Brain and Cognition 173 (2023) 106090

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Brain and Cognition

journal homepage: www.elsevier.com/locate/b&c

Combined effects of transcranial direct current stimulation and aerobic

exercise on inhibitory control function in healthy young adults: An
event-related potential study
Yingying Ji a, 1, Xuemei Ni a, 1, Kai Zheng a, 1, Ying Jiang a, Caili Ren a, Haohao Zhu a, *,
Ming Xiao b, *, Tong Wang c, *
a
The Affiliated Mental Health Center of Jiangnan University, Wuxi Central Rehabilitation Hospital, Wuxi, Jiangsu, China
b
Jiangsu Province Key Laboratory of Neurodegeneration, Center for Global Health, Nanjing Medical University, Nanjing, Jiangsu, China
c
Rehabilitation Medicine Center, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China

A R T I C L E I N F O A B S T R A C T

Keywords: Transcranial direct current stimulation (tDCS) and aerobic exercise (AE) have been demonstrated to enhance
Transcranial direct current stimulation inhibitory control function in healthy individuals separately. However, the potential benefits of combining these
Aerobic exercise two interventions have yet to be fully explored. In this study, we aimed to use multiple event-related potential
Inhibitory control function
(ERP) components (P200, N200, and N450) to investigate the combined effects of tDCS and AE on the
Event-related potentials
improvement of inhibitory control ability in healthy young adults. We evaluated the influence of this combined
Healthy young adults
intervention on cognitive tasks involving inhibitory control function and basic information processing by per­
forming the Stroop Word Color task. Our results showed that compared to the application of tDCS or AE alone,
the combined intervention of tDCS and AE had a greater effect on improving inhibitory control function in
healthy young adults. The amplitude of P200, N200, and N450 ERP components also changed more significantly
during the Stroop Word Color task. We concluded that the mechanism of tDCS combined with AE in improving
inhibitory control ability may involve synergistic effects on brain structures at different levels, such as regulating
interactions at the reticular activating system level and activating corresponding brain regions at the medial
frontal lobe and frontal lobe levels.

1. Introduction Common experimental paradigms used to assess inhibitory control

Inhibitory control, a crucial aspect of executive functioning, plays a
vital role in various cognitive tasks by enabling individuals to suppress
or ignore irrelevant information while maintaining focus on task-
relevant information. This cognitive ability is essential for efficient
learning, working, decision-making, and emotional regulation, thereby
contributing to overall cognitive performance (Biggs & Pettijohn, 2022).
Impairments in inhibitory control can lead to significant cognitive
dysfunction, such as distractibility, impulsivity, and poor decision-
making, which may adversely affect academic and professional
achievements, interpersonal relationships, and emotional well-being.
Given the importance of inhibitory control in daily life and cognitive
tasks, it is imperative to explore strategies and interventions to enhance
this function and understand the underlying neural mechanisms.
include the Stroop task (Periáñez et al., 2021), Flanker task (Eriksen,
1995) and Simon task (Rubichi et al., 2000). The performance of the
Stroop Word Color task, for example, requires subjects to overcome
interference from lexical meaning to judge the color of a word, thereby
assessing the ability to resolve stimulus-based conflicts (van Veen &
Carter, 2005; Houwer, 2003; Banich et al., 2001; Zhang et al., 1999;
Zhang & Kornblum, 1998).
The extensive Stroop inhibition control detection theory suggests
that the dorsolateral prefrontal cortex (DLPFC), along with the medial
prefrontal cortex (MPC) and anterior cingulate cortex (ACC), plays an
important role in image conflict resolution (Ebitz & Hayden, 2016;
Smith et al., 2014; Carter & van Veen, 2007). In recent years, many
studies have attempted to improve or enhance inhibitory control by
enhancing the plasticity of the brain, such as improving neuroplasticity

* Corresponding authors.
E-mail addresses: zhuhh@jiangnan.edu.cn (H. Zhu), mingx@njmu.edu.cn (M. Xiao), wangtong60621@163.com (T. Wang).
1
These authors contributed equally to this work.

