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Evidence-Based Complementary and Alternative Medicine
Volume 2013 (2013), Article ID 297839, 11 pages
http://dx.doi.org/10.1155/2013/297839
Review Article

What Is the de-qi-Related Pattern of BOLD Responses? A Review of Acupuncture Studies in fMRI

1Life Sciences Research Center, School of Life Sciences and Technology, Xidian University, Xi’an, Shaanxi 710071, China
2Institute of Automation, Chinese Academy of Sciences, Beijing 100190, China

Received 25 September 2012; Revised 24 December 2012; Accepted 6 January 2013

Academic Editor: Vitaly Napadow

Copyright © 2013 Jinbo Sun et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

de-qi, comprising mostly subjective sensations during acupuncture, is traditionally considered as a very important component for the possible therapeutic effects of acupuncture. However, the neural correlates of de-qi are still unclear. In this paper, we reviewed previous fMRI studies from the viewpoint of the neural responses of de-qi. We searched on Pubmed and identified 111 papers. Fourteen studies distinguishing de-qi and sharp pain and eight studies with the mixed sensations were included in further discussions. We found that the blood oxygenation level-dependent (BOLD) responses associated with de-qi were activation dominated, mainly around cortical areas relevant to the processing of somatosensory or pain signals. More intense and extensive activations were shown for the mixed sensations. Specific activations of sharp pain were also shown. Similar BOLD response patterns between de-qi evoked by acupuncture stimulation and de-qi-like sensations evoked by deep pain stimulation were shown. We reckon that a standardized method of qualification and quantification of de-qi, deeper understanding of grouping strategy of de-qi and sharp pain, and making deep pain stimulation as a control, as well as a series of improvements in the statistical method, are crucial factors for revealing the neural correlates of de-qi and neural mechanisms of acupuncture.

1. Introduction

Acupuncture, as a key component of traditional Chinese medicine (TCM) and an alternative and complementary therapy in western society, has been widely used all over the world. As an old concept that appeared in a very early Chinese classic text, de-qi was believed to be an indispensable component of acupuncture treatment [1]. In recent years, the importance of de-qi has been investigated based on the modern biological and medical framework [214]. Several studies reported the correlation between the de-qi sensations and analgesic effects [24, 1012] or the electroencephalogram changes [9], whereas others do not [8, 13, 14]. Therefore, the role of de-qi in acupuncture treatment is still controversial [1, 5, 6, 15].

Many researchers have begun to qualify and quantify sensations of de-qi [1527], because they argued that the lack of a competent measure of de-qi affected the association between de-qi and the clinical outcomes [1, 18, 19]. Most studies reported that de-qi sensations involved numbness, heaviness, aching, dull pain, and tingling [1, 16, 18, 19, 23, 25, 27]. Other sensations such as fullness/distention, soreness, and pressure were also included in part of the studies [1, 16, 19, 27]. The dimensions of sensations of de-qi were largely different, which ranged from four [19] to seventeen [25]. Although there have not a consensus that which sensations were involved in de-qi, researchers focused on qualifying and quantifying sensations of de-qi, and they agreed that deqi includes specific sensations for acupuncture stimulation [1, 16, 18, 27]. Besides, another consensus was reached that as a conventional component of the needling sensations presented during acupuncture manipulation, sharp pain is noxious and is what acupuncturists try to avoid during needle manipulation [1, 16, 18, 25]. It is often excluded from the components of de-qi and regarded as the sensation that is irrelevant to the acupuncture effect [1, 16, 18, 25].

With the aid of functional magnetic resonance imaging (fMRI) techniques, it is possible to explore the neural responses of de-qi and further interpret the neural mechanisms of acupuncture. More than one hundred studies have been published to explore the neurobiological mechanisms of acupuncture in the past few decades [2836]. However, few of them paid close attention to the neural correlation of de-qi. Therefore, several fundamental issues about the central responses of de-qi remain open to debate. First of all, although researchers agreed that de-qi has specific sensations for acupuncture stimulation [16], the sensory quality of de-qi was similar to that of deep pain constructed by intramuscular injections of hypertonic saline, which mainly included tenderness, heaviness, aching, cramping, throbbing, and gnawing [25, 37]. Thus, the quality of the sensation of de-qi was likely nonspecific [38, 39]. Up to now, however, direct comparisons of blood oxygenation level-dependent (BOLD) responses between de-qi sensations evoked by acupuncture stimulation and de-qi-like sensations evoked by deep pain stimulation have not yet been investigated. Only one recent study involved the indirect comparisons of these two stimulations, which had a similar sensory quality, in the discussion [40]. Secondly, in the domain of pain studies, it is generally known that differences in the quality and origin between sharp pain and deep pain are remarkable [41]. Abundant evidence from animal investigations [42, 43], clinical data [4446], and human neuroimage studies [37, 4752] indicated different brain processing pathways for acute superficial pain (sharp pain) and deep pain. The sharp pain following acupuncture stimulation is sometimes perceived by subjects. However, most previous acupuncture fMRI studies did not explicitly distinguish the needle sensations into de-qi and sharp pain. To make matters worse, significant incompatibilities were shown across the results of several studies which excluded subjects who experienced sharp pain [22, 23, 25] or divided subjects into two groups according to whether subjects experienced sharp pain during acupuncture manipulation [33, 5355].

In this paper, we would like to summarize the results of fMRI-based acupuncture studies from the perspective of the general pattern of central BOLD responses of de-qi. We aim to organize the evidence about three fundamental questions. First, what is the pattern of central responses of de-qi evoked by during acupuncture stimulation? Second, how are the distinct patterns of central BOLD responses associated with de-qi and sharp pain? Thirdly, are the patterns of central BOLD responses associated with de-qi specific from those of deep pain in pain studies? In addition, we hope to offer several suggestions for future studies of the neural correlates of de-qi evoked by acupuncture stimulation.

