Acupuncture has been used to treat various disorders in China and some other eastern countries for thousands of years. Nowadays, acupuncture is gradually accepted as an alternative and complementary method in western countries for its undeniable therapeutic effects. However, its central mechanism is still unclear. It is especially difficult to reveal how different regions in the brain influence one another and how the relationship is among these regions responding to acupuncture treatment. Recently, by applying neuroimaging techniques and network theory, acupuncture studies can make further efforts to investigate the influence of acupuncture on regional cerebral functional connectivity (FC) and the modulation on “acupuncture-related” networks. Connectomics appears to be a new direction in research to further understand the central mechanism underlying acupuncture. In this paper, an overview of connectomics application in acupuncture research will be discussed, with special emphasis on present findings of acupuncture and its influence on cerebral FC. Firstly, the connectomics concept and its significance on acupuncture will be outlined. Secondly, the commonly used brain imaging techniques will be briefly introduced. Thirdly, the influence of acupuncture on FC will be discussed in greater detail. Finally, the possible direction in forthcoming research will be reviewed by analyzing the limitation of present studies.
As one of the major medical resources, acupuncture has been widely used to treat various diseases in China and some other eastern countries for thousands of years. As an alternative and complementary method, acupuncture is gradually accepted in western countries for its undeniable therapeutic effects especially in analgesia [
In recent years, using the methods and techniques of connectome to explore the functional and structural networks of human brain has become one of the research hotspots in neuroscience [
In this review, an overview of the basic concept of connectomics will be discussed and the significance of connectomics on central mechanism research of acupuncture will be highlighted. Secondly the commonly used neuroimaging techniques in acupuncture researches will be briefly introduced. Subsequently, the preliminary application of functional connectivity (FC) in acupuncture research will be discussed by reviewing published neuroimaging studies. Finally, the limitation of present research and future direction will be considered.
Connectomics is a new research field that has been emerging for studying the structure-function relationship of connectomes among numbers of neuronal elements at all levels, from small microcircuits to cortical columns than to larger areas in the brain [
Recently, by the data analysis such as multivariate Granger Causality Analysis (mGCA) and the whole brain FC analysis of imaging modalities, connectomics research is able to quantitatively characterize the FC among segregated but functionally connected brain regions, which may help to further investigate why the FC is context-sensitive and state-dependent especially in the task-specific state (i.e., attention, memory) although it is constrained by the structural connectivity. Therefore, the connectomics research would have profound influence on neuroscience, which may lead us to a whole understanding of both the human brain activity and its disorders.
Connectomics will significantly influence the central mechanism research of acupuncture in the future, which can be viewed from two perspectives. On the one hand, the regulation of acupuncture is characterized by complexity and holism. Acupuncture can modulate intricate multisystems ranging from peripheral to pivotal. The current neuroimaging data has confirmed that the influence of acupuncture on the CNS is extensive and complex, and the relationship between an acupoint and brain region is not a one-to-one correspondence [
The commonly used neuroimaging techniques in acupuncture researches include MRI, PET/CT, Single-Photon Emission Computed Tomography (SPECT), electroencephalography (EEG), and magnetoencephalography (MEG).
Among these techniques, fMRI, with a high temporal-spatial resolutions, is a predominant technique for observing the FC changes in acupuncture studies [
From 2006 to 2013, the number of studies focusing on investigating the cerebral FC changes elicited by acupuncture is increasing year by year. There were totally 41 articles elaborating these studies, with 28 published in English and 13 published in Chinese (shown in Table
Studies on the acupuncture and cerebral functional connectivity.
Author | Year | Language | Participants | Case number | Group number | Intervention | Points | Control |
---|---|---|---|---|---|---|---|---|
Qin et al. [ |
2006 | E | HS | 14 | 1 | MA | ST36 | Baseline versus after acupuncture |
Bai et al. [ |
2007 | E | HS | 8 | 2 | MA | ST36 | Acupuncture versus sham acupuncture |
Napadow et al. [ |
2007 | E | CTS, HS | 25 (13 CTS patients) | 2 | MA | LI-4 | Baseline versus after acupuncture |
Qin et al. [ |
2008 | E | HS | 18 | 2 | MA | ST36 | Acupuncture versus sham acupuncture |
Dhond et al. [ |
2008 | E | HS | 15 | 2 | MA | left PC6 | Acupuncture versus sham acupuncture |
Zhang et al. [ |
2009 | E | HS | 36 | 3 | EA | GB 37, KI 8 | EA versus light flash stimulation |
Liu et al. [ |
2009 | E | HS | 56 | 4 | EA | GB37, BL60, KI8, a sham point | Acupuncture versus sham acupuncture |
Liu et al. [ |
2009 | E | HS | 28 | 2 | EA | GB37, KI8 | Puncturing at GB37 versus puncturing at K18 |
Hui et al. [ |
2009 | E | HS | 48 | 3 | MA | LI4, ST36, LV3 | Acupuncture versus superficial tactile stimulation |
Liu et al. [ |
2009 | C | HS | 21 | 2 | MA | ST36 | Puncturing at nonacupoints versus puncturing at ST36 |
Long et al. [ |
2009 | C | HS | 17 | 1 | MA | ST36 | Baseline versus after acupuncture |
Zyloney et al. [ |
2010 | E | HS | 48 | 4 | EA | LI3, LI4 | Acupuncture versus sham acupuncture |
Qiu et al. [ |
2010 | E | HS | 38 | 2 | MA | LV3 | Female versus male |
Ren et al. [ |
2010 | E | HS | 36 | 3 | MA | PC6, PC7, GB37 | Puncturing at PC6 versus puncturing at PC7 versus puncturing at GB37 |
Hui et al. [ |
2010 | E | HS | 37 | 3 | MA | LI4, ST36, LV3 | Acupuncture versus sham acupuncture |
Liu et al. [ |
2011 | E | HS | 14 | 2 | MA | ST36 | Acupuncture versus sham acupuncture |
Feng et al. [ |
2011 | E | HS | 36 | 3 | MA | PC6, PC7, GB37 | Puncturing at PC6 versus puncturing at PC7 versus puncturing at GB37 |
Feng et al. [ |
2011 | E | HS | 36 | 3 | MA | PC6, PC7, GB37 | Puncturing at PC6 versus puncturing at PC7 versus puncturing at GB37 |
Feng et al. [ |
2011 | E | HS | 14 | 2 | MA | ST36 | Acupuncture versus sham acupuncture |
Ye et al. [ |
2011 | C | HS | 10 | 1 | MA | EX-UE7 |
Baseline versus after acupuncture |
Ye et al. [ |
2011 | C | LIDP, HS | 20 (10 HS) | 2 | MA | EX-UE7 |
Baseline versus after acupuncture; |
Ye et al. [ |
2011 | C | LIDP | 10 | 1 | MA | EX-UE7 |
Baseline versus after acupuncture |
Li et al. [ |
2011 | C | HS | 9 | 1 | MA | ST36 | Baseline versus after acupuncture |
Fang et al. [ |
2011 | C | HS | 21 | 1 | EA | RN12 | Baseline versus after acupuncture |
Zhong et al. [ |
2012 | E | HS | 12 | 2 | MA | GB40, KI3 | Baseline versus after acupuncture; |
You et al. [ |
2012 | E | HS | 28 | 2 | MA | ST36 | Acupuncture versus sham acupuncture |
Jiang et al. [ |
2012 | E | HS | 40 | 2 | TEAS | TEAS versus intermittent minimal TEAS | |
Fang et al. [ |
2012 | E | HS | 21 | 2 | EA | CV4, CV12 | Puncturing at CV4 versus puncturing at CV12 |
Feng et al. [ |
2012 | E | MCI | 24 | 2 | MA | KI3 | Baseline versus after acupuncture |
Li et al. [ |
2012 | C | Chronic sciatica, HS | 20 (10 HS) | 2 | EA | GB30, BL40, BL25, BL23, BL57 | Chronic sciatica patients versus HS |
Zhao et al. [ |
2012 | C | HS | 20 | 1 | MA | LI4 | Baseline versus after acupuncture |
Yi et al. [ |
2012 | C | Depression, HS | 39 (13 HS) | 3 | MA | LV3 | HS versus puncturing at nonacupoints in depressed patients versus puncturing at LV3 in depressed patients |
Fang et al. [ |
2012 | C | HS | 47 | 3 | MA | LV3 | Puncturing at LV3 with deqi versus puncturing at LV3 with deqi mixed with sharp pain versus superficial tactile stimulation at LV3 |
Dai et al. [ |
2012 | C | HS | 16 | 1 | MA | SP6 | Puncturing at nonacupoints versus puncturing at SP6 |
Zhang et al. [ |
2013 | E | HS | 12 | 1 | EA | GV20, EX-HN3 | 5 min versus 15 min after acupuncture |
You et al. [ |
2013 | E | HS | 28 | 2 | MA | ST36 | Acupuncture versus sham acupuncture |
Jiang et al. [ |
2013 | E | HS | 18 | 4 | MA, EA, TEAS | ST36 | MA versus EA versus TEAS versus sensory stimulation |
Dong et al. [ |
2013 | E | HS | 32 | 2 | NA | NA | Acupuncturist versus nonacupuncturist |
Chen et al. [ |
2013 | E | MCI | 24 | 2 | MA | KI4 | Baseline versus after acupuncture |
Chen et al. [ |
2013 | E | Primary hypertension | 30 | 2 | MA | GV20,GV23, EX-HN1 (Sishencong), LI4, ST36, SP6, LR3 | Baseline versus after acupuncture |
Chen et al. [ |
2013 | C | MCI | 6 | 1 | MA | DU26 | Baseline versus after acupuncture |
E: English; C: Chinese; HS: healthy subjects; CTS: carpal tunnel syndrome; MCI: mild cognitive impairment; LIDP: lumbar intervertebral disc protrusion; MA: manual acupuncture; EA: electro-acupuncture; TEAS: transcutanclus electrical acupoint stimulation.
The earliest FC analysis applied in acupuncture studies could be traced back to 2006. Qin et al. [
Subsequently, Hui et al. [
Following an increase in studies concentrating on the investigation of FC exerted by the immediate effect of acupuncture, Feng et al. [
Recently, a study conducted by You and his colleagues combined fMRI and MEG to explore spatiotemporally whether or not band-specific DMN hub configurations would be induced by verum acupuncture, compared with sham control [
Besides, other studies performed on GB37 (Guangming), KI8 (Jiaoxin), PC6 (Neiguan), PC7 (Daling), CV4 (Guanyuan), CV12 (Zhongwan), and GV20 (Baihui) of HS also identified the influence of acupuncture on cerebral FC [
In 2007, Napadow and his coinvestigators explored the influence of acupuncture on patients with Carpal Tunnel Syndrome (CTS) using fMRI and FC analysis [
With whole brain FC analysis, Feng et al. found that patients with Mild Cognitive Impairment (MCI) showed abnormal FC in memory-related brain regions including the hippocampus, thalamus, and fusiform gyrus, and acupuncture could significantly influence FC in these abnormal regions [
With fMRI and within-condition interregional covariance analysis (WICA), Chen et al. found that although short-term acupuncture did not significantly decrease blood pressure, it appeared to decrease body pain and improve vitality. After acupuncture treatment, the hypothalamus-related brain network showed increased FC with the medulla, brainstem, cerebellum, limbic system, thalamus, and frontal lobes [
With fMRI and seed-based FC analysis, Ye et al. [
Yi et al. [
Furthermore, Li et al. [
Taken together, by using fMRI and FC analysis methods, more and more studies found that acupuncture may have profound influence on extensive regions of the limbic system. Furthermore, acupuncture may have the function of mobilizing the anticorrelated functional networks of the brain, especially deactivating the LPNN/DMN, which may help to explore the central mechanism of acupuncture.
Although FC has greatly expanded our horizon and enhanced our ability to investigate the central mechanism of acupuncture, it is still at a preliminary stage in connectomics. The limitations in the current studies are as follows: (1) the majority of these studies are performed on HS, while little attention was given to patients. Actually, the therapeutic effect of acupuncture focuses on pathological changes not the physiological condition. Therefore, studies performed on patients are more important for exploring the therapeutic mechanism of acupuncture and (2) among the techniques used in acupuncture research for observing brain FC changes, the fMRI is the most popular. However, it is limited by its indirect nature via BOLD response measurement rather than electrical neuronal activity or substance metabolism. Combining fMRI with other neuroimaging techniques such as MEG, EEG, Diffusion Weighed Imaging (DWI), or PET would be a superior method to improve the results’ repeatability in future research and (3) for analysis method, most studies used the whole brain FC analysis and mGCA. Other methods such as “small world” and so forth are also suitable for acupuncture neuroimaging study and (4) for the study design, most studies focused on the immediate effect elicited by acupuncture, while the achievement of acupuncture efficacy usually need a duration of treatment. So investigating the mechanism of the sustained effect or long last effect of acupuncture is more important in the future study and (5) for the quality control of acupuncture neuroimaging, the selection of nonacupoint, the manipulation of manual acupuncture, and the qualification of acupuncturist have effect on result and need for needs for specification and normalization.
In conclusion, connectomics based on neuroimaging techniques, is one of the forefront of neuroscience. Although the multitarget, multifactorial nature of acupuncture therapy and the current limitations make research in acupuncture central mechanism complex and difficult, we believe that connectomics will provide an important approach for further exploring the central mechanism of acupuncture.
The authors declare that they have no conflict of interests.
This study was supported by the “Youth Foundation of National Natural Science Foundation of China (no. 81001504),” the “State Key Program for Basic Research of China (no. 2011CB505205),” the “Youth Foundation of Sichuan Province" (no. 2012JQ053), and the “Project of Innovation Team in the Education Department of Sichuan Province (no. 12TD002).” The authors thank Danhua Zhang and Yiwei Liu for assistance in this study.