https://doi.org/10.1016/j.bandc.2023.106090
Received 29 April 2023; Received in revised form 12 September 2023; Accepted 2 October 2023
Available online 8 October 2023
0278-2626/© 2023 Elsevier Inc. All rights reserved.
Y. Ji et al.
and improving functional connections between brain regions associated
with it. Both DLPFC and MPC were prefrontal cortex (PFC), so it was
possible to improve the inhibitory control function by modifying the
plasticity of PFC. In recent years, researchers have proposed that
multimodal rehabilitation intervention approaches (i.e., more than one
intervention technique) may induce synergistic or additive effects to
achieve faster, better, more comprehensive and lasting rehabilitation
effects (Menon & D’Esposito, 2022; Ward et al., 2017), such as
combining brain stimulation with physical exercise (i.e., aerobic exer­
cise) (Steinberg et al., 2018; Hendrikse et al., 2017; Moreau et al., 2015),
specifically within the cognitive domain (Steinberg et al., 2018).
Transcranial direct current stimulation (tDCS) is a noninvasive and
safe method for modulating neuronal activity, leading to changes in
neural plasticity. It can enhance cognitive ability by regulating cerebral
cortical plasticity through the excitatory effect and inhibitory effects
produced by the anode and cathode, respectively. tDCS not only stim­
ulates specific brain regions but also affects the cerebral network related
to cognitive abilities, altering functional connections within the con­
cerned cerebral network. This technique improves cognitive ability by
enhancing the collaborative efficiency between different brain regions
(Ward et al., 2017). Conventional 2.0 mA anodal-tDCS over the PFC and
especially over the DLPFC lasting 10–30 min one-time can improve in­
hibition (i.e., reaction times) in Flanker tasks, Stroop tasks,Go/No-Go
tasks and Stop-Signal tasks paradigms (Angius et al., 2019; Dubreuil-
Vall et al., 2019; Hogeveen et al., 2016; Loftus et al., 2015). Proposed
tDCS effects on brain activity from a neurophysiological perspective
include the modulation of resting-state activity, brain oscillations, brain
perfusion, and oxygenation, bioenergetics, functional connectivity,
event-related spectral perturbations (ERSPs), and ERPs (Wörsching
et al., 2016). Khan et al. found that after a single MPC 2 mA 15 min of
high-definition transcranial direct current stimulation (HD-tDCS) in
healthy young people, the incongruent of Stroop Word Color task and
the reaction time (RT) of neutral test were reduced. The Stroop effect
was significantly reduced, but no significant changes were observed in
the amplitudes and latency of N200, P200, and N450 ERPs (Khan et al.,
2022). Dubreuil-Vall et al. found that anodal tDCS to the left DLPFC led
to a significant improvement in reaction time, an increase in P300
amplitude and a decrease in N200 amplitude in a state-dependent
manner: baseline ERP amplitudes conditioned the effects of tDCS
(Dubreuil-Vall et al., 2019). Given the role of these ERPs in conflict-
related tasks, we speculate that tDCS modulates the subconstructs of
selective attention, conflict monitoring and response inhibition
(Dubreuil-Vall, 2019). tDCS technology is safe, convenient, and flexible.
One of its advantages is that related evaluations can be conducted on­
line, or it can be combined with other therapies in an online condition.
This is a benefit that other neuromodulation techniques do not possess.
However, its effects may be limited by individual differences and the
complexity of the targeted neural networks. Moreover, tDCS typically
focuses on specific brain regions, potentially overlooking the broader
network of interactions involved in inhibitory control.
Comparable effects on brain activity with that of tDCS are well-
known in the AE field. Numerous studies have demonstrated that
long-term moderate AE can improve central nervous system function
and enhance brain plasticity. AE significantly improves executive
function, particularly exerting a more substantial influence on inhibi­
tory control than on other subfunctions (Katja et al., 2014; Chen et al.,
2014; Drollette et al., 2014). Discovered by functional near - infrared
spectroscopy (FNIRS) and functional magnetic resonance imaging
(fMIR), only a single moderate-intensity AE for 20–30 min can improve
the neural activation level of L-DLPFC and PFC, resulting in changes in
the functional plasticity of brain executive control network and frontal
parietal network related regions, and enhance the ability to utilize brain
neural resources in the process of processing inhibitory control tasks,
improved inhibition (i.e., reaction times and accuracy) in Stroop tasks
(Wen et al., 2015; Byun et al., 2014; Yanagisawa et al., 2010). Zhou et al.
found that although no significant improvement was observed in the
2
Brain and Cognition 173 (2023) 106090
accuracy and response time of Stroop word task after an acute moderate-
intensity AE, P2 amplitude was found to increase significantly under
congruent and incongruent tasks in ERP, and no effect was found on N2,
P3b and N450 components (Zhou & Qin, 2019). Wen and Tsai (2020)
found that after acute AE in healthy young people, there was no sig­
nificant improvement on response time or accuracy of Stroop task, N2
and P3 amplitudes were found to increase significantly under congruent
and incongruent tasks in ERP, and no effect was found on P2 compo­
nents (Wen & Tsai, 2020). These findings suggest that acute moderate-
intensity exercise may have a generally beneficial effect on mobilizing
attention resources associated with perceptual processing and exercise-
related physiological arousal (Zhou & Qin, 2019).However, the optimal
intensity, duration, and type of AE for maximizing its benefits on
inhibitory control remain unclear, and individual physical limitations
may restrict the applicability of certain exercise regimens.
The combination of tDCS and AE presents a promising strategy for
cognitive enhancement, leveraging synergistic effects on cortical excit­
ability and neuroplasticity. AE and tDCS engage diverse mechanistic
pathways. AE enhances catecholamine release tied to cognitive
improvement, while tDCS primarily affects the resting membrane po­
tential. Their combination might see these distinct enhancement
mechanisms converge, potentially leading to superior cognitive perfor­
mance. AE may also activate wider neural networks, including those
involved in inhibitory processes inaccessible to tDCS, suggesting AE’s
complementary role in supporting executive functions and other
cognitive processes. AE could function as a brain primer before tDCS,
optimizing neuroplasticity by boosting brain excitability and BDNF
levels. Alternatively, tDCS might be administered before AE to amplify
exercise’s cognitive effects (Steinberg et al., 2018). Conceição et al.
found after the addition of anodal tDCS over the PFC to a session of
aerobic exercise led to immediate positive effects on gait variability,
processing speed, and executive control of walking in people with PD
(Parkinson’s disease) (Conceição et al., 2021). Talar et al. found after a
meta-analysis: pairing AE with tDCS may have the potential to slow
