TYPE Clinical Trial

PUBLISHED 18 January 2023

DOI 10.3389/fneur.2022.1053642

The effects of acupuncture on

OPEN ACCESS clinical efficacy and steady-state
visual evoked potentials in
EDITED BY
Xi-jian Dai,
Second Affiliated Hospital of
Nanchang University, China
REVIEWED BY
insomnia patients with
Chuanhai Cao,
University of South Florida,
United States
emotional disorders: A
Mailan Liu,
Hunan University of Chinese
Medicine, China
randomized single-blind
*CORRESPONDENCE
Youping Hu
sham-controlled trial
hypcdutcm@yeah.net
Ning Li
zhenjiuhuaxi@163.com Leixiao Zhang1 , Yanli Deng2 , Ruting Hui3 , Yu Tang4 , Siyi Yu5 ,
SPECIALTY SECTION Ying Li5 , Youping Hu5* and Ning Li1*
This article was submitted to
1
Sleep Disorders, Department of Integrated Traditional and Western Medicine, West China Hospital, Sichuan
a section of the journal University, Chengdu, China, 2 Sichuan Second Chinese Medicine Hospital, Chengdu, China,
3
Frontiers in Neurology Chengdu First People’s Hospital, Chengdu, China, 4 Chongqing Emergency Medical Center,
Chongqing, China, 5 Acupuncture and Tuina School, Chengdu University of Traditional Chinese
RECEIVED 26 September 2022 Medicine, Chengdu, China
ACCEPTED 13 December 2022
PUBLISHED 18 January 2023

CITATION
Zhang L, Deng Y, Hui R, Tang Y, Yu S,
The aim of this study was to observe the clinical effects and brain electrical
Li Y, Hu Y and Li N (2023) The effects potential changes following acupuncture in the treatment of insomnia patients
of acupuncture on clinical efficacy and with mood disorders. Ninety patients with insomnia who met the inclusion
steady-state visual evoked potentials
in insomnia patients with emotional criteria were randomly divided into the active acupuncture group (AA group,
disorders: A randomized single-blind n = 44) and sham acupuncture group (SA group, n = 46) at a ratio of 1:1.
sham-controlled trial.
The primary outcome was the total score of the Pittsburgh Sleep Quality Index
Front. Neurol. 13:1053642.
doi: 10.3389/fneur.2022.1053642 (PSQI), and the secondary outcomes were the total effective rate, Self-Rating
COPYRIGHT
Anxiety Scale (SAS), Self-Rating Depression Scale (SDS) scores, and values
© 2023 Zhang, Deng, Hui, Tang, Yu, Li, of steady-state visual evoked potentials (SSVEP). The two groups received
Hu and Li. This is an open-access
acupuncture or sham acupuncture 10 times (2 weeks). Finally, the total PSQI
article distributed under the terms of
the Creative Commons Attribution scores of the AA group and SA group were significantly different (p < 0.05) at
License (CC BY). The use, distribution 2 weeks (6.11 ± 2.33 vs. 10.37 ± 4.73), 6 weeks (6.27 ± 1.39 vs. 11.93 ± 3.07),
or reproduction in other forums is
permitted, provided the original 18 weeks (6.32 ± 2.84 vs. 11.78 ± 2.95) and 42 weeks (8.05 ± 3.14 vs. 12.54
author(s) and the copyright owner(s) ± 2.81). Further analysis found that AA group patients received acupuncture
are credited and that the original
treatment at any age after the same effect (p > 0.05). The SAS and SDS scores
publication in this journal is cited, in
accordance with accepted academic of the AA group were also significantly different from those of the SA group at
practice. No use, distribution or each assessment time point (p < 0.05). The total effective rate of the AA group
reproduction is permitted which does
not comply with these terms.
was 81.82%, while that of the SA group was 30.43% (p < 0.05). There was no
significant difference between the AA group and SA group only in the brain
potential of the parietal lobe (F4), left temporal lobe (C3) and right temporal
lobe (T8) (P > 0.05), but there was a significant difference between other brain
regions (P < 0.05). In addition, correlation analysis showed that there was a
certain positive correlation between the total PSQI score, SAS score, efficacy
level, and SSVEP value in the AA group as follows: C4 and the total PSQI score (r
= 0.595, P = 0.041), F3 and SAS score (r = 0.604, P = 0.037), FPz and efficiency

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Zhang et al. 10.3389/fneur.2022.1053642

level of the frontal lobe (r = 0.581, P = 0.048), and O2 and efficiency level of
the occipital lobe (r = 0.704, P = 0.011). Therefore, acupuncture have a good
clinical effect on patients with insomnia and emotional disorders and have a
significant regulatory effect on abnormally excited brain potentials.

