Clinical study of electroacupuncture improving sleep electroencephalogram and event-related potential in patients with somatoform disorders

LIU Zhanwen (劉占文), ZHANG Li (張酈), ZHANG Minmin (張敏敏), HU Xueqian (胡學(xué)謙), CHEN Xingshi (陳興時),SU Jie (蘇杰)

1 Shanghai Changning Mental Health Center/Affiliated Mental Health Center, East China Normal University, Shanghai 200335, China

2 Shanghai Mental Health Center, Shanghai 200030, China

Abstract Objective: To observe the effects of electroacupuncture (EA) on sleep electroencephalogram (EEG) and event-related potential (ERP) in patients with somatoform disorders (SFD).

Keywords: Acupuncture Therapy; Electroacupuncture; Point, Baihui (GV20); Point, Shenting (GV24); Somatoform Disorders;Event Related Potentials; Polysomnography; Mismatch Negativity

Somatoform disorders (SFD) are a type of neurosis.People with SFD persistently worry about or believe in the existence of various physical symptoms.Therefore,they will repeatedly visit the hospital for these symptoms but finally find no organic diseases.However,neither negative results of clinical examinations nor physicians’ explanation can banish their worries[1-2].Consequently, SFD patients often visit psychiatry departments, counseling, and traditional Chinese medicine departments for help.It is found that the core complaint of this group of people is about sleep disorders and cognitive impairments, which are usually accompanied by significant depression and anxiety.

Psychological intervention and medication are the main approaches for managing SFD, and long-term systematic treatment is required to keep symptoms under control[3].Nevertheless, adverse reactions to medicines, time cost to visit the hospital, and financial burden may interrupt the treatment.Chronic subjective discomforts and anxiety may interfere with the daily study and work of the patients or even affect social interactions, resulting in great torment among them and their families.Hence, it is important to seek a safe,economical, and effective method to treat SFD with fewer adverse reactions.

Acupuncture is safe and effective in treating SFD[3-5],though subjective measurements mostly prove it and lack objective evidence.Quisi is a portable sleep electroencephalogram (EEG) detector that can measure,record, and automatically analyze data.It is compatible with any computer and smartphone.Also, it is lightweight and easy to operate so that people can do it by themselves to condense and directly display the features of their sleep EEG overnight.It is more convenient and sensitive than ordinary polysomnography (PSG)[6-10].

To have a comprehensive and objective review of the effects of electroacupuncture (EA) on SFD, we conducted this research to monitor SFD patients’ sleep EEG using PSG-guided Quisi[11]and detect the mismatch negativity (MMN) of event-related potential (ERP) and P300 amplitude and latency[11]to provide objective evidence supporting the treatment of SFD with EA.

1 Clinical Materials

1.1 Diagnostic criteria

Taking the relevant criteria in the tenth revision ofInternational Classification of Diseases(ICD-10)[1], at least two attending physicians made the diagnosis of SFD.

1.2 Inclusion criteria

Ages between 18 and 60 years; the disease lasted 1.0-9.0 years; gender unlimited; with stable vital signs and clear consciousness; did not use any antidepressants, anti-anxiety agents, or antipsychotic drugs within the latest 2 weeks before recruitment;minimum years of education 11 years; agreed to participate in this trial and signed the informed consent.

1.3 Exclusion criteria

Those with depression, anxiety, hypochondriasis,schizophrenia, or heart diseases; with a family history of mental disorders; with alcohol or substance abuse;severe organic diseases; pregnant or lactating women;mental disorders caused by brain or other physical diseases.

1.4 Dropout criteria

Those quit on their own; those with poor compliance;loss to follow-up.

1.5 Statistical methods

The SPSS version 19.0 software was adopted for data analyses.The normally distributed measurement data were expressed as mean ± standard deviation (±s).The intra-group comparisons of Quisi sleep indicators and MMN and P300 of ERP before and after treatment were checked by the paired samplest-test, and the between-group comparisons were examined by the two independent samplest-test.P<0.05 indicated statistical significance.