2. Identification of the Relevant Literature

The acupuncture studies involved in this paper were first identified by searching on Pubmed using the key words “acupuncture” or “electroacupuncture” in the title and “fMRI” or “functional magnetic resonance imaging” in the title/abstract (four combinations of key words: “acupuncture” and “fMRI,” “acupuncture” and “functional magnetic resonance imaging,” “electroacupuncture” and “fMRI,” and “electroacupuncture” and “functional magnetic resonance imaging”). About 111 original studies published in peer-reviewed journals in English were included in the search (two studies in the Evidence-Based Complementary and Alternative Medicine with the state of “in press” were also involved). Firstly, 17 review articles were excluded. Secondly, 23 studies which did not evaluate and record subjects’ needling sensations were discarded from further discussions. Thirdly, 13 studies that were based on data-driven methods were excluded. Fourthly, 4 studies that aimed to explore the continuous effect of acupuncture were also excluded. Fifthly, other 15 studies were also not included because of the lack of de-qi-related BOLD responses (2 were behavioral studies, 2 were magnetoencephalogram-based studies, 4 studies were associated with the therapeutic/placebo effect of acupuncture, 1 study was laser-acupuncture-based, and 5 studies lacked the whole brain’s one-sample t-test results). In the remaining 39 studies, 17 studies asked or evaluated the subjects’ de-qi but did not mention whether subjects underwent sharp pain [36, 38, 5670]. Eight studies which asked or evaluated the subjects’ de-qi and sharp pain but did not distinguish de-qi and sharp pain in the fMRI analysis [53, 7177] were named as “mixed pattern studies” and summarized in Table 3. Fourteen studies that excluded subjects who experienced sharp pain for the fMRI data analysis [32, 34, 7885] or divided subjects into two groups according to whether subjects experienced sharp pain during acupuncture manipulation [33, 40, 54, 55] were named as “pure de-qi pattern studies” and are summarized in Table 2. The experimental details and the methodological details of the 14 de-qi-related studies are shown in Table 1 and Table 5, respectively.

tab1
Table 1: Experimental details of fMRI studies on BOLD responses of de-qi.
tab2
Table 2: de-qi-related BOLD responses evoked by acupuncture stimulation.
tab3
Table 3: mixed-related BOLD responses evoked by acupuncture stimulation.

3. General Observations

Reviewing the studies of acupuncture in fMRI, we found that de-qi and sharp pain were not distinguished in most studies (97 out of 111, 87%). Therefore, limited resources could be used for summarizing the de-qi BOLD response patterns. We suggest that it is necessary to differentiate de-qi and sharp pain in further fMRI acupuncture studies. In the following part, we will summarize the BOLD response patterns of pure de-qi, the BOLD response patterns of mixed sensations, the similarities/differences of BOLD response patterns between pure de-qi and mixed sensations, similarities/differences of BOLD response patterns between pure de-qi and de-qi-like sensations evoked by deep pain stimulation, and the comparison of de-qi-related regions with regions generally activated in acupuncture fMRI studies, which were summarized in other reviews [39, 86].

3.1. The BOLD Responses Pattern of Pure de-qi

The common activations (frequency 4 or 29%) of de-qi were the SI, SII, thalamus, MI, cerebellum, insula, inferior parietal lobe, and anterior MCC. The common deactivations of de-qi were the ACC, amygdala, hippocampus, parahippocampus, hypothalamus, temporal pole, and PCC. Most of the commonly responding regions (11/15 or 73%) were divergent across studies.

3.2. The BOLD Response Patterns of Mixed Sensations

The common activations (frequency   2 or 25%) of mixed sensations were the SI, SII, MI, cerebellum, SMA, insula, IMG, DLPFC/VLPFC, and pMCC. The common deactivations of de-qi were the STG, inferior temporal gyrus, precuneus, lingual gyrus, occipital gyrus, and PCC.

3.3. The Similarities/Differences of BOLD Response Patterns between Pure de-qi and Mixed Sensations

In the 14 “pure de-qi pattern studies,” only two studies performed the between-group analysis that statistically compared the de-qi group and mixed group (de-qi  + sharp pain) based on a two-sample unpaired t-test [40, 55]. In Hui et al., 2009, significant differences in the posterior cingulate/precuneus, pregenual cingulate/frontal pole, subgenual area, orbitofrontal cortex, temporal pole, amygdala, hippocampus, parahippocampus, hypothalamus, cerebellar vermis (lobules VII and VIII), SII, and anterior middle cingulate were shown between the de-qi group and mixed group. Specifically, activity of BOLD signals was significantly less activated or more deactivated in the de-qi group than that in the mixed group. In Sun et al., 2012, significantly stronger activations of the mixed group were presented in the bilateral putamen, the bilateral thalamus, and the bilateral cerebellum (CrusI and CrusII) [40]. In these regions, BOLD signals of the de-qi group were barely changed, while significant BOLD responses were shown in the mixed group.

3.4. The Similarities/Differences of BOLD Response Patterns between Pure de-qi and de-qi-Like Sensations Evoked by Deep Pain Stimulation

In contrast to superficial (cutaneous) pain, deep pain (originating from muscle, joints or viscera) is dull, diffuse, and difficult to localize [37, 50]. In Henderson et al., 2006, the researchers used intramuscular injections of hypertonic saline to construct a deep pain model [37]. The subjective sensations under this deep pain mainly included tenderness, heaviness, aching, cramping, throbbing, and gnawing, which were similar to that of de-qi evoked by acupuncture stimulation. Table 4 summarizes the activations and deactivations from the deep pain studies [37, 48, 50, 87, 88]. Common activations (frequency 2 or 40%) were seen in the anterior cingulate, posterior cingulate, SI, SII, MI, insula, cerebellar cortices, inferior parietal, claustrum, and thalamus. A common deactivation was in the perigenual cingulate. Most of the activations for deep pain were consistent with that of de-qi evoked by acupuncture stimulation, except for the anterior cingulate and posterior cingulate, which were commonly deactivated during de-qi. Besides, the amygdala, hippocampus, parahippocampus, hypothalamus, and temporal pole were deactivated for de-qi but not for deep pain.

tab4
Table 4: BOLD responses evoked by deep pain stimulation.
tab5
Table 5: Methodological details of fMRI studies on BOLD responses for de-qi.
3.5. The Comparison of de-qi-Related Regions with Regions Generally Activated in Acupuncture fMRI Studies

Huang et al., 2012, summarized the general BOLD responses in acupuncture fMRI studies [86]. The supramarginal gyrus/insula/SII, presupplementary motor area/middle cingulate, thalamus, and precentral gyrus were the most commonly found activations. Besides, the anterior cingulate, subgenual cortex, amygdala/hippocampal formation, ventromedial prefrontal cortex, and posterior cingulate were the most common deactivations. Beissner, 2011, summarized the common BOLD responses evoked by acupuncture stimulation based on studies which met the methodological inclusion criteria [39]. The most frequently activated cortical areas were the SII, insula, SI, cerebellum, thalamus, MI, STG, visual cortices, IFG, SMA/pre-SMA, basal ganglia, MTG, and ACC. Significant differences in the regions generally activated in acupuncture fMRI studies were shown between these two previous reviews. When comparing our results with theirs, we found that our results were more similar to the results of Huang et al., 2012, but were more extensive (particularly showing more deactivations) than the results of Beissner, 2011. We argued that it was because our review of de-qi-related patterns and results of Huang et al., 2012, lacked the methodological inclusion criteria [39].

