Neuroimaging and Neuromonitoring Effects of Electro and Manual Acupuncture on the Central Nervous System: A Literature Review and Analysis

Table 1

fMRI studies on the effect of MA and EA.

Author	Year	Title	Objective	Outcomes
Bai et al. [44]	2010	Acupuncture modulates temporal neural responses in wide brain networks: evidence from fMRI study	Temporal investigation of (late) MA effects at ST36 (r) versus nearby NAP	They found that the amygdala and perigenual anterior cingulate cortex (pACC) exhibited increased activities during needling but decreased to reach a peak below the baseline. The PAG and hypothalamus presented intermittent activations across the whole session.; Apart from the time-dependent responses, relatively persistent activities were also identified in the anterior insula and PFCs. In comparison, verum and sham shared a similar activation pattern in somatosensory areas (S1 and S2) during needling. However, during the postacupuncture resting period acupuncture at ST36 was followed by sustained activation of the S2, whereas acupuncture at NAP showed inhibition of the S1.
Cheng et al. [45]	2013	Exploration of whole brain networks modulated by acupuncture at analgesia acupoint ST36 using scale-specific wavelet correlation analysis	Investigation of MA effects at ST36 (r) versus nearby NAP effects on pairwise correlations between 90 cortical and subcortical regions	Their correlations presented frequency-specific modularity functional brain networks during poststimulus resting state following acupuncture at ST36 and NAP.; Graph metrics in brain activity are different in verum and sham groups and also show that the brain network following manual acupuncture has higher global and local efficiency in parallel information transfer in the brain network compared with acupuncture at a NAP.
Cho et al. [46]	2010	fMRI study of effect on brain activity according to stimulation method at LI11, ST36: Painful pressure and acupuncture stimulation of same acupoints	Investigation of differences between MA versus painful sham stimulation at LI11 (l) versus ST36 (l)	In comparison to painful tactile stimulation, MA at LI11 led to activation of both sides of the parahippocampal gyrus, cerebellum, left side of thalamus, and right side of posterior cingulate regions.; Acupuncture but not tactile stimulation at ST36 produced activation at the secondary motor cortex (M2), limbic system (cingulate gyrus, posterior cingulate), primary visual cortex, pons, and medulla regions, at the left BA6, BA8, and ACC. In comparison with the left LI11 acupuncture stimulation, left BA6, BA8, and ACC were more activated by the left ST36 acupuncture stimulation. Acupuncture activated more regions than painful tactile stimulation, especially areas of the limbic system, such as the parahippocampal gyrus and ACC.
Dong et al. [47]	2012	Tempo-spatial analysis of vision-related acupoint specificity in the occipital lobe using fMRI: An ICA study	Spatial and temporal investigation of the effects of MA at vision-related GB37 versus BL60 versus nearby NAP on the occipital lobe	Although the ICA of all kinds of acupuncture showed activity at the visual cortex V1 in the occipital lobe, temporal activities in this region differed for acupuncture at GB37 versus NAP, as well as for BL60 versus NAP.
Feng et al. [48]	2011	Investigation of the large-scale functional brain networks modulated by acupuncture	Spatial investigation of MA effects at ST36 (r) versus nearby NAP	Within a network of 90 predefined regions in the poststimulus resting brain, limbic/paralimbic regions (such as the amygdala, hippocampus, and anterior cingulate gyrus) emerged as network hubs after verum but not sham acupuncture.; Compared with needling at a NAP, manual acupuncture at ST36 presented increased correlations, related with the limbic/paralimbic and subcortical regions (such as the insula, amygdala, and anterior cingulate gyrus) and thalamus. Decreased correlations for verum acupuncture were related with the sensory and frontal cortex.