1.6 General data

This trial was approved by the Medical Ethics Committee of Shanghai Changning Mental Health Center (Approval No.M202024).

The EA group recruited 75 cases from the outpatient or inpatient of Shanghai Changning Mental Health Center between December 2020 and August 2023.With 13 cases eliminated due to incomplete data during the trial, 62 cases finished the trial, and their years of education ranged from 12 to 21 years.

The normal control group recruited 40 people between December 2020 and August 2023 who were the staff of Shanghai Changning Mental Health Center or community residents screened by the same criteria as the EA group, and their years of education ranged from 12 to 21 years.

There was no statistical significance in comparing the gender, age, and education years between the two groups, suggesting the comparability of the baseline data between the two groups (P>0.05).The details are shown in Table 1.

Table 1 Comparison of the general data between the two groups

2 Methods

2.1 Physical symptoms investigation

Before the intervention, we established a physical symptom checklist according to the common SFD symptoms reported[2]to record and score the physical symptoms of each patient in the EA group.The checklist consisted of 10 items: discomforts of the five sense organs, bodily pain, motor dysfunction, sensory disturbance, cardiovascular problems, respiratory issues,digestive issues, urinary and reproductive issues, sleep disorders, and cognitive dysfunction.Each symptom was scored on a 5-grade scale based on its severity: no symptoms, 1 point; accidentally occurred symptoms not affecting living and social activities, 2 points; often occurred symptoms causing a certain impact on living and social activities, 3 points; frequently occurred symptoms causing a notable impact on living and social activities, 4 points; persistent symptoms, significant perceived by the patient, causing a major impact on living and social activities, 5 points.

2.2 Grouping and interventions

2.2.1 EA group

The EA group patients received EA treatments.

Points: Baihui (GV20) and Shenting (GV24).

Method: Disposable filiform needles of 0.30 mm in diameter and 50 mm in length were chosen for the treatment.After standard sterilization, Baihui (GV20)and Shenting (GV24) were punctured 20-30 mm deep with the needle tip backward beneath the galea aponeurotica.The needles were connected to HANS EA apparatus after the arrival of Qi induced by liftingthrusting and twirling manipulations, with intermittent waves and gradually enhanced electric currents, which meant 1 mA, 2 mA, and 3 mA lasting 10 min each.This 30-min session was performed once daily with successive 6 d as 1 treatment course for 4 courses at 1-day intervals.Two universally trained associate chief physicians of Chinese medicine departments were in charge of acupuncture treatment to reduce operational errors.Quisi parameters and MMN and P300 of ERP were observed before and after 4 courses of treatment.

2.2.2 Normal control group

The normal control group only received the detection of Quisi and the MMN and P300 of ERP at the same time points as the EA group before treatment without any interventions.

3 Observation of Outcomes

3.1 Endpoints

3.1.1 Quisi parameters

The SEEG1500K PSG instrument (Japan) and Quisi(Germany), provided by Shanghai Mental Health Center,Shanghai Jiao Tong University School of Medicine, were used for detection[9-11].The operation of Quisi and its analysis consulted relevant references[10-11], and the sleep brainwave analysis program Polysmith/QP-260A(Japan) was used.The two groups received Quisi detection for 2 consecutive nights, the first night for adaption and the second for formal testing.

The Quisi testing system consisted of a portable sleep monitor and DOS software (version 3.0).The electrodes(standard electrode plates, Fp1-Fz-Fp2) were affixed to Quisi, which was turned on when the patient was going to sleep to put EEG signals into Quisi.After the amplification and storage of brainwaves, the connected laptop or smartphone automatically analyzed and displayed the features of the whole night’s condensed brainwaves using Quisi 3.0.This would be the whole detection process.This trial studied the following Quisi parameters.

Total sleep time (TST): The actual time of sleep from falling asleep to awake.

Rapid eye movement sleep (REM) latency (RL): The time from falling asleep to the first REM.

REM time (RT): The total time of REM during the whole sleep.

