Characterizing acupuncture stimuli using brain imaging with FMRI--a systematic review and meta-analysis of the literature

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.

Figure 1. Flow of information through the different phases of the systematic review.

Figure 2. Number of publications on acupuncture and fMRI identified in the last 11 years.

Figure 3. Map of brain response to 18 different acupuncture points.

Red: activation; Blue: deactivation; Yellow: overlap.

Figure 4. Results from the ALE meta-analyses.

Meta-analyses were performed to evaluate brain response to acupuncture across studies, and contrast verum and sham acupuncture. (A) Brain response to verum acupuncture demonstrated activation in sensorimotor and affective/salience processing brain regions and deactivation in the amygdala and DMN brain regions. (B) Differences in brain response for verum and sham acupuncture from direct contrast showed significance in somatosensory areas, limbic regions, visual processing regions and cerebellum. (C) Brain response to verum and sham acupuncture individually demonstrated activation in sensorimotor and affective/salience processing brain regions and deactivation in the amygdala and DMN brain regions associated with verum acupuncture; while sham acupuncture produced activation in somatosensory regions, affective/salience processing regions, cerebellum and deactivation in limbic regions. (D) Differences in brain response between verum and sham acupuncture from subtraction analysis showed more activation in the sensorimotor affective/cognitive processing brain regions and more deactivation in the amygdala/hippocampal formation for verum acupuncture. For subfigures A–C, p<0.05, cluster level FDR corrected, color bar showed ALE value; for subfigure D, p<0.05, cluster level uncorrected, color bar showed Z value. Amyg: amygdala; Ce: cerebellum; dlPFC: dorsolateral prefrontal cortex; FG: fusiform gyrus; H: hippocampal formation; IN: insula; MCC: middle cingulate cortex; Nac: nucleus accumbens; paraHG: parahippocampal gyrus; PCC: posterior cingulate cortex; preCG: precentral gyrus; pre-SMA: pre-supplementary motor area; SI: primary somatosensory cortex; SII: secondary somatosensory cortex; sgACC: subgenual anterior cingulate cortex; SMG: supramarginal gyrus; Th: thalamus; vmPFC: ventromedial prefrontal cortex.