KEYWORDS

acupuncture, sham acupuncture, insomnia, anxiety, depression, SSVEP,

electroencephalogram

1. Introduction (BCI) technology provides a new cognitive channel for human

beings by encoding and decoding brain activity. SSVEP-based
Insomnia is a painful and disabling condition that BCI stands out from other BCI paradigms because of its
affects a large proportion of the general population. It is advantages of being noninvasive, requiring little user training,
a risk factor for impaired functioning and other medical and yielding a high information transfer rate (13). SSVEP are
and mental disorders (1). Approximately 10–20% of the widely used in electroencephalogram (EEG) responses elicited
world’s population suffers from insomnia, and there has by periodic visual stimuli. It has also been widely used to record
been an increased incidence of insomnia worldwide (2). mood changes (14) as a research tool in social and emotional
The prevalence of insomnia among Chinese adults reaches neuroscience (15).
up to 19.6% (2). Moreover, insomnia is 1.5 times more Much remains to be known about the key mechanisms
common in women than in men (3). Long-term chronic regulating the cerebral cortex. Therefore, to determine whether
insomnia can cause major health problems and other chronic acupuncture is an effective treatment option for patients
diseases, such as diabetes (4), obesity (5), and mood disorders with insomnia, a technique is needed to track the transient
(6). Insomnia may be a symptom of other diseases (e.g., electrophysiological effects of acupuncture and to record the
stroke) and often coexists with mental and physical health cortex’s response to electrophysiological changes. Based on
conditions (7). the above discussion, we observed the clinical efficacy and
Insomnia is a cross-diagnostic symptom associated with the brain electrical potential changes of patients with insomnia and
development of mental disorders and is most closely related emotional disorders treated with acupuncture for the first time,
to depression (8). While developing sleep disorders, depression taking the brain potential based on the SSVEP as an indicator
also has a positive influence on mood adjustment (9). The and combining it with the clinical scale.
economic and treatment costs for insomnia are also high,
totaling more than 100 billion US dollars each year. The
indirect costs of productivity losses caused by insomnia include
2. Research methods
lower work performance, increased healthcare utilization, and 2.1. Ethics and design
increased accident risks (10). Psychological treatment methods
such as cognitive behavioral therapy for insomnia (CBT-I) are The design and reporting of our controlled trials conformed
internationally recommended treatment options for insomnia. to the following principles: The Uniform Standards for
Further evidence from meta-analysis results has shown that Reporting Trials (CONSORT) and the Standards for Reporting
compared with fake acupuncture/placebo acupuncture or the Interventions in Acupuncture Clinical Trials (STRICTA)
effects of waiting for treatment, acupuncture can increase total Guidelines (16, 17). After obtaining ethical approval from the
sleep time, improve sleep efficiency, reduce wakefulness after Sichuan Traditional Chinese Medicine (TCM) Regional Ethical
falling asleep, and reduce the number of awakenings. (11). Review Committee (No. 2013KL-016), we started to recruit
In addition, the results from our previous research have also patients for the study. Due to the maintenance of the Chinese
confirmed that acupuncture can significantly improve the sleep clinical trial registration website, this study was reregistered
quality of patients with insomnia affected by mood disorders and on October 18, 2018 (ChiCTR1800018958). All patients or
that the posttreatment effect can last for more than 6 weeks (12). authorized guardians signed written informed consent forms.
However, these issues remain unexplored in the literature.
Previous studies have shown that the efficacy evaluation of
acupuncture for insomnia is still mainly based on the scale, 2.2. Participants
but there have been few studies using steady-state visual
evoked potential (SSVEP) as an objective indicator to evaluate The insomnia patients in this study were recruited through
the improvement of sleep quality. Brain computer interface outpatient advertisements and recommendations. All patients

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TABLE 1 Description of each acupoint and acupuncture method.

No. Acupoint Description of acupoints Needling method Needles

1 Anmian (EX-HN22) The midpoint between the depression behind the The needle is punctured 0.5–0.8 cun 0.25∗ 25 mm
ear and the suboccipital depression. vertically

2 Neiguan (PC6) Between the tendons of palmaris longus and flexor The needle is punctured 0.5–0.8 cun 0.25∗ 25 mm
carpi radialis, 2 cun above the transverse crease of vertically
the wrist.

3 Shenmen (HT7) On the palmar ulnar end of the transverse crease The needle is punctured 0.3–0.5 cun 0.25∗ 25 mm
of the wrist, and on the radial aspect of the tendon vertically
of the ulnar flexor of the wrist.

4 Hegu (LI4) Between the 1st and 2nd metacarpal bones, and in The needle is punctured 0.5–0.8 cun 0.25∗ 25 mm
the midpoint of the radial side of the 2nd vertically
metacarpal bone.

5 Zusanli (ST36) 3 cun directly below lateral depression of the The needle is punctured 1.0–1.3 cun 0.25∗ 40 mm
patella ligament, and one finger-breadth lateral to vertically
the anterior border of the tibia.

6 Zhaohai (KI6) In the depression directly below the tip of the The needle is punctured 0.2–0.5 cun 0.25∗ 25 mm
medial malleolus. vertically

7 Shenmai (BL62) In the depression directly below the tip of the The needle is punctured 0.2–0.5 cun 0.25∗ 25 mm
lateral malleolus. vertically

8 Taichong (LR3) In the depression anterior to the junction of 1st The needle is punctured 0.3–0.5 cun 0.25∗ 25 mm
and 2nd metatarsal bones. vertically