symptom progression of cognitive decline in mild cognitive impairment
(MCI) and dementia (Talar et al., 2022). Many of the above studies have
tended to focus on the immediate effects of tDCS, AE or tDCS + AE on
subjects, and have not focused much on the relatively stable effects of
both over time. Although the separate application of tDCS and AE is
known to improve cognitive performance, the long-term effects of their
combined approach have been poorly studied, while their neuro­
electrophysiology has not been studied.Thus, it remains somewhat
speculative how the two approaches might specifically interact when
coupled. To investigate the cerebral basis of inhibitory control function,
ERP has been widely used to study fast-occurring temporal activity in
the brain during inhibitory control tasks, and several time-locked events
have been identified as markers for different cognitive processing stages,
thus providing a neural basis for the inhibitory control mechanisms in
the prefrontal cortex. By using ERPs, we can precisely examine the ef­
fects of tDCS and AE on the neural mechanisms underlying inhibitory
control, enabling a more in-depth understanding of how these in­
terventions may interact and contribute to improvements in this
essential cognitive function. P200 is a positive-going deflection in the
frontoparietal regions in the time window of 120–250 ms and has been
linked with selective attentional processes required for stimulus evalu­
ation (Potts, 2004). Conflict resolution is typically linked with N200 and
N450 peaks in the frontocentral region (Mckay et al., 2017) with N200
reflecting ongoing negative potential at the earlier stage of conflict and
peaking in the time window of 200–350 ms after the onset of the stim­
ulus (Folstein & Van Petten, 2007) while N450 reflects conflict resolu­
tion at approximately 400 ms after the onset of the event (Hanslmayr
et al., 2008). By using ERPs, we can precisely examine the effects of tDCS
and AE on the neural mechanisms underlying inhibitory control,
enabling a more in-depth understanding of how these interventions may
interact and contribute to improvements in this essential cognitive
function.
Y. Ji et al. Brain and Cognition 173 (2023) 106090

In summary, this study explores the effects of tDCS combined with
AE for 4 weeks on inhibitory control function, aiming to provide a new
strategy and theoretical basis for the improvement of inhibitory control
function. We expect to gain a more complete understanding of the role of
tDCS and AE in inhibitory control function and the potential benefits
that their combination may bring. We explore the mechanism of the
combination effect on regulating the spontaneous cerebral electrical
activity of frontal regions (Fz point) through the use of ERP of healthy
young adults undertaking the classical Stroop Word Color task con­
cerning inhibitory control to observe and analyse the amplitude and
latency of the inhibitory control-related ERP components of frontal re­
gions, including P200, N200 and N450. The findings of this study are
expected to provide valuable insights into the combined effects of tDCS
and AE on inhibitory control function and their potential implications in
improving cognitive functioning in various populations, including
healthy individuals, elderly people, and those with neurological condi­
tions. By examining the changes in ERP components associated with
inhibitory control, this research will contribute to a better understand­
ing of the neural mechanisms underlying the combination of tDCS and
AE interventions.
2. Material and methods
2.1. Study design and settings
The current study was a randomized controlled study (Fig. 1A). The
experimental protocol was explained to the participants on the day of
the experiment, and they were asked to complete a tDCS questionnaire
and sign a consent form. The questionnaire assessed their eligibility for
the study and inquired about any psychostimulant use before the
experiment. Participants were randomly assigned to the tDCS + AE,
tDCS and AE groups. The Stroop task was performed at two time points,
i.e., one day before and after the experiment, with EEG collected
throughout the Stroop task (Fig. 1C). All experiments were performed in
the early morning (8–10 am) or early afternoon (1–3 pm). After the
experiment, participants completed a tDCS experience questionnaire to
report any side effects of stimulation, including minor discomfort, mild
headache, neck pain, tingling, itching, burning sensation, sleepiness,
metallic/iron taste, fatigue, trouble concentrating, acute mood change,
investigator, skin redness, and skin irritation. This study was approved
by the Ethics Committee of Wuxi Mental Health Center (Ethics
WXMHCIRB2021LLky145) and conducted in accordance with the Hel­
sinki Declaration. The trial was registered in the Chinese Clinical Trial
Registry (ChiCTR2200057170). All participants signed informed con­
sent forms before being randomly assigned to their respective groups.
2.2. Participants
The sample size was calculated using G*Power software based on the
results of a previous study with an effect size of − 0.73 (Conceição et al.,
2021). We expect that the target effect size had 90% power with a type I
error of 5% (α = 0.05). Thus, the sample size of each group was at least
16. Considering an estimated dropout rate of 20%, the required sample
size increases to 20 participants per group. Consequently, a total of 60
participants (20 per group) were targeted for this study. The choice of n
= 60 (20 per group) ensured adequate size for within-group analyses as
well. A total of 63 college students (23 male and 40 female) signed up for
the trial, and sixty college students (22 male and 38 female) were
recruited through advertisements according to the following inclusion
criteria: being between 18 and 25 years of age, being right-handed,
having normal or corrected vision and color vision, having a body
mass index (BMI) of <25, having no mental or neurological disease,
cardiovascular disease or physical disability and having no exercise
habits. To overcome the ceiling effect of exercise, participants must not
have exercise habits [the criteria of exercise habits were exercising at
least 3 times a week, each time lasting over 30 min at moderate exercise

Fig. 1. The protocols of the study. Flow diagram of the progress through the phases of a parallel randomized trial of 3 groups (that is, enrolment, intervention
allocation, follow-up and data analysis) (A). Illustration of the intervention protocol for AE and tDCS (sham and active) included 30-s periods of RU/RD (B). A
stimulation current of 2 mA was applied for 30 min and 10 s in the active- and sham-tDCS sessions, respectively (B). Study timeline (C). First, participants reported
demographic information. Stroop task and ERP were then measured one day before and after intervention. During the intervention period, the experimental group
underwent a four-week intervention. This involved five sessions each week, with each session lasting 30 min. Abbreviations: HR, heart rate; RD, ramp down; RU,
ramp up; tDCS, transcranial direct current stimulation.

