Yuanyuan Feng

FMRI connectivity analysis of acupuncture effects on the whole brain network in mild cognitive impairment patients

The increased risk for the elderly with mild cognitive impairment (MCI) to progress to Alzheimers disease makes it an appropriate condition for investigation. While the use of acupuncture as a complementary therapeutic method for treating MCI is popular in certain parts of the world, the underlying mechanism is still elusive. We sought to investigate the acupuncture effects on the functional connectivity throughout the entire brain in MCI patients compared to healthy controls (HC). The functional magnetic resonance imaging experiment was performed with two different paradigms, namely, deep acupuncture (DA) and superficial acupuncture (SA), at acupoint KI3. We first identified regions showing abnormal functional connectivity in the MCI group compared to HC during the resting state and subsequently tested whether these regions could be modulated by acupuncture. Then, we made the comparison of MCI vs. HC to test whether there were any specific modulatory patterns in the poststimulus resting brain between the two groups. Finally, we made the comparisons of DA vs. SA in each group to test the effect of acupuncture with different needling depths. We found the temporal regions (hippocampus, thalamus, fusiform gyrus) showing abnormal functional connectivity during the resting state. These regions are implicated in memory encoding and retrieving. Furthermore, we found significant changes in functional connectivity related with the abnormal regions in MCI patients following acupuncture. Compared to HC, the correlations related with the temporal regions were enhanced in the poststimulus resting brain in MCI patients. Compared to SA, significantly increased correlations related with the temporal regions were found for the DA condition. The enhanced correlations in the memory-related brain regions following acupuncture may be related to the purported therapeutically beneficial effects of acupuncture for the treatment of MCI. The heterogeneous modulatory patterns between DA and SA may suggest that deep muscle insertion of acupuncture is necessary to achieve the appreciable clinical effect.

Altered topological patterns of brain networks in mild cognitive impairment and Alzheimer's disease: A resting-state fMRI study

Recent studies have shown that cognitive and memory decline in patients with Alzheimers disease (AD) is coupled with losses of small-world attributes. However, few studies have investigated the characteristics of the whole brain networks in individuals with mild cognitive impairment (MCI). In this functional magnetic resonance imaging (fMRI) study, we investigated the topological properties of the whole brain networks in 18 AD patients, 16 MCI patients, and 18 age-matched healthy subjects. Among the three groups, AD patients showed the longest characteristic path lengths and the largest clustering coefficients, while the small-world measures of MCI networks exhibited intermediate values. The finding was not surprising, given that MCI is considered to be the prodromal stage of AD. Compared with normal controls, MCI patients showed decreased nodal centrality mainly in the medial temporal lobe as well as increased nodal centrality in the occipital regions. In addition, we detected increased nodal centrality in the medial temporal lobe and frontal gyrus, and decreased nodal centrality mainly in the amygdala in MCI patients compared with AD patients. The results suggested a widespread rewiring in AD and MCI patients. These findings concerning AD and MCI may be an integrated reflection of reorganization of the brain networks accompanied with the cognitive decline that may lead to AD.

Investigation of the large-scale functional brain networks modulated by acupuncture

Previous neuroimaging studies have primarily focused on the neural activities involving the acute effects of acupuncture. Considering that acupuncture can induce long-lasting effects, several researchers have begun to pay attention to the sustained effects of acupuncture on the resting brain. Most of these researchers adopted functional connectivity analysis based on one or a few preselected brain regions and demonstrated various function-guided brain networks underlying the specific effect of acupuncture. Few have investigated how these brain networks interacted at the whole-brain level. In this study, we sought to investigate the functional correlations throughout the entire brain following acupuncture at acupoint ST36 (ACUP) in comparison with acupuncture at nearby nonacupoint (SHAM). We divided the whole brain into 90 regions and constructed functional brain network for each condition. Then we examined the network hubs and identified statistically significant differences in functional correlations between the two conditions. Following ACUP, but not SHAM, the limbic/paralimbic regions such as the amygdala, hippocampus and anterior cingulate gyrus emerged as network hubs. For direct comparisons, increased correlations for ACUP compared to SHAM were primarily related with the limbic/paralimbic and subcortical regions such as the insula, amygdala, anterior cingulate gyrus, and thalamus, whereas decreased correlations were mainly related with the sensory and frontal cortex. The heterogeneous modulation patterns between the two conditions may relate to the functional specific modulatory effects of acupuncture. The preliminary findings may help us to better understand the long-lasting effects of acupuncture on the entire resting brain, as well as the neurophysiological mechanisms underlying acupuncture.

Investigation of the effective connectivity of resting state networks in Alzheimer's disease: a functional MRI study combining independent components analysis and multivariate Granger causality analysis.

Recent neuroimaging studies have shown that the cognitive and memory decline in patients with Alzheimers disease (AD) is coupled with abnormal functions of focal brain regions and disrupted functional connectivity between distinct brain regions, as well as losses in small‐world attributes. However, the causal interactions among the spatially isolated, but functionally related, resting state networks (RSNs) are still largely unexplored. In this study, we first identified eight RSNs by independent components analysis from resting state functional MRI data of 18 patients with AD and 18 age‐matched healthy subjects. We then performed a multivariate Granger causality analysis (mGCA) to evaluate the effective connectivity among the RSNs. We found that patients with AD exhibited decreased causal interactions among the RSNs in both intensity and quantity relative to normal controls. Results from mGCA indicated that the causal interactions involving the default mode network and auditory network were weaker in patients with AD, whereas stronger causal connectivity emerged in relation to the memory network and executive control network. Our findings suggest that the default mode network plays a less important role in patients with AD. Increased causal connectivity of the memory network and self‐referential network may elucidate the dysfunctional and compensatory processes in the brain networks of patients with AD. These preliminary findings may provide a new pathway towards the determination of the neurophysiological mechanisms of AD. Copyright

Modulatory effects of acupuncture on resting-state networks: a functional MRI study combining independent component analysis and multivariate Granger causality analysis.