received free treatment in the Acupuncture Department of sample size was 40 in each group. Considering a drop-out rate
Sichuan Provincial Hospital of Traditional Chinese Medicine in of 10%, the total sample size required was 44 for each group in
China between May of 2014 and August of 2016. The diagnostic this study.
criteria for patients with insomnia are based on the “Diagnostic
and Statistical Manual 5 criteria” (18).
Inclusion criteria were as follows: patients who met the 2.4. Randomization and blinding
diagnostic criteria for insomnia (male or female 18–65 years
old); patients in whom insomnia symptoms occurred at least 3 The random number table was generated using SPSS
times a week and lasted for more than 1 month; and patients 22.0 R software. The random Arabic numeral 0 represents
with insomnia who had not taken any anti-insomnia drugs the active acupuncture (AA) group, and 1 represents the
before. There were notable symptoms of anxiety and depression sham acupuncture (SA) group. The random distribution cards
or withdrawal anxiety in patients for more than 7 days (PSQI containing random numbers, serial numbers, and groups
score >7, SAS score ≥50, SDS score ≥50). Informed consent was and were put in opaque, serial-numbered, leather envelopes.
obtained from the patients. Insomnia patients then unsealed the envelopes after meeting
Exclusion criteria were as follows: patients who had systemic the inclusion criteria according to the order of visit. The
diseases such as psychosomatic disorder, fever, cough or included patients were randomly divided into the AA and
serious diseases involving vital organs and the haematopoietic SA groups at a ratio of 1:1. This random assignment is
system; patients who were alcohol- and drug-dependent or single-blind, and the patients do not know which group
were pregnant or lactating; and patients who participated in they are in. Due to the particularity of the acupuncture
other studies. therapy, acupuncture treatment allocation was concealed from
everyone (e.g., evaluators and data processing statisticians)
except the acupuncturist.
2.3. Sample size calculation

Previous studies (19) have found a difference of at least 2.7 2.5. Intervention protocols
points in PSQI scores between active acupuncture treatment
and sham acupuncture treatment. We expected a 3.2 point The acupuncture treatments in this study were all completed
difference in active vs. sham acupuncture treatment in this study. by the same acupuncturist, who had a master’s degree and
Therefore, at the significance level of 0.05, the difference in at least 5 years of clinical experience. The acupuncturist
detection ability between the two groups was 95%, and the chose the same acupuncture points in the patients from

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FIGURE 1
Location of acupoints.

(the PSD) to match real needles and blunt needles in both

groups (the PSD approval number: 9018390000, DONGBANG
Acupuncture Inc.) (Figure 2). The 8 acupoints we selected were
artificially stimulated every 15 min, and the duration of each
acupoint was 5 s. Patients are treated once a day for 30 min.
The treatment was continued for five consecutive days, followed
by 2 days of rest. Both the AA group and the SA group
received 10 acupuncture (2 weeks) treatments. The follow-up
period was half a year, with assessments completed at 6, 18, and
42 weeks.
FIGURE 2 Patients were not allowed to take any sleep medications
The active or sham acupuncture intervention (PSD, real an d
blunt needles).
during the entire study period. However, patients who could not
tolerate sleep disorders in special circumstances were allowed
to take estazolam tablets as a rescue medication (0.5–2 mg,
both the AA group and the SA group (Table 1, Figure 1). approval number: H37023047, Shandong Xinyi Pharmaceutical
These acupuncture points included bilateral Anmian (EX- Co., Ltd.) before going to bed. After their condition was
HN22), Neiguan (PC6), Shenmen (HT7), Hegu (LI4), Zusanli relieved, the patients were asked to stop taking the medication
(ST36), Zhaohai (KI6), Shenmai (BL62) and Taichong (LR3). immediately. Their medications were recorded in a notebook.
The acupuncturist used the Park Sham Acupuncture Device The trial flow diagram is shown in Figure 3.

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2.5.1. Active acupuncture group the needle through the skin at acupuncture points while
We allowed patients to lie quietly in bed during acupuncture sticking the PSD to the skin at the same time. The angle
treatment. After the acupuncturist disinfected their hands and and depth of needle insertion into each acupoint are shown
the patients’ acupoint skin with 75% alcohol, the Xin Xinglin in Table 1. During the entire 30 min needle retention period,
disposable needle (0.30 × 25 mm/0.30 × 40 mm) was used, the acupuncturist rotated or lifted the needle every 10 min
together with the PSD (12). The acupuncturist exposed the to achieve the “deqi” sensation (pain, heaviness, numbness,
needle tip and used a suitable insertion method to penetrate swelling or radiation).

FIGURE 3
Trial flow diagram (The Screening, Enrolment, Randomization, Interventions, Follow-up, and Analysis). ITT indicates intention to treat.

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FIGURE 4
Equipment and data acquisition of SSVEP.

TABLE 2 Baseline characteristics.

Variables Active acupuncture Sham acupuncture (n = χ ² or ta Pa

(n = 44) 46)
Age, mean, y 38.09 ± 13.33 39.41 ± 13.93 −0.460 0.647

Female 28(63.64%) 30(65.22%) 0.03 0.876

Total score of PSQI 13.45 ± 1.76 13.17 ± 1.91 0.724 0.471

SAS score 59.66 ± 6.59 61.24 ± 6.99 −1.102 0.273

SDS score 60.00 ± 4.53 61.59 ± 6.12 −1.393 0.167

Data are presented as the mean ± SD or number (%).
PSQI, Pittsburgh Sleep Quality Index; SAS, Zung Self-Rating Anxiety Scale; SDS, Zung Self-Rating Deprssion Scale.
a Comparison between active acupuncture and sham acupuncture by χ² or unpaired t-test.

