Neural encoding of acupuncture needling sensations: evidence from a FMRI study.

Deqi response, a psychophysical response characterized by a spectrum of different needling sensations, is essential for Chinese acupuncture clinical efficacy. Previous neuroimaging research works have investigated the neural correlates of an overall deqi response by summating the scores of different needling sensations. However, the roles of individual sensations in brain activity and how they interact with each other remain to be clarified. In this study, we applied fMRI to investigate the neural correlates of individual components of deqi during acupuncture on the right LV3 (Taichong) acupoint. We selected a subset of deqi responses, namely, pressure, heaviness, fullness, numbness, and tingling. Using the individual components of deqi of different subjects as covariates in the analysis of percentage change of bold signal, pressure was found to be a striking sensation, contributing to most of negative activation of a limbic-paralimbic-neocortical network (LPNN). The similar or opposite neural activity in the heavily overlapping regions is found to be responding to different needling sensations, including bilateral LPNN, right orbitofrontal cortex, and bilateral posterior parietal cortex. These findings provide the neuroimaging evidence of how the individual needle sensations interact in the brain, showing that the modulatory effects of different needling sensations contribute to acupuncture modulations of LPNN network.

Commonality and specificity of acupuncture action at three acupoints as evidenced by FMRI.

Previous work from our team and others has shown that manual acupuncture at LI4 (hegu), ST36 (zusanli), and LV3 (taichong) deactivates a limbic-paralimbic-neocortical brain network, and at the same time activates somatosensory regions of the brain. The objective of the present study was to explore the specificity and commonality of the brain response to manual acupuncture at LI4, ST36, and LV3, acupoints that are located on different meridians and are used to treat pain disorders. We used functional magnetic resonance imaging (fMRI) to monitor the brain responses to acupuncture at three different acupoints; we examined 46 healthy subjects who, according to their psychophysical responses, experienced deqi sensation during acupuncture. Brain responses to stimulation at each of the acupoints were displayed in conjunction with one another to show the spatial distribution. We found clusters of deactivation in the medial prefrontal, medial parietal and medial temporal lobes showing significant convergence of two or all three of the acupoints. The largest regions showing common responses to all three acupoints were the right subgenual BA25, right subgenual cingulate, right isthmus of the cingulum bundle, and right BA31. We also noted differences in major sections of the medial prefrontal and medial temporal lobes, with LI4 predominating in the pregenual cingulate and hippocampal formation, ST36 predominating in the subgenual cingulate, and LV3 predominating in the posterior hippocampus and posterior cingulate. The results suggest that although these acupoints are commonly used for anti-pain and modulatory effects, they may mobilize the same intrinsic global networks, with substantial overlap of common brain regions to mediate their actions. Our findings showing preferential response of certain limbic-paralimbic structures suggests acupoints may also exhibit relative specificity.

The effects of acupuncture on the brain networks for emotion and cognition: an observation of gender differences.

Acupuncture modulates brain activity at the limbic-paralimbic-neocortical network (LPNN) and the default mode network (DMN). Since these brain networks show gender differences when mediating emotional and cognitive tasks, we thus hypothesize that women and men may also respond differently to acupuncture procedure at these brain regions. In order to test this hypothesis, we retrieved the data of 38 subjects, 19 females and 19 males, who had brain fMRI during acupuncture from previous studies and reanalyzed them based on sex status. Deactivation at the LPNN/DMN during needle manipulation of acupuncture was more extensive in females than in males, particularly in the posterior cingulate (BA31), precuneus (BA7m) and angular gyrus (BA39). The functional correlations between the right BA31 and pregenual cingulate (BA32), hippocampus or contralateral BA31 were significantly stronger in females than in males. The angular gyrus (BA39) was functionally correlated with BA31 in females; in contrast, it was anticorrelated with BA31 in males. Soreness, a major component of the psychophysical responses to needle manipulation, deqi, was correlated in intensity with deactivation of the angular gyrus in females; no such relationships were observed in males. In contrast to lesser deactivation at the LPNN/DMN networks, needle manipulation during acupuncture induced greater activation at the secondary somatosensory cortex and stronger functional connectivity with the anterior-middle cingulate (BA32/24) in males than in females. Our study suggests that brains with sex dimorphism may process the acupuncture stimulation differently between women and men.

Monitoring acupuncture effects on human brain by FMRI.

Functional MRI is used to study the effects of acupuncture on the BOLD response and the functional connectivity of the human brain. Results demonstrate that acupuncture mobilizes a limbic-paralimbic-neocortical network and its anti-correlated sensorimotor/paralimbic network at multiple levels of the brain and that the hemodynamic response is influenced by the psychophysical response. Physiological monitoring may be performed to explore the peripheral response of the autonomic nerve function. This video describes the studies performed at LI4 (hegu), ST36 (zusanli) and LV3 (taichong), classical acupoints that are commonly used for modulatory and pain-reducing actions. Some issues that require attention in the applications of fMRI to acupuncture investigation are noted.

Acupuncture mobilizes the brain's default mode and its anti-correlated network in healthy subjects.

