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

Abstract

Background: 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.

Results: 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.

Conclusions: 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.

Figure 1

Results of psychophysical deqi sensations. A. The percentage of subjects who reported having experienced the given sensation (at least one subject experienced the seven sensations listed). Numbness, fullness, and soreness were found greater for acupuncture at ST36. B. The intensity of the reported sensations measured by an average score (with standard error bars) on a scale from 0 denoting no sensation to 10 denoting an unbearable sensation. The average stimulus intensities (mean ± SE) were approximately similar during acupuncture at ST36 (2.4 ± 1.7) and nonacupoint (2.2 ± 1.9).

Figure 2

Differential temporal neural responses induced by acupuncture at ST36 as a function of time. The baseline period was indicated by the shaded gray box, and the EWMA-statistic was shown by the thick black line (corrected over time and FDR corrected at α = 0.05 over space), with gray shading denoting the standard error across participants. The estimated CP for onset activity was presented in green line. The control limits were shown by dashed lines. Abbreviations: SII-secondary somatosensory cortex.

Figure 3

Differential temporal neural responses induced by acupuncture at nonacupoint as a function of time. The baseline period was indicated by the shaded gray box, and the EWMA-statistic was shown by the thick black line (corrected over time and FDR corrected at α = 0.05 over space), with gray shading denoting the standard error across participants. The estimated CP for onset activity was presented in green line. The control limits were shown by dashed lines. Abbreviations: SII-secondary somatosensory cortex. Abbreviations: SI-primary somatosensory cortex; SII-secondary somatosensory cortex.

Figure 4

Experimental design paradigm. Acupuncture needle manipulation was performed at an acupoint ST36 (Zusanli, arrow pointing to red dot) or a nonmeridian-point focus approximately 2-3 cm distant laterally (NMP, arrow pointing to green dot) on the right leg, respectively. Functional run incorporated the NRER paradigm, incorporating 1.5 min needle manipulation, preceded by 1 min rest epoch and followed by 12.5 min rest scanning.

Figure 5

The detailed scheme for HEWMA analysis. A. Group results of the rostral ventromedial medulla generated from the HEWMA analysis. The estimated change-point (CP) for onset activation was indicated as green line. Grey shading presented the standard error of EWMA statistic. B. The corrected p-value generated from the Monte Carlo simulations. Black line: observed max T; distribution: null hypothesis max T. C. Case weights equaled to the inverse of total variation (including within-subject and between-subject variation) for certain subject. Weights are based on variability during the baseline interval, meaning that higher variance may result in a lower weight for that subject. D. The individual time courses for the 16 subjects.