Effectiveness and cerebral responses of multi-points acupuncture for primary insomnia: a preliminary randomized clinical trial and fMRI study

Yu-Kai Wang, Tie Li, Li-Juan Ha, Zhong-Wen Lv, Fu-Chun Wang, Zhi-Hong Wang, Jing Mang, Zhong-Xin Xu, Yu-Kai Wang, Tie Li, Li-Juan Ha, Zhong-Wen Lv, Fu-Chun Wang, Zhi-Hong Wang, Jing Mang, Zhong-Xin Xu

Abstract

Background: Primary insomnia (PI) is characterized by difficulties in initiating sleep or maintaining sleep, which lead to many serious diseases. Acupuncture for PI has drawn attention with its effectiveness and safety. However, the operation of choosing acupoints lacks scientific suggestion. Our trial aims to provide reference and scientific basis for the selection of acupoints and to explore its possible mechanism.

Methods: A patient-assessor-blinded, randomized and sham controlled trial was designed to compare the efficacy of 5-weeks acupuncture at a single acupoint, the combination of multi-acupoints, and a sham point. The Pittsburgh sleep quality index and Athens Insomnia Scale questionnaire were used for the primary clinical outcomes, while polysomnography was performed for the secondary clinical outcomes. The resting state functional MRI was employed to detect the cerebral responses to acupuncture. The brain activity in resting state was measured by calculating the fractional amplitude of low-frequency fluctuations (fALFF), which reflected the idiopathic activity level of neurons in the resting state. These results were analyzed by two factorial ANOVA test and post-hoc t-tests.

Results: The clinical outcomes suggest that acupuncture could improve clinical symptoms, and the combination of multi-acupoints might lead to a better clinical efficacy. The rs-fMRI results suggested that the brain activity of certain regions was related to the sleep experience, and acupuncture could regulate the activity of these regions. Furthermore, the combination of multi-acupoints could impact more regions which were influenced by the sleep experience.

Conclusions: Acupuncture has been proven to be beneficial for PI patients, and the combination of multi-acupoints might improve its efficacy.

Trial registration: This trial has been registered on the U.S. National Library of Medicine (https://ichgcp.net/clinical-trials-registry/NCT02448602" title="See in ClinicalTrials.gov">NCT02448602 . Registered date: 14/04/2015.

Keywords: Acupuncture; Functional magnetic resonance imaging; Polysomnography; Primary insomnia.

Conflict of interest statement

Yu-Kai Wang declares that she has no conflict of interest. Tie Li declares that he has no conflict of interest. Li-Juan Ha declares that she has no conflict of interest. Zhong-Wen Lv declares that he has no conflict of interest. Fu-Chun Wang declares that he has no conflict of interest. Zhi-Hong Wan declares that he has no conflict of interest. Jing Mang declares that he has no conflict of interest. Zhong-Xin Xu declares that he has no conflict of interest.

Figures

Fig. 1
Fig. 1
The location of the acupoints and diagrammatic sketch of the fMRI scan process. a The location of the acupoint in S-Acu group. a-c The location of acupoints in M-Acu group. d The location of the sham point in N-Acu group
Fig. 2
Fig. 2
The brain regions with altered fALFF of S-Acu group after acupuncture treatment (P < 0.001, FWE correct P = 0.05, cluster size> 30). R: right brain. a: right cerebellum posterior lobe, b: left cerebellum posterior lobe, c: brainstem, d: right inferior temporal gyrus, e: left middle temporal gyrus, f: right parahippocampa gyrus, g: left precuneus, h: right superior frontal gyrus, k: left superior frontal gyrus. Colorbar refer to the increased fALFF value
Fig. 3
Fig. 3
The brain regions with altered fALFF of M-Acu group after acupuncture treatment (P < 0.001, FWE correct P = 0.05, cluster size> 30). R: right brain. a: right cerebellum posterior lobe, b: left parahippocampa gyrus, c: left superior temporal gyrus and middle temporal gyrus, d: right superior temporal gyrus and middle temporal gyrus, e: left inferior frontal gyrus, f: left supramarginal gyrus, g: right precentral gyrus, h: right precuneus, k: left middle frontal gyrus, m: left postcentral gyrus. Colorbar refer to the increased fALFF value
Fig. 4
Fig. 4
The brain regions with altered fALFF of N-Acu group after acupuncture treatment (P < 0.001, FWE correct P = 0.05, cluster size> 30). R: right brain. a: right superior frontal gyrus and medial frontal gyrus, b: left superior frontal gyrus, c: right middle frontal gyrus, d: left middle frontal gyrus, e: right inferior frontal gyrus. Colorbar refer to the increased fALFF value
Fig. 5
Fig. 5
The distribution of brain regions where fALFF were negative correlation with AIS scores, and brain regions which were regulated by three acupuncture regimens. Colorbar refer to the increased fALFF value

