Acupuncture Modulates Disrupted Whole-Brain Network after Ischemic Stroke: Evidence Based on Graph Theory Analysis.

Background: Stroke can lead to disruption of the whole-brain network in patients. Acupuncture can modulate the functional network on a large-scale level in healthy individuals. However, whether and how acupuncture can make a potential impact on the disrupted whole-brain network after ischemic stroke remains elusive. Methods: 26 stroke patients with a right hemispheric subcortical infarct were recruited. We gathered the functional magnetic resonance imaging (fMRI) from patients with stroke and healthy controls in the resting state and after acupuncture intervention, to investigate the instant alterations of the large-scale functional networks. The graph theory analysis was applied using the GRETNA and SPM12 software to construct the whole-brain network and yield the small-world parameters and network efficiency. Results: Compared with the healthy subjects, the stroke patients had a decreased normalized small-worldness (σ), global efficiency (E g), and the mean local efficiency (E loc) of the whole-brain network in the resting state. There was a correlation between the duration after stroke onset and E loc. Acupuncture improved the patients' clustering coefficient (C p) and E loc but did not make a significant impact on the σ and E g. The postacupuncture variables of the whole-brain network had no association with the time of onset. Conclusion: The poststroke whole-brain network tended to a random network with reduced network efficiency. Acupuncture was able to modulate the disrupted patterns of the whole-brain network following the subcortical ischemic stroke. Our findings shed light on the potential mechanisms of the functional reorganization on poststroke brain networks involving acupuncture intervention from a large-scale perspective.

Strategic white matter injury associated with long-term information processing speed deficits in mild traumatic brain injury.

Deficits in information processing speed (IPS) are among the earliest and most prominent cognitive manifestations in mild traumatic brain injury (mTBI). We investigated the impact of white matter fiber location on IPS outcome in an individual basis assessment. A total of 112 acute mild TBI with all CT negative underwent brain DTI and blood sampling for inflammation cytokines within 7 days postinjury and 72 age- and sex matched healthy controls with same assessments were enrolled. IPS outcome was assessed by the trail making test at 6-12 month postinjury in mild TBI. Fractional anisotropy (FA) features were extracted using a novel lesion-load analytical strategy to capture spatially heterogeneous white matter injuries and minimize implicit assumptions of uniform injury across diverse clinical presentations. Acute mild TBI exhibited a general pattern of increased and decreased FA in specific white matter tracts. The power of acute FA measures to identify patients developing IPS deficits with 92% accuracy and further improved to 96% accuracy by adding inflammation cytokines. The classifiers predicted individual's IPS and working memory ratings (r = .74 and .80, respectively, p < .001). The thalamo-cortical circuits and commissural tracts projecting or connecting frontal regions became important predictors. This prognostic model was also verified by an independent replicate sample. Our findings highlighted damage to frontal interhemispheric and thalamic projection fiber tracts harboring frontal-subcortical neuronal circuits as a predictor for processing speed performance in mild TBI.

[Professor SHENG Can-ruo's academic thoughts and acupoint selection experience for hot flashes].

Professor SHENG Can-ruo is a well-known national veteran doctor with over 70 years of clinical experience. He has unique academic thoughts and clinical experience for common diseases and some difficult and complicated diseases. This paper mainly introduces professor SHENG 's syndrome-differentiation thought and experience of acupoint selection for hot flashes. It is emphasized that common hot flashes, such as hot flashes and night sweats, are different between yin and yang. While regulating yin and yang, more attention should be paid to ying-wei harmony, which is not only suitable for women's perimenopausal syndrome, but also for a series of clinical diseases caused by refractory drugs such as endocrine therapy after breast cancer surgery. At the same time of acupoint selection based on syndrome differentiation, a more rational prescriptions should be made according to the duration of the disease and the experience acupoints to improve the clinical efficacy.

Acupuncture Enhances Communication between Cortices with Damaged White Matters in Poststroke Motor Impairment.