Number of REM period (NRP): The total number of REM periods during a whole night’s sleep.

Sleep latency (SL): The time from turning off the light to the occurrence of stage 1 (S1) of the non-rapid eye movement sleep (NREM).

Awaking time (AT): The total time of being awake from falling asleep to the final waking.

Sleep efficiency (SE): The ratio of TST to the total recording time.

S1, S2, S3, and S4percent: The percentage of stages 1,2, 3, and 4 of the NREM, respectively.

3.1.2 MMN and P300 latencies and amplitudes of ERP

We used the Nicolet Bravo evoked potential instrument to record the MMN and P300 latencies and amplitudes.The recording electrodes were attached to frontal Fpz, the ground electrodes to the center of the forehead, and the reference electrodes to the earlobes.The standard stimuli were 500 Hz 80 dB pure tones with a probability of 0.8, and the deviant stimuli were 2 000 Hz 85 dB pure tones with a probability of 0.2.The inter-stimulus interval was 1 s.The total frequency of the two kinds of stimuli was 200 times during 1 round of test.The first round was the MMN test, during which the participant was not required to memorize the occurrence of deviant stimuli.The second round was the P300 test, during which the participant was required to remember the number of deviant stimuli.

3.2 Results

3.2.1 Main somatoform symptoms of the EA group

We recorded the number of people and their ratio with the mean score of single factor ≥3 points on the physical symptom checklist.The investigation showed that the main problems disturbing SFD patients were cognitive impairments, sleep disorders, respiratory symptoms, digestive symptoms, five-sense organ problems, and cardiovascular symptoms in order.The details are presented in Table 2.

3.2.2 Comparison of the Quisi testing results

In comparing Quisi parameters before treatment, the EA group had shorter TST, RL, and RT, reduced NRP,longer SL, increased AT, decreased SE, higher percent of S1, and lower percents of S2and slow wave sleep (SWS),i.e., S2and S3plus S4, compared with the normal control group, all showing significant differences (P<0.01 orP<0.05).After 4 courses of treatment, the TST and RL became longer, SL was shorter, AT decreased, and SE improved in the EA group, and the changes were statistically significant (P<0.01 orP<0.05); regarding the sleep architecture, the percent of S1dropped, and that of S2increased in the EA group, also showing statistical significance (P<0.01), though the change in the NRP was unnoticeable (P>0.05).In comparing the 10 Quisi parameters after treatment, there were no significant differences in the RL, NRP, SL, AT, SE, or the percent of S2between the EA group and normal control group(P>0.05), suggesting that EA can correct the abnormal sleep architecture in SFD patients.Please find details in Table 3.

Table 2 Number of people and their ratio with single factor scored ≥3 points on the SFD physical symptom checklist (n=75)1)

Table 3 Comparison of Quisi parameters between the two groups ( ±s)

Table 3 Comparison of Quisi parameters between the two groups ( ±s)

Note: TST=Total sleep time; RL=Rapid eye movement sleep latency; RT=Rapid eye movement sleep time; NRP=Number of rapid eye movement sleep period; SL=Sleep latency; AT=Awaking time; SE=Sleep efficiency; SWS=Slow wave sleep; compared with the normal control group, 1) P<0.01, 2) P<0.05; compared with the same group before treatment, 3) P<0.01, 4) P<0.05.

Item Normal control group(n=40)Electroacupuncture group (n=62)Before treatment After treatment TST/min 468.6±22.3 351.1±27.51)RL/min 84.1±9.2 53.0±19.01)RT/min 83.2±10.2 62.3±16.01)NRP/time 5.6±2.7 4.2±2.12)SL/min 19.3±9.2 38.6±14.41)415.3±36.51)3)76.0±22.03)68.0±26.01)5.0±1.2 20.5±9.33)AT/min 16.8±6.5 41.6±18.51) 22.5±7.63)SE/% 94.1±7.1 85.8±7.21) 90.5±5.44)S1/% 8.9±1.9 27.5±16.41) 15.2±7.12)3)S2/% 52.3±5.9 41.4±16.21) 61.6±6.33)SWS (S3+S4)/% 18.2±4.8 8.2±6.21) 12.1±6.11)