To investigate acupuncture specificity by exploring causal relationships of brain networks following acupuncture at GB40 (Qiuxu), with the acupoint KI3 (Taixi) as a control (belonging to the same nerve segment but different meridians).

Investigation of acupoint specificity by functional connectivity analysis based on graph theory

Acupoint specificity is still a contentious issue and remains to be verified whether brain, response is as specific as the purported indication of different acupoints. Previous fMRI acupuncture, studies based on multiple-block design may not be able to fully disclose acupuncture effects. Both, recent studies and certain clinical reports have indicated that there exists time-sustainability during, acupuncture even after the stimulus being terminated. Further understanding of how such external, intervention interacts with post-stimulus resting brain networks may enlighten us to gain an, appreciation of the physiological function and integrated mechanisms involved in acupuncture. In our, study, we adopted a modified non-repeated event-related (NRER) design, and utilized the graph theory, based functional connectivity analysis to investigate the neural specificity of the PC6, with the same, meridian acupoint PC7 and a different meridian acupoint GB37 as separate controls. Under the, construct of this network model, some brain regions with a larger degree of connectivity indicated, stronger interactions with other brain regions and were considered to be important nodes in this, network. We identified that the two most important brain areas were the right nodule and right uvula, following acupuncture at PC6, and the right amygdala and right inferior parietal lobe following, acupuncture at PC7. Following the GB37, the two regions with the larger degree of connectivity were, the posterior cingulate cortex (PCC) and middle occipital gyrus. These specific regions may mediate the, specific effects of acupuncture. Results showed that different modulatory brain networks may support, the point specificity of acupuncture.

Investigation of acupoint specificity by multivariate granger causality analysis from functional MRI data

To investigate the acupoint specificity by exploring the effective connectivity patterns of the poststimulus resting brain networks modulated by acupuncture at the PC6, with the same meridian acupoint PC7 and different meridian acupoint GB37.

Investigation of acupoint specificity by whole brain functional connectivity analysis from fMRI data

Previous neuroimaging studies on acupuncture have primarily adopted functional connectivity analysis associated with one or a few preselected brain regions. Few have investigated how these brain regions interacted at the whole brain level. In this study, we sought to investigate the acupoint specificity by exploring the whole brain functional connectivity analysis on the post-stimulus resting brain modulated by acupuncture at acupoint PC6, with the same meridian acupoint PC7 and different meridian acupoint GB37. We divided the whole brain into 90 regions and analyzed functional connectivity for each condition. Then we identified statistically significant differences in functional correlations throughout the entire brain following acupuncture at PC6 in comparison with PC7 as well as GB37. For direct comparisons, increased correlations for PC6 compared to PC7 were primarily between the prefrontal regions and the limbic/paralimbic and subcortical regions, whereas decreased correlations were mainly between the parietal regions and the limbic/paralimbic and subcortical regions. On the other hand, increased correlations for PC6 compared to GB37 were primarily between the prefrontal regions and somatosensory regions, whereas decreased correlations were mainly related with the occipital regions. Our findings demonstrated that acupuncture at different acupoints may exert heterogeneous modulatory effects on the post-stimulus resting brain, providing new evidences for the relatively function-oriented specificity of acupuncture effects.

Differential neural responses to acupuncture revealed by MEG using wavelet-based time-frequency analysis: A pilot study

Acupoint specificity, lying at the core of the Traditional Chinese Medicine, still faces many controversies. As previous neuroimaging studies on acupuncture mainly adopted relatively low time-resolution functional magnetic resonance imaging (fMRI) technology and inappropriate block-designed experimental paradigm due to sustained effect, in the current study, we employed a single block-designed paradigm together with high temporal-resolution magnetoencephalography (MEG) technology. We applied time-frequency analysis based upon Morlet wavelet transforming approach to detect differential oscillatory brain dynamics induced by acupuncture at Stomach Meridian 36 (ST36) using a nearby nonacupoint (NAP) as control condition. We observed that frequency power changes were mainly restricted to delta band for both ST36 group and NAP group. Consistently increased delta band power in contralateral temporal regions and decreased power in the counterparts of ipsilateral hemisphere were detected following stimulation at ST36 on the right leg. Compared with ST36, no significant delta ranges were found in temporal regions in NAP group, illustrating different oscillatory brain patterns. Our results may provide additional evidence to support the specificity of acupuncture modulation effects.

Exploring the evolution of post-acupuncture resting-state networks combining ICA and multivariate Granger causality

The sustained effects of acupuncture have been widely applied to clinical treatment, thus it can be assumed that the relatively functional specificity of acupoints may evolve as the function of time. In this study, we originally combined ICA and multivariate Granger causality analysis to explore the causal interactions within and among the post-acupuncture resting-state networks (RSNs) at a hearing-related acupoint GB40, with the cognition-related acupoint KI3 as a control. Following acupuncture at GB40, the superior temporal gyrus (STG) and anterior insula (AI) within auditory network appeared persistent bidirectional connection with maximal strength, and the interactions between the auditory network and others became more complex as time passed. For KI3, both the superior parietal lobule (SPL) and dorsolateral prefrontal cortex (DLPFC), as vital nuclei of cognitive function, emerged increased causal outflows and inflows as time went on. We concluded that acupuncture at different acupoints may exert different evolutive effects on causal interactions within and across the RSNs during segmented post-stimulus resting states.