| In this research,a randomized controlled study was conducted to treat patients with primary insomnia(PI)with different acupuncture scheme,single acupoint,combination of multiple acupoints,sham-point acupuncture intervention.Athens Insomnia Scale(AIS),Pittsburgh Sleep Index scale(PSQI)were employed to observe the clinical symptom,and polysomnography(PSG)was employed to evaluate the sleep quality,and together to evaluate the efficacy of acupuncture on PI with different acupuncture scheme.Based on the clinical efficacy study,functional magnetic resonance imaging(fMRI)study was designed to study the instant effect of acupuncture on PI.Task-based fMRI were performed during the acupuncture stimulation.By analyzing and comparing the activation patterns of the brain under different intervention conditions,the instant effect of acupuncture,that is,it can produce activation or deactivation in the brain,was verified.Furthermore,the activated cerebral regions were different among the different acupuncture scheme.Resting state fMRI(rs-fMRI)were performed to detect and analysis the ALFF(amplitude of low frequency fluctuation)of PI under the resting state without stimulation,and contrast with the task-based fMRI results.The results suggested that combination of multi-acupoints could activate more regions which the activity was affected by sleep quality,which proved that the activity of some brain regions was correlated with sleep quality.Objective:To observe the effect of different acupuncture intervention on sleep quality and sleep cycle of PI patients,and explore the difference of clinical efficacy;To observe the effect of different acupuncture intervention on brain activation pattern in PI patients,and explore the possible central mechanism of acupuncture intervention in PI.Methods:1.Research sources and diagnostic criteriaThis study is a multi-center randomized controlled trial which come from the National Key Basic Research and Development Projects(973 Projects),and multi-central trials were registered on the U.S.National Library of Medicine(Clinical Trials.gov Identifier: NCT02448602).All procedures performed in studies involving human participants were in accordance with the ethical standards of the National 973 projects(Reference: CCZYFYLL2014-043)and approved by the Ethics Committee.The inclusion and exclusion criteria were made according to the diagnostic criteria of primary insomnia(DSM-5).2.Patient grouping and intervention methodsOne hundred and fifty-six PI patients were recruited in the study from the outpatient clinic in the Neurological Department,Cerebropathy Department and Acupuncture Department of China-Japan Union Hospital of Jilin University,Affiliated Hospital of Changchun University of Chinese medicine.PI patients were randomly divided into 3 groups: single acupoint group(Shenmen HT-7),the combination of acupoints group(Shenmen HT-7;Baihui GV-20;Sanyinjiao SP-6)and sham point group(junction of biceps brachii muscle and triceps brachii tendon).The intervention method is to connect the electroacupuncture machine after the injection of the acupoints,and select the continuous wave with frequency of 60 HZ.The stimulation time is 30 minutes,1 time/day,1 course last for 5 days,rest for 2 days between each course,and total of 5 courses of treatment.Finally,one hundred and forty-five patients completed all treatment.3.The evaluation with AIS and PSQISleep experience were evaluated at the beginning of acupuncture treatment period(0 ±3 days),the end of acupuncture treatment period(5 weeks ±3 days)by AIS and PSQI.The AIS questionnaire observe sleep time,wake up at night,wake up earlier than expected time,mood during the day,physical function during the day,sleep during the day,total sleep time,total sleep quality,and judge whether the patient has insomnia symptoms or not.The PSQI questionnaire observe sleep quality,sleep duration,time of fall asleep,sleep efficiency,and daytime function,and so on.The score of AIS and PSQI were used to evaluate the difference of sleep experience and compare the efficacy of single acupoint,combination of multi-acupoints and sham point acupuncture on primary insomnia.4.The evaluation with PSGPSG assessment was performed for PI at the beginning of acupuncture treatment period(0 ±3 days)and the end of acupuncture treatment period(5 weeks ±3 days),which is used for recording the total sleep time,sleep efficiency,waking time after sleep onset,sleep stage duration of the PI patient.The results were used to objectively evaluate the sleep quality of patients,and to compare the different effect on the sleep quality of PI patients with acupuncture on single acupoint,combination of multi-acupoints and sham point.5.Task-based fMRI assessment(1)Fifteen subjects of the single acupoint group,combination of multi-acupoints group and sham point group,which came from China-Japan Union Hospital of Jilin University and Affiliated Hospital of Changchun University of Chinese medicine,were randomly selected to accept task-based fMRI assessment.(2)Task-based fMRI scan were performed during the acupuncture stimulation.During the task-based fMRI scan,acupuncture needles were inserted in the acupoints,and connected to the electro-acupuncture machine.A block design was adapted in the task-based fMRI experiment(non-stimulation state,electro-acupuncture stimulation state,non-stimulation state…).6.Statistical analysis(1)The clinical data were analyzed using SPSS 19.0 statistical software.The AIS / PSQI scores and the PSG data at baseline and after the treatment were analyzed with paired-T-test to verify the clinical efficacy of different acupuncture interventions.The data among three group were analyzed with ANOVA analyses to compare the differences in clinical outcomes.All data were expressed as mean ± standard deviation,P<0.05 was statistically significant.