3.2.3 Comparison of the MMN and P300 of ERP

Compared with the normal control group before treatment, the MMN and P300 latencies were longer,and their amplitudes were smaller in the EA group(P<0.05 orP<0.01).After 4 courses of treatment, Fpz electrodes captured larger MMN and P300 amplitudes and shorter latencies in the EA group, and the intragroup differences were statistically significant (P<0.05);the between-group differences were statistically insignificant after treatment (P>0.05).Table 4 provides more details.

Table 4 Comparison of the MMN and P300 of ERP before and after treatment ( ±s)

Table 4 Comparison of the MMN and P300 of ERP before and after treatment ( ±s)

Note: MMN=Mismatch negativity; ERP=Event related potentials; compared with the normal control group, 1) P<0.01, 2) P<0.05;compared with the same group before treatment, 3) P<0.01, 4) P<0.05.

Item Normal control group(n=40)Electroacupuncture group (n=62)Before treatment After treatment MMN Latency/ms 183.3±20.3 208.4±25.12) 191.5±26.34)Amplitude/μV 9.5±2.6 6.3±2.22) 8.4±1.84)P300 Latency/ms 314.6±37.8 332.6±43.21) 327.3±42.13)Amplitude/μV 5.3±1.9 2.2±0.91) 4.6±1.23)

4 Discussion

SFD is a neurosis that has diverse and versatile physical symptoms as the chief complaint, which,however, can find no organic reasons to explain.It affects 0.2%-2.0% of the European and American people[1]; an epidemiological investigation conducted in Hebei Province of China found that the prevalence in the population over 18 years old reached 6.92%[12].

This study revealed various physical symptoms in SFD patients: cognitive impairments, sleep disorders,respiratory symptoms, digestive symptoms, five-sense organ issues, and cardiovascular symptoms, introduced in the descending order of their frequencies.This indicates the variety of SFD manifestations and involved organ systems, of which cognitive impairments and sleep disorders rank at the top.However, there is some inconsistency between our results and previous reports in the frequency order of SFD symptoms[2,13].This study found a higher frequency of respiratory symptoms in SFD patients, for which Corona Virus Disease 2019(COVID-19) was thought to be blamed these years,though the detailed reasons require further research.

ERP is a novel approach commonly used to monitor advanced brain cognitive function[11,14].This technique does not need the subject to recognize the deviate stimuli but can reflect their process of differentiating between the standard and deviate stimuli.This pattern can obtain a more objective detection result and overcome some subjects’ poor compliance[15-16].Although conventional PSG can detect multiple ERPrelated physiological indicators during sleep, there is difficulty promoting this technique due to its complicated analysis results[17-18].As a portable sleep EEG detector, Quisi is considered a great progress in sleep analysis technique as it can connect to smartphones and detect, record, and automatically analyze brainwaves during sleep[9-11].The current trial adopted PSG-guided Quisi to detect ERP and sleep indicators overnight and automatically generate the whole night’s sleep architecture, which can avoid data loss due to human error in sleep staging.We found alterations in Quisi results of SFD patients involving the sleep progression, sleep architecture, and REM parameters, such as shorter TST, RL, RT, and NRP, longer SL, increased AT, decreased SE, higher S1percent, lower S2and S3plus S4percents, prolonged MMN and P300 latencies, and smaller MMN and P300 amplitudes.These results substantially align with previous reports[19-22].

This study also introduced novel software to extract MMN from P300 without demanding the subject to recognize the deviant stimuli during the test, displaying a significant clinical application advantage.After 4 courses of EA treatment, the MMN and P300 latencies were shorter, the amplitudes were larger in SFD patients (P<0.01 orP<0.05), and the between-group differences were statistically insignificant (P>0.05).In the meantime, the abnormal Quisi indicators had improvements.These results demonstrate that EA at Shenting (GV24) and Baihui (GV20) can correct the abnormal sleep architecture in SFD patients.

