[Effects on the regional homogeneity of resting-state brain function in the healthy subjects of gastric distention treated with acupuncture at the front-mu and back-shu points of the stomach, Weishu (BL 21) and Zhongwan (CV 12)].

OBJECTIVE: To observe the regional homogeneity (ReHo) of resting-state brain function in the healthy subjects of gastric distention treated with acupuncture at the back-shu and front-mu points of the stomach, Weishu (BL 21) and Zhongwan (CV 12) and the correlation with gastric motility so as to explore the mechanism on the central integration of the front-mu and back-shu points of the stomach. METHODS: The crossover test design was adopted. Twenty-four healthy subjects were assigned to a Weishu group, a Zhongwan group and a combined-point group separately, 8 cases in each one in each of the three times. Totally, 24 subjects were included in each group. Under the water load condition, the subjects received acupuncture at Weishu (BL 21), Zhongwan (CV 12) and the combined Weishu (BL 21) and Zhongwan (CV 12). Before and after each acupuncture, the resting-state brain functional magnetic resonance imaging (fMRI) scan and electrogastrogram (EGG) test were applied. The ReHo value was calculated in the collected fMRI imaging data. The changes in ReHo values were analyzed and compared before and after acupuncture in each group, as well as among the groups. The gastric motility was analyzed before and after acupuncture. Additionally, the correlative analysis was conducted between the gastric motility and ReHo changes before and after acupuncture. RESULTS: (1) After acupuncture, EGG amplitudes in the subjects of each group were lower remarkably as compared with those before acupuncture (all P<0.01). The EGG frequencies were not different significantly as compared with those before acupuncture (all P>0.05). The EGG amplitudes in the Weishu group and the Zhongwan group were higher than those in the combined-point group (both P<0.05). (2) As compared with the conditions before acupuncture, acupuncture at the combined front-mu and the back-shu points as well as Weishu (BL 21) and Zhongwan (CV 12) separately all induced the changes in the brain ReHo. Acupuncture at the combined front-mu and the back-shu points significantly increased Reho values in the right inferior temporal gyrus, the left thalamus, the precuneus and the posterior cingulate gyrus (all P<0.05) and remarkably reduced the ReHo values in the the middle temporal gyrus of the right temporal pole, sulcus calcarinus and precuneus (all P<0.05). Compared with the single point groups, acupuncture at the combined front-mu and the back-shu points induced the increase of ReHo value in the posterior cingulate gyrus and the decrease of ReHo in the temporal pole (all P<0.05). (3) The correlative analysis showed that the changes in the ReHo values in the posterior cingulate gyrus, the thalamus and the precuneus were positively correlated to the changes of the gastric motility amplitudes. The changes in the ReHo values in the temporal pole was negatively correlated to the changes of the gastric motility amplitudes. CONCLUSION: Acupuncture at the combined back-shu and front-mu points of the stomach, as well as acupuncture at single Weishu (BL 21) and Zhongwan (CV 12) induce the ReHo changes in the different brain regions. Acupuncture at the combined back-shu and front-mu points of the stomach may induce the ReHo changes in some new brain regions as compared with the acupuncture at the single point. The thalamus, the posterior cingulate gyrus and the precuneus may be the the important integrated brain regions for acupuncture at the back-shu and the front-mu points in regulating the gastric motility. The effects of acupuncture at the back-shu and the front-mu points for the regulation of the gastric motility are closely related to the thalamus, the limbic system and the default network of the brain regions.

Study on Lesion Assessment of Cerebello-Thalamo-Cortical Network in Wilson's Disease with Diffusion Tensor Imaging.

Wilson's disease (WD) is a genetic disorder of copper metabolism with pathological copper accumulation in the brain and any other tissues. This article aimed to assess lesions in cerebello-thalamo-cortical network with an advanced technique of diffusion tensor imaging (DTI) in WD. 35 WD patients and 30 age- and sex-matched healthy volunteers were recruited to accept diffusion-weighted images with 15 gradient vectors and conventional magnetic resonance imaging (MRI). The DTI parameters, including fractional anisotropy (FA) and mean diffusion (MD), were calculated by diffusion kurtosis estimator software. After registration, patient groups with FA mappings and MD mappings and normal groups were compared with 3dttest and receiver-operating characteristic (ROC) curve analysis, corrected with FDR simulations (p = 0.001, α = 0.05, cluster size = 326). We found that the degree of FA increased in the bilateral head of the caudate nucleus (HCN), lenticular nucleus (LN), ventral thalamus, substantia nigra (SN), red nucleus (RN), right dentate nucleus (DN), and decreased in the mediodorsal thalamus and extensive white matter. The value of MD increased in HCN, LN, SN, RN, and extensive white matter. The technique of DTI provides higher sensitivity and specificity than conventional MRI to detect Wilson's disease. Besides, lesions in the basal ganglia, thalamus, and cerebellum might disconnect the basal ganglia-thalamo-cortical circuits or dentato-rubro-thalamic (DRT) track and disrupt cerebello-thalamo-cortical network finally, which may cause clinical extrapyramidal symptoms.

Functional Connectivity Modulation by Acupuncture in Patients with Bell's Palsy.

Bell's palsy (BP), an acute unilateral facial paralysis, is frequently treated with acupuncture in many countries. However, the mechanism of treatment is not clear so far. In order to explore the potential mechanism, 22 healthy volunteers and 17 BP patients with different clinical duration were recruited. The resting-state functional magnetic resonance imaging scans were conducted before and after acupuncture at LI4 (Hegu), respectively. By comparing BP-induced functional connectivity (FC) changes with acupuncture-induced FC changes in the patients, the abnormal increased FC that could be reduced by acupuncture was selected. The FC strength of the selected FC at various stages was analyzed subsequently. Our results show that FC modulation of acupuncture is specific and consistent with the tendency of recovery. Therefore, we propose that FC modulation by acupuncture may be beneficial to recovery from the disease.

[Effects of acupuncture at left and right Hegu (LI 4) for cerebral function laterality].

OBJECTIVE: To explore the cerebral function laterality of acupuncture at left and right Hegu (LI 4) by using functional magnetic resonance imaging (fMRI) and provide objective evidences for side selection of Hegu (LI 4) in the clinical application. METHODS: Eighty healthy volunteers were randomly divided into a left-acupoint group and a right-acupoint group, and they were treated with acupuncture at left Hegu (LI 4) and right Hegu (LI 4) respectively. After the arrival of qi, the task-state fMRI data in both groups was collected, and analysis of functional neuroimages (AFNI) software was used to perform intra-group and between-group comparisons. After acupuncture, acupuncture feelings were recorded and MGH acupuncture sensation scale (MASS) was recorded. RESULTS: The difference of MASS between the two groups was not significant (P>0. 05). The result of left-acupoint group showed an increased signal on right cerebral hemisphere, while the right-acupoint group showed extensive signal changes in both cerebral hemispheres. The analysis between left-acupoint group and retroflex right-acupoint group showed differences in brain areas. CONCLUSIONS: The central effect of acupuncture at left and right Hegu (LI 4) is dissymmetry, indicating right hemisphere laterality. The right lobus insularis and cingulate gyrus may be the key regions in the acupuncture at Hegu (LI 4).

Effect of Acupuncture on Functional Connectivity of Anterior Cingulate Cortex for Bell's Palsy Patients with Different Clinical Duration.

Acupuncture is widely used in the treatment of Bell's palsy (BP) in many countries, but its underlying physiological mechanism remained controversial. In order to explore the potential mechanism, changes of functional connectivity (FC) of anterior cingulate gyrus (ACC) were investigated. We collected 20 healthy (control group) participants and 28 BP patients with different clinical duration accepted resting state functional MRI (rfMRI) scans before and after acupuncture, respectively. The FC of ACC before and after acupuncture was compared with paired t-test and the detailed results are presented in the paper. Our results showed that effects of the acupuncture on FC were closely related to clinical duration in patients with BP, which suggested that brain response to acupuncture was closely connected with the status of brain functional connectivity and implied that acupuncture plays a homeostatic role in the BP treatment.

Increasing functional connectivity of the anterior cingulate cortex during the course of recovery from Bell's palsy.

Bell's palsy (BP), a unilateral and idiopathic palsy of the facial nerve, is a common disorder generally followed by a good natural recovery. The aim of this study was to investigate the relationship between the functional connectivity of the anterior cingulate cortex (ACC) and the recovery process of BP. Thirty-seven healthy volunteers and 67 patients were studied by functional MRI (fMRI). The seed regions of bilateral ACC were first extracted from the task-state fMRI data of healthy participants performing the task of mouth opening and closing. The connectivity of bilateral ACC was calculated from resting-state fMRI data of patients in whom only resting-state fMRI data were collected. The correlation between the strength of ACC's connectivity with the duration (time course of disease) was computed by analysis of covariance. It was found that the functional connectivity of the ACC ipsilateral to the lesioned side was enforced as the duration increased. The enforced brain areas included the sensorimotor areas and the ACC contralateral to the palsy. It was suggested that enforced functional connectivity of ACC might be related to cortical reorganization, which is important in the process of BP recovery.

Acupuncture-induced changes in functional connectivity of the primary somatosensory cortex varied with pathological stages of Bell's palsy.

Bell's palsy is the most common cause of acute facial nerve paralysis. In China, Bell's palsy is frequently treated with acupuncture. However, its efficacy and underlying mechanism are still controversial. In this study, we used functional MRI to investigate the effect of acupuncture on the functional connectivity of the brain in Bell's palsy patients and healthy individuals. The patients were further grouped according to disease duration and facial motor performance. The results of resting-state functional MRI connectivity show that acupuncture induces significant connectivity changes in the primary somatosensory region of both early and late recovery groups, but no significant changes in either the healthy control group or the recovered group. In the recovery group, the changes also varied with regions and disease duration. Therefore, we propose that the effect of acupuncture stimulation may depend on the functional connectivity status of patients with Bell's palsy.

Prolonged repeated acupuncture stimulation induces habituation effects in pain-related brain areas: an FMRI study.

Most previous studies of brain responses to acupuncture were designed to investigate the acupuncture instant effect while the cumulative effect that should be more important in clinical practice has seldom been discussed. In this study, the neural basis of the acupuncture cumulative effect was analyzed. For this experiment