(2)Task-based fMRI data was pre-processed and analyzed with the statistical parametric mapping(SPM8)software.The range and activation degree of activation or deactivation of brain induced by different acupuncture acupoints were obtained(P<0.001,FWE corrected P=0.05,cluster size >20).Result:1.AIS results showed that after 5 weeks of treatment,the three groups could improve the clinical symptoms,and the AIS scores before and after treatment were statistically different(P<0.001),sleep duration was prolonged and sleep quality was improved.Decreased AIS score in single acupoint group was(9.50±2.37),decreased AIS score in combination of multi-acupoints group was(9.69±3.59),decreased AIS score in sham point group was(5.15±2.46),the efficacy of single acupoint group and combination of multi-acupoints group were better than that of sham point group(P<0.001),however,no statistically difference were found between single acupoint group and combination of multi-acupoints group.2.PSQI results showed that after 5 weeks of treatment,the three groups could improve the clinical symptoms,and the PSQI scores before and after treatment were statistically different(P<0.001).Decreased PSQI score in single acupoint group was(6.51±2.31),decreased PSQI score in sham point group was(4.25±1.65),the efficacy of single acupoint group was better than that of sham point group(P<0.01).Decreased PSQI score in combination of multi-acupoints group was(8.85±2.83),the efficacy of combination of multi-acupoints group was better than that of sham point group(P<0.001),and also better than that of single acupoint group(P<0.01).3.The result of PSG showed that after acupuncture treatment,in sham point group,the TST was prolonged(P<0.005),SE was improved(P<0.05);In single acupoint group,the TST was prolonged(P<0.001),SE was improved(P<0.001),WASO was decreased(P<0.001);In the multi-acupoints group,the TST was prolonged(P<0.001),SE was improved(P<0.001),WASO was decreased(P<0.001).The efficacy of single acupoint group and combination of multi-acupoints group were better than that of sham point group,and the efficacy of combination of multi-acupoints group was better than that of single acupoint group.After 5 weeks of acupuncture intervention,the sleep structure of single acupoint group changed,REM% was increased(P<0.05),NREM3% was decreased(P<0.05);the sleep structure of combination of multi-acupoints group changed,REM% was increased(P<0.05),NREM1% and NREM2% were decreased(P<0.05);there was no significant difference of the sleep structure was found in sham point group.4.In task-based fMRI results,positive T value reflected activation was evoked in the regions,and negative T value reflected deactivation was evoked in the regions.Stimulating HT-7 evoked activation in left brainstem(T=5.05),right cerebellum anterior lobe(T=4.12)and cerebellum posterior lobe(T=3.65),right inferior parietal lobe(T=4.29),left postcentral gyrus(T=4.91),right fusiform gyrus(T=3.65),and right middle temporal gyrus(T=3.96),left middle temporal gyrus(T=4.03).Deactivation were observed in right medial frontal gyrus(T=-4.31),left middle occipital gyrus(T=-3.76),and right anterior cingulate(T=-4.88);Stimulating HT-7,GV-20 and SP-6 evoked activation in right cerebellum posterior lobe(T=5.84),left cerebellum posterior lobe(T=6.85),left cerebellum anterior lobe(T=6.53),left fusiform gyrus(T=4.20),left postcentral gyrus(T=7.26)and precentral gyrus(T=5.12),right postcentral gyrus(T=7.00)and precentral gyrus(T=4.99),right superior temporal gyrus(T=5.89),left middle temporal gyrus(T=5.55),right superior frontal gyrus(T=5.13),left inferior frontal gyrus(T=5.96),right inferior frontal gyrus(T=5.06),left middle frontal gyrus(T=6.53),right middle frontal gyrus(T=4.67),right medial frontal gyrus(T=4.84),right insula(T=5.04),right thalamus(T=8.12)and left thalamus(T=5.99).Deactivation was observed in right precuneus(T=-5.18).Stimulating sham point evoked activation in left inferior parietal lobe(T=4.39),right inferior parietal lobe(T=4.72),left middle temporal gyrus(T=4.52),right middle temporal gyrus(T=3.44),and left cingulate gyrus(T=3.62).Regions which the activity could be affected by the sleep experience could be evoked in three groups.The single acupoint could affect the right cerebellum posterior lobe,left postcentral gyrus,left middle temporal gyrus;the combination of multi-acupoints could affect left middle temporal gyrus,left middle frontal gyrus,left superior frontal gyrus,bilateral inferior frontal gyrus,left postcentral gyrus,left precentral gyrus,left middle temporal gyrus;the sham point could affect the left inferior parietal lobule,left middle temporal gyrus.Hence,the combination of multi-acupoints group could activate more regions which the activity was affected by sleep experience.Conclusions:1.Different acupuncture intervention could improve the sleep experience and sleep quality of PI patients.The clinical efficacy of combination of multi-acupoints was better than that of single acupoint.Sleep quality may be improved by regulating sleep structure.2.The REM% of combination of multi-acupoints group and single acupoint group were improved after acupuncture treatment.And the enhanced REM% of combination of multi-acupoints group was better than that of single acupoint group(but there was no statistical difference).Furthermore,the increased total sleep time and sleep efficiency of multi-acupoints group were better than those of single acupoint group.3.Instant effect could induce by acupuncture,which could activate or deactivate brain regions.The regions were associated with emotional and cognitive functions,which could be the potential mechanism for improving sleep quality by regulating sleep structure,acupuncture may regulate sleep by activating brain functional areas associated with emotional and cognitive functions.4.Compared with acupuncture at single acupoint,combination of acupoints could modulate activity of more regions associated with emotional and cognitive functions and produce central effect to regulate sleep.This may be the potential central mechanism for combination of multi-acupoints could improve the clinical efficacy of acupuncture. |
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