There are rare studies on EEG of cognitive dysfunction in mental disorders treated with acupuncture[20-22].Two Governor Vessel points, Baihui(GV20) and Shenting (GV24), were selected for this study.The Governor Vessel connects with the brain and Conception Vessel.Therefore, acupuncture at the Governor Vessel points can harmonize Yin and Yang,regulate the marrow sea, and unblock brain collaterals.Head points have a significant role in treating cognitive dysfunction[23].Acupuncture at Baihui (GV20) and Shenting (GV24), two key head points, can awaken the brain and open orifices, calm the mind, and benefit the memory of cognitive dysfunction patients.The mechanism is closely related to regulating brain functional areas and improving brain microcirculation[24-25].For instance, ZHONG Hui’s study[24]demonstrated that acupuncture at Shenting(GV24) and Baihui (GV20) improved the short-term,long-term, and overall memory of patients with poststroke cognitive impairments, and fMRI found augmented neuronal activities in the right middle frontal gyrus, left posterior cingulate gyrus, and right inferior parietal lobule.The two points’ locations are the prefrontal cortex’s projection areas.The subcutaneous needling method used in this study can enlarge and strengthen the stimulation to the functional area of the prefrontal lobe, and the encoding and processing of episodic memories mainly rely on the prefrontal cortex[26].

Besides, we selected intermittent waves and gradually increased the current intensity in EA treatments.This wave is a waveform modulated through rectangular pulses based on continuous waves.Intermittent in form, this combined waveform can excite nerves and muscles and prevent adaptive responses to the continuous waveform[27].It can also maximize muscle contraction and promote blood and lymph circulation[28].Different EA stimulation intensities at the same point lead to different brain function activities, and high-intensity EA stimulation can more extensively affect the brain than lower ones[29].Animal experiments also demonstrated that EA at the same point with different stimulation intensity levels could boost metabolic balance, fortify memory, and improve dementia symptoms, and the moderate intensity level produced the most significant effect[30-31].

To summarize, this study explored the mechanism by which EA at Baihui (GV20) and Shenting (GV24) treats SFD using the PSG-guided Quisi technique.We found that the predominant symptoms of SFD were cognitive dysfunction and sleep disorders.Abnormal sleep EEG and ERP were also discovered.The results demonstrated that EA at Baihui (GV20) and Shenting(GV24) corrected abnormal sleep EEG and ERP in SFD patients, equivalent to escitalopram oxalic acid[16],providing a reference for the mechanism study on EA treating SFD.However, this study lacked long-term and follow-up observations and did not perform a dynamic psychological scale assessment.Hence, future studies should expand the sample size, extend the observation period, and add both subjective and objective evaluations to reveal further the mechanism of EA treating SFD and provide scientific evidence for using EA to treat SFD.Moreover, a medical history investigation should be done before EA treatment, as intermittent wave EA should be cautiously used for people with cardiac diseases.We also need to pay close attention to the patient’s expressions and communicate with them to learn their feelings during EA treatments with an intermittent waveform because the intermittent waveform pulse is rather thrilling and was reported to induce cardiac emergency[32].

Conflict of Interest

The authors declare that there is no potential conflict of interest in this article.

Acknowledgments

This work was supported by the Project of Shanghai Changning District Science and Technology Commission( 上海市長寧區(qū)科學(xué)技術(shù)委員會項目, No.CNKW2020Y34); Sub-professional Project of Shanghai Changning District Medical Master and Doctor Innovative Talent Base (上海市長寧區(qū)醫(yī)學(xué)碩博士創(chuàng)新人才基地亞專業(yè)課題, No.RCJD2021S05).

Statement of Informed Consent

This trial was approved by the Medical Ethics Committee of Shanghai Changning Mental Health Center(Approval No.M202024).Informed consent was obtained from all individual participants.

Received: 29 August 2023/Accepted: 8 November 2023