Stroke is a leading cause of motor disability. Acupuncture is an effective therapeutic strategy for poststroke motor impairment. However, its mechanism is still elusive. Twenty-two stroke patients having a right-hemispheric subcortical infarct and 22 matched healthy controls were recruited to undergo diffusion tensor imaging (DTI) and functional magnetic resonance imaging (fMRI) scanning. The resting-state fMRI was implemented before and after needling at GB34 (Yanglingquan). The stroke patients presented a substantially reduced fractional anisotropy value in the right superior longitudinal fasciculus (SLF), corticospinal tract, and corpus callosum. The structural integrity of the frontoparietal part of the SLF (SLF-FP) correlated with the motor scores of lower limbs in stroke patients. This corticocortical association bundle originated from the premotor cortex (PM) and the adjacent supplementary motor area (SMA), known as secondary motor areas, and terminated in the supramarginal gyrus (SMG). After acupuncture intervention, the corresponding functional connectivity between the PM/SMA and SMG was enhanced in stroke patients compared with healthy controls. These findings suggested that the integrity of the SLF is a potential neuroimaging biomarker for motor disability of lower limbs following a stroke. Acupuncture could increase the communication between the cortices connected by the impaired white matter tracts, implying the neural mechanism underlying the acupuncture intervention.

The role of insula-cerebellum connection underlying aversive regulation with acupuncture.

Acupuncture at pericardium 6 (PC6) shows a consistently positive efficacy in nausea response suggested by consensus expert guidelines. Nausea encompasses aversive symptom as well as strong emotional components. Disgust is a subjective emotion of uneasy commonly accompanying with a physiological response that is accompanied by strong visceral sensations (e.g., nausea). Understanding the brain circuitry by which acupuncture influences the disgust emotion may further elucidate the modulation effect of acupuncture on aversive experience. In the present study, a well-established aversive conditioning model on healthy subjects was combined with acupuncture intervention at PC6, as well as different acupoints (both local PC7 and distant GB37) as separate controls, to investigate the brain network involved aversive regulation with acupuncture; 48 healthy subjects were enrolled and randomized into four parallel groups: group 1 received disgust-induced (DI) stimuli only; groups 2, 3, and 4 received acupuncture at three single acupoints separately prior to the DI. Disgust sensations were rated at baseline and following disgust stimuli. Acupuncture PC6 can induce significant attenuations in disgust sensations than that of no intervention and acupuncture at other acupoints. Neuroimaging further showed that increased causal interaction strength between the cerebellum (nodulus) and insula can predict greater attenuations in aversive experiences. We also found evidence for radical reorganizations of local stronger casual interaction patterns to disgust-induced brain responses targeted by acupuncture at different acupoints. This study provided the brain substrate for acupuncture on aversion modulation. The coupling between the cerebellum (nodulus) and insula supported interoception system and vestibular control which provided the specific neural basis.

Interaction of acupuncture treatment and manipulation laterality modulated by the default mode network.

Appropriate selection of ipsilateral or contralateral electroacupuncture (corresponding to the pain site) plays an important role in reaching its better curative effect; however, the involving brain mechanism still remains unclear. Compared with the heat pain model generally established in previous study, capsaicin pain model induces reversible cutaneous allodynia and is proved to be better simulating aspects of clinical nociceptive and neuropathic pain. In the current study, 24 subjects were randomly divided into two groups with a 2 × 2 factorial design: laterality (ipsi- or contralateral side, inter-subject) × treatment with counter-balanced at an interval of one week (verum and placebo electroacupuncture, within-subject). We observed subjective pain intensity and brain activations changes induced by capsaicin allodynia pain stimuli before and after electroacupuncture treatment at acupoint LI4 for 30 min. Analysis of variance results indicated that ipsilateral electroacupuncture treatment produced significant pain relief and wide brain signal suppressions in pain-related brain areas compared with contralateral electroacupuncture. We also found that verum electroacupuncture at either ipsi- or contralateral side to the pain site exhibited comparable significant magnitudes of analgesic effect. By contrast, placebo electroacupuncture elicited significant pain reductions only on the ipsilateral rather than contralateral side. It was inferred that placebo analgesia maybe attenuated on the region of the body (opposite to pain site) where attention was less focused, suggesting that analgesic effect of placebo electroacupuncture mainly rely on the motivation of its spatial-specific placebo responses via attention mechanism. This inference can be further supported by the evidence that the significant interaction effect of manipulation laterality and treatment was exclusively located within the default mode network, including the bilateral superior parietal lobule, inferior parietal lobule, precuneus, and left posterior cingulate cortex. It is also proved that disruptions of the default mode network may account for the cognitive and behavioral impairments in chronic pain patients. Our findings further suggested that default mode network participates in the modulation of spatial-oriented attention on placebo analgesia as a mechanism underlying the degree to which treatment side corresponding to the pain.

