 0 min) with during and after sti-mulation
blocks using the paired t-test. Statistical sig-nificance
was defined as P less than 0.05 (SPSS 19;
SPSS Inc., Chicago, Illinois, USA).
Results
None of the participants reported any discomfort or pain.
ANOVA detects effects of the dependent variable (the
power of frequency bands) on time condition (stimulation)
for slow alpha [F(13)=2.533, P=0.004], fast alpha
[F(13)=2.368, P=0.007], beta [F(13)=2.089, P=0.019],
and gamma [F(13)=4.211, P=0.00]. Through the paired
t-test, we found a significant beta-frequency power increase
in the 4–6-min block during stimulation [t(9)=2.568,
P=0.03], compared with the beta-frequency power of the
2-min baseline resting state (−2 to 0min) before starting
stimulation (Fig. 1). Other meaningful beta-power increases
were found before and after the significant beta-power
increase [2–4 min, t(9)=2.138, P=0.061, and 6–8min,
t(9)=2.055, P=0.07], compared with the baseline block.
Discussion
We performed a DC stimulation experiment while
monitoring EEG recordings. We found beta-power
enhancement during the stimulation. We could record
significant EEG changes through tDCS in a resting state,
during which no distractions endangered the experiment.
Moreover, it is known that tDCS changes the subthres-hold
excitability [16]. However, through the findings of
the present study, we can speculate that tDCS has a
greater potential to trigger the neuronal firings even in
the resting state.
The beta-frequency wave has been known to appear on
the EEG when there is mental effort or cognitive func-tioning
in our brain [17]. One study suggested that there
was an enhancement of beta-frequency waves in the
resting state when participants just opened their eyes
from a closed state [18]. The improvement was not only
the result of eye movements, but it appears that there
were mental and physical state changes when the parti-cipants
opened their eyes. We speculate that tDCS of the
left DLPFC changed the brain to a ready state for effi-cient
cognitive functioning. Another study showed that
the mean level of upper alpha and beta-frequency bands
in Alzheimer’s disease patients, characterized by impaired
cognition, was lower than that of normal controls [19].
Beta-frequency EEG activity increased during tDCS Song et al. 1435
We suppose that the beta-frequency activity is positively
correlated with cognitive functioning in the resting state
and tDCS could enhance cognition by increasing beta-frequency
power.
Keeser et al. [20] recorded and compared the EEG signals
of real and sham tDCS participants as soon as the sti-mulation
was completed. They found significant EEG
delta power reduction in the effect in the 10-min period
after the stimulation, and even greater differences were
found in the first 5-min period. However, the study did
not directly compare the EEG signals before and after the
stimulation. As each participant has his/her own baseline
brain waves, there is a probability that these EEG power
variations would not be significant. To be more accurate,
comparison of the EEG signals of participants both before
and after the stimulation, and using a paired t-test to
examine the significance of the results are recommended.
Merzagora et al. [21] examined the hemodynamic changes
after the stimulation. They measured the concentration of
oxyhemoglobin through functional near-infrared spectro-scopy
to indirectly observe the level of brain activity. Their
results indicate that a high concentration of oxyhemoglobin
was maintained in the frontal lobe for 8–10min after the
10-min stimulation. They suggest that the physiological
effect of the stimulation endured for 8–10min after the
tDCS. The oxyhemoglobin concentration responds to
change as tDCS alters the brain activity; it takes time to
observe these changes. Our study, in contrast, has directly
shown the disappearance of effect after the stimulation in
terms of electrophysiological response. It is possible though
that the oxyhemoglobin response would take more time to
wear off as compared with a much sudden neural
response [22].
No participant reported severe side effects and dis-comfort.
Eight of 10 participants reported mild tingling
during the stimulation. After the stimulation, mild skin
redness temporarily appeared around the site at which
the stimulation patches were attached, and they dis-appeared
within 30 min. A previous meta-analysis
reported the same adverse effects as in our study in 199
studies and also showed that the frequency of adverse
effects in the 199 studies was not different between
active and sham stimulation groups [23].
We chose F3 and F4 based on the 10–20 system to sti-mulate
the left and the right DLPFCs. The MPFC was
targeted by choosing the center, halfway between Fp1
and Fp2. This method of localization has been used
in tDCS and transcranial magnetic stimulation studies
[8,24]. Targeting DLPFC and MPFC using an EEG
10–20 system is known as an accurate method of locali-zation
[24].