2.5.2. Sham acupuncture group 2.6. Primary outcomes

The acupuncturist used the PSD combined with a blunt
needle (0.30 × 25 mm/0.30 × 40 mm) in treating the patients We completed PSQI assessments at baseline, after treatment
in the SA group. Blunt needle is composed of a hollow needle (week 2), and during follow-up (weeks 6, 18, and 42). Each
shaft that can be stretched and a blunt needle head (20). The observation index is scored from 0 to 3 points, and the total score
acupuncturist completed the same disinfection process as used ranges from 0 to 21 points. The higher the score, the worse the
in the AA group and then tapped the blunt needle of the sleep quality (22).
PSD gently against the surface of the skin at the acupuncture
points. The blunt needle was not manipulated to minimize any
physiological effects. In the SA group, unless the patients did 2.7. Secondary outcomes
not experience “deqi”, the operations were the same as those
conducted in the AA group, including acupoint selection, needle According to the “Guiding Principles of Clinical Research
placement times, and needle withdrawal methods (21). on the Treatment of Insomnia with New Traditional Chinese

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TABLE 3 Primary outcomes.

Variables Active acupuncture Sham acupuncture (n = ta Pa

(n = 44) 46)
Total score of PSQI
Week 2 6.11 ± 2.33 10.37 ± 4.73 −5.370 0.000⋆

Week 6 6.27 ± 1.39 11.93 ± 3.07 −11.203 0.000⋆

Week 18 6.32 ± 2.84 11.78 ± 2.95 −8.940 0.000⋆

Week 42 8.05 ± 3.14 12.54 ± 2.81 −7.168 0.000⋆

Data are presented as the mean ± SD or number (%).
PSQI, Pittsburgh Sleep Quality Index.
a Comparison between active acupuncture and sham acupuncture by unpaired t-test.
⋆ There was statistical significance between the two groups.

Medicines”, the criteria for measuring the treatment efficacy

in insomnia are established as follows: (1) Clinically cured:
Sleep returns to normal, or normal night sleep lasts more than
6 h. There is an increase in deep sleep. Patients are full of
energy after wake-up. (2) Markedly effective: sleep is clearly
improved, sleep time increases by more than 3 h, and sleep
depth increases. (3) Effective: the symptoms are alleviated, and
the sleep time increases by <3 h compared with the previous
period. (4) Invalid: no obvious improvement or aggravation after
treatment. Total effective rate = [(number of clinically cured
cases+number of markedly effective cases+number of effective
cases)/total number of cases] × 100%. The acupuncturist
completed the assessment at the end of treatment (week 2). We FIGURE 5
Total PSQI scores were compared between the two groups.
assessed the patient’s emotional and psychological changes by
the total score of SAS and SDS. If a total score of ≥50 indicates
anxiety or depression, the higher the score, the more severe the
symptoms (23). The acupuncturist completed the assessment The acupuncturist put the flash stimulator ∼30 cm in front
before treatment, at the end of treatment (week 2) and during of the patient’s eyes and instructed the patient to look at
follow-up (weeks 6, 18, and 42). the screen with both eyes. The acupuncturist then started to
The data collected from SSVEP were used to obtain the stimulate vision for 30 s with a frequency between 1 and 16 Hz.
potential value through Fourier coefficients (24) (Figure 4). After a rest period of 2 s, the next frequency stimulation was
Equipment: HP Compaq Presario V3212 computer, UEA-16FZ started. The measurement was finished after 16 consecutive
EEG amplifier (Beijing Zhongke Xintuo Instrument Co., Ltd.), times. The low potential presents a blue image, which represents
16-channel Lycra electrode cap, EEG conductive paste (Jining EEG inhibition; the high potential presents a red image,
High-tech Zone Jinnot Medical Gel Factory, batch number: which represents EEG excitement. Potential difference = after
2013040), dedicated 5 ml conductive paste syringe, 3 M anti- treatment − before treatment. The acupuncturist completed
noise earplugs. The steps followed by the acupuncturist for the assessment before treatment and at the end of treatment
SSVEP data collection are as follows: (i) The acupuncturist (week 2).
asked the patient to sit down and let the patients wear earplugs.
Measures were taken to avoid obvious yhead movement of
the patients and inability to test questions. The door and 2.8. Statistical analysis
windows were closed, and the lights were turned off. (ii) The
acupuncturist disinfected the patients’ skin of the head, and The baseline characteristics and clinical results of this study
electrode pads were installed. (iii) Placement region for the brain were based on intention to treat (ITT) analysis. The included
on the patient’s head were in accordance with international patients received at least 1 treatment and 1 primary outcome
standards using electric collection point (2 reference electrodes, measurement. The measurement data was tested for normality
16 recording electrodes). (iv) The acupuncturist injected the first, the unpaired t-test or one-way ANOVA test was then
electrode paste and then started the scalp resistance test. (v) used for normal distribution and homogeneity of variance,

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TABLE 4 Difference of curative effect in different age segments of active acupuncture group.

Variables Age, y Fa Pa
18-40 (n = 25) 41-55 (n = 13) 56-65 (n = 6)
Total score of PSQI
Week 0 13.24 ± 1.88 13.92 ± 1.66 13.33 ± 1.51 0.651 0.527

Week 2 5.92 ± 2.22 6.31 ± 2.56 6.50 ± 2.66 0.205 0.815

Week 6 6.20 ± 1.32 6.38 ± 1.45 6.33 ± 1.75 0.079 0.924

Week 18 6.00 ± 2.47 6.92 ± 3.86 6.33 ± 1.75 0.439 0.648

Week 42 7.40 ± 2.75 8.15 ± 2.34 10.50 ± 5.09 2.539 0.091

Data are presented as the mean ± SD or number (%).
PSQI, Pittsburgh Sleep Quality Index.
a Comparison between different age segments by unpaired one-way ANOVA.

TABLE 5 Secondary outcomes (1).