Frequency-dependent changes of local resting oscillations in sleep-deprived brain.

Sleep deprivation (SD) adversely affects brain function and is accompanied by frequency dependent changes in EEG. Recent studies have suggested that BOLD fluctuations pertain to a spatiotemporal organization with different frequencies. The present study aimed to investigate the frequency-dependent SD-related brain oscillatory activity by using the amplitude of low-frequency fluctuation (ALFF) analysis. The ALFF changes were measured across different frequencies (Slow-4: 0.027-0.073 Hz; Slow-5: 0.01-0.027 Hz; and Typical band: 0.01-0.08 Hz) in 24 h SD as compared to rested wakeful during resting-state fMRI. Sixteen volunteers underwent two fMRI sessions, once during rested wakefulness and once after 24 h of SD. SD showed prominently decreased ALFF in the right inferior parietal lobule (IPL), bilateral orbitofrontal cortex (OFC) and dorsolateral prefrontal cortex (DLPFC), while increased ALFF in the visual cortex, left sensorimotor cortex and fusiform gyrus. Across the Slow-4 and Slow-5, results differed significantly in the OFC, DLPFC, thalamus and caudate in comparison to typical frequency band; and Slow-4 showed greater differences. In addition, negative correlations of behavior performance and ALFF patterns were found mainly in the right IPL across the typical frequency band. These observations provided novel insights about the physiological responses of SD, identified how it disturbs the brain rhythms, and linked SD with frequency-dependent alterations in amplitude patterns.

Acupuncture Induces Time-Dependent Remodelling Brain Network on the Stable Somatosensory First-Ever Stroke Patients: Combining Diffusion Tensor and Functional MR Imaging.

Different treatment interventions induce distinct remodelling of network architecture of entire motor system. Acupuncture has been proved to be of a promising efficacy in motor recovery. However, it is still unclear whether the reorganization of motor-related brain network underlying acupuncture is related with time since stroke and severity of deficit at baseline. The aim of study was to characterize the relation between motor-related brain organization following acupuncture and white matter microstructural changes at an interval of two weeks. We demonstrated that acupuncture induced differential reorganization of motor-related network for stroke patients as time-lapse since stroke. At the baseline, acupuncture can induce the increased functional connectivity between the left primary motor cortex (M1) and the right M1, premotor cortex, supplementary motor area (SMA), thalamus, and cerebellum. After two-week recovery, the increased functional connectivity of the left M1 was more widely distributed and primarily located in the insula, cerebellum, basal ganglia, and SMA. Furthermore, a significant negative relation existed between the FA value in the left M1 at the baseline scanning and node centrality of this region following acupuncture for both baseline and two-week recovery. Our findings may shed a new insight on understanding the reorganization of motor-related theory underlying motor impairments after brain lesions in stroke patients.

Differential activation patterns of FMRI in sleep-deprived brain: restoring effects of acupuncture.