4. Discussion

This paper summarized the results of fMRI-based acupuncture studies from the perspective of the general pattern of central BOLD responses of de-qi. Three fundamental issues are discussed later. In addition, several suggestions for future studies of the neural correlates of de-qi evoked by acupuncture stimulation were offered.

4.1. Activation-Dominated BOLD Responses Associated with de-qi during Acupuncture Stimulation

The most robust BOLD responses evoked by acupuncture stimulation were in the SII, insula, SI, cerebellum, thalamus, MI, STG, visual cortices, IFG, SMA/pre-SMA, basal ganglia, MTG, and ACC. Under the methodological inclusion criteria [39], only the deactivation of the occipital cortex was shown. For the de-qi-related BOLD responses, a similar activation pattern was shown, including in the SI, SII, thalamus, MI, cerebellum, insula, inferior parietal lobe, and anterior MCC. Besides, several deactivations were seemingly the common pattern of de-qi. However, we argued that the reliability of these deactivations was poor. We inferred that several possible reasons might contribute to these deactivation patterns. Firstly, the average of the repeated runs for each subject was applied. Repetition may itself alter the distribution of the activated regions due to the influence of memory and expectation [48]. Secondly, global normalization, a questionable data processing step adopted in several fMRI-based acupuncture studies, can introduce an artificially negative relationship with the task [83, 8992]. Particularly, our recent study clarified that for the fMRI-based acupuncture data, global normalization significantly changed the activation-dominated results to deactivation-dominated ones [83]. Therefore, we suggested that BOLD responses associated with de-qi during acupuncture stimulation should be activation dominated.

4.2. Distinct Patterns of Central BOLD Responses Associated with de-qi and Sharp Pain

Since subjects with pure sharp pain during acupuncture stimulation were difficult to obtain, the differences between de-qi and sharp pain evoked by acupuncture stimulation could not be presented directly. Therefore, we had to infer their differences between the de-qi and mixed sensations. However, studies which were statistically compared with the BOLD responses between de-qi and mixed sensations were also a scarcity [40, 55]. Our recent study focused on these issues and indicated that both the quantitative and qualitative differences of BOLD responses between de-qi and mixed sensations evoked by acupuncture stimulation were distinct [40]. We inferred that the pattern of BOLD responses for sharp pain might be partly separated from that of de-qi in the spatial distribution. The subjects with sharp pain should be excluded from those with only de-qi when exploring the central BOLD responses during acupuncture stimulation [40].

4.3. Similar BOLD Response Patterns between de-qi Evoked by Acupuncture Stimulation and de-qi-Like Sensations Evoked by Deep Pain Stimulation

Most common activations of de-qi in this paper were shown in the aforementioned deep pain studies, which might indicate similar central processing of the same origin of stimulation and similar subjective sensations. Due to individual variability of brain morphology and differences in experimental design, the central patterns of activation during deep pain and acupuncture stimulation were difficult to compare between studies. Therefore, we suggested that a specific central effect of de-qi during acupuncture stimulation might be illustrated after comparing it directly to deep pain stimulation.

4.4. Several Suggestions for Future Studies of the Neural Correlates of de-qi Evoked by Acupuncture Stimulation

First of all, for better understanding what de-qi is and exploring its possible role in acupuncture, many researchers have been engaged in qualifying and quantifying de-qi [1, 1527]. However, in the aforesaid fMRI-based acupuncture studies about de-qi, different sensation questionnaires were used to quantify subjects’ acupuncture sensations (see Table 1 for details). This may lead to two results. One is that the kinds of acupuncture sensations recorded by different studies are partially different. The other is that the same score of an acupuncture sensation between different studies refers to a different subjective intensity experienced by subjects due to the various definitions of the same score between different studies. Thus, acupuncture sensations recorded by different studies are inappropriate to compare. We suggest that further studies should pay more attention to the quantification questionnaire of de-qi and try to apply a standardized quantification method to better control the experimental conditions [38, 76].

Secondly, another important discrepancy among studies is the definition of grouping. In Hui et al. and Asghar et al. [33, 53], they both grouped subjects into two groups (the de-qi group and mixed group). But the definition of the “de-qi group” was totally different in the two studies. In the studies of Hui, the de-qi group referred to subjects who only experienced de-qi during acupuncture, while in Asghar et al., the de-qi group referred to subjects whose de-qi scores were greater than sharp pain, which were similar to the Sun et al.’s sharp pain group (de-qi sensation mixed with sharp pain). Sun et al.’s study indicated that even a little sharp pain mixed in, both the quantitative and qualitative differences of BOLD responses between de-qi and mixed sensations evoked by acupuncture stimulation were significant [40]. Therefore, we proposed that subjects with sharp pain should be separated from those with only de-qi when exploring the central BOLD responses during acupuncture stimulation. Further comparisons between de-qi and sharp pain should be accumulated. Besides, the deep pain stimulations, which had a similar sensory quality to de-qi evoked by acupuncture stimulation, could serve as a valid control for acupuncture.

At last, methodological problems and differences may partly contribute to the discrepancies among studies which were reviewed here. Beissner and Henke found that most acupuncture studies lacked adequate strict statistical methods and suggested that several methodological problems should be solved to facilitate acupuncture studies [93]. The improvements for obtaining more reliable results included a larger sample size, corrected threshold, and a more robust method of statistical inference [94]. With regards to the studies reviewed in this paper, an inappropriate group analysis method, a too small sample size, and the liberal threshold applied by the studies could be the most important problems (see Table 3 for details). For instance, first, Hui et al. [33] applied the fixed-effect model in the group analysis, which could produce positive group results even when only a single subject has strong activations [93]. Second, Hui et al. recruited 13 subjects in their study, and only two subjects experienced the mixed sensation [54]. Hui et al. recruited 15 subjects and a mixed group with 4 subjects [33]. Such a sample size (2 subjects and 4 subjects) is too small to obtain group results with sufficient statistical power. Third, several studies adopted global normalization [33, 53, 55], which is a questionable data processing step and can introduce an artificially negative relationship with the task [8992, 9598]. Particularly, our recent study clarified that for the fMRI-based acupuncture data, global normalization significantly changed the activation-dominated results to deactivation-dominated ones [83]. As a whole, solving these crucial methodological problems could greatly help studies on neural correlates of de-qi to obtain more repeatable and reliable results. Thus, we suggest that future studies should focus on improvements in their methodological problems which we believe could shed light on studies of neural correlates of de-qi.