Variables AA group (n = 44) SA group (n = 46) χ ² or tb Pb

SAS score
Week 2 39.59 ± 5.94 59.74 ± 6.15 −15.797 0.000⋆

Week 6 40.34 ± 5.18 63.63 ± 6.78 −18.256 0.000⋆

Week 18 41.05 ± 5.57 59.07 ± 5.94 −14.828 0.000⋆

Week 42 44.55 ± 8.09 63.74 ± 6.67 −12.304 0.000⋆

SDS score
Week 2 43.14 ± 10.79 61.20 ± 4.40 −10.480 0.000⋆

Week 6 43.48 ± 7.28 62.78 ± 5.17 −14.557 0.000⋆

Week 18 44.09 ± 7.62 61.28 ± 4.49 −13.107 0.000⋆

Week 42 47.23 ± 10.70 63.46 ± 4.67 −9.392 0.000⋆

Efficacy level
Clinically cured 11 (25%) 2 (4.35%)

Markedly effective 19 (43.19%) 3 (6.52%)

Effective 6 (13.64%) 9 (19.57%)

Invalid 8 (18.19%) 32 (69.57%)

Total effective ratea 81.82% 30.43% −5.454 0.000⋆

Data are presented as the mean ± SD or number (%).
SAS, Zung Self-Rating Anxiety Scale; SDS, Zung Self-Rating Depression Scale; AA group, Active Acupuncture Group; SA group, Sham Acupuncture Group.
a Total effective rate (%) = [(number of patients clinically cured + markedly effective + effective)/number of patients] × 100%.
b Comparison between active acupuncture and sham acupuncture by χ² or unpaired t-test.
⋆ There was statistical significance between the two groups.

and the Wilcoxon Signed-Rank or Mann–Whitney U test was 2.9. Quality control
used for nonnormality testing. Enumeration data will be tested
using χ ² analysis. Categorical variables are shown as numbers This study was under the supervision of Chengdu University
and percentages. Using the last observation carried forwards of Traditional Chinese Medicine. Our SSVEP data were analyzed
method, the missing data of participants who had dropped and completed by experts from both the University of Electronic
out were replaced. Using Statistical analysis SPSS R version Science and Technology of the University of Life Science and
22.0, the difference was considered statistically significant at p Technology. In addition, a qualified expert in clinical trial
< 0.05. research supervised this study.

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FIGURE 6
SAS and SDS scores were compared between the two groups.

3.2. Primary outcomes

After 2 weeks of intervention, the total PSQI score was 6.11

± 2.33 in the AA group and 10.37 ± 4.73 in the SA group (t =
−5.370, p < 0.05). During the whole follow-up period, although
the total PSQI score of the AA group showed repeated increases
to varying degrees, the long-term efficacy of the AA group was
still better than that of the SA group (2 weeks: 6.27 ± 1.39 vs.
11.93 ± 3.07, t = –11.203, p < 0.05/18 weeks: 6.32 ± 2.84 vs.
11.78 ± 2.95, t = –8.940, p < 0.05/42 weeks: 8.05 ± 3.14 vs. 12.54
± 2.81, t = –7.168, p < 0.05) (Table 3, Figure 5). We statistically
analyzed 44 patients in the AA group according to the ages of
18–40, 41–55, and 56–65 years. It was found that the clinical
FIGURE 7
effect of acupuncture was improved at any age (all p > 0.05)
Efficacy level and total effective rate were compared between (Table 4).
the two groups.

3.3. Secondary outcomes

The SAS score in the AA group decreased to 39.59 ± 5.94

after 2 weeks of intervention, and it was 59.74 ± 6.15 in the SA
group (t = –15.797, p < 0.05). The SDS scores of the two groups
3. Results were 43.14 ± 10.79 and 61.20 ± 4.40, respectively (t = –10.480,
p < 0.05). The SAS and SDS scores of the two groups were
3.1. Baseline characteristics significantly different throughout the follow-up period (Table 5,
Figure 6). After 10 treatments, the total effective rate of the AA
A total of 162 patients were approached in this study, group was 81.82%, while that of the SA group was 30.43% (χ ²
and 72 participants met the exclusion criteria. A total of 90 = −5.454, p < 0.05). The most obvious difference was that the
patients met the inclusion criteria (44 in the AA group and 46 ratio of patients who were clinically cured or markedly improved
in the SA group). We found that the average age of patients in the AA group was significantly higher than that in the SA
with insomnia was 38.77 years and that 64.4% of the subjects group (11:2; 19:3) (p < 0.05). The remaining results are shown
were women. The total PSQI scores of the AA group and in Table 5, Figure 7.
the SA group in this study were 13.45 ± 1.76 and 13.17 ± After the treatment, the brain electrical potential changes in
1.91, respectively. There were no significant differences in the the frontal lobe, right temporal lobe, and occipital lobe in the
SAS and SDS scores between the other two groups (p > 0.05) patients from the AA group were significantly different (P <
(Table 2). 0.05). Although there was a downwards trend in brain potentials