Previous studies suggested a remediation role of acupuncture in insomnia, and acupuncture also has been used in insomnia empirically and clinically. In this study, we employed fMRI to test the role of acupuncture in sleep deprivation (SD). Sixteen healthy volunteers (8 males) were recruited and scheduled for three fMRI scanning procedures, one following the individual's normal sleep and received acupuncture SP6 (NOR group) and the other two after 24 h of total SD with acupuncture on SP6 (SD group) or sham (Sham group). The sessions were counterbalanced approximately two weeks apart. Acupuncture stimuli elicited significantly different activation patterns of three groups. In NOR group, the right superior temporal lobe, left inferior parietal lobule, and left postcentral gyrus were activated; in SD group, the anterior cingulate cortex, bilateral insula, left basal ganglia, and thalamus were significantly activated while, in Sham group, the bilateral thalamus and left cerebellum were activated. Different activation patterns suggest a unique role of acupuncture on SP6 in remediation of SD. SP6 elicits greater and anatomically different activations than those of sham stimuli; that is, the salience network, a unique interoceptive autonomic circuit, may indicate the mechanism underlying acupuncture in restoring sleep deprivation.

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

PURPOSE: To investigate the different responses to acupuncture in MCI patients and age-matched healthy subjects reflected by the Regional Homogeneity (ReHo) indices. METHODS: 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. RESULTS: 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. CONCLUSION: 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 Enhances Effective Connectivity between Cerebellum and Primary Sensorimotor Cortex in Patients with Stable Recovery Stroke.

Recent neuroimaging studies have demonstrated that stimulation of acupuncture at motor-implicated acupoints modulates activities of brain areas relevant to the processing of motor functions. This study aims to investigate acupuncture-induced changes in effective connectivity among motor areas in hemiparetic stroke patients by using the multivariate Granger causal analysis. A total of 9 stable recovery stroke patients and 8 healthy controls were recruited and underwent three runs of fMRI scan: passive finger movements and resting state before and after manual acupuncture stimuli. Stroke patients showed significantly attenuated effective connectivity between cortical and subcortical areas during passive motor task, which indicates inefficient information transmissions between cortical and subcortical motor-related regions. Acupuncture at motor-implicated acupoints showed specific modulations of motor-related network in stroke patients relative to healthy control subjects. This specific modulation enhanced bidirectionally effective connectivity between the cerebellum and primary sensorimotor cortex in stroke patients, which may compensate for the attenuated effective connectivity between cortical and subcortical areas during passive motor task and, consequently, contribute to improvement of movement coordination and motor learning in subacute stroke patients. Our results suggested that further efficacy studies of acupuncture in motor recovery can focus on the improvement of movement coordination and motor learning during motor rehabilitation.

Acupuncture modulates the functional connectivity of the default mode network in stroke patients.

Abundant evidence from previous fMRI studies on acupuncture has revealed significant modulatory effects at widespread brain regions. However, few reports on the modulation to the default mode network (DMN) of stroke patients have been investigated in the field of acupuncture. To study the modulatory effects of acupuncture on the DMN of stroke patients, eight right hemispheric infarction and stable ischemic stroke patients and ten healthy subjects were recruited to undergo resting state fMRI scanning before and after acupuncture stimulation. Functional connectivity analysis was applied with the bilateral posterior cingulate cortices chosen as the seed regions. The main finding demonstrated that the interregional interactions between the ACC and PCC especially enhanced after acupuncture at GB34 in stroke patients, compared with healthy controls. The results indicated that the possible mechanisms of the modulatory effects of acupuncture on the DMN of stroke patients could be interpreted in terms of cognitive ability and motor function recovery.

Multivariate granger causality analysis of acupuncture effects in mild cognitive impairment patients: an FMRI study.

