When studying the neural responses to acupuncture with a block-designed paradigm, its temporal dynamics predicted by the general linear model (GLM) conforms to typical "on-off" variations during a limited period of the experiment manipulation. Despite a lack of direct evidence associating its psychophysiological response, numerous clinical reports suggest that acupuncture can provide pain relief beyond a needling session. Therefore, a typical GLM analysis may be insensitive or inappropriate for identifying altered neural responses resulting from acupuncture. We developed a new approach to investigate the dynamics underlying sustained effects of acupuncture. Specifically, we designed two separate models to evaluate the baseline activities (prior to stimulation) and neural activities in sequential epochs, using three block-designed functional runs: acupuncture at acupoint ST36, nonmeridian point (NMP) stimulation, and a visual task. We found that the activity patterns during rest were associated with the stimulus types and that the resting activities might be even higher than that of stimulation phases. Such effects of the elevated activity during rest may reduce or eliminate the activity during stimulus conditions or even reverse the sign of brain activation using conventional GLM analysis. Moreover, such sustained responses, followed by acupuncture at ST36 and NMP, exhibited distinct patterns in wide brain structures, particularly in the limbic system and brainstem. These findings may pose great implications for the design and interpretation of a range of acupuncture neuroimaging studies.

BackgroundRecently, increasing evidence has indicated that the primary acupuncture effects are mediated by the central nervous system. However, specific brain networks underpinning these effects remain unclear.ResultsIn the present study using fMRI, we employed a within-condition interregional covariance analysis method to investigate functional connectivity of brain networks involved in acupuncture. The fMRI experiment was performed before, during and after acupuncture manipulations on healthy volunteers at an acupuncture point, which was previously implicated in a neural pathway for pain modulation. We first identified significant fMRI signal changes during acupuncture stimulation in the left amygdala, which was subsequently selected as a functional reference for connectivity analyses. Our results have demonstrated that there is a brain network associated with the amygdala during a resting condition. This network encompasses the brain structures that are implicated in both pain sensation and pain modulation. We also found that such a pain-related network could be modulated by both verum acupuncture and sham acupuncture. Furthermore, compared with a sham acupuncture, the verum acupuncture induced a higher level of correlations among the amygdala-associated network.ConclusionOur findings indicate that acupuncture may change this amygdala-specific brain network into a functional state that underlies pain perception and pain modulation.

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