Zyloney et al. [60]	2010	Manipulation of and sustained effects on the human brain induced by different modalities of acupuncture: An fMRI study	Spatial + temporal investigation of MA effects versus EA versus TEAS at ST36 (l)	Using a modified generalized linear model analysis to compare block-designed and resting-state fMRI scans they detected positive activation in the sensorimotor areas and negative activation in the default mode areas in both areas in both of the two 1-min-stimulation periods for tactile stimulation with a von Frey filament and in the first 1-min-stimulation of MA, EA, and TEAS. However, in the second 1-min-stimulation period, no positive activation result was observed and EA showed a more extensive deactivation compared to MA and TEAS.
Li et al. [49]	2010	Exploring vision-related acupuncture point specificity with multivoxel pattern analysis	Spatial investigation of MA effects at vision-related GB37 versus nearby NAP	They found different effects for verum acupuncture versus NAP in the subregions of occipital cortex (left cuneus of occipital gyrus and regions of lingual gyrus, middle occipital gyrus and fusiform gyrus), the limbic-cerebellar system (including insula, rACC and pACC, pons, amygdala, culmem in anterior lobe and declive of vermis in posterior lobe of cerebellum), and the somatosensory cortex. For GLM, the neutral response patterns of acupuncture stimulation at acupoints and NAP had multiple overlapping regions and did not differ significantly from each other.
Liu et al. [50]	2010	The hybrid GLM-ICA investigation on the neural mechanism of acupoint ST36: An fMRI study	Spatial and temporal investigation of MA effects at ST36 (r) versus nearby NAP	Their results showed manipulation-related effects and sustained acupuncture effects in the cortical-subcortical areas, including the ACC, ventrolateral prefrontal cortex (VLPFC), and supplementary motor area (SMA) and decreases in the S1 and S2. These reactions lasted until the resting period after needling, where then activations were induced in many regions including the insula, caudate, putamen, and thalamus.
Jiang et al. [58]	2013	Divergent neural processes specific to the acute and sustained phases of verum and sham acupuncture	Spatial investigation of immediate and delayed effects of MA at ST36 (r) versus nearby NAP	The immediate effect of verum as well as sham acupuncture consisted of signal changes in the limbic/paralimbic areas, neocortical regions, brainstem, and cerebellum. For a delayed effect, several regions showed strong functional connectivity. During the overall process of acupuncture, the insula played a critical role. Acupuncture at NAP produced positive activations with a small extent of spatial distribution and less intensive signal changes compared to ST36, mainly in the insula, S2, and cerebellum.
Liu et al. [51]	2012	Altered small-world efficiency of brain functional networks in acupuncture at ST36: A functional MRI study	Spatial investigation of MA effects at ST36 versus nearby NAP	The results presented increased local efficiency after acupuncture stimulation. No significant differences were found for sham acupuncture at a NAP. Significant effects of real acupuncture but not sham were detected on nodal degree of the left hippocampus. Point-related effects were observed in the ACC, frontal and occipital regions, while stimulation-related effects were found in various brain regions of frontal, parietal, and occipital cortex regions. Several limbic and subcortical brain regions exhibited point- and stimulation-related alterations in their regional homogeneity.
Liu et al. [52]	2012	Determining the precise cerebral response to acupuncture: An improved fMRI study	Investigation of effects of MA at LR3 versus nearby NAP, each tested with expectations versus no expectations	The superior part of the secondary visual cortex (V2) was activated in real acupuncture versus sham, and the interior part of V2 was activated in the other contrasting condition. All three contrasting conditions aimed to elicit cerebral responses to expectancy, the ipsilateral MFG, contralateral orbitofrontal cortex (OFC), contralateral S2, and contralateral cerebellum were activated. The contralateral DLPFC, temporal pole, and hippocampi uncus were activated in groups with expectation versus no expectation (medial frontal gyrus- and DLPFC-related expectancy is validated for emotion and cognitive control).