3
Y. Ji et al.
intensity (heart rate >110 times/min) and maintained for more than a
year]. Participants completed the Physical Activity Readiness Ques­
tionnaire (PAR-Q) (Warburton et al., 2020), the Edinburgh handedness
inventory (Oldfield, 1971), the international physical activity ques­
tionnaire (IPAQ) and the shortened version of Raven’s Advanced Pro­
gressive Matrices test (sRAPM) (Marzecová et al., 2013). Participants
were randomly assigned to the tDCS + AE group, tDCS group, or AE
group, with an equal number of males and females in each group. Par­
ticipants were instructed to stop exercising 24 h before the experiment
and to wear comfortable clothes and shoes for all interventions. The trial
is to be discontinued under certain conditions: if the treatment is not
administered according to the study protocol, if symptoms such as fa­
tigue, headache, dizziness, and tension persist without relief, or if the
participant voluntarily requests to withdraw. If the participants have not
completed 20 interventions as required by the trial, it will also be treated
as dropouts.
2.3. Randomization
SPSS v.22.0 was used for random group assignment. Males were
numbered 1–22 according to the order of enrolment. Initially, a starting
point was set in random number generators, and then Rv. Uniform(0,1)
in Compute Variable was used to generate a random number for each
participant. Next, a cut-off point was set in Equal Percentiles Based on
Scanned Cases in Visual Binning, and then males were randomly
assigned to the tDCS + AE, tDCS, AE experiment groups. Afterward,
these operations were repeated to ensure that females were randomly
assigned to the three experimental groups. However, due to having a
cold or having to return to school, 1 woman in the tDCS group did not
complete the experiment, 4 women in the AE group did not complete the
experiment, and 2 women in the tDCS + AE group did not complete the
experiment, leaving the remaining 53 participants who successfully
completed the experiment. The total number of participants in each
group who completed the experiment was 19 in the tDCS group, 16 in
the AE group, and 18 in the tDCS + AE group. The specific test methods
were as follows (Fig. 1A).
2.4. Treatment methods
This study utilized a randomized design in which individuals
participated in three experimental sessions separated by 20 days (5
times a week for 4 weeks): 1) tDCS - anodal tDCS only at rest, 2) AE -
aerobic exercise with sham tDCS, and 3) AE + tDCS - aerobic exercise
with anodal tDCS (Fig. 1C).
tDCS: Facilitatory anodal tDCS was used in the tDCS and AE + tDCS
sessions. tDCS was provided by a battery-driven stimulator (YZB/Chuan
0185-2014, Sichuan Machinery Note 20142210040, Sichuan Smart
Electronics Industry Co., Ltd.) through a pair of saline-soaked sponge
electrodes (7 cm × 5 cm). Stimulation targets the L-DLPFC. The anode
electrode was placed at the F3 position of the 10–20 international EEG
system. The cathodal electrode was located in the contralateral supra­
orbital area (FP2). The stimulation current intensity was 2 mA for 30
min and was accelerated at the beginning of stimulation and decelerated
at the end of stimulation, each lasting 30 s. Sham (placebo) stimulation
included ramping up and down the current for 30 s, but no current was
delivered while the participants exercised (AE session). Participants
were blinded to the type of tDCS during the AE + tDCS and AE sessions
(Fig. 1B).
AE: The AE was carried out on a power bike (model motion cycle
600med, Germany) with moderate intensity and personalized to an in­
dividual maximum heart rate (HRmax). HRmax was estimated using the
following formula: HRmax = (220 - Age) × 0.7. The AE program lasted
40 min and consisted of 3 phases: (1) a 5-minute warm-up with heart
rate maintained between 55% and 60% of HRmax; (2) a 30-minute ex­
ercise at intensity between 60% and 70% of HRmax; and (3) 5 min of
finishing exercise, keeping the heart rate below 65% of HRmax. HR was
4
Brain and Cognition 173 (2023) 106090
recorded using a heart rate monitor (model DB18, Philips, Suzhou Erda
Medical Equipment Co., Ltd.) throughout the exercise period (Fig. 1B).
The entire process will have a timer for timing, and the trial operators
will supervise and control the heart rate.
2.5. Collection of behavioural and EEG data
2.5.1. Behavioural data
The inhibitory control function of patients was evaluated using the
Stroop Word Color task before and after a 4-week trial (Fig. 2). The
Stroop Word Color task was programmed using E-prime 3.0 software
and presented on a 19-inch computer screen with a resolution of 1280 ×
1024 and a refresh rate of 60 Hz. The stimulus material was presented in
the center of the screen in a well-lit soundproof room. The distance
between the subject and the display screen was 60–80 cm. The experi­
ment only used a block consisting of two types of tasks: congruent and
incongruent. The congruent test consists of one of four color words
printed in Chinese with the same color [i.e. (RED), (YELLOW), (GREEN)
or (BLUE), mean red, yellow, green or blue, respectively]. Incongruent
trials consist of the same four-word color, but printed in a different color
[e.g., (RED) printed in blue ink]. The block consisted of 120 trials, of
which 60 were congruent and 60 were incongruent, and the presenta­
tion of the trials was random. At the beginning of each experiment, a
fixation point was presented for 500 ms, followed by a Chinese char­
acter, which was presented until the subject responded, and the subject
was asked to identify the color of the written word as quickly and
accurately as possible by pressing a button based on the color. Partici­
pants sat comfortably in a chair and viewed the screen with a horizontal
visual angle of 6.0◦ ×7.0◦ and a vertical visual angle of 6.0◦ ×7.0◦ , with
their eyes approximately 60–80 cm from the display.
Before the experiment, participants were told they would be taking
part in a color-naming task. In the auditory isolation room, the subjects
sat about 60–80 cm away from a computer screen. They were asked to
place their left middle finger, left index finger, right index finger and
right middle finger on the DFJ and K keys, with each key representing a
color. At the beginning of each experiment, a fixation point was pre­
sented for 500 ms, followed by a Chinese character, which was pre­
sented until the subject responded, and the subject was asked to identify
the color of the written word as quickly and accurately as possible by
pressing a button based on the color. An exercise session consisting of 10
experiments was used to allow subjects to create a map of responding
fingers and colors. This process was repeated until 90% accuracy was
reached. The subjects were then allowed to participate in the experi­
ment. Prior to the start of the experiment, participants had their hair
washed, put on an electrode cap, attached external electrodes, applied
conductive gel, and had their brainwave signals checked to ensure good
signal acquisition. Throughout the experiment, subjects were asked to
keep their eyes on a computer screen. The entire experiment lasted 45
min.
2.5.2. Behavioral data processing
Behavioral data were automatically collected using E-Prime 3.0
software. Data were merged using E-Merge software and analysed using
E-DataAid software. The analysis included calculating the percentage
accuracy and reaction time for the sets of responses to Stroop task.
2.5.3. EEG data
ERP data were collected using the BrainVision Recorder event-
related potential system from Brain Products. The EEG was recorded
using a 64-electrode cap (EasyCap, manufactured by Herrsching in
Germany) based on the extended 10/20 system. Horizontal (HEOG) and
vertical (VEOG) electrooculograms were also recorded. The HEOG
electrodes were placed on the outer corner of each eye, while the VEOG
electrodes were placed in the middle of the lower eyelid of each eye. The
reference electrodes were placed on the left and right mastoid. The
sampling rate was 500 Hz, and the bandpass filter range was DC − 100
Y. Ji et al.
Fig. 2. Schematic illustration of the behavioral procedure in Stroop Word Color task.
Hz. The scalp electrode impedance was <5 kΩ. The experimental pro­
gram was run using E-prime 3.0 software on a separate computer, and
events were automatically marked on the corresponding EEG recordings
during the experiment.
2.5.4. EEG data preprocessing
The EEG data were preprocessed using MATLAB (MathWorks) in
combination with the EEGLAB toolbox (Delorme & Makeig, 2004) and
custom scripts. The preprocessing pipeline included several steps
including electrode localization, interpolation of bad channels, re-
referencing, filtering, independent component analysis (ICA), segmen­
tation and averaging, baseline correction, identification of extreme
values and exclusion of bad segments.Specifically, the interpolation of
bad channels was performed using the spherical method, and the
average of bilateral mastoids was used for re-referencing. The data un­
derwent high-pass filtering at 0.1 Hz and low-pass filtering at 30 Hz. IC
components related to eye movements, myoelectric activity, and elec­
trocardiogram were removed manually. After then, data were
segmented from 200 ms before stimulation to 1000 ms after stimulation,
and baseline correction was conducted using the 200 ms pre-stimulus
interval. Segments with amplitudes exceeding ±75 μV were excluded
from further analysis. Subsequently, peak detection of ERP components
was performed, and the data were exported for subsequent analysis
using SPSS software.
Trials that exhibited artifacts due to amplifier clipping or peak-to-
peak deflection exceeding 100 mV were excluded from the averaging,
and trials with response errors were also rejected. On average, approx­
imately 15% of the trials were removed for each participant for each
condition. The mean ± SE of the remaining trials after behavioral cor­
rectness analysis and EEG artifact rejection (mean ± SE for congruent/
incongruent trials) are as follows: tDCS + AE group pre-test (55.64 ±
0.84/50.63 ± 0.75); tDCS + AE group post-test (53.62 ± 0.28/51.38 ±
0.75); tDCS group pre-test (54.38 ± 0.53/52.12 ± 0.58); tDCS group
post-test (52.58 ± 0.38/50.39 ± 0.85); AE group pre-test (54.72 ±
0.55/53.08 ± 0.29); AE group post-test (53.75 ± 0.59/52.53 ± 0.35).
Separate stimulus-locked ERP averages for congruent and incongruent
tasks were computed for each participant.
2.5.5. ERP analysis
Consistent with previous research (Chang et al., 2017; Feng et al.,
2014; Ilan and Polich, 1999), P200, N200, and N450 components were
selected for analysis. These ERPs were primarily observed at electrodes
located on the frontal pole. The analysis included changes in ERP
measures such as average amplitude and peak latency (Luck, 2005).
The visually prominent grand-average ERP waveforms (difference
waves between congruent and incongruent conditions) were observed
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Brain and Cognition 173 (2023) 106090
for the P200 component within the 120–250 ms time window, the N200
component within the 250–350 ms time window, and the N450
component within the 350–600 ms time window. All of these were
observed at frontal central scalp sites (i.e., Fz, FCz, F3, F4, FC1, and FC2
electrodes). In addition, according to the topographic maps displaying
the differences in average amplitude before and after both the congruent
and incongruent task experiments (Fig. 7), it was observed that the most
significant changes in this study’s EEG components in the frontal lobe
occurred at the Fz electrode, consistent with previous studies (Khan
et al., 2022).
2.6. Statistical analysis
Statistical analysis was conducted using SPSS v.26.0. One-way
analysis of variance (ANOVA) was performed to analyze continuous
variables, while the chi-square test was used for categorical variables,
examining the differences among the three groups.
For the analysis of behavioural performance measures, a two-way
repeated-measures analysis of covariance (ANCOVA) was utilized.
This analysis aimed to examine the change in Stroop’s accuracy and
reaction time before and after interventions, with Treatments (tDCS +
AE vs. tDCS vs. AE) as between-group factors and Tasks (congruent vs.
incongruent) as within-group factors. To mitigate potential individual
differences prior to the interventions, baseline values were incorporated
as covariates in the analysis.
Similarly, a two-way repeated-measures ANCOVA was conducted to
assess the change in ERP measures, including average amplitude and
peak latency for the P200 component (at Fz in the 120–250 ms time
window), the N200 component (at Fz in the 250–350 ms time window),
and the N450 component (at Fz in the 350–600 ms time window). To
mitigate potential individual differences prior to the interventions,
baseline values were incorporated as covariates in the analysis.
When the data violate the sphericity assumption, employing the
Greenhouse-Geisser correction is a customary practice. This correction is
used to adjust the degrees of freedom, thereby controlling the risk of
Type I error and ensuring the robustness of the test results. Post hoc
multiple comparisons were corrected using Bonferroni method with a
familywise alpha level set at 0.05.
3. Results
3.1. Analysis of the demographic data
As Table 1 shows, the ANOVA results indicated no significant dif­
ferences in the demographic characteristics among the three groups.
Regarding the adverse effects of tDCS or AE, the most commonly
Y. Ji et al. Brain and Cognition 173 (2023) 106090

