Acupuncture modulates temporal neural responses in wide brain networks: evidence from fMRI study

<p>Abstract</p> <p>Background</p> <p>Accumulating neuroimaging studies in humans have shown that acupuncture can modulate a widely distributed brain network, large portions of which are overlapped with the pain-related areas. Recently, a striking feature of acupuncture-induced analgesia is found to be associated with its long-last effect, which has a delayed onset and gradually reaches a peak even after acupuncture needling being terminated. Identifying temporal neural responses in these areas that occur at particular time -- both acute and sustained effects during acupuncture processes -- may therefore shed lights on how such peripheral inputs are conducted and mediated through the CNS. In the present study, we adopted a non-repeated event-related (NRER) fMRI paradigm and control theory based approach namely change-point analysis in order to capture the detailed temporal profile of neural responses induced by acupuncture.</p> <p>Results</p> <p>Our findings demonstrated that neural activities at the different stages of acupuncture presented distinct temporal patterns, in which consistently positive neural responses were found during the period of acupuncture needling while much more complex and dynamic activities found during a post-acupuncture period. These brain responses had a significant time-dependent effect which showed different onset time and duration of neural activities. The amygdala and perigenual anterior cingulate cortex (pACC), exhibited increased activities during the needling phase while decreased gradually to reach a peak below the baseline. The periaqueductal gray (PAG) and hypothalamus presented saliently intermittent activations across the whole fMRI session. Apart from the time-dependent responses, relatively persistent activities were also identified in the anterior insula and prefrontal cortices. The overall findings indicate that acupuncture may engage differential temporal neural responses as a function of time in a wide range of brain networks.</p> <p>Conclusions</p> <p>Our study has provided evidence supporting a view that acupuncture intervention involves complex modulations of temporal neural response, and its effect can gradually resolve as a function of time. The functional specificity of acupuncture at ST36 may involve multiple levels of differential activities of a wide range of brain networks, which are gradually enhanced even after acupuncture needle being terminated.</p

Acupuncture induces divergent alterations of functional connectivity within conventional frequency bands: evidence from MEG recordings.

As an ancient Chinese healing modality which has gained increasing popularity in modern society, acupuncture involves stimulation with fine needles inserted into acupoints. Both traditional literature and clinical data indicated that modulation effects largely depend on specific designated acupoints. However, scientific representations of acupoint specificity remain controversial. In the present study, considering the new findings on the sustained effects of acupuncture and its time-varied temporal characteristics, we employed an electrophysiological imaging modality namely magnetoencephalography with a temporal resolution on the order of milliseconds. Taken into account the differential band-limited signal modulations induced by acupuncture, we sought to explore whether or not stimulation at Stomach Meridian 36 (ST36) and a nearby non-meridian point (NAP) would evoke divergent functional connectivity alterations within delta, theta, alpha, beta and gamma bands. Whole-head scanning was performed on 28 healthy participants during an eyes-closed no-task condition both preceding and following acupuncture. Data analysis involved calculation of band-limited power (BLP) followed by pair-wise BLP correlations. Further averaging was conducted to obtain local and remote connectivity. Statistical analyses revealed the increased connection degree of the left temporal cortex within delta (0.5-4 Hz), beta (13-30 Hz) and gamma (30-48 Hz) bands following verum acupuncture. Moreover, we not only validated the closer linkage of the left temporal cortex with the prefrontal and frontal cortices, but further pinpointed that such patterns were more extensively distributed in the ST36 group in the delta and beta bands compared to the restriction only to the delta band for NAP. Psychophysical results for significant pain threshold elevation further confirmed the analgesic effect of acupuncture at ST36. In conclusion, our findings may provide a new perspective to lend support for the specificity of neural expression underlying acupuncture

Schematic illustration of BLP correlation alterations for the delta band.

<p>A. ST36 group. B. NAP group. Lines correspond to significant changes for the average Band-Limited Power (BLP) correlation induced by acupuncture and squares to significant change in the local BLP correlation (red: local increase in the BLP correlation following acupuncture; thin line: <i>P</i><0.05; thick line: <i>P</i><0.01; significance is based upon a paired <i>t</i>-test).</p

Schematic illustration of BLP correlation alterations for the beta band.

<p>A. ST36 group. B. NAP group. Lines correspond to significant changes for the average Band-Limited Power (BLP) correlation induced by acupuncture and squares to significant change in the local BLP correlation (red: local increase in the BLP correlation following acupuncture; thin line: <i>P</i><0.05; thick line: <i>P</i><0.01; significance is based upon a paired <i>t</i>-test).</p

Schematic illustration of BLP correlation alterations for the gamma band.

<p>A. ST36 group. B. NAP group. Lines correspond to significant changes for the average Band-Limited Power (BLP) correlation induced by acupuncture and squares to significant change in the local BLP correlation (red: local increase in the BLP correlation following acupuncture; thin line: <i>P</i><0.05; thick line: <i>P</i><0.01; significance is based upon a paired <i>t</i>-test).</p

Functional connectivity within and between main regions and statistical results in the beta bands for the ST36 and NAP groups.

<p>Significant differences are indicated in bold (<i>P</i><0.05). L = left, R = right. C = central, F = frontal, O = occipital, P = parietal, T = temporal. B_rest, resting data before acupuncture. P_rest, resting data after acupuncture.</p

Experimental paradigm.

<p>Panel A indicates that acupuncture stimulation was performed at acupoint ST36 on the right leg (Zusanli, arrow pointing to the red dot). Panel B indicates that needling was performed at an adjacent nonacupoint on the right leg (NAP, arrow pointing to the green dot). The red line refers to needle administration, and the blue line represents no acupuncture manipulation but with needles inserted, while the green long line indicates a 6 min resting state or post-stimulus resting state. In this study, the two 6 min resting epochs were employed, while the rest were used for further analysis.</p

Averaged psychophysical response.

<p>A. The percentage of subjects that reported the given sensations. The frequency of aching was found to be greater following acupuncture at ST36. B. The intensity of sensations measured by average score (with standard error bars) on a scale from 0 denoting no sensation to 10 denoting an unbearable sensation. Sore, soreness; Numb, numbness; Full, fullness; Cool, coolness; Warm, warmth; SP, sharp pain; DP, dull pain; Heav, heaviness; Tinl, tingling; Ach, aching; Press, pressure. C. The pain threshold evaluated by average score (with standard error bars) before and after acupuncture at ST36 and NAP. Significant elevation of the pain threshold was observed following acupuncture at ST36.</p