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in the SA group, there was no significant difference (P > 0.05). After 2 weeks of acupuncture treatment, the curative effect will
When the two groups were compared, there was no difference in reach a more obvious level and reach the extreme value at 4
the parietal lobe (F4), left temporal lobe (C3), or right temporal weeks. Therefore, a total of 10 treatments were performed in 2
lobe (T8) between the AA group and the SA group (P > 0.05); weeks in this study. The advantage is that such accumulation
however, there were statistically significant differences in brain can not only result in therapeutic effects but also avoid the
electrical potential changes in other brain regions (P < 0.05). potential effects of excessive acupuncture and increase the
The difference in brain electrical potential changes in specific body’s tolerance.
SSVEP is shown in Table 6, Figures 8, 9. Acupoints are not only a special place where Qi and
In addition, our results also demonstrated a certain positive blood are infused in the meridian but also the reaction points
correlation between the total PSQI score, SAS score, efficacy of the disease and the stimulation points of acupuncture.
level, and SSVEP value in the AA group. This positive According to Chinese medicine theory, insomnia results from
correlation is reflected in the following results: C4 and the total the vicious cycle of fatigue during the day or from a mental
score of PSQI (r = 0.595, P = 0.041), F3 and SAS score (r = condition of extreme excitement at night. Therefore, this study
0.604, P = 0.037), FPz and the efficiency level of the frontal lobe selected Shenmen, Neiguan, Anmian, and other acupoints that
(r = 0.581, P = 0.048), and O2 and efficiency level of the occipital are commonly used for treating insomnia (29). The Anmian
lobe (r = 0.704, P = 0.011) (Figure 10). is the traditional acupoint used to treat insomnia. Shenmen
can calm the heart and spirit. Zusanli affects the spleen
and regulates the stomach. Taichong regulates the liver and
4. Discussion gallbladder. The Neiguan enlarges the chest and adjusts Qi
(30). These acupoints can be used together to calm and soothe
In our study, we found that, compared with sham the mind and achieve hypnotic induction. The combination
acupuncture, active acupuncture can significantly improve sleep of Hegu and Taichong can regulate the liver and Qi. Zhaohai
quality and the clinical cure rate of insomnia. This effect can and Shenmai are special meridians and collaterals in the
be maintained for a long time without being affected by age. treatment of insomnia and have the advantage of regulating
At the same time, acupuncture has a significant downregulation internal organs (31). In traditional Chinese medicine, “deqi”
effect on the SSVEP of abnormal brain excitement. This is believed to be the basis for effective results (32). Through
downregulation was positively correlated with clinical efficacy. acupuncture stimulation of certain acupoints that elicit “deqi”
Our study is one of the few that evaluated the observation of sensations, acupuncture can help restore the normal sleep-
acupuncture for insomnia with mood disorders by clinical scales wake cycle by correcting the imbalance of Yin and Yang
and SSVEP. toward harmony.
Acupuncture has long been used for the treatment of Our study found that acupuncture treatment does not affect
primary insomnia in China. Under current circumstances where the natural sleep-wake cycle. After 10 acupuncture treatments,
oral medication is unfavorable, patients with insomnia often the patient’s sleep quality and emotional state were significantly
choose acupuncture as an alternative therapy. Compared with improved. In our study, the total PSQI score decreased from
the use of drugs for the treatment of insomnia, acupuncture 13.45 ± 1.76 to 6.11 ± 2.33. This is still due to the real
treatment can contribute to significant improvement in the stimulation of the acupoints, so that the functions of the
symptoms of insomnia (25). Immediate and sustained effects acupoints can be brought into play. Fu Cong et al. confirmed that
are the two main manifestations of the curative effect of the PSQI score decreased by 8.03 points after 10 acupuncture
acupuncture. The onset of the effect of acupuncture on insomnia treatments (28). This is consistent with our research results.
is a process of transitioning from “quantitative change” to However, in the SA group, the blunt needle could not penetrate
“qualitative change”. The total treatment cycle and the time the skin, so the acupoints could not receive useful stimulation.
interval between acupuncture and the onset of symptoms are Therefore, the sleep quality of the SA group was still poor.
the two most significant factors influencing the sustained effect. Other test results show that acupuncture can increase the
According to the report, to maintain the continuity and stability content of serotonin and aminobutyric acid and reduce the
of the acupuncture effect, it is necessary to compound the level of glutamate (33). Therefore, acupuncture treatment can
number of acupuncture treatments to achieve the best effect improve central inhibitory function and thus help people fall
(26). Hachul and colleagues reported that there was a 3 point asleep (34). It has been reported that the correlation between
decline in the PSQI score after 10 sessions of acupuncture insomnia and anxiety is 62.2%, and the correlation between
treatment (27). Fu et al. divided 10 acupuncture treatments insomnia and depression is 59.7%. This shows that insomnia
into 2 weeks to improve the compliance of patients. After 10 and emotional disorders have a high degree of correlation (35).
treatments, the PSQI score of the acupuncture group decreased The frontal lobe is the thinking control center of the brain,
by 8.03 points from baseline, and the PSQI score of the sham which is closely related to the changes in cognitive functions
acupuncture group decreased by 1.29 points from baseline (28). of patients with depression, such as task execution, memory

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Zhang et al.
TABLE 6 Secondary outcomes (2).