Table 1 Table 3
Participant characteristics of the tDCs + AE, tDCS and AE groups (x ± SE). Behavioral data (mean ± SE) across treatment and Stroop tasks.
Factors tDCS + AE tDCS AE Component tDCS + AE group tDCS group AE group

Number（n） 18（8/10） 19（7/12） 16（7/9） Pre-test Post- Pre-test Post- Pre-test Post-
Female（%） 55.56 63.16 56.25 test test test
Age（years） 21.08 ± 1.31 21.85 ± 1.34 21.61 ± 1.23
Con. 98.26 96.84 99.10 96.80 98.12 97.18
Height（cm） 167.47 ± 0.00 166.84 ± 7.02 166.94 ± 10.28
Accuracy ± 2.71 ± 4.13 ± 1.52 ± 3.86 ± 2.60 ± 2.83
Weight（kg） 62.32 ± 11.66 61.53 ± 12.04 61.24 ± 11.14
Change in − 0.01 ± 0.05 − 0.02 ± 0.04 − 0.01 ± 0.04
Con.
Accuracy
reported sensations were as follows: in the tDCS + AE group and tDCS InCon. 94.84 96.05 96.26 97.68 92.47 95.65
group, mild tingling (100%, 94.74%), itching (94.44%, 94.74%), Accuracy ± 6.64 ± 3.63 ± 3.33 ± 2.77 ± 5.71 ± 3.33
burning sensation (55.56%, 57.89%), sleepiness (5.56%, 0%), skin Change in − 0.01 ± 0.05 − 0.01 ± 0.03 − 0.03 ± 0.06
redness (94.44%, 94.74%), and skin irritation (88.89%, 89.47%) InCon.
Accuracy
(Table 2).
Con.Time 718.78 506.42 698.00 572.12 706.10 568.43
± ± 79.08 ± ± 78.78 ± ±
3.2. Analysis of the behavior data 112.07 103.09 103.89 117.45
Change in 212.35 ± 80.88 125.88 ± 69.27 133.18 ± 94.03
Con.Time
3.2.1. Accuracy InCon.Time 829.38 542.48 803.07 652.85 802.98 674.81
Using the difference in accuracy between the groups before and after ± ± 80.85 ± ± 96.26 ± ±
the intervention as the dependent variable, with congruent and incon­ 146.89 131.21 110.61 134.33
gruent task accuracy rates before the intervention as covariates, results Change in 286.90 ± 120.66 150.22 ± 102.85 128.18 ± 87.09
InCon.
of the two-way ANCOVA revealed no significant interaction effect or
Time
main effects for the Tasks (congruent vs. incongruent) × Treatments
(tDCS + AE vs. tDCS vs. AE).
3.3. Analysis of the ERP data
3.2.2. Reaction time
Using the difference in reaction time between the groups before and Table 4 displays the ERP values obtained for each experimental
after the intervention as the dependent variable, with congruent and condition, while Table 5 presents the changes in amplitude of the ERP
incongruent task reaction time before the intervention as covariates, the data. In Table 6, a comprehensive statistical summary table is provided,
results showed a significant interaction effect of Tasks (congruent vs. highlighting significant effects observed in the study.
incongruent) × Treatments (tDCS + AE vs. tDCS vs. AE) (F2,51 = 7.739, p The interaction effect of the change in P200, N200, and N450 am­
= 0.001, η2p = 0.233), a main effect of Treatments (tDCS + AE vs. tDCS plitudes between Tasks (congruent vs. incongruent) and Treatments
vs. AE) (F2,51 = 14.408, p = 0.000, η2p = 0.361). See Table 3 and Fig. 3. (tDCS + AE vs. tDCS vs. AE) is depicted in Fig. 4. Furthermore, Fig. 5 and
In the congruent task condition, the tDCS + AE group (212.35 ± Fig. 6 showcase the grand-averaged ERP waveforms for each treatment
80.88 ms ) had a statistically significant difference compared to the tDCS and task condition. Lastly, Fig. 7 presents the topographic scalp distri­
group (125.88 ± 69.27 ms) and the AE group (133.18 ± 94.03 ms) bution of the P200, N200, and N450 components.
(F2,51 = 7.908, p = 0.002, η2p = 0.237) (F2,51 = 7.908, p = 0.006, η2p =
0.237). There was no statistically significant difference between the 3.3.1. P200
tDCS group and the AE group (F2,51 = 7.908, p = 1.000, η2p = 0.237). Taken the difference amplitude of P200 before and after intervention
In the incongruent task condition, the tDCS + AE group (286.90 ± as the dependent variable, and the amplitude of P200 before interven­
120.66 ms) had a statistically significant difference compared to the tion as the covariate. The results showed a significant interaction effect
tDCS group (150.22 ± 102.85 ms) and the AE group (128.18 ± 87.09 of Tasks (congruent vs. incongruent) × Treatments (tDCS + AE vs. tDCS
ms) (F2,51 = 17.404, p = 0.000, η2p = 0.406) (F2,51 = 17.404, p = 0.000, vs. AE) (F2,193 = 80.847, p = 0.000, η2p = 0.456), a main effect of Tasks
η2p = 0.406). There was no statistically significant difference between (F1,193 = 36.735, p = 0.000, η2p = 0.160), a main effect of Treatments
the tDCS group and the AE group (F2,51 = 17.404, p = 1.000, η2p = (F2,193 = 99.536, p = 0.000, η2p = 0.508).
0.406). In the congruent task condition, the tDCS + AE group (− 2.88 ± 1.87
In the tDCS + AE group, there was a statistically significant differ­ µV) had a statistically significant difference compared to the tDCS group
ence between congruent and incongruent tasks (F1,51 = 30.297, p = (− 1.96 ± 1.57 µV) and the AE group (− 0.75 ± 1.61 µV) (F2,193 =
0.000, η2p = 0.373); in the tDCS group, there was no statistically sig­ 49.876, p = 0.000, η2p = 0.341) (F2,193 = 49.876, p = 0.000, η2p =
nificant difference between congruent and incongruent tasks (F1,51 = 0.341), while there was no statistically significant difference between
3.976, p = 0.052, η2p = 0.072); in the AE group, there was no statisti­ the tDCS and AE groups (F2,193 = 49.876, p = 1.000, η2p = 0.341).
cally significant difference between congruent and incongruent tasks In the incongruent task condition, the tDCS + AE group (-3.03 ±
(F1,51 = 0.013, p = 0.908, η2p = 0.000). 1.55 µV) had a statistically significant difference compared to the tDCS
group (-1.08 ± 1.35 µV) and the AE group (-1.29 ± 1.41 µV) (F2,193 =
Table 2 181.221, p = 0.000, η2p = 0.653) (F2,193 = 181.221, p = 0.000, η2p =
Adverse effects of each intervention session. 0.653); the tDCS group had a statistically significant difference
Adverse effects tDCS + AE tDCS AE
compared to the AE group (F2,193 = 181.221, p = 0.027, η2p = 0.653).
In the tDCS + AE group, there was a statistically significant differ­
Participants’report
ence between congruent and incongruent tasks (F1,193 = 25.180, p =
Headache 0 0 0
Neck pain 0 0 0 0.000, η2p = 0.115); in the tDCS group, there was a statistically signif­
Tingling 18 18 0 icant difference between congruent and incongruent tasks (F1,193 =
Itching 17 18 0 120.028, p = 0.000, η2p = 0.383); in the AE group, there was no sta­
Burning sensation 10 11 0
tistically significant difference between congruent and incongruent
Sleepiness 1 0 0
Skin redness 17 18 0 tasks (F1,193 = 1.575, p = 0.211, η2p = 0.008).
Skin irritation 16 17 0 There were no significant two-way interactions or main effects

6
Y. Ji et al.
Fig. 3. The interaction effect of change in response time of three groups. ****p < 0.0001, 0.0001<***p < 0.001, 0.001 < **p < 0.01, 0.01 <*p < 0.05.
observed in terms of P200 latency.
3.3.2. N200
Taken the difference amplitude of N200 before and after interven­
tion as the dependent variable, and the amplitude of N200 before
intervention as the covariate. The results showed a significant interac­
tion effect of Tasks (congruent vs. incongruent) × Treatments (tDCS +
AE vs. tDCS vs. AE) (F2,148 = 17.229, p = 0.000, η2p = 0.189), a main
effect of Tasks (F1,148 = 63.355, p = 0.000, η2p = 0.300), a main effect of
Treatments (F2,148 = 190.924, p = 0.000, η2p = 0.721).
In the congruent task condition, the tDCS + AE group (− 4.57 ± 0.58
µV) showed a significant difference compared to the tDCS group (− 2.50
± 1.60 µV) and AE group (− 2.34 ± 0.53 µV) (F2,148 = 89.957, p = 0.000,
η2p = 0.549) (F2,148 = 89.957, p = 0.000, η2p = 0.549), and there was a
significant difference between the tDCS group and the AE group (F2,148
= 89.957, p = 0.022, η2p = 0.549).
In the incongruent task condition, the tDCS + AE group (-4.92 ±
0.78 µV) showed a significant difference compared to the tDCS group
(-2.53 ± 0.83 µV) and AE group (-3.60 ± 0.51 µV) (F2,148 = 403.438, p
= 0.000, η2p = 0.845) (F2,148 = 403.438, p = 0.000, η2p = 0.845). There
was a significant difference between the tDCS group and the AE group
(F2,148 = 403.438, p = 0.000, η2p = 0.845).
In the tDCS + AE group, there was a significant difference between
the congruent and incongruent tasks (F1,148 = 16.609, p = 0.000, η2p =
0.101); in the tDCS group, there was no significant difference between
the congruent and incongruent tasks (F1,148 = 0.329, p = 0.567, η2p =
0.002); in the AE group, there was a significant difference between the
congruent and incongruent tasks (F1,148 = 81.572, p = 0.000, η2p =
0.355).
There were no significant two-way interactions or main effects
observed in terms of N200 latency.
7
Brain and Cognition 173 (2023) 106090
3.3.3. N450
Taken the difference amplitude of N450 before and after interven­
tion as the dependent variable, and the amplitude of N450 before
intervention as the covariate. The results showed a significant interac­
tion effect of Tasks (congruent vs. incongruent) × Treatments (tDCS +
AE vs. tDCS vs. AE) (F2,373 = 130.815, p = 0.000, η2p = 0.412), a main
effect of Tasks (F1,373 = 5.265, p = 0.022, η2p = 0.014), a main effect of
Treatments (F2,373 = 488.578, p = 0.000, η2p = 0.724).
In the congruent task, the tDCS + AE group (− 1.61 ± 0.46 µV)
showed a significant difference compared to the tDCS group (1.83 ±
1.45 µV) and AE group (− 1.47 ± 1.06 µV) (F2,373 = 435.727, p = 0.000,
η2p = 0.700) (F2,373 = 435.727, p = 0.000, η2p = 0.700). While the tDCS
group showed no significant difference compared to the AE group
(F2,373 = 435.727, p = 0.130, η2p = 0.700).
In the incongruent task, the tDCS + AE group (− 2.80 ± 0.64 µV)
showed a significant difference compared to the tDCS group (− 0.04 ±
0.69 µV) and the AE group (− 1.18 ± 0.93 µV) (F2,373 = 337.913, p =
0.000, η2p = 0.644) (F2,373 = 337.913, p = 0.000, η2p = 0.644). The tDCS
group showed a significant difference compared to the AE group (F2,373
= 337.913, p = 0.000, η2p = 0.644).
In the tDCS + AE group, there was a significant difference between
the congruent and incongruent tasks (F1,373 = 13.452, p = 0.000, η2p =
0.035); in the tDCS group, there was a significant difference between the
congruent and incongruent tasks (F1,373 = 335.510, p = 0.000, η2p =
0.474); in the AE group, there was no significant difference between the
congruent and incongruent tasks (F1,373 = 0.951, p = 0.330, η2p =
0.003).
There were no significant two-way interactions or main effects
observed in terms of N450 latency.
Y. Ji et al. Brain and Cognition 173 (2023) 106090