References

    1. Buysse DJ. Insomnia. JAMA. 2013;309:706–716. doi: 10.1001/jama.2013.193.
    1. Kessler RC, Berglund PA, Coulouvrat C, et al. Insomnia and the performance of US workers: results from the America insomnia survey. Sleep. 2011;34(9):1161–1171. doi: 10.5665/SLEEP.1230.
    1. Irwin MR. Why sleep is important for health: a psychoneuroimmunology perspective. Annu Rev Psychol. 2015;66:143–172. doi: 10.1146/annurev-psych-010213-115205.
    1. Lai MM, Lin CC, Lin CC, Liu CS, Li TC, Kao CH. Long-term use of zolpidem increases the risk of major injury: a population-based cohort study. Mayo Clin Proc. 2014;89:589–594. doi: 10.1016/j.mayocp.2014.01.021.
    1. Guo J, Wang LP, Liu CZ, et al. Efficacy of acupuncture for primary insomnia: a randomized controlled clinical trial. Evid Based Complement Alternat Med. 2013;2013:163850. doi: 10.1155/2013/163850.
    1. Shergis JL, Ni X, Jackson ML, et al. A systematic review of acupuncture for sleep quality in people with insomnia. Complement Ther Med. 2016;26:11–20. doi: 10.1016/j.ctim.2016.02.007.
    1. Wang H, Yang G, Wang S, Zheng X, Zhang W, Li Y. The Most commonly treated acupuncture indications in the United States: a cross-sectional study. Am J Chin Med. 2018;9:1–33. doi: 10.1142/S0192415X18500738.
    1. Fang J, Jin Z, Wang Y, et al. The salient characteristics of the central effects of acupuncture needling: limbic-Paralimbic-neocortical network modulation. Hum Brain Mapp. 2009;30:1196–1206. doi: 10.1002/hbm.20583.
    1. Huang W, Kutner N, Bliwise DL. Autonomic activation in insomnia: the case for acupuncture. J Clin Sleep Med. 2011;7:95–102. doi: 10.5664/jcsm.28048.
    1. Napadow V, Lee J, Kim J, et al. Brain correlates of phasic autonomic response to acupuncture stimulation: an event-related fMRI study. Hum Brain Mapp. 2013;34:2592–2606. doi: 10.1002/hbm.22091.
    1. Zheng Y, Qu S, Wang N, et al. Post-stimulation effect of electroacupuncture at Yintang (EX-HN3) and GV20 on cerebral functional regions in healthy volunteers: a resting functional MRI study. Acupunct Med. 2012;30:307–315. doi: 10.1136/acupmed-2011-010123.
    1. Chen JE, Glover GH. Functional magnetic resonance imaging methods. Neuropsychol Rev. 2015;25(3):289–313. doi: 10.1007/s11065-015-9294-9.
    1. Fransson P. Spontaneous low-frequency BOLD signal fluctuations: an fMRI investigation of the resting-state default mode of brain function hypothesis. Hum Brain Mapp. 2005;26(1):15–29. doi: 10.1002/hbm.20113.
    1. Zou QH, Zhu CZ, Yang Y, et al. An improved approach to detection of amplitude of low-frequency fluctuation (ALFF) for resting-state fMRI: fractional ALFF. J Neurosci Methods. 2008;172:137–141. doi: 10.1016/j.jneumeth.2008.04.012.
    1. Wang YK, Shi XH, Wang YY, et al. Evaluation of the age-related and gender-related differences in patients with primary insomnia by fractional amplitude of low-frequency fluctuation: A resting-state functional magnetic resonance imaging study. Medicine (Baltimore) 2020;99(3):e18786. doi: 10.1097/MD.0000000000018786.
    1. Zhao K. Acupuncture for the treatment of insomnia. Int Rev Neurobiol. 2013;111:217–234. doi: 10.1016/B978-0-12-411545-3.00011-0.
    1. Huang K, Liang S, Xu Y, Lu S. Law of acupoint selection in acupuncture treatment for insomnia based on data mining method. Zhongguo Zhen Jiu. 2015;35(9):960–963. doi: 10.13703/j.0255-2930.2018.07.030.