Evidence from clinical reports has indicated that acupuncture has a promising effect on mild cognitive impairment (MCI). However, it is still unknown that by what way acupuncture can modulate brain networks involving the MCI. In the current study, multivariate Granger causality analysis (mGCA) was adopted to compare the interregional effective connectivity of brain networks by varying needling depths (deep acupuncture, DA; superficial acupuncture, SA) and at different cognitive states, which were the MCI and healthy control (HC). Results from DA at KI3 in MCI showed that the dorsolateral prefrontal cortex and hippocampus emerged as central hubs and had significant causal influences with each other, but significant in HC for DA. Moreover, only several brain regions had remarkable causal interactions following SA in MCI and even few brain regions following SA in HC. Our results indicated that acupuncture at KI3 at different cognitive states and with varying needling depths may induce distinct reorganizations of effective connectivities of brain networks, and DA at KI3 in MCI can induce the strongest and more extensive effective connectivities related to the therapeutic effect of acupuncture in MCI. The study demonstrated the relatively functional specificity of acupuncture at KI3 in MCI, and needling depths play an important role in acupuncture treatments.

Characterizing acupuncture de qi in mild cognitive impairment: relations with small-world efficiency of functional brain networks.

As an intermediate state between normal aging and dementia, mild cognitive impairment (MCI) became a hot topic and early treatments can improve disease prognosis. Acupuncture is shown to have possible effect in improving its cognitive defect. However, the underlying neural mechanism of acupuncture and relations between De Qi and different needling depths are still elusive. The present study aimed to explore how acupuncture can exert effect on the reorganization of MCI and to what extent needling depths, associating with De Qi sensations, can influence the acupuncture effects for MCI treatment. Our results presented that MCI patients exhibited losses of small-world attributes indicated by longer characteristic path lengths and larger clustering coefficients, compared with healthy controls. In addition, acupuncture with deep needling can induce much stronger and a wide range of De Qi sensations both in intensity and prevalence. Acupuncture with deep needling showed modulatory effect to compensate the losses of small-world attributes existed in MCI patients while acupuncture with superficial needling did not. Furthermore, acupuncture with deep needling enhanced the nodal centrality primarily in the abnormal regions of MCI including the hippocampus, postcentral cortex as well as anterior cingulate cortex. This study provides evidence to understand neural mechanism underlying acupuncture and the key role of De Qi for MCI treatment.

Acupuncture de qi in stable somatosensory stroke patients: relations with effective brain network for motor recovery.

Acupuncture has been widely used for treating stroke and De Qi may play an important role. In spite of its acceptance, the neural mechanism underlying acupuncture for motor recovery is still elusive. Particularly, by what extent De Qi sensations can reliably predict the therapeutical acupuncture effect on the mediating recovery from stroke is urgent to investigate. Nine stroke patients were assessed by De Qi, neurological examination, and scanned with acupuncture stimuli across two time points at an interval of two weeks. And we adopted multivariate Granger causality analysis to explore the interregional influences within motor executive brain network during post-acupuncture resting state. Our findings indicated that acupuncture at GB34 can enhance the recovery of stroke mainly by strengthening causal influences between the ipsilesional and contralesional motor cortex. Moreover, centrality of some motor-related regions correlated with clinical variables and thus served as a predictor of stroke recovery. Along the same line, the centrality of these motor-related regions has also high relations with the De Qi sensation. Our findings suggest that De Qi having relatively stable reliability may be essential and used as a predictor to the therapeutic effectiveness of acupuncture for stroke recovery.

Exploration of whole brain networks modulated by acupuncture at analgesia acupoint ST36 using scale-specific wavelet correlation analysis.