Previous work has shown that acupuncture stimulation evokes deactivation of a limbic-paralimbic-neocortical network (LPNN) as well as activation of somatosensory brain regions. This study explores the activity and functional connectivity of these regions during acupuncture vs. tactile stimulation and vs. acupuncture associated with inadvertent sharp pain. Acupuncture during 201 scans and tactile stimulation during 74 scans for comparison at acupoints LI4, ST36 and LV3 was monitored with fMRI and psychophysical response in 48 healthy subjects. Clusters of deactivated regions in the medial prefrontal, medial parietal and medial temporal lobes as well as activated regions in the sensorimotor and a few paralimbic structures can be identified during acupuncture by general linear model analysis and seed-based cross correlation analysis. Importantly, these clusters showed virtual identity with the default mode network and the anti-correlated task-positive network in response to stimulation. In addition, the amygdala and hypothalamus, structures not routinely reported in the default mode literature, were frequently involved in acupuncture. When acupuncture induced sharp pain, the deactivation was attenuated or became activated instead. Tactile stimulation induced greater activation of the somatosensory regions but less extensive deactivation of the LPNN. These results indicate that the deactivation of the LPNN during acupuncture cannot be completely explained by the demand of attention that is commonly proposed in the default mode literature. Our results suggest that acupuncture mobilizes the anti-correlated functional networks of the brain to mediate its actions, and that the effect is dependent on the psychophysical response.

The salient characteristics of the central effects of acupuncture needling: limbic-paralimbic-neocortical network modulation.

Human and animal studies suggest that acupuncture produces many beneficial effects through the central nervous system. However, the neural substrates of acupuncture actions are not completely clear to date. fMRI studies at Hegu (LI4) and Zusanli (ST36) indicated that the limbic system may play an important role for acupuncture effects. To test if this finding applies to other major classical acupoints, fMRI was performed on 10 healthy adults during manual acupuncture at Taichong (LV3), Xingjian (LV2), Neiting (ST44), and a sham point on the dorsum of the left foot. Although certain differences could be observed between real and sham points, the hemodynamic response (BOLD signal changes) and psychophysical response (sensory experience) to acupuncture were generally similar for all four points. Acupuncture produced extensive deactivation of the limbic-paralimbic-neocortical system. Clusters of deactivated regions were seen in the medial prefrontal cortex (frontal pole, pregenual cingulate), the temporal lobe (amygdala, hippocampus, and parahippocampus) and the posterior medial cortex (precuneus, posterior cingulate). The sensorimotor cortices (somatosensory cortices, supplementary motor cortex), thalamus and occasional paralimbic structures such as the insula and anterior middle cingulate cortex showed activation. Our results provide additional evidence in support of previous reports that acupuncture modulates the limbic-paralimbic-neocortical network. We hypothesize that acupuncture may mediate its antipain, antianxiety, and other therapeutic effects via this intrinsic neural circuit that plays a central role in the affective and cognitive dimensions of pain as well as in the regulation and integration of emotion, memory processing, autonomic, endocrine, immunological, and sensorimotor functions.

Characterization of the "deqi" response in acupuncture.

BACKGROUND: Acupuncture stimulation elicits deqi, a composite of unique sensations that is essential for clinical efficacy according to traditional Chinese medicine (TCM). There is lack of adequate experimental data to indicate what sensations comprise deqi, their prevalence and intensity, their relationship to acupoints, how they compare with conventional somatosensory or noxious response. The objective of this study is to provide scientific evidence on these issues and to characterize the nature of the deqi phenomenon in terms of the prevalence of sensations as well as the uniqueness of the sensations underlying the deqi experience. METHODS: Manual acupuncture was performed at LI4, ST36 and LV3 on the extremities in randomized order during fMRI in 42 acupuncture naïve healthy adult volunteers. Non-invasive tactile stimulation was delivered to the acupoints by gentle tapping with a von Frey monofilament prior to acupuncture to serve as a sensory control. At the end of each procedure, the subject was asked if each of the sensations listed in a questionnaire or any other sensations occurred during stimulation, and if present to rate its intensity on a numerical scale of 1-10. Statistical analysis including paired t-test, analysis of variance, Spearman's correlation and Fisher's exact test were performed to compare responses between acupuncture and sensory stimulation. RESULTS: The deqi response was elicited in 71% of the acupuncture procedures compared with 24% for tactile stimulation when thresholded at a minimum total score of 3 for all the sensations. The frequency and intensity of individual sensations were significantly higher in acupuncture. Among the sensations typically associated with deqi, aching, soreness and pressure were most common, followed by tingling, numbness, dull pain, heaviness, warmth, fullness and coolness. Sharp pain of brief duration that occurred in occasional subjects was regarded as inadvertent noxious stimulation. The most significant differences in the deqi sensations between acupuncture and tactile stimulation control were observed with aching, soreness, pressure and dull pain. Consistent with its prominent role in TCM, LI4 showed the most prominent response, the largest number of sensations as well as the most marked difference in the frequency and intensity of aching, soreness and dull pain between acupuncture and tactile stimulation control. Interestingly, the dull pain generally preceded or occurred in the absence of sharp pain in contrast to reports in the pain literature. An approach to summarize a sensation profile, called the deqi composite, is proposed and applied to explain differences in deqi among acupoints. CONCLUSION: The complex pattern of sensations in the deqi response suggests involvement of a wide spectrum of myelinated and unmyelinated nerve fibers, particularly the slower conducting fibers in the tendinomuscular layers. The study provides scientific data on the characteristics of the 'deqi' response in acupuncture and its association with distinct nerve fibers. The findings are clinically relevant and consistent with modern concepts in neurophysiology. They can provide a foundation for future studies on the deqi phenomenon.