4. Discussion

155.15 ± 3.13
296.67 ± 4.08
442.25 ± 4.86
− 2.93 ± 1.18
incongruent
2.74 ± 2.76

1.80 ± 0.63
Neuroimaging studies have confirmed that inhibitory control ability
in cognition requires coordination and interaction among various re­
gions of the prefrontal cortex (Constantinidis & Luna, 2019). L-DLPFC
anodal tDCS stimulation has been proven to improve inhibitory control
ability to some extent by activating the prefrontal cortex, enhancing its

159.23 ± 3.27
284.23 ± 4.40
461.95 ± 3.76
− 2.05 ± 1.55
2.42 ± 2.92

2.29 ± 0.60
plasticity, and changing the functional connectivity of relevant brain

congruent
Post-test
networks (Angius et al., 2019; Palmisano et al., 2021). Meanwhile, long-
term moderate-intensity AE can improve inhibitory control function by
regulating the plasticity of brain regions related to the executive control
network and the frontoparietal network (Huang et al., 2022). As both

164.32 ± 4.99
300.05 ± 3.56
452.25 ± 4.86
incongruent
4.04 ± 1.78
0.67 ± 0.94
2.98 ± 0.48
methods can initiate and regulate neural plasticity in the human brain
and change the efficiency of different brain regions’ coordination, this
study found that combining tDCS with moderate-intensity AE may have
beneficial effects on improving inhibitory control function, and its
related mechanisms may occur at multiple levels of stimulus processing,
166.52 ± 3.49
288.26 ± 3.25
450.23 ± 4.82
3.17 ± 1.81
0.30 ± 1.31
3.76 ± 0.65

involving the regulation of attention resources related to perceptual

congruent

processing and motor-related arousal. This may be achieved through the

Pre-test

mutual regulation of brain network activation levels, activating the

AE

medial and lateral prefrontal cortex and enhancing their plasticity to

improve conflict inhibition ability.
149.34 ± 4.52
252.56 ± 4.13
446.58 ± 4.17
− 4.99 ± 1.69

The Stroop task is considered to reflect the combined effects of

incongruent
0.49 ± 3.31

0.58 ± 0.76

stimulus conflict and response conflict (Sjoberg et al., 2023; Viviani

et al., 2023; Paap et al., 2020). However, from the perspective of conflict
source, in the Stroop task, conflict arises due to the semantic in­
compatibility between the relevant and irrelevant stimulus dimensions;
149.67 ± 4.29

458.23 ± 3.58
− 0.47 ± 3.51
− 5.44 ± 2.73

thus, the Stroop task represents stimulus-based conflic (Parris et al.,

2.52 ± 1.39

275 ± 3.38
congruent

2022; Augustinova et al., 2022). Prior to stimulus presentation, we

Post-test

observed a strong “Stroop effect” between congruent trials and incon­

gruent trials. Although there was no significant difference in accuracy
between the three groups in the congruent and incongruent trials, this
151.48 ± 4.67
292.15 ± 4.58
428.62 ± 4.39
− 2.45 ± 1.02

consideration with the difficulty of the Stroop task may have a certain
incongruent
1.57 ± 2.00

0.62 ± 0.55

ceiling effect on healthy young people. According to the response times,

the three groups to incongruent trials were significantly longer than
those to congruent trials, which supports the Stroop task design used in
our study and suggests that incongruent trials require greater inhibitory
143.75 ± 4.70
290.36 ± 3.62
491.75 ± 3.71
− 2.95 ± 1.50

cognitive control (Chang et al., 2017). However, after 4 weeks of

1.49 ± 2.02

0.69 ± 0.34
congruent

intervention in the three groups, although longer response times were

Pre-test
ERP average amplitude and latency data (mean ± SE) across treatments and Stroop tasks.

still required for incongruent trials, there was no significant difference

tDCS

between congruent and incongruent trials in the tDCS + AE group after

intervention, while significant differences still existed in the other two
144.25 ± 4.98
286.82 ± 4.89
478.23 ± 3.25

groups.The shortened response time to incongruent tasks was more

− 6.66 ± 2.15
− 1.19 ± 0.33
incongruent
0.85 ± 4.37

convincing for the improvement in inhibitory control. At the same time,

it was found that the tDCS + AE group showed significant improvements
in both congruent and incongruent responses after intervention
compared to the tDCS and AE groups, and the improvement was sta­
141.85 ± 4.76
292.16 ± 3.58
451.12 ± 4.12

tistically significant. This indicates that L-DLPFC anodal tDCS stimula­

− 6.31 ± 2.19
− 0.70 ± 0.43
1.26 ± 4.60

tion combined with moderate-intensity AE can improve the inhibitory

congruent
Post-test

control ability of healthy young people to a certain extent after 4 weeks

of intervention, and the effect is better than that obtained by using only
one of the methods, especially in the performance of shortened re­
sponses time to incongruent tasks.
147.95 ± 3.02
292.05 ± 3.86
491.17 ± 5.86
− 1.74 ± 1.48
incongruent
3.89 ± 2.99

1.61 ± 0.40

The P200 component appeared approximately 120–250 ms after the

stimulus was presented (Khan et al., 2022). Related studies have sug­
gested that the P200 component in the frontal area might be related to
attention resources in early perceptual processing (Cao et al., 2021;
Zhou et al., 2020). There was also a close correlation between the P200
147.58 ± 4.75
282.15 ± 3.55
456.28 ± 3.82
− 1.74 ± 1.68
4.16 ± 2.97

0.91 ± 0.47

component and arousal level (Paul & Pourtois, 2017). The level of
tDCS + AE

congruent

arousal is determined by the level of reticular activation (including the

Pre-test

cerebral cortex, reticular structure, hypothalamus, and limbic system),

Amplitude (µV)

the adrenal medulla, and the interaction between the somatic and
Latency (ms)

autonomic nervous systems. According to the inverted U-shape theory, a

Component

moderate level of physiological arousal can play a greater role in

Table 4

N200
N450

N200
N450
P200

P200

cognitive function (Kumfor et al., 2019). In this study, it was found that
regardless of the tDCS group, AE group or tDCS + AE group, the

8
Y. Ji et al. Brain and Cognition 173 (2023) 106090

Table 5
Change in average amplitude of ERP data.
Component tDCS + AE tDCS AE

congruent incongruent congruent incongruent congruent incongruent

Change in Amplitude (µV)

P200 − 2.88 ± 1.87 − 3.03 ± 1.55 − 1.96 ± 1.57 − 1.08 ± 1.35 − 0.75 ± 1.61 − 1.29 ± 1.41
N200 − 4.57 ± 0.58 − 4.92 ± 0.78 − 2.50 ± 1.60 − 2.53 ± 0.83 − 2.34 ± 0.53 − 3.60 ± 0.51
N450 − 1.61 ± 0.46 − 2.80 ± 0.64 1.83 ± 1.45 − 0.04 ± 0.69 − 1.47 ± 1.06 − 1.18 ± 0.93

Change in Latency (ms)