Liu et al. [53]	2013	Additional evidence for the sustained effect of acupuncture at the vision-related acupuncture point, GB37	Spatial and temporal investigation of MA effects at vision-related GB37 versus nearby NAP	GLM analysis showed a more extensive spatial distribution signal decrease in the limbic-cerebellar regions (such as the occipital cortex, pons, PH/Hipp, putamen, and cerebellum) but with a smaller signal increase (such as in the STG, S2, and thalamus). Special temporal investigation showed that the neural response evoked by acupuncture did not turn on and off rapidly but lasted longer, violating the basic assumption of standard GLM analysis. fMRI signals of the limbic-paralimbic-neocortical system increased, so that changes in the occipital cortex showed different temporal patterns between GB37 and NAP.
Murase et al. [54]	2013	Deconvolution analyses with tent functions reveal delayed and long-sustained increases of BOLD signals with acupuncture stimulation	Temporal + spatial investigation of MA effects versus von Frey filament sham acupuncture at LI4 (r) versus tactile stimulation right palm	MA showed activation on both sides in the S2 and the insula, on both sides in the S1, the primary motor cortex (M1), ACC, SMA, thalamus, and PFC. Sham acupuncture with von Frey filament showed that activation in the contralateral S1 and SMA and on both sides in the S2 and insula. Tactile stimulation showed activated areas in the contralateral S1, M1, and SMA and on both sides in the S2 and insula. Real acupuncture induced more widespread, more delayed, and long-sustained increases and decreases of BOLD signal in the somatosensory region and in areas related to pain perception.
Napadow et al. [55]	2013	Brain correlated of phasic autonomic response to acupuncture stimulation: An event-related fMRI study	Spatial + temporal investigation of ANS response and psychophysiological response patterns to MA at ST36 (l) versus SP9 (l) versus von Frey filament sham acupuncture at NAP (near ST36 (l))	GLM measurements showed that acupuncture events with strong skin conductance response produced greater anterior insula activation and acupuncture at SP9, which produced greater skin conductance response and also produced stronger sharp pain sensation and greater anterior insula activation. Acupuncture-induced heart rate (HR) deceleration was associated with greater DMN deactivation. This association was strongest for ST36, which produced more robust HR deceleration. DMN deactivation was significantly more pronounced across acupuncture stimuli producing HR deceleration versus those events characterized by acceleration.
Yeo et al. [56]	2010	Consecutive acupuncture stimulations lead to significantly decreased neural responses	Temporal investigation of repeated MA effects versus blunt sham acupuncture at BL62 (r)	They found that, after the first verum acupuncture stimulation block at the left BL62, the left hemisphere showed activation in the hypothalamus, thalamus, claustrum, cerebellum, inferior frontal gyrus, and the superior temporal gyrus, while the right hemisphere presented activation in the middle frontal gyrus. In both hemispheres, a significant focus of activation was found in the inferior parietal lobule. During the second block, only the cerebellum in the left hemisphere and the inferior parietal lobule in the right hemisphere were significantly activated, showing decreased activations during the second verum acupuncture stimulation. During sham, no significant brain activations were found.
You et al. [57]	2013	Altered hub configurations within default mode network following acupuncture at ST36: A multimodal investigation combining fMRI and MEG	Spatial + temporal investigation of MA effects at ST36 (r) versus nearby NAP on DMN hub configurations	They found that after sham acupuncture at NAP, the PCC remained to serve consistently as DMN hub across all five frequency bands. However, the PCC was regulated and only acted as a DMN hub within delta and gamma bands after verum acupuncture at ST36.
Liu et al. [59]	2011	Imaging the functional connectivity of the periaqueductal gray during genuine and sham electroacupuncture treatment	Spatial investigation of EA effects on PAG functional connectivity versus sham EA with Streitberger needles at LI3 (r) and LI4 (r), each with high versus low expectancy	They found greater connectivity between the PAG, left PCC, and precuneus in the comparison of verum EA versus Streitberger sham EA, whereas there was greater connectivity in the PAG and right anterior insula for sham EA. No significant differences were observed between high and low expectancy groups.