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Characterizing Acupuncture Stimuli Using Brain Imaging with fMRI - A Systematic Review and Meta-Analysis of the Literature Wenjing Huang 1,2 , Daniel Pach 1 , Vitaly Napadow 4,5 , Kyungmo Park 6 , Xiangyu Long 8 , Jane Neumann 8,9 , Yumi Maeda 4,5 , Till Nierhaus 7,8 , Fanrong Liang 2 , Claudia M. Witt 1,3 * 1 Institute for Social Medicine, Epidemiology and Health Economics, Charite  University Medical Center, Berlin, Germany, 2 Chengdu University of Traditional Chinese Medicine, Chengdu, China, 3 Center for Integrative Medicine, University of Maryland School of Medicine, Baltimore, Maryland, United States of America, 4 Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Charlestown, Massachusetts, United States of America, 5 Department of Radiology, Logan College of Chiropractic, Chesterfield, Missouri, United States of America, 6 Department of Biomedical Engineering, Kyung Hee University, Yongin, Republic of Korea, 7 Berlin NeuroImaging Center and Department Neurology, Charite  , Berlin, Germany, 8 Max Planck Institute for Human Cognitive and Brain Sciences, Leipzig, Germany, 9 Leipzig University Medical Center, IFB Adiposity Diseases, Leipzig, Germany Abstract Background: The mechanisms of action underlying acupuncture, including acupuncture point specificity, are not well understood. In the previous decade, an increasing number of studies have applied fMRI to investigate brain response to acupuncture stimulation. Our aim was to provide a systematic overview of acupuncture fMRI research considering the following aspects: 1) differences between verum and sham acupuncture, 2) differences due to various methods of acupuncture manipulation, 3) differences between patients and healthy volunteers, 4) differences between different acupuncture points. Methodology/Principal Findings: We systematically searched English, Chinese, Korean and Japanese databases for literature published from the earliest available up until September 2009, without any language restrictions. We included all studies using fMRI to investigate the effect of acupuncture on the human brain (at least one group that received needle- based acupuncture). 779 papers were identified, 149 met the inclusion criteria for the descriptive analysis, and 34 were eligible for the meta-analyses. From a descriptive perspective, multiple studies reported that acupuncture modulates activity within specific brain areas, including somatosensory cortices, limbic system, basal ganglia, brain stem, and cerebellum. Meta-analyses for verum acupuncture stimuli confirmed brain activity within many of the regions mentioned above. Differences between verum and sham acupuncture were noted in brain response in middle cingulate, while some heterogeneity was noted for other regions depending on how such meta-analyses were performed, such as sensorimotor cortices, limbic regions, and cerebellum. Conclusions: Brain response to acupuncture stimuli encompasses a broad network of regions consistent with not just somatosensory, but also affective and cognitive processing. While the results were heterogeneous, from a descriptive perspective most studies suggest that acupuncture can modulate the activity within specific brain areas, and the evidence based on meta-analyses confirmed some of these results. More high quality studies with more transparent methodology are needed to improve the consistency amongst different studies. Citation: Huang W, Pach D, Napadow V, Park K, Long X, et al. (2012) Characterizing Acupuncture Stimuli Using Brain Imaging with fMRI - A Systematic Review and Meta-Analysis of the Literature. PLoS ONE 7(4): e32960. doi:10.1371/journal.pone.0032960 Editor: Ben J. Harrison, The University of Melbourne, Australia Received June 14, 2011; Accepted February 8, 2012; Published April 9, 2012 Copyright: ß 2012 Huang et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Funding: Funding provided by Carstens Foundation and Chinese Scholarship Council. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Competing Interests: The authors have declared that no competing interests exist. * E-mail: [email protected] Introduction Acupuncture is a therapy of inserting and manipulating fine filiform needles into specific body locations (acupuncture points) to treat diseases. Acupuncture is an ancient Chinese treatment that has been systematically used for over 2000 years [1]. Currently, acupuncture is used widely all over the world, but its biological mechanism is not well understood. From a neurophysiological aspect acupuncture can be regarded as a complex somatosensory stimulation [2]. Although the clinical effect of acupuncture is generally accepted for certain diagnoses [3], such as knee pain, low back pain etc., there exists controversy regarding the specific effect of acupuncture, especially for the specificity of acupuncture points and meridians. In clinical studies large effects produced by sham acupuncture were observed [4±6]. Interest in investigating acupuncture mechanisms with imaging techniques has been growing since the mid 1990 s [7,8]. Positron emission tomography (PET), single photon emission computed tomography (SPECT), and magnetic resonance imaging (MRI) PLoS ONE | www.plosone.org 1 April 2012 | Volume 7 | Issue 4 | e32960
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