Outcome measure Active acupuncture (n = 12) Sham acupuncture (n = 12)

Baseline, 0 End of zb Pb Baseline, 0 End of zb Pb zc Pc
week treatment, week treatment,
2 week 2 week
SSVEP values
Brain regions Collection
pointa

Frontal lobe Fp1 1837.48 ± 527.78 −1005.37 ± 534.92 −3.059 0.002⋆ 1777.95 ± 570.19 1480.37 ± 513.78 −1.274 0.213 −4.161 0.000⋆

Fpz 1678.89 ± 943.97 −1188.33 ± 503.67 −3.059 0.002⋆ 1364.02 ± 1053.03 1341.60 ± 1023.07 −0.079 0.937 −4.159 0.000⋆

Fp2 1804.94 ± 660.26 −1028.08 ± 614.92 −3.059 0.002 ⋆

1777.18 ± 820.98 1240.12 ± 598.48 −1.571 0.116 −4.164 0.000⋆

Parietal lobe F3 1591.05 ± 863.06 93.01 ± 910.75 −2.824 0.005⋆ 1164.15 ± 957.03 1553.78 ± 1307.15 −0.393 0.695 −3.004 0.003⋆

Cz 2763.39 ± 2554.71 1106.17 ± 504.41 −2.275 0.023⋆ 2076.01 ± 579.12 1756.16 ± 762.25 −1.256 0.209 −2.112 0.035⋆

F4 1773.88 ± 764.79 2523.65 ± 303.62 −2.353 0.019⋆ 1577.77 ± 860.06 1746.99 ± 1159.90 −0.236 0.814 −1.451 0.147

Po5 6303.71 ± 2553.20 231.15 ± 198.63 −3.061 0.002 ⋆

3988.84 ± 3251.68 3228.09 ± 2223.94 −0.392 0.695 −3.239 0.001⋆
11

Po6 5347.00 ± 3408.52 −1555.04 ± 229.01 −3.061 0.002⋆ 5266.82 ± 3862.88 3315.32 ± 1610.80 −1.412 0.158 −4.160 0.000⋆

Pz 5704.06 ± 2708.39 −387.94 ± 215.27 −3.062 0.002⋆ 3447.92 ± 3475.78 2874.76 ± 1941.17 −0.314 0.754 −4.161 0.000⋆

Left temporal C3 2559.53 ± 1941.23 1659.54 ± 603.56 −1.412 0.158 2590.58 ± 874.17 2249.87 ± 712.02 −1.178 0.239 −1.911 0.056
lobe

T7 2845.63 ± 1529.37 1835.62 ± 380.84 −1.963 0.050 2911.82 ± 1666.74 3840.75 ± 1816.45 −1.256 0.209 −2.693 0.007⋆

Right temporal C4 3309.66 ± 2050.11 −623.20 ± 1410.03 −3.059 0.002⋆ 2917.48 ± 1048.98 2634.10 ± 1185.69 −0.628 0.530 −4.100 0.000⋆
lobe

T8 4118.42 ± 1839.36 3140.23 ± 1351.55 −1.542 0.123 3406.89 ± 1228.21 3847.49 ± 1240.96 −0.785 0.433 −0.925 0.355

Occipital O1 7741.35 ± 1005.20 −3401.61 ± 1046.62 −3.059 0.002 ⋆

7255.62 ± 1777.63 6658.14 ± 2010.85 −0.549 0.583 −4.159 0.000⋆
lobe

Oz 8261.32 ± 5089.34 −2743.79 ± 1801.79 −3.059 0.002⋆ 8031.33 ± 3639.41 5694.58 ± 3843.58 −1.334 0.182 −4.160 0.000⋆

10.3389/fneur.2022.1053642
O2 7989.59 ± 5127.49 −2723.28 ± 1026.82 −3.059 0.002⋆ 7847.87 ± 3334.90 5689.32 ± 5254.53 −1.099 0.272 −4.159 0.000⋆
SSVEP, steady-state visual evoked potentials.
a The collection points of SSVEP are symbols, with no special significance.
b Comparison within-group between active acupuncture and sham acupuncture by Wilcoxon Signed-Rank test.
frontiersin.org

c Comparison between groups treated with active acupuncture and sham acupuncture by the Mann–Whitney U test.
⋆ The difference between the two groups or within-group was statistically significant.
Zhang et al. 10.3389/fneur.2022.1053642

FIGURE 8
Before and after treatment of the active acupuncture group (SSVEP).

FIGURE 9
Before and after treatment of the sham acupuncture group (SSVEP).

retrieval, information integration, and emotional regulation. depression. The change in the frontal lobe may be one of
Studies have shown that the frontal lobe, temporal lobe and the mechanisms of acupuncture treatment of depression (37).
the nerve circuits between them are significantly abnormal In our study, the SAS and SDS scores of the AA group
in patients with depression (36). It has been observed by decreased significantly. Regardless of treatment or follow-up, the
resting-state functional magnetic resonance imaging (fMRI) that improvement in emotional state in the AA group was better than
acupuncture at the Taichong point can inhibit the bilateral that in the SA group. This situation, we believe, is inseparable
frontal lobe and most of the temporal lobe in patients with from the relief of sleep disorders. Excitingly, the mood

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Zhang et al. 10.3389/fneur.2022.1053642

FIGURE 10
The correlation between sleep improvement and the change in SSVEP values (active acupuncture group).