P200 − 5.89 ± 2.75 − 3.36 ± 1.98 − 5.99 ± 1.86 − 2.97 ± 1.26 − 6.21 ± 2.03 − 4.18 ± 2.35
N200 − 10.97 ± 3.15 − 7.02 ± 1.14 − 12.97 ± 4.05 − 10.88 ± 2.27 − 7.95 ± 3.25 − 6.87 ± 4.16
N450 − 10.57 ± 3.86 − 12.05 ± 5.26 − 14.57 ± 5.78 − 14.92 ± 5.49 − 12.89 ± 4.98 − 12.01 ± 5.61

neurotransmitter regulation (Mahalakshmi et al., 2020) and enable in­

Table 6 dividuals to present optimal cognitive performance. The inverted U-
Statistical summary table for behavioral and ERP data.
shaped theory of exercise holds that different levels of AE have different
Measure Effect df F p η2p effects on inhibitory ability, mainly due to different levels of evoked
Change in RT Task × Treatment 2,51 7.739 0.001 0.233 arousal (Egbert et al., 2022). This study found that moderate intensity
Treatment（tDCS + 2,51 14.408 0.000 0.361 AE significantly reduced the amplitude of P200, whether it was related
AE＞tDCS＞AE） to the relative optimization of exercise by adjusting the arousal level.
Based on the behavioral changes of Stroop in the three groups and the U-
Change in P200 Task × Treatment 2,193 80.847 0.000 0.456 shaped theory of arousal, it is considered that L-DLPFC anodal tDCS and
amplitude Task(congruent > 1,193 36.735 0.000 0.160
moderate AE may regulate cortical excitability related to arousal level,
incongruent)
Treatment（tDCS + 2,193 99.536 0.000 0.508 thus adjusting attention allocation ability in early perceptual processing
AE＞AE＞tDCS） and making people more relaxed during inhibitory control tasks. At the
same time, we found that tDCS was better at congruent tasks than
Change in N200 Task × Treatment 2,148 17.229 0.000 0.189 moderate-intensity AE. Interestingly, we found that tDCS combined with
amplitude Task(incongruent > 1,148 63.355 0.000 0.300 AE might play a synergistic role in the congruent task and incongruent
congruent) task state, leading to a more significant decrease in the amplitude of
Treatment（tDCS + 2,148 190.924 0.000 0.721
P200, which may also be related to the mutual regulation of tDCS and
AE＞AE＞tDCS）
AE on the brain reticular activation level, and the combination of the
two may have an effect similar to superposition. Previous studies on the
Change in N450 Task × Treatment 2,373 130.815 0.000 0.412
effects of tDCS or AE on cognitive control have mainly focused on N200
amplitude Task(incongruent > 1,373 5.265 0.022 0.014
congruent) components (Dubreuil-Vall et al., 2019). However, this study found that
Treatment（tDCS + 2,373 488.578 0.000 0.724 AE also had an impact on the early components of EEG, which was
AE＞AE＞tDCS） somewhat innovative. At the same time, our study also found that the
P200 amplitude of tDCS group deepened more significantly in the
congruent task state than in the AE group, while the opposite was true in
amplitude difference of P200 decreased to a certain extent under
the incongruent task state, but there was no significant behavioral dif­
congruent and incongruent tasks, and the tDCS + AE group > tDCS
ference between the two groups. Dubreuil-Vall et al. found that after a
group > AE group under congruent conditions, while the tDCS + AE
single 2.0 mA anodal-tDCS over L-DLPFC stimulation in healthy people,
group > AE group > tDCS group under incongruent conditions. Studies
the response time of Flanker Task was significantly shortened, and the
have found that L-DLPFC anode tDCS stimulation has a good effect on
amplitude of P200 was significantly decreased (Dubreuil-Vall et al.,
improving the sleep status of patients with poststroke insomnia (PSI)
2019). Wen and Tsai (2020) found that the Accuracy, Reaction time and
and depression. Considering that it could inhibit the overexcited cortex
Amplitude of P2 of Stroop task in healthy people did not change
and reduce the excitability of the reticular activation level (Novak et al.,
significantly after a single moderate-intensity AE (Wang et al., 2017).
2020); it was closely related to the decline in the amplitude of P200.
Due to the limitation of the literature on inhibition of P200 components
Exercise can induce arousal to make the nervous system respond to

Fig. 4. The interaction effect of the change in P200, N200, and N450 amplitudes between tasks (congruent vs. incongruent) × treatments (tDCS + AE vs. tDCS vs
AE). ****p < 0.0001, 0.0001<***p < 0.001, 0.001 < **p < 0.01, 0.01 <*p < 0.05.

9
Y. Ji et al.
Fig. 5. Grand-averaged ERP waveforms as a function of treatments and Stroop tasks.
in the control task, the findings of this study are considered to be related
to the regulation of cortical excitability and reticular activation level
after the intervention of 4-week tDCS and AE, but the significant dif­
ferences between the two treatments under congruent and incongruent
tasks require further exploration and research.
The prefrontal N200 component is mainly derived from the anterior
cingulate cortex and the right inferior frontal lobe; however, fMRI
studies have shown that anterior N200 may be influenced by activity in
several different frontal brain regions (Chatzichristos et al., 2020). N200
appears approximately 250–350 ms after stimulus presentation,
reflecting the process of conflict detection and the process of conflict
response (Liu et al., 2019). After intervention, the amplitude of N200
was significantly enhanced in all groups, and the amplitude enhance­
ment was the tDCS + AE group > tDCS group > AE group under
congruent conditions and the tDCS + AE group > AE group > tDCS
group under incongruent conditions. Anode tDCS intervention of the L-
DLPFC can improve interference control of sad and neutral faces in the
Stroop task of major depressive disorder (MDD) and improve interfer­
ence control of sad and neutral faces in the emotional Stroop task, as
shown by faster reaction times (Bennabi & Haffen, 2018). For obesity,
anodal tDCS to the L-DLPFC improved performance on a food-related
inhibitory control task, providing evidence of the potential therapeutic
benefit of neuromodulation in areas controlling executive function. In
another study, after 4 weeks of anodal HD-tDCS stimulation of the L-
DLPFC in healthy young adults, HD-tDCS provided a positive benefit on
executive control and psychomotor efficiency and had an obvious cu­
mulative effect after 9 or more interventions compared to sham HD-
tDCS (He et al., 2021). While the above studies are congruent with
this study in terms of behavior, this study found that the relevant
mechanism may improve the inhibitory control ability of the L-DLPFC
cortex by stimulating it to induce a stronger N200 amplitude. For AE,
some researchers found that moderate intensity AE significantly
10
Brain and Cognition 173 (2023) 106090
improved the inhibitory ability of healthy young people, which was
mainly reflected in the increase in N200 amplitude induced by incon­
gruent tasks in the Flanker task (Ligeza et al., 2018). It was also found
that compared with novice athletes, expert athletes who have conducted
AE for a long time are more active in N200 components in inhibitory
control tasks, have better performance in attention mobility and inhib­
itory control ability and are less likely to make mistakes in competitions
due to inattention and other problems (Javier, 2016); which is consis­
tent with the results of this study. After the combination of tDCS and AE,
the improvement in behavior and both before and after the intervention,
N200 amplitude was more significant than that in the tDCS and AE
groups in both congruent and incongruent conditions. At the same time,
the response time of congruent and incongruent conditions in the tDCS
+ AE group was significantly shorter after intervention than before
intervention, and there was a significant difference between the two
groups. This might be related to the synergistic effect of tDCS combined
with AE, which could better activate the medial frontal lobe and frontal
lobe-related brain regions. It might exert the effect of 1 + 1 > 2, so that
the subjects have stronger inhibitory control ability and are less sus­
ceptible to the interference of word color inconsistency. Interestingly,
our study also found that the N200 amplitude of tDCS group deepened
more significantly in the congruent task state than in the AE group,
while the opposite was true in the incongruent task state, but there was
no significant behavioral difference between the two groups. Wang et al.
(2017) found that patients with Metham-phetamine dependency expe­
rienced moderate-intensity AE for 30 min × 3 /week in 12 weeks, the
accuracy of patients in Standard Go-/No-go task and Methamphetamine-
related Go-/No-go task (visual) was significantly improved, and the
induced N200 amplitude was significantly deepened, particularly in the
anterior cortex (Wang et al., 2017; Dongshi et al., 2020).Unexpectedly,
no signifificant effects of AE on theta 2 were observed in the post-test
neutral cue condition. Similar trends were also exhibited in the N2d
Y. Ji et al. Brain and Cognition 173 (2023) 106090

Fig. 6. Grand-averaged ERP waveforms as a function of treatments and Stroop tasks.