This study has several limitations. First, we recorded the
EEG and performed tDCS at the same time but not in
the same region. An EEG and tDCS fusion sensor should
Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
- 4. be devised to further understand the underlying electro-physiological
dynamics at the specific stimulated region.
Second, we did not use multiple EEG electrodes to
record the electrical activity of the entire cortical region.
Using only one EEG sensor debilitated us from further
analyzing the EEG signal to identify cortical interactions,
such as phase synchrony [25,26], cortical complexity [27],
and theta–gamma coupling [28]. However, we expect that
there existed activations of functionally connected regions
with stimulation site. A previous repetitive transcranial
magnetic stimulation study showed that mid-dorsolateral
frontal stimulation increased the cerebral blood flow of
the functionally connected anterior cingulate cortex [29].
Another study found that tDCS on the DLPFC increased
the frontoparietal networks revealed by functional MRI
[30]. Third, we did not use any task for quantifying task-relevant
EEG changes during and after stimulation.
Further studies are warranted to underpin the causal
relationship between tDCS-related behavioral perfor-mance
enhancement and EEG activity.
In conclusion, we have illustrated how tDCS can influ-ence
beta-frequency power. We believe that, to the best
of our knowledge, this is the first attempt to simulta-neously
stimulate the brain and record an EEG, and
then systematically analyze the prestimulation, during-stimulation,
and poststimulation EEG data.
Acknowledgements
This study was supported by Research-Oriented Startup
Grant, Small and Medium Business Administration
(SMBA), Korea, and Basic Science Research Program
through the National Research Foundation of Korea
(NRF) funded by the Ministry of Education
(2013R1A6A3A03020772).
Conflicts of interest
There are no conflicts of interest.
References
1 Nitsche MA, Cohen LG, Wassermann EM, Priori A, Lang N, Antal A, et al.
Transcranial direct current stimulation: state of the art 2008. Brain Stimul
2008; 1:206–223.
2 Boggio PS, Ferrucci R, Mameli F, Martins D, Martins O, Vergari M, et al.
Prolonged visual memory enhancement after direct current stimulation in
Alzheimer’s disease. Brain Stimul 2012; 5:223–230.
3 Brunoni AR, Ferrucci R, Fregni F, Boggio PS, Priori A. Transcranial direct
current stimulation for the treatment of major depressive disorder: a summary
of preclinical, clinical and translational findings. Prog Neuropsychopharmacol
Biol Psychiatry 2012; 39:9–16.
4 Jacobson L, Ezra A, Berger U, Lavidor M. Modulating oscillatory brain activity
correlates of behavioral inhibition using transcranial direct current stimulation.
Clin Neurophysiol 2012; 123:979–984.
5 Boggio PS, Zaghi S, Villani AB, Fecteau S, Pascual-Leone A, Fregni F.
Modulation of risk-taking in marijuana users by transcranial direct current
stimulation (tDCS) of the dorsolateral prefrontal cortex (DLPFC). Drug
Alcohol Depend 2010; 112:220–225.
6 Fregni F, Boggio PS, Nitsche M, Bermpohl F, Antal A, Feredoes E, et al.
Anodal transcranial direct current stimulation of prefrontal cortex enhances
working memory. Exp Brain Res 2005; 166:23–30.
7 Reis J, Schambra HM, Cohen LG, Buch ER, Fritsch B, Zarahn E, et al.
Noninvasive cortical stimulation enhances motor skill acquisition over multiple
days through an effect on consolidation. Proc Natl Acad Sci USA 2009;
106:1590–1595.
8 Chib VS, Yun K, Takahashi H, Shimojo S. Noninvasive remote activation of
the ventral midbrain by transcranial direct current stimulation of prefrontal
cortex. Transl Psychiatry 2013; 3:e268.
9 Ruff CC, Ugazio G, Fehr E. Changing social norm compliance with
noninvasive brain stimulation. Science 2013; 342:482–484.
10 Fritsch B, Reis J, Martinowich K, Schambra HM, Ji Y, Cohen LG, Lu B. Direct
current stimulation promotes BDNF-dependent synaptic plasticity: potential
implications for motor learning. Neuron 2010; 66:198–204.
11 Liebetanz D, Nitsche MA, Tergau F, Paulus W. Pharmacological approach to
the mechanisms of transcranial DC-stimulation-induced after-effects of
human motor cortex excitability. Brain 2002; 125:2238–2247.
