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

Stain-free histopathology by programmable supercontinuum pulses

The preparation, staining, visualization, and interpretation of histological images of tissue is well-accepted as the gold standard process for the diagnosis of disease. These methods were developed historically, and are used ubiquitously in pathology, despite being highly time and labor intensive. Here we introduce a unique optical imaging platform and methodology for label-free multimodal multiphoton microscopy that uses a novel photonic crystal fiber source to generate tailored chemical contrast based on programmable supercontinuum pulses. We demonstrate collection of optical signatures of the tumor microenvironment, including evidence of mesoscopic biological organization, tumor cell migration, and (lymph-)angiogenesis collected directly from fresh ex vivo mammary tissue. Acquisition of these optical signatures and other cellular or extracellular features, which are largely absent from histologically processed and stained tissue, combined with an adaptable platform for optical alignment-free programmable-contrast imaging, offers the potential to translate stain-free molecular histopathology into routine clinical use

Altered hub configurations within default mode network following acupuncture at ST36: a multimodal investigation combining fMRI and MEG.

Acupuncture, an externally somatosensory stimulation in the Traditional Chinese Medicine, has been proposed about its modulations on the brain's default mode network (DMN). However, it is still unknown on how the internal brain resting networks are modulated and what inferences can be made about the physiological processes underlying these changes. Combining high spatial resolution of functional magnetic resonance imaging (fMRI) with high temporal resolution of magnetoencephalography (MEG), in the current multimodal study, we sought to explore spatiotemporally whether or not band-specific DMN hub configurations would be induced by verum acupuncture, compared with sham control. Spatial independent component analysis was applied to fMRI data, followed by the discrete regional sources seeded into MEG data. Partial correlation analysis was further adopted to estimate the intrinsic functional connectivity and network hub configurations. One of the most striking findings is that the posterior cingulate cortex is not only validated as a robust DMN hub, but served as a hub only within the delta and gamma bands following the verum acupuncture, compared with its consistently being a DMN hub in sham control group. Our preliminary results may provide a new perspective to lend support for the specificity of neural mechanism underlying acupuncture

Exploring the patterns of acupuncture on mild cognitive impairment patients using regional homogeneity.

To investigate the different responses to acupuncture in MCI patients and age-matched healthy subjects reflected by the Regional Homogeneity (ReHo) indices.The experiment was performed at the acupoint KI3 in 12 MCI patients and 12 healthy controls, respectively. A novel non-repeated event-related (NRER) fMRI design paradigm was applied to separately detect neural activities related to different stages of acupuncture (pre-acupuncture resting state, needling manipulation and post-acupuncture resting state). ReHo values were calculated for MCI patients and healthy controls in pre- and post-acupuncture resting state. Then, a two-way ANCOVA with repeated measures with post-hoc two sample t-tests was performed to explore the different responses to acupuncture in the two groups.The ANCOVA revealed a significant main effect of group, but no significant main effect of acupuncture and interactions between group and acupuncture. During the pre-acupuncture resting state, ReHo values increased in the precentral gyrus (PCG), superior frontal gyrus (SFG), and insula (INS) and decreased mainly in middle temporal gyrus (MTG), parahippocampal (PHIP) and cingulate cortex in MCI patients compared with healthy controls. Furthermore, we found that the regions including precuneus (PCUN), and cingulate cortex showed increased ReHo values for MCI patients following acupuncture. For healthy controls, the medial frontal gyrus, PCG, anterior cingulate cortex (ACC) and INS showed enhanced ReHo values following acupuncture. During the post-acupuncture resting state, MCI patients showed increased ReHo values mainly in the MTG, superior parietal lobule (SPL), middle frontal gyrus (MFG), supramarginal (SMG), and PCG, and decreased ReHo values mainly in the frontal regions, PHIP, and posterior cingulated cortex (PCC) compared to healthy controls.Though we found some ReHo changes between MCI patients and healthy controls, the two-way ANCOVA results showed no significant effects after multiple corrections. Further study is needed to reveal the real acupuncture effects on MCI patients

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

Brain areas with significant different ReHo values between MCI and HC groups during the resting state are shown.

<p>Warm and cool colors indicate the significantly increased and decreased ReHo values in MCI patients compared with healthy controls at P<0.01 (Alphasim corrected, p<0.01, 30 voxels). (Abbreviation: PCG- Precentral Gyrus).</p

Brain areas with significant different ReHo values between MCI patients and healthy controls during the resting state at <i>P</i><0.01 (Alphasim corrected, <i>p</i><0.01, 30 voxels).

<p>Brain areas with significant different ReHo values between MCI patients and healthy controls during the resting state at <i>P</i><0.01 (Alphasim corrected, <i>p</i><0.01, 30 voxels).</p

Brain areas with significant different ReHo values between healthy controls and MCI patients after acupuncture at <i>P</i><0.01 (Alphasim corrected, <i>p</i><0.01, 30 voxels).

<p>Brain areas with significant different ReHo values between healthy controls and MCI patients after acupuncture at <i>P</i><0.01 (Alphasim corrected, <i>p</i><0.01, 30 voxels).</p

Experimental paradigm.

<p>Panel A indicated that acupuncture stimulation was performed at acupoint ST36 on the right leg (Zusanli, arrow pointing to dark pink dot). Panel B indicated that needling was performed at a nearby nonacupoint on the right leg (NAP, arrow pointing to dark cyan dot). The red line refers to needle administration, and the green line represents no acupuncture manipulation with needle inserted, the blue line indicates a 6-minute resting state or post-acupuncture resting state.</p