Fig. 7. Topographic scalp distributions of the P200, N200 and N450 components.

amplitude in the post-test (Dongshi et al., 2020), this is similar to the
results of this experiment, after 4 weeks of moderate-intensity AE, the
N200 amplitude induced by the incongruent task under the Stroop task
is deeper than the congruent task. Dubreuil-Vall (2019) found 2.0Am
anode L-DLPFC single stimulation of Attention-deficit/hyperactivity
disorder (ADHD) patients, although it can significantly improve the
accuracy and response time of Flanker Task, but there is no significant
difference in the amplitude of N200 before and after intervention,
regardless of whether it is congruent or incongruent. Although this
experiment found that after 4 weeks of 2.0Am anode L-DLPFC stimu­
lation, the response time of Stroop task was significantly shortened, and
the N200 amplitude induced by congruent and incongruent tasks was
deepened, compared with 4 weeks of moderate intensity AE, possiblely
due to the limited stimulation range of tDCS, the ability to improve brain
plasticity is slightly worse than AE, which activates the frontal parietal
network more broadly and activates the prefrontal cortex nerves asso­
ciated with inhibitory control tasks.
The main neurogenetic source of the N450 component is the anterior
cingulate gyrus and anterior frontal cortex (Chang et al., 2017); which is
an extension of the N200 component that appears approximately 350 to
600 ms after the stimulus is presented (Kamil et al., 2017). It reflects not
only the detection and response of stimulus tasks but also the resolution
and processing of inhibitory control tasks. In this study, it was found that
after intervention, N450 amplitude changes were not the same in all
groups. Under congruent conditions, the tDCS + AE group and AE group
showed a deepening trend (tDCS + AE > AE), while the amplitude of the
tDCS group decreased. In the incongruent conditions, tDCS + AE group
> AE group > tDCS group. Studies have used the Stroop Word Color test

11
Y. Ji et al.
to look at changes in the N450 composition, and in the midfront part of
the brain, incongruent tasks elicit greater N450 amplitude than
congruent tasks (Huang & Chen, 2020); therefore, the deepening of
N450 amplitude at the Fz point indicates better response and solving
ability to the suppression control task. The anodal tDCS intervention of
L-DLPFC did not cause changes in N450 during congruent tasks and may
even make it difficult to solve and handle inhibitory control tasks, while
the improvement of tDCS on incongruent tasks was not obvious.
Although the AE group and the tDCS + AE group could activate the
N450 amplitude in the congruent task, the AE group still did not perform
better than the tDCS + AE group in the incongruent task. Therefore,
based on this study, it might be speculated that, compared with the tDCS
group and AE group, tDCS + AE group could increase the amplitude of
N450 more significantly in the Fz points of the middle and anterior re­
gions of the brain, considering that it is related to better activation of the
anterior cingulate gyrus and prefrontal cortex, so that subjects can better
detect, solve and process stimulus tasks. This might be related to L-
DLPFC activation of tDCS and widespread prefrontal activation caused
by moderate AE. As there are few studies on the effects of tDCS and AE
intervention on N450, there are fewer relevant EEG studies on the
combination of central and peripheral regulation, which both have the
potential to initiate and regulate human neural plasticity. This is also
one of the interesting findings of this study.
5. Limitation
This study aimed to observe the enhancement of inhibitory control
function through the concurrent application of tDCS (2.0 mA L-DLPFC
anodic stimulation), a central nervous system modulation technique,
and AE, a peripheral modulation technique. At the same time, observe
whether the combination of these two methods can produce the effect of
1 + 1 > 2. Additionally, we expect to gain a more complete under­
standing of the role of tDCS and AE in inhibitory control function and the
potential benefits that their combination may confer. Indeed, the lack of
a blank control group is one of the limitations of this experiment. In
future studies, we will continue to improve this research. Future
research should investigate different treatment sequences, stimulus in­
tensities, exercise intensities, larger sample sizes, and long-term follow-
up evaluations to further explore the effectiveness and optimal combi­
nation of tDCS and AE interventions. Additionally, further studies could
examine the effects of these interventions in different populations, such
as older adults or individuals with cognitive impairments, to better
understand their therapeutic potential in various contexts. This study
primarily targeted healthy young individuals, a population character­
ized by superior cortical plasticity. It did not extensively explore groups
with diminished cortical plasticity, such as the elderly, patients with
mild cognitive impairment (MCI), or those afflicted with Alzheimer’s
disease (AD), which constitutes one of the limitations of our investiga­
tion. Further, we employed ERP to scrutinize treatment-related neuro­
electrophysiological changes, yet we omitted an examination of the
correlations between brain regions and the alterations in brain func­
tional networks. This is an area that our study did not cover, marking
another limitation. Additionally, our research was narrowly focused on
inhibitory control function, neglecting the other two sub-components of
executive function: working memory and cognitive flexibility. This
limited scope is an additional constraint of our study. In future research,
a more comprehensive investigation encompassing these overlooked
aspects would be advantageous to provide a holistic understanding of
these complex cognitive functions.
6. Conclusion and perspectives
In conclusion, this study provides evidence that combining anodal
tDCS stimulation of the L-DLPFC with moderate-intensity AE can
enhance inhibitory control ability in healthy young adults more effec­
tively than either method alone. The underlying mechanisms may
12
Brain and Cognition 173 (2023) 106090
involve the mutual regulation of brain network activation levels, acti­
vating the medial and lateral prefrontal cortex and enhancing their
plasticity to improve conflict inhibition ability. The improvements in
inhibitory control function were reflected in the changes in the P200,
N200, and N450 components of EEG, suggesting that the combined
intervention influences early perceptual processing, conflict detection,
and response processing.
At present, our research utilizes the central regulation of tDCS
combined with peripheral regulation of AE to provide a “1 + 1 > 2″
rehabilitation treatment method for enhancing inhibitory control func­
tion. Due to the simplicity, safety, and convenience of tDCS and AE in
clinical use, the combined use of these two methods is not only better
than using either method alone, but also shortens the rehabilitation
treatment time, making it more suitable for patients with MCI, AD, PD,
poststroke cognitive impairment (PSCI), and other disorders related to
inhibitory control dysfunction to undergo rehabilitation treatment.
Moreover, because inhibitory control dysfunction can make it difficult
for these patients to respond correctly when faced with sudden risks.
Through the Stroop task and ERP, it has been found that the combined
effect may to a certain extent enhance or improve the subjects’ inhibi­
tory control abilities. It can speed up the processing speed when subjects
encounter obstacles and help patients with cognitive impairments in
daily activities identify dangerous stimuli more quickly and respond by
shortening reaction times, transitioning tasks faster, and making pro­
active decisions.
Ethics approval and consent to participate
This study was approved by the Ethics Committee of Wuxi Mental
Health Centre, with grant number WXMHCIRB2021LLKY145.
Consent for publication
The patient understood the report and signed informed consent.
Funding
The work is supported by the National Key R&D Program of China
(Grant No.:2018YFC 2001600, 2018YFC 2001603), Wuxi Municipal
Science and Technology Bureau (Y20222014 and Y20221040), Wuxi
Municipal Health Commission (No. Q202101, Q202167, M202211,
Q202247 and ZH202110), and Wuxi Taihu Talent Project
(WXTTP2021).
Declaration of Competing Interest
The authors declare that they have no known competing financial
interests or personal relationships that could have appeared to influence
the work reported in this paper.
Data availability
Data will be made available on request.
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