12 Faria P, Fregni F, Sebastião F, Dias AI, Leal A. Feasibility of focal transcranial
DC polarization with simultaneous EEG recording: preliminary assessment in
healthy subjects and human epilepsy. Epilepsy Behav 2012; 25:417–425.
13 Laufs H, Krakow K, Sterzer P, Eger E, Beyerle A, Salek-Haddadi A,
Kleinschmidt A. Electroencephalographic signatures of attentional and
cognitive default modes in spontaneous brain activity fluctuations at rest.
Proc Natl Acad Sci USA 2003; 100:11053–11058.
14 Loo CK, Martin D, Alonzo A, Gandevia S, Mitchell PB, Sachdev P. Avoiding
skin burns with transcranial direct current stimulation: preliminary
considerations. Int J Neuropsychopharmacol 2011; 14:425–426.
15 Arrouët C, Congedo M, Marvie J-E, Lamarche F, Lécuyer A, Arnaldi B. Open-
ViBE: a three dimensional platform for real-time neuroscience. J Neurother
2005; 9:3–25.
16 Nitsche MA, Paulus W. Excitability changes induced in the human motor
cortex by weak transcranial direct current stimulation. J Physiol 2000; 527 Pt
3:633–639.
17 RayWJ, Cole HW. EEG alpha activity reflects attentional demands, and beta
activity reflects emotional and cognitive processes. Science 1985;
228:750–752.
18 Berger H. Über das elektrenkephalogramm des menschen. Eur Arch
Psychiatry Clin Neurosci 1929; 87:527–570.
19 Stam CJ, Montez T, Jones BF, Rombouts SA, van der Made Y,
Pijnenburg YA, Scheltens P. Disturbed fluctuations of resting state EEG
synchronization in Alzheimer’s disease. Clin Neurophysiol 2005;
116:708–715.
20 Keeser D, Padberg F, Reisinger E, Pogarell O, Kirsch V, Palm U, et al.
Prefrontal direct current stimulation modulates resting EEG and event-related
potentials in healthy subjects: a standardized low resolution
tomography (sLORETA) study. Neuroimage 2011; 55:644–657.
21 Merzagora AC, Foffani G, Panyavin I, Mordillo-Mateos L, Aguilar J, Onaral B,
Oliviero A. Prefrontal hemodynamic changes produced by anodal direct
current stimulation. Neuroimage 2010; 49:2304–2310.
22 Miezin FM, Maccotta L, Ollinger JM, Petersen SE, Buckner RL.
Characterizing the hemodynamic response: effects of presentation rate,
sampling procedure, and the possibility of ordering brain activity based on
relative timing. Neuroimage 2000; 11 (6 Pt 1):735–759.
23 Brunoni AR, Amadera J, Berbel B, Volz MS, Rizzerio BG, Fregni F. A
systematic review on reporting and assessment of adverse effects
associated with transcranial direct current stimulation. Int J
Neuropsychopharmacol 2011; 14:1133–1145.
24 Herwig U, Satrapi P, Schönfeldt-Lecuona C. Using the international 10–20
EEG system for positioning of transcranial magnetic stimulation. Brain
Topogr 2003; 16:95–99.
25 Yun K, Watanabe K, Shimojo S. Interpersonal body and neural
synchronization as a marker of implicit social interaction. Sci Rep 2012;
2:959.
26 Kim SP, Kang JH, Choe SH, Jeong JW, Kim HT, Yun K, et al. Modulation of
theta phase synchronization in the human electroencephalogram during a
recognition memory task. Neuroreport 2012; 23:637–641.
27 Yun K, Park HK, Kwon DH, Kim YT, Cho SN, Cho HJ, et al. Decreased
cortical complexity in methamphetamine abusers. Psychiatry Res 2012;
201:226–232.
28 Lee J, Yun K. Alcohol reduces cross-frequency theta-phase gamma-amplitude
coupling in resting electroencephalography. Alcohol Clin Exp Res
2014; 38:770–776.
29 Paus T, Castro-Alamancos MA, Petrides M. Cortico-cortical connectivity of
the human mid-dorsolateral frontal cortex and its modulation by repetitive
transcranial magnetic stimulation. Eur J Neurosci 2001; 14:1405–1411.
30 Keeser D, Meindl T, Bor J, Palm U, Pogarell O, Mulert C, et al. Prefrontal
transcranial direct current stimulation changes connectivity of resting-state
networks during fMRI. J Neurosci 2011; 31:15284–15293.
1436 NeuroReport 2014, Vol 25 No 18
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