BACKGROUND: Previous studies have demonstrated that acupuncture could modulate various brain systems in the resting brain networks. Graph theoretical analysis offers a novel way to investigate the functional organization of the large-scale cortical networks modulated by acupuncture at whole brain level. In this study, we used wavelets correlation analysis to estimate the pairwise correlations between 90 cortical and subcortical human brain regions in normal human volunteers scanned during the post-stimulus resting state. METHODS: Thirty-two college students, all right-handed and acupuncture naïve, participated in this study. Every participant received only one acupoint stimulation, resulting in 16 subjects in one group. Both structural functional magnetic resonance imaging (fMRI) data (3D sequence with a voxel size of 1 mm(3) for anatomical localization) and functional fMRI data (TR = 1500 ms, TE = 30 ms, flip angle = 90°) were collected for each subject. After thresholding the resulting scale-specific wavelet correlation matrices to generate undirected binary graphs, we compared graph metrics of brain organization following verum manual acupuncture (ACU) and sham acupuncture (SHAM) groups. RESULTS: The topological parameters of the large-scale brain networks in ACU group were different from those of the SHAM group at multiple scales. There existed distinct modularity functional brain networks during the post-stimulus resting state following ACU and SHAM at multiple scales. CONCLUSIONS: The distinct modulation patterns of the resting brain attributed to the specific effects evoked by acupuncture. In addition, we also identified that there existed frequency-specific modulation in the post-stimulus resting brain following ACU and SHAM. The modulation may be related to the effects of verum acupuncture on modulating special disorder treatment. This preliminary finding may provide a new clue to understand the relatively function-oriented specificity of acupuncture effects.

Manipulation of and sustained effects on the human brain induced by different modalities of acupuncture: an fMRI study.

The javascript:void(0)manipulation and sustained effects of acupuncture have been investigated in multiple studies, but several findings are inconsistent with one another. One possible explanation for these discrepancies is that different modalities of acupuncture were utilized in these studies. In the present study, we investigated both the manipulation and sustained effects of acupuncture in different modalities, including manual acupuncture (MA), electroacupuncture (EA) and transcutaneous electrical acupoint stimulation (TEAS). MA, EA, TEAS and sensory control stimulation were applied to 18 healthy subjects, and combined block-designed and resting-state fMRI scans were performed. In analyzing these data, the block-designed datasets were used to assess the manipulation effect by employing a modified general linear model. The data from the resting states, before and after stimulation, were used to explore the brain networks involved in the sustained effect. The results showed that the two 1-min stimulation periods produced similar activation patterns in the sensory control with positive activation in the sensorimotor areas and negative activation in the default mode areas. Although similar patterns could be detected in the first stimulation period in MA, EA and TEAS, no positive activation result was observed in the second stimulation period, and EA showed a more extensive deactivation compared to MA and TEAS. Additionally, all three of the modalities of acupuncture stimulation could increase the instinct brain network in rest. A more secure and spatially extended connectivity of the default mode network was observed following MA and EA, and TEAS specifically increased the functional connectivity in the sensorimotor network. The present study suggested that different brain mechanisms might be recruited in different acupuncture modalities. In addition, the findings from our work could provide methodological information for further research into the mechanism of acupuncture.

Hypothalamus-related resting brain network underlying short-term acupuncture treatment in primary hypertension.

The present study attempted to explore modulated hypothalamus-seeded resting brain network underlying the cardiovascular system in primary hypertensive patients after short-term acupuncture treatment. Thirty right-handed patients (14 male) were divided randomly into acupuncture and control groups. The acupuncture group received a continuous five-day acupuncture treatment and undertook three resting-state fMRI scans and 24-hour ambulatory blood pressure monitoring (ABPM) as well as SF-36 questionnaires before, after, and one month after acupuncture treatment. The control group undertook fMRI scans and 24-hour ABPM. For verum acupuncture, average blood pressure (BP) and heart rate (HR) decreased after treatment but showed no statistical differences. There were no significant differences in BP and HR between the acupuncture and control groups. Notably, SF-36 indicated that bodily pain (P = 0.005) decreased and vitality (P = 0.036) increased after acupuncture compared to the baseline. The hypothalamus-related brain network showed increased functional connectivity with the medulla, brainstem, cerebellum, limbic system, thalamus, and frontal lobes. In conclusion, short-term acupuncture did not decrease BP significantly but appeared to improve body pain and vitality. Acupuncture may regulate the cardiovascular system through a complicated brain network from the cortical level, the hypothalamus, and the brainstem.