disturbances of insomnia patients improved synchronously downregulated. Interestingly, this study also found a certain
and were consistent with the quality of sleep. This result positive correlation between the curative effect, SAS of the AA
has also been confirmed by animal experiments. Cheng group and the SSVEP value. When the brain potentials of the
Cisong et al. found that electroacupuncture at the Shenmen frontal, parietal, and occipital lobes were downregulated, sleep
and Sanyinjiao points can inhibit the overexcitation of the quality and mood disorders were effectively adjusted. Using
sympathetic adrenal medullary system in rats with insomnia, resting-state fMRI, studies have observed that acupuncture
thereby improving insomnia and alleviating anxiety and other may improve sleep quality by regulating the local consistency
emotional disorders (38). Previous studies have also confirmed of the prefrontal cortex and the parietal precuneus (41),
that acupuncture can improve the sleep efficiency of patients which is consistent with our results. Other modern studies
with insomnia, extend their sleep, and improve insomnia have also found that acupuncture can activate the thalamus,
severity (21). frontal lobe and other sleep central functions and can smooth
Our results demonstrated that the AA group had better emotions, relieve stress and improve sleep through different
improvement in SSVEP brain potential than the SA group, neural pathways (42, 43). Because the fibers from the thalamus
especially in the frontal and occipital lobes. The frontal lobe project to the hypothalamus, the prefrontal lobe of the cerebral
is in front of the anterior central sulcus, which accounts cortex, the orbital region or the posterior parietal lobe contact
for 40% of the cerebral cortex. It is the high-level executive area, this also confirms that acupuncture can play a strong
center for brain activity where mental activity occurs. It is inhibitory role on the SSVEP potential values of the frontal
inseparably correlated with the symptoms of insomnia and lobe and the occipital lobe brain region, thus effectively
anxiety. The occipital cortex is involved in visual processing. improving insomnia and emotional disorders. Acupuncture
Studies have found that increased gray matter volumes in this treatment can not only effectively improve the quality of sleep
cortex are associated with the levels of anxiety severity (39), and emotional state but also improve the quality of life for
which may be regulated through the frontoparietal connected the subjects.
networks (40). As the AA group effectively improved sleep Visual evoked potentials are widely used in frontier
quality, the abnormal excitation potential of the cerebral cortex fields such as brain-computer interfaces and are divided
was reduced; the response of the optic nerve in the occipital into instantaneous visual evoked potentials and steady-state
area was reduced when visual stimulation was received; and visual evoked potentials. When vision is stimulated by an
the abnormal brain potential of the frontal lobe was also external stimulus at a constant frequency, the brain produces

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Zhang et al. 10.3389/fneur.2022.1053642

a response at the same frequency as the external stimulus Data availability statement
frequency and its harmonics. The strength of this response
can be represented by the voltage signal measured on the The raw data supporting the conclusions of this article will
scalp, that is, SSVEP. Through cortical homeostasis probe be made available by the authors, without undue reservation.
morphology technology, studies have found that anxiety
is related to the frontal, temporal, and occipital cortical
areas (44). In addition, SSVEP are often used in research Ethics statement
on depression, autism and migraine headaches (45, 46).
Compared with polysomnography, SSVEP have a strong anti- The studies involving human participants were reviewed and
interference ability and can monitor the dynamic changes in approved by the Sichuan Traditional Chinese Medicine (TCM)
the cognitive process stimulated by external stimuli. Compared Regional Ethical Review Committee. The patients/participants
with fMRI, SSVEP do not have the problem of haemodynamic provided their written informed consent to participate in
delay and are more economical, but they do not have this study. Written informed consent was obtained from the
the role of accurately positioning functional brain activation individual(s) for the publication of any potentially identifiable
areas (47). images or data included in this article.
Using SSVEP, we made a new attempt to explore the effects
of the brain electrical potential changes following acupuncture
for the improvement of sleep quality. However, our study
Author contributions
has some limitations, such as a small sample size and a
Conceptualization: LZ and YD. Project administration: LZ,
lack of reference to polysomnography. Given the complexity
RH, and YT. Funding acquisition: YH and NL. Formal analysis:
of the disease and the diversification of research approaches,
SY and YL. Writing—original draft: LZ. All authors contributed
future research can explore the effective combination of
to the article and approved the submitted version.
SSVEP and fMRI technology to provide a more comprehensive
approach to visual analysis of acupuncture treatment for
insomnia (48). Funding
In addition, there has been an increase in RCTs of
acupuncture for the treatment of insomnia. However, due The study was partly supported by the Science and
to variations in methodological quality, previous studies Technology Bureau of Chengdu (Topological Characteristics
have yielded mixed results. Our study employed the PSD of Steady-State Visual Evoked Potentials Acupuncture
as the main research tool with real needles or blunt needles Improves Postinsomnia Emotional Disorder) [grant number
(49). During operations in which the blunt needle is used, 11DXYB146JH-027] and the Natural Science Foundation of
the patient can see the doctor’s acupuncture action but Sichuan Province-Exploring the multidimensional regulatory
does not experience actual needle sensation (50). This mechanism of acupuncture on the default network of chronic
is an effective single-blind control method (51, 52). In spontaneous urticaria based on spatiotemporal analysis
clinical research studies on acupuncture treatment in technology (No. 2022NSFSC1492).
low back pain, temporomandibular arthritis, and other
systemic diseases, their findings verified the reliability of
the Park simulation needle (53, 54). Therefore, to improve Conflict of interest
the blinding effect, Park analog needles were used in
our study in both the acupuncture group and the sham The authors declare that the research was conducted in the
acupuncture group. absence of any commercial or financial relationships that could
be construed as a potential conflict of interest.

5. Conclusion
Publisher’s note
In summary, our research found that acupuncture
has a good clinical effect on insomnia patients with All claims expressed in this article are solely those of the
emotional disorders and has a significant regulatory authors and do not necessarily represent those of their affiliated
effect on abnormally excited brain potentials. Our organizations, or those of the publisher, the editors and the
results provide further evidence for the effectiveness reviewers. Any product that may be evaluated in this article, or
and possible mechanism of acupuncture in treating claim that may be made by its manufacturer, is not guaranteed
sleep disorders. or endorsed by the publisher.

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Zhang et al. 10.3389/fneur.2022.1053642

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