Lijun Bai

FMRI connectivity analysis of acupuncture effects on an amygdala-associated brain network

BackgroundRecently, increasing evidence has indicated that the primary acupuncture effects are mediated by the central nervous system. However, specific brain networks underpinning these effects remain unclear.ResultsIn the present study using fMRI, we employed a within-condition interregional covariance analysis method to investigate functional connectivity of brain networks involved in acupuncture. The fMRI experiment was performed before, during and after acupuncture manipulations on healthy volunteers at an acupuncture point, which was previously implicated in a neural pathway for pain modulation. We first identified significant fMRI signal changes during acupuncture stimulation in the left amygdala, which was subsequently selected as a functional reference for connectivity analyses. Our results have demonstrated that there is a brain network associated with the amygdala during a resting condition. This network encompasses the brain structures that are implicated in both pain sensation and pain modulation. We also found that such a pain-related network could be modulated by both verum acupuncture and sham acupuncture. Furthermore, compared with a sham acupuncture, the verum acupuncture induced a higher level of correlations among the amygdala-associated network.ConclusionOur findings indicate that acupuncture may change this amygdala-specific brain network into a functional state that underlies pain perception and pain modulation.

Dysfunctional connectivity patterns in chronic heroin users: An fMRI study

Recent functional neuroimaging studies have examined cognitive inhibitory control, decision-making and stress regulation in heroin addiction using a cue-reactivity paradigm. Few studies have considered impairments in heroin users from an integrated perspective for evaluation of their brain functions. We hypothesized that the brain regions that are dysregulated in the chronic heroin users during cue-reactivity studies may also show dysfunctional connectivity in memory, inhibition and motivation-related dysfunctions during a resting state free of cues. The present study used resting functional magnetic resonance imaging (fMRI) to compare the interaction of brain regions between 12 chronic heroin users and 12 controls by employing a novel graph theory analysis (GTA) method. As a data-driven approach, GTA has the advantage of evaluating the strength as well as the temporal and spatial patterns of interactions among the brain regions. Abnormal topological properties were explored in the brain of chronic heroin users, such as the dysfunctional connectivity in the prefrontal cortex, ACC, SMA, ventral striatum, insula, amygdala and hippocampus. Our results suggest that GTA is a useful tool in defining dysregulated neural networks even during rest. This dysfunctional brain connectivity may contribute to decrease self-control, impaired inhibitory function as well deficits in stress regulation in chronic heroin users.

Time-varied characteristics of acupuncture effects in fMRI studies.

When studying the neural responses to acupuncture with a block‐designed paradigm, its temporal dynamics predicted by the general linear model (GLM) conforms to typical “on‐off” variations during a limited period of the experiment manipulation. Despite a lack of direct evidence associating its psychophysiological response, numerous clinical reports suggest that acupuncture can provide pain relief beyond a needling session. Therefore, a typical GLM analysis may be insensitive or inappropriate for identifying altered neural responses resulting from acupuncture. We developed a new approach to investigate the dynamics underlying sustained effects of acupuncture. Specifically, we designed two separate models to evaluate the baseline activities (prior to stimulation) and neural activities in sequential epochs, using three block‐designed functional runs: acupuncture at acupoint ST36, nonmeridian point (NMP) stimulation, and a visual task. We found that the activity patterns during rest were associated with the stimulus types and that the resting activities might be even higher than that of stimulation phases. Such effects of the elevated activity during rest may reduce or eliminate the activity during stimulus conditions or even reverse the sign of brain activation using conventional GLM analysis. Moreover, such sustained responses, followed by acupuncture at ST36 and NMP, exhibited distinct patterns in wide brain structures, particularly in the limbic system and brainstem. These findings may pose great implications for the design and interpretation of a range of acupuncture neuroimaging studies. Hum Brain Mapp, 2009.

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

BackgroundAccumulating 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.ResultsOur 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.ConclusionsOur 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.

A longitudinal study of hand motor recovery after sub-acute stroke: a study combined FMRI with diffusion tensor imaging.

Previous studies have shown that motor recovery of stroke can be assessed by the cortical activity and the structural integrity of the corticospinal tract (CST), but little is known about the relation between the cortical activity and the structural integrity during motor recovery. In the present study, we investigated the changes in brain activities evoked by twenty days’ functional electrical stimulation (FES) training in twelve sub-acute stroke patients with unilateral upper-limb disability. We compared cortex activity evoked by wrist movement of eleven stroke patients to that of eleven age-matched healthy subjects to figure out how cortex activity changed after stroke. We also measured the structural integrity represented by the fractional anisotropy (FA) asymmetry of the posterior limb of the internal capsule (PLIC) to find the relationship between the brain activity and the structure integrity. In our study, we found that patients with sub-acute stroke have shown greater activity in the contralesional primary motor cortex (M1) during the affected hand’s movement compared with healthy group, while the activity in ipsilesional M1 was decreased after the therapy compared to that before therapy, and the contralesional non-primary motor cortex showed greater activity after therapy. At the baseline we found that the positive correlation between the FA asymmetry of PLIC and the contralesional non-primary motor cortex activity showed that the greater damaged CST, the greater contralesional non-primary motor cortex recruited. While the negative correlation between them after the FES training indicates that after recovery the non-primary motor cortex plays different role in different stroke phases. Our study demonstrates that functional organization of a residual distributed motor system is related to the degree of disruption to the CST, and the non-primary motor areas plays an important role in motor recovery.

Neural specificity of acupuncture stimulation at pericardium 6: Evidence from an FMRI study

To investigate the neural specificity of pericardium PC6, with the same meridian acupoint PC7 and a treatment‐irrelevant acupoint GB37 as separate controls.

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.

Combining spatial and temporal information to explore function-guide action of acupuncture using fMRI

To investigate the brain response patterns of modulation of GB37 (Guangming) and KI8 (Jiaoxin).

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.