    1. Wang J, Wang J, Wang L, Zhang Y. Senile insomnia treated with integrated acupuncture and medication therapy: a randomized controlled trial. Zhongguo Zhen Jiu. 2015;35(6):544–548.
    1. Zhan, J., Pan, R., Guo, Y., et al. Acupuncture at Baihui(GV 20) and Shenting(GV 24) combined with basic treatment and regular rehabilitation for post-stroke cognitive impairment:a randomized controlled trial. Zhongguo Zhen Jiu. 2016;36(8):803-806. 10.13703/j.0255-2930.2016.08.007. Chinese. .
    1. Yeung WF, Chung KF, Zhang SP, Yap TG, Law AC. Electroacupuncture for primary insomnia: a randomized controlled trial. Sleep. 2009;32(8):1039–47. 10.1093/sleep/32.8.1039 URL: .
    1. Takamoto K, Hori E, Urakawa S, et al. Cerebral hemodynamic responses induced by specific acupuncture sensations during needling at trigger points: a near-infrared spectroscopic study. Brain Topogr. 2010;23:279–291. doi: 10.1007/s10548-010-0148-8.
    1. Soldatos CR, Dikeos DG, Paparrigopoulos TJ. Athens insomnia scale: validation of an instrument based on iCD-10 criteria. J Psychosom Res. 2000;48:555–560. doi: 10.1016/s0022-3999(00)00095-7.
    1. Buysse DJ, Reynolds CF, Monk TH, Berman SR, Kupfer DJ. The Pittsburgh sleep quality index: a new instrument for psychiatric practice and research. J Psychiatry Res. 1989;28:193–213. doi: 10.1016/0165-1781(89)90047-4.
    1. He Y, Wang L, Zang Y, et al. Regional coherence changes in the early stages of Alzheimer’s disease: a combined structural and resting-state functional MRI study. Neuroimage. 2007;35:488–500. doi: 10.1016/j.neuroimage.2006.11.042.
    1. Song XW, Dong ZY, Long XY, et al. REST: a toolkit for resting-state functional magnetic resonance imaging data processing. PLoS One. 2011;6:e25031. doi: 10.1371/journal.pone.0025031.
    1. Shi GX, Li QQ, Liu CZ, et al. Effect of acupuncture on Deqi traits and pain intensity in primary dysmenorrhea: analysis of data from a larger randomized controlled trial. BMC Complement Altern Med. 2014;14:69. doi: 10.1186/1472-6882-14-69.
    1. Makary MM, Lee J, Lee E, et al. Phantom acupuncture induces placebo credibility and vicarious sensations: a parallel fMRI study of low Back pain patients. Sci Rep. 2018;8(1):930. doi: 10.1038/s41598-017-18870-1.
    1. Li W, Ma L, Yang G, Gan WB. REM sleep selectively prunes and maintains new synapses in development and learning. Nat Neurosci. 2017;20(3):427–437. doi: 10.1038/nn.4479.
    1. Zhou F, Huang S, Zhuang Y, Gao L, Gong H. Frequency-dependent changes in local intrinsic oscillations in chronic primary insomnia: a study of the amplitude of low-frequency fluctuations in the resting state. Neuroimage Clin. 2016;15:458–465. doi: 10.1016/j.nicl.2016.05.011.
    1. Li C, Ma X, Dong M, et al. Abnormal spontaneous regional brain activity in primary insomnia: a resting-state functional magnetic resonance imaging study. Neuropsychiatr Dis Treat. 2016;12:1371–1378. doi: 10.2147/NDT.S109633.
    1. Kay DB, Karim HT, Soehner AM, et al. Sleep-wake differences in relative regional cerebral metabolic rate for glucose among patients with insomnia compared with good sleepers. Sleep. 2016;39(10):1779–94. 10.5665/sleep.6154 URL: .

Source: PubMed

赞助者和合作者

医疗条件

药物干预

3
订阅