5. Synopsis and Possible Solutions

de-qi, comprising mostly of subjective sensations during acupuncture, is traditionally considered as a very important component of the possible therapeutic effects of acupuncture. Thus, it is of great importance to reveal the neural correlates of de-qi which may benefit the understanding of neural mechanisms of acupuncture. However, previous studies in fMRI involving the BOLD response of de-qi were limited and did not reach consistent conclusions on the neural response pattern of de-qi in the brain. In this paper, we summarized previous fMRI studies on the neural responses of de-qi and answered three fundamental questions. For the first question concrning the pattern of the central responses of de-qi evoked by acupuncture stimulation, our answer was that the BOLD responses associated with de-qi during acupuncture stimulation were activation dominated, mainly around cortical areas relevant to the processing of somatosensory or pain signals. For the second question on how the distinct patterns of central BOLD responses are associated with de-qi and sharp pain, our answer was that more intensive and extensive activations were shown for the mixed sensations evoked by acupuncture stimulation. Specific activations of sharp pain were also shown. For the third question asking if the patterns of central BOLD responses were associated with de-qi specifically from those of deep pain in pain studies, our answer was that similar BOLD response patterns between de-qi evoked by acupuncture stimulation and de-qi-like sensations evoked by deep pain stimulation were shown. Finally, we reckon that a standardized method of qualification and quantification of de-qi, a deeper understanding of grouping strategy of de-qi and sharp pain, and marking the deep pain stimulation as a control, as well as a series of improvements in the statistical method, are crucial factors for revealing the neural correlates of de-qi and neural mechanisms of acupuncture.

Conflict of Interests

The authors declare that they have no conflict of interests.

Acknowledgments

This study was supported by the Project for the National Key Basic Research and Development Program (973) under Grant nos. 2012CB518501 and 2011CB707702, the National Natural Science Foundation of China under Grant nos. 30930112, 30970774, 81000640, 81000641, 81030027, 81101036, 81101108, 31150110171, 30901900, 81271644, and 31200837, and the Fundamental Research Funds for the Central Universities.

References

  1. J. Kong, R. Gollub, T. Huang et al., “Acupuncture De Qi, from qualitative history to quantitative measurement,” Journal of Alternative and Complementary Medicine, vol. 13, no. 10, pp. 1059–1070, 2007. View at Publisher · View at Google Scholar · View at Scopus
  2. C. Y. Chiang, C. T. Chang, H. L. Chu, and L. F. Yang, “Peripheral afferent pathway for acupuncture analgesia,” Scientia Sinica, pp. 210–217, 1973.
  3. J. Kong, D. T. Fufa, A. J. Gerber et al., “Psychophysical outcomes from a randomized pilot study of manual, electro, and sham acupuncture treatment on experimentally induced thermal pain,” Journal of Pain, vol. 6, no. 1, pp. 55–64, 2005. View at Publisher · View at Google Scholar · View at Scopus
  4. W. Takeda and J. Wessel, “Acupuncture for the treatment of pain of osteoarthritic knees,” Arthritis Care and Research, vol. 7, no. 3, pp. 118–122, 1994. View at Scopus
  5. A. Benham and M. I. Johnson, “Could acupuncture needle sensation be a predictor of analgesic response?” Acupuncture in Medicine, vol. 27, no. 2, pp. 65–67, 2009. View at Publisher · View at Google Scholar · View at Scopus
  6. M. I. Johnson and A. E. Benham, “Acupuncture needle sensation: the emerging evidence,” Acupuncture in Medicine, vol. 28, no. 3, pp. 111–114, 2010. View at Publisher · View at Google Scholar · View at Scopus
  7. D. C. E. Lim, “What do we know about needling sensation (de qi) and pain outcomes?” Focus on Alternative and Complementary Therapies, vol. 16, no. 2, pp. 126–127, 2011. View at Publisher · View at Google Scholar · View at Scopus
  8. P. White, P. Prescott, and G. Lewith, “Does needling sensation (de qi) affect treatment outcome in pain? Analysis of data from a larger single-blind, randomised controlled trial,” Acupuncture in Medicine, vol. 28, no. 3, pp. 120–125, 2010. View at Publisher · View at Google Scholar · View at Scopus
  9. C. S. Yin, H. J. Park, S. Y. Kim et al., “Electroencephalogram changes according to the subjective acupuncture sensation,” Neurological Research, vol. 32, supplement 1, pp. S31–S36, 2010. View at Publisher · View at Google Scholar · View at Scopus
  10. J. Vas, E. Perea-Milla, C. Méndez et al., “Efficacy and safety of acupuncture for chronic uncomplicated neck pain: a randomised controlled study,” Pain, vol. 126, no. 1–3, pp. 245–255, 2006. View at Publisher · View at Google Scholar · View at Scopus
  11. C. Witt, B. Brinkhaus, S. Jena et al., “Acupuncture in patients with osteoarthritis of the knee: a randomised trial,” The Lancet, vol. 366, no. 9480, pp. 136–143, 2005. View at Publisher · View at Google Scholar · View at Scopus
  12. B. M. Berman, L. Lao, P. Langenberg, W. L. Lee, A. M. K. Gilpin, and M. C. Hochberg, “Effectiveness of acupuncture as adjunctive therapy in osteoarthritis of the knee. A randomized, controlled trial,” Annals of Internal Medicine, vol. 141, no. 12, pp. 901–910, 2004. View at Scopus
  13. H. P. Scharf, U. Mansmann, K. Streitberger et al., “Acupuncture and knee osteoarthritis: a three-armed randomized trial,” Annals of Internal Medicine, vol. 145, no. 1, pp. 12–20, 2006. View at Scopus
  14. M. Haake, H. H. Müller, C. Schade-Brittinger et al., “German Acupuncture Trials (GERAC) for chronic low back pain: randomized, multicenter, blinded, parallel-group trial with 3 groups,” Archives of Internal Medicine, vol. 167, no. 17, pp. 1892–1898, 2007. View at Publisher · View at Google Scholar · View at Scopus
  15. A. Benham, G. Phillips, and M. I. Johnson, “An experimental study on the self-report of acupuncture needle sensation during deep needling with bi-directional rotation,” Acupuncture in Medicine, vol. 28, no. 1, pp. 16–20, 2010. View at Publisher · View at Google Scholar · View at Scopus
  16. K. K. S. Hui, E. E. Nixon, M. G. Vangel et al., “Characterization of the “deqi” response in acupuncture,” BMC Complementary and Alternative Medicine, vol. 7, article 33, 2007. View at Publisher · View at Google Scholar · View at Scopus
  17. A. Y. Leung, J. Park, G. Schulteis, J. R. Duann, and T. Yaksh, “The electrophysiology of De Qi sensations,” Journal of Alternative and Complementary Medicine, vol. 12, no. 8, pp. 743–750, 2006. View at Publisher · View at Google Scholar · View at Scopus
  18. H. MacPherson and A. Asghar, “Acupuncture needle sensations associated with De Qi: a classification based on experts' ratings,” Journal of Alternative and Complementary Medicine, vol. 12, no. 7, pp. 633–637, 2006. View at Publisher · View at Google Scholar · View at Scopus
  19. J. J. Mao, J. T. Farrar, K. Armstrong, A. Donahue, J. Ngo, and M. A. Bowman, “De qi: Chinese acupuncture patients' experiences and beliefs regarding acupuncture needling sensation—an exploratory survey,” Acupuncture in Medicine, vol. 25, no. 4, pp. 158–165, 2007. View at Scopus
  20. D. Pach, C. Hohmann, R. Lüdtke, F. Zimmermann-Viehoff, C. M. Witt, and C. Thiele, “German translation of the southampton needle sensation questionnaire: use in an experimental acupuncture study,” Forschende Komplementarmedizin, vol. 18, no. 6, pp. 321–326, 2011. View at Publisher · View at Google Scholar
  21. J. Park, H. Park, H. Lee, S. Lim, K. Ahn, and H. Lee, “Deqi sensation between the acupuncture-experienced and the Naïve: a Korean study II,” American Journal of Chinese Medicine, vol. 33, no. 2, pp. 329–337, 2005. View at Publisher · View at Google Scholar · View at Scopus
  22. J. Park, A. White, C. Stevinson, E. Ernst, and M. James, “Validating a new non-penetrating sham acupuncture device: two randomised controlled trials,” Acupuncture in Medicine, vol. 20, no. 4, pp. 168–174, 2002. View at Scopus
  23. C. A. Vincent, P. H. Richardson, J. J. Black, and C. E. Pither, “The significance of needle placement site in acupuncture,” Journal of Psychosomatic Research, vol. 33, no. 4, pp. 489–496, 1989. View at Publisher · View at Google Scholar · View at Scopus
  24. A. White, M. Cummings, P. Barlas et al., “Defining an adequate dose of acupuncture using a neurophysiological approach—a narrative review of the literature,” Acupuncture in Medicine, vol. 26, no. 2, pp. 111–120, 2008. View at Scopus
  25. P. White, F. Bishop, H. Hardy et al., “Southampton needle sensation questionnaire: development and validation of a measure to gauge acupuncture needle sensation,” Journal of Alternative and Complementary Medicine, vol. 14, no. 4, pp. 373–379, 2008. View at Publisher · View at Google Scholar · View at Scopus
  26. D. T. W. Yu, A. Y. M. Jones, and M. Y. C. Pang, “Development and validation of the chinese version of the massachusetts general hospital acupuncture sensation scale: an exploratory and methodological study,” Acupuncture in Medicine, vol. 30, no. 3, pp. 214–221, 2012. View at Publisher · View at Google Scholar
  27. K. Zhou, J. Fang, X. Wang et al., “Characterization of De Qi with electroacupuncture at acupoints with different properties,” Journal of Alternative and Complementary Medicine, vol. 17, no. 11, pp. 1007–1013, 2011. View at Publisher · View at Google Scholar
  28. L. Bai, W. Qin, J. Tian et al., “Acupuncture modulates spontaneous activities in the anticorrelated resting brain networks,” Brain Research, vol. 1279, pp. 37–49, 2009. View at Publisher · View at Google Scholar · View at Scopus
  29. L. Bai, J. Tian, C. Zhong et al., “Acupuncture modulates temporal neural responses in wide brain networks: evidence from fMRI study,” Molecular Pain, vol. 6, article 73, 2010. View at Publisher · View at Google Scholar · View at Scopus
  30. R. P. Dhond, C. Yeh, K. Park, N. Kettner, and V. Napadow, “Acupuncture modulates resting state connectivity in default and sensorimotor brain networks,” Pain, vol. 136, no. 3, pp. 407–418, 2008. View at Publisher · View at Google Scholar · View at Scopus
  31. W. Qin, J. Tian, L. Bai et al., “FMRI connectivity analysis of acupuncture effects on an amygdala-associated brain network,” Molecular Pain, vol. 4, article 55, 2008. View at Publisher · View at Google Scholar · View at Scopus
  32. J. Fang, Z. Jin, Y. Wang et al., “The salient characteristics of the central effects of acupuncture needling: limbic-paralimbic-neocortical network modulation,” Human Brain Mapping, vol. 30, no. 4, pp. 1196–1206, 2009. View at Publisher · View at Google Scholar · View at Scopus
  33. K. K. S. Hui, J. Liu, O. Marina et al., “The integrated response of the human cerebro-cerebellar and limbic systems to acupuncture stimulation at ST 36 as evidenced by fMRI,” NeuroImage, vol. 27, no. 3, pp. 479–496, 2005. View at Publisher · View at Google Scholar · View at Scopus
  34. V. Napadow, N. Makris, J. Liu, N. W. Kettner, K. K. Kwong, and K. K. S. Hui, “Effects of electroacupuncture versus manual acupuncture on the human brain as measured by fMRI,” Human Brain Mapping, vol. 24, no. 3, pp. 193–205, 2005. View at Publisher · View at Google Scholar · View at Scopus
  35. S. S. Yoo, E. K. Teh, R. A. Blinder, and F. A. Jolesz, “Modulation of cerebellar activities by acupuncture stimulation: evidence from fMRI study,” NeuroImage, vol. 22, no. 2, pp. 932–940, 2004. View at Publisher · View at Google Scholar · View at Scopus
  36. J. Sun, W. Qin, M. Dong et al., “Evaluation of group homogeneity during acupuncture stimulation in fMRI studies,” Journal of Magnetic Resonance Imaging, vol. 32, no. 2, pp. 298–305, 2010. View at Publisher · View at Google Scholar · View at Scopus
  37. L. A. Henderson, R. Bandler, S. C. Gandevia, and V. G. MacEfield, “Distinct forebrain activity patterns during deep versus superficial pain,” Pain, vol. 120, no. 3, pp. 286–296, 2006. View at Publisher · View at Google Scholar · View at Scopus
  38. F. Beissner, R. Deichmann, C. Henke, and K.-J. Bär, “Acupuncture—deep pain with an autonomic dimension?” NeuroImage, vol. 60, no. 1, pp. 653–660, 2012. View at Publisher · View at Google Scholar
  39. F. Beissner, “Functional magnetic resonance imaging studies of acupuncture mechanisms: a critique,” Focus on Alternative and Complementary Therapies, vol. 16, no. 1, pp. 3–11, 2011. View at Publisher · View at Google Scholar · View at Scopus
  40. J. Sun, Y. Zhu, L. Jin, et al., “Partly separated activations in the spatial distribution between de-qi and sharp pain during acupuncture stimulation: an fMRI-based study,” Evidence-Based Complementary and Alternative Medicine, vol. 2012, Article ID 934085, 11 pages, 2012. View at Publisher · View at Google Scholar
  41. T. Lewis, Pain, McMillan, New York, NY, USA, 1942.
  42. R. Bandler, J. L. Price, and K. A. Keay, “Brain mediation of active and passive emotional coping,” Progress in Brain Research, vol. 122, pp. 333–349, 2000. View at Scopus
  43. B. M. Lumb, “Hypothalamic and Midbrain Circuitry That Distinguishes between Escapable and Inescapable Pain,” News in Physiological Sciences, vol. 19, no. 1, pp. 22–26, 2004. View at Publisher · View at Google Scholar · View at Scopus
  44. P. W. Nathan, M. C. Smith, and A. W. Cook, “Sensory effects in man of lesions of the posterior columns and of some other afferent pathways,” Brain, vol. 109, no. 5, pp. 1003–1041, 1986. View at Scopus
  45. H. J. W. Nauta, V. M. Soukup, R. H. Fabian et al., “Punctate midline myelotomy for the relief of visceral cancer pain,” Journal of Neurosurgery, vol. 92, no. 2, pp. 125–130, 2000. View at Scopus
  46. W. Noordenbos and P. D. Wall, “Diverse sensory functions with an almost totally divided spinal cord. A case of spinal cord transection with preservation of part of one anterolateral quadrant,” Pain, vol. 2, no. 2, pp. 185–195, 1976. View at Publisher · View at Google Scholar · View at Scopus
  47. A. C. N. Chen, M. Shimojo, P. Svensson, and L. Arendt-Nielsen, “Brain dynamics of scalp evoked potentials and current source densities to repetitive (5-pulse train) painful stimulation of skin and muscle: central correlate of temporal summation,” Brain Topography, vol. 13, no. 1, pp. 59–72, 2000. View at Publisher · View at Google Scholar · View at Scopus
  48. L. A. Henderson, S. C. Gandevia, and V. G. Macefield, “Gender differences in brain activity evoked by muscle and cutaneous pain: a retrospective study of single-trial fMRI data,” NeuroImage, vol. 39, no. 4, pp. 1867–1876, 2008. View at Publisher · View at Google Scholar · View at Scopus
  49. D. M. Niddam, T. Graven-Nielsen, L. Arendt-Nielsen, and A. C. N. Chen, “Non-painful and painful surface and intramuscular electrical stimulation at the thenar and hypothenar sites: differential cerebral dynamics of early to late latency SEPs,” Brain Topography, vol. 13, no. 4, pp. 283–292, 2001. View at Publisher · View at Google Scholar · View at Scopus
  50. D. M. Niddam, T. C. Yeh, Y. T. Wu et al., “Event-related functional MRI study on central representation of acute muscle pain induced by electrical stimulation,” NeuroImage, vol. 17, no. 3, pp. 1437–1450, 2002. View at Publisher · View at Google Scholar · View at Scopus
  51. M. Shimojo, P. Svensson, L. Arendt-Nielsen, and A. C. N. Chen, “Dynamic brain topography of somatosensory evoked potentials and equivalent dipoles in response to graded painful skin and muscle stimulation,” Brain Topography, vol. 13, no. 1, pp. 43–58, 2000. View at Publisher · View at Google Scholar · View at Scopus
  52. P. Svensson, A. Beydoun, T. J. Morrow, and K. L. Casey, “Non-painful and painful stimulation of human skin and muscle: analysis of cerebral evoked potentials,” Electroencephalography and Clinical Neurophysiology—Evoked Potentials, vol. 104, no. 4, pp. 343–350, 1997. View at Publisher · View at Google Scholar · View at Scopus
  53. A. U. Asghar, G. Green, M. F. Lythgoe, G. Lewith, and H. MacPherson, “Acupuncture needling sensation: the neural correlates of deqi using fMRI,” Brain Research, vol. 1315, pp. 111–118, 2010. View at Publisher · View at Google Scholar · View at Scopus
  54. K. K. S. Hui, J. Liu, N. Makris et al., “Acupuncture modulates the limbic system and subcortical gray structures of the human brain: evidence from fMRI studies in normal subjects,” Human Brain Mapping, vol. 9, no. 1, pp. 13–25, 2000. View at Publisher · View at Google Scholar
  55. K. K. S. Hui, O. Marina, J. D. Claunch et al., “Acupuncture mobilizes the brain's default mode and its anti-correlated network in healthy subjects,” Brain Research, vol. 1287, pp. 84–103, 2009. View at Publisher · View at Google Scholar · View at Scopus
  56. M. T. Wu, J. M. Sheen, K. H. Chuang et al., “Neuronal specificity of acupuncture response: a fMRI study with electroacupuncture,” NeuroImage, vol. 16, no. 4, pp. 1028–1037, 2002. View at Publisher · View at Google Scholar · View at Scopus
  57. G. Li, L. Huang, R. T. F. Cheung, S. R. Liu, Q. Y. Ma, and E. S. Yang, “Cortical activations upon stimulation of the sensorimotor-implicated acupoints,” Magnetic Resonance Imaging, vol. 22, no. 5, pp. 639–644, 2004. View at Publisher · View at Google Scholar · View at Scopus
  58. G. Li, C. R. Jack, and E. S. Yang, “An fMRI study of somatosensory-implicated acupuncture points in stable somatosensory stroke patients,” Journal of Magnetic Resonance Imaging, vol. 24, no. 5, pp. 1018–1024, 2006. View at Publisher · View at Google Scholar · View at Scopus
  59. D. D. Dougherty, J. Kong, M. Webb, A. A. Bonab, A. J. Fischman, and R. L. Gollub, “A combined [11C]diprenorphine PET study and fMRI study of acupuncture analgesia,” Behavioural Brain Research, vol. 193, no. 1, pp. 63–68, 2008. View at Publisher · View at Google Scholar · View at Scopus
  60. L. Li, H. Liu, Y. Z. Li et al., “The human brain response to acupuncture on same-meridian acupoints: evidence from an fMRI study,” Journal of Alternative and Complementary Medicine, vol. 14, no. 6, pp. 673–678, 2008. View at Publisher · View at Google Scholar · View at Scopus
  61. G. Li and E. S. Yang, “An fMRI study of acupuncture-induced brain activation of aphasia stroke patients,” Complementary Therapies in Medicine, vol. 19, supplement 1, pp. S49–S59, 2011. View at Publisher · View at Google Scholar · View at Scopus
  62. S. Shukla, A. Torossian, J. R. Duann, and A. Leung, “The analgesic effect of electroacupuncture on acute thermal pain perception-a central neural correlate study with fMRI,” Molecular Pain, vol. 7, article 45, 2011. View at Publisher · View at Google Scholar · View at Scopus
  63. J. L. Fang, T. Krings, J. Weidemann, I. G. Meister, and A. Thron, “Functional MRI in healthy subjects during acupuncture: different effects of needle rotation in real and false acupoints,” Neuroradiology, vol. 46, no. 5, pp. 359–362, 2004. View at Publisher · View at Google Scholar · View at Scopus
  64. S. M. Wang, R. T. Constable, F. S. Tokoglu, D. A. Weiss, D. Freyle, and Z. N. Kain, “Acupuncture-induced blood oxygenation level-dependent signals in awake and anesthetized volunteers: a pilot study,” Anesthesia and Analgesia, vol. 105, no. 2, pp. 499–506, 2007. View at Publisher · View at Google Scholar · View at Scopus
  65. W. Wang, L. Liu, X. Zhi et al., “Study on the regulatory effect of electro-acupuncture on Hegu point (LI4) in cerebral response with functional magnetic resonance imaging,” Chinese Journal of Integrative Medicine, vol. 13, no. 1, pp. 10–16, 2007. View at Publisher · View at Google Scholar · View at Scopus
  66. Y. Zhou and J. Jia, “Effect of acupuncture given at the HT 7, ST 36, ST 40 and KI 3 acupoints on various parts of the brains of Alzheimer's disease patients,” Acupuncture and Electro-Therapeutics Research, vol. 33, no. 1-2, pp. 9–17, 2008. View at Scopus
  67. S. U. Park, A. S. Shin, G. H. Jahng, S. K. Moon, and J. M. Park, “Effects of scalp acupuncture versus upper and lower limb acupuncture on signal activation of blood oxygen level dependent (BOLD) fMRI of the brain and somatosensory cortex,” Journal of Alternative and Complementary Medicine, vol. 15, no. 11, pp. 1193–1200, 2009. View at Publisher · View at Google Scholar · View at Scopus
  68. J. H. Zhang, J. Li, X. D. Cao, and X. Y. Feng, “Can electroacupuncture affect the sympathetic activity, estimated by skin temperature measurement? A functional MRI study on the effect of needling at GB 34 and GB 39 on patients with pain in the lower extremity,” Acupuncture and Electro-Therapeutics Research, vol. 34, no. 3-4, pp. 151–164, 2009. View at Scopus
  69. S. Yeo, I. H. Choe, M. Van Den Noort, P. Bosch, and S. Lim, “Consecutive acupuncture stimulations lead to significantly decreased neural responses,” Journal of Alternative and Complementary Medicine, vol. 16, no. 4, pp. 481–487, 2010. View at Publisher · View at Google Scholar · View at Scopus
  70. S. Yeo, S. Lim, I.-H. Choe et al., “Acupuncture stimulation on gb34 activates neural responses associated with parkinson's disease,” CNS Neuroscience and Therapeutics, vol. 18, no. 9, pp. 781–790, 2012. View at Publisher · View at Google Scholar
  71. J. Kong, F. Li, R. Li et al., “A pilot study of functional magnetic resonance imaging of the brain during manual and electroacupuncture stimulation of acupuncture point (LI-4 Hegu) in normal subjects reveals differential brain activation between methods,” Journal of Alternative and Complementary Medicine, vol. 8, no. 4, pp. 411–419, 2002. View at Scopus
  72. K. Li, B. Shan, J. Xu et al., “Changes in fMRI in the human brain related to different durations of manual acupuncture needling,” Journal of Alternative and Complementary Medicine, vol. 12, no. 7, pp. 615–623, 2006. View at Publisher · View at Google Scholar · View at Scopus
  73. V. Napadow, N. Kettner, J. Liu et al., “Hypothalamus and amygdala response to acupuncture stimuli in carpal tunnel syndrome,” Pain, vol. 130, no. 3, pp. 254–266, 2007. View at Publisher · View at Google Scholar · View at Scopus
  74. H. MacPherson, G. Green, A. Nevado et al., “Brain imaging of acupuncture: comparing superficial with deep needling,” Neuroscience Letters, vol. 434, no. 1, pp. 144–149, 2008. View at Publisher · View at Google Scholar · View at Scopus
  75. V. Napadow, R. Dhond, K. Park et al., “Time-variant fMRI activity in the brainstem and higher structures in response to acupuncture,” NeuroImage, vol. 47, no. 1, pp. 289–301, 2009. View at Publisher · View at Google Scholar · View at Scopus
  76. V. Napadow, R. P. Dhond, J. Kim et al., “Brain encoding of acupuncture sensation—coupling on-line rating with fMRI,” NeuroImage, vol. 47, no. 3, pp. 1055–1065, 2009. View at Publisher · View at Google Scholar · View at Scopus
  77. V. Napadow, J. Lee, J. Kim et al., “Brain correlates of phasic autonomic response to acupuncture stimulation: an event-related fMRI study,” Human Brain Mapping, 2012. View at Publisher · View at Google Scholar
  78. S. S. Jeun, J. S. Kim, B. S. Kim et al., “Acupuncture stimulation for motor cortex activities: a 3T fMRI Study,” American Journal of Chinese Medicine, vol. 33, no. 4, pp. 573–578, 2005. View at Publisher · View at Google Scholar · View at Scopus
  79. J. Kong, R. L. Gollub, J. M. Webb, J. T. Kong, M. G. Vangel, and K. Kwong, “Test-retest study of fMRI signal change evoked by electroacupuncture stimulation,” NeuroImage, vol. 34, no. 3, pp. 1171–1181, 2007. View at Publisher · View at Google Scholar · View at Scopus
  80. B. J. Na, G. H. Jahng, S. U. Park et al., “An fMRI study of neuronal specificity of an acupoint: electroacupuncture stimulation of Yanglingquan (GB34) and its sham point,” Neuroscience Letters, vol. 464, no. 1, pp. 1–5, 2009. View at Publisher · View at Google Scholar · View at Scopus
  81. L. Bai, H. Yan, N. Li et al., “Neural specificity of acupuncture stimulation at pericardium 6: evidence from an fMRI study,” Journal of Magnetic Resonance Imaging, vol. 31, no. 1, pp. 71–77, 2010. View at Publisher · View at Google Scholar · View at Scopus
  82. W. Q. Qiu, J. Claunch, J. Kong et al., “The effects of acupuncture on the brain networks for emotion and cognition: an observation of gender differences,” Brain Research, vol. 1362, pp. 56–67, 2010. View at Publisher · View at Google Scholar · View at Scopus
  83. J. Sun, W. Qin, L. Jin, et al., “Impact of global normalization in fMRI acupuncture studies,” Evidence-Based Complementary and Alternative Medicine, vol. 2012, Article ID 467061, 22 pages, 2012. View at Publisher · View at Google Scholar
  84. J. H. Zhang, X. D. Cao, J. Li, W. J. Tang, H. Q. Liu, and X. Y. Feng, “Neuronal specificity of needling acupoints at same meridian: a control functional magnetic resonance imaging study with electroacupuncture,” Acupuncture and Electro-Therapeutics Research, vol. 32, no. 3-4, pp. 179–193, 2007. View at Scopus
  85. J. Fang, X. Wang, H. Liu, et al., “The limbic-prefrontal network modulated by electroacupuncture at CV4 and CV12,” Evidence-Based Complementary and Alternative Medicine, vol. 2012, Article ID 515893, 11 pages, 2012. View at Publisher · View at Google Scholar
  86. W. Huang, D. Pach, V. Napadow et al., “Characterizing acupuncture stimuli using brain imaging with fMRI—a systematic review and meta-analysis of the literature,” PLoS ONE, vol. 7, no. 4, Article ID e32960, 2012. View at Publisher · View at Google Scholar
  87. V. G. Macefield, S. Gandevia, and L. A. Henderson, “Discrete changes in cortical activation during experimentally induced referred muscle pain: a single-trial fMRI study,” Cerebral Cortex, vol. 17, no. 9, pp. 2050–2059, 2007. View at Publisher · View at Google Scholar · View at Scopus
  88. L. Maeda, M. Ono, T. Koyama et al., “Human brain activity associated with painful mechanical stimulation to muscle and bone,” Journal of Anesthesia, vol. 25, no. 4, pp. 523–530, 2011. View at Publisher · View at Google Scholar
  89. G. K. Aguirre, E. Zarahn, and M. D'Esposito, “The inferential impact of global signal covariates in functional neuroimaging analyses,” NeuroImage, vol. 8, no. 3, pp. 302–306, 1998. View at Publisher · View at Google Scholar · View at Scopus
  90. A. E. Desjardins, K. A. Kiehl, and P. F. Liddle, “Removal of confounding effects of global signal in functional MRI analyses,” NeuroImage, vol. 13, no. 4, pp. 751–758, 2001. View at Publisher · View at Google Scholar · View at Scopus
  91. M. Gavrilescu, M. E. Shaw, G. W. Stuart, P. Eckersley, I. D. Svalbe, and G. F. Egan, “Simulation of the effects of global normalization procedures in functional MRI,” NeuroImage, vol. 17, no. 2, pp. 532–542, 2002. View at Publisher · View at Google Scholar · View at Scopus
  92. M. Junghöfer, H. T. Schupp, R. Stark, and D. Vaitl, “Neuroimaging of emotion: empirical effects of proportional global signal scaling in fMRI data analysis,” NeuroImage, vol. 25, no. 2, pp. 520–526, 2005. View at Publisher · View at Google Scholar · View at Scopus
  93. F. Beissner and C. Henke, “Methodological problems in fMRI studies on acupuncture: a critical review with special emphasis on visual and auditory cortex activations,” Evidence-Based Complementary and Alternative Medicine, vol. 2011, Article ID 607637, 7 pages, 2011. View at Publisher · View at Google Scholar · View at Scopus
  94. R. A. Poldrack, “The future of fMRI in cognitive neuroscience,” Neuroimage, vol. 62, no. 12, pp. 1216–1220, 2011. View at Publisher · View at Google Scholar
  95. K. Murphy, R. M. Birn, D. A. Handwerker, T. B. Jones, and P. A. Bandettini, “The impact of global signal regression on resting state correlations: are anti-correlated networks introduced?” NeuroImage, vol. 44, no. 3, pp. 893–905, 2009. View at Publisher · View at Google Scholar · View at Scopus
  96. G. K. Aguirre, E. Zarahn, and M. D'Esposito, “Empirical analyses of BOLD fMRI statistics. II. Spatially smoothed data collected under null-hypothesis and experimental conditions,” NeuroImage, vol. 5, no. 3, pp. 199–212, 1997. View at Publisher · View at Google Scholar · View at Scopus
  97. J. L. R. Andersson, “How to estimate global activity independent of changes in local activity,” NeuroImage, vol. 6, no. 4, pp. 237–244, 1997. View at Publisher · View at Google Scholar · View at Scopus
  98. P. M. Macey, K. E. Macey, R. Kumar, and R. M. Harper, “A method for removal of global effects from fMRI time series,” NeuroImage, vol. 22, no. 1, pp. 360–366, 2004. View at Publisher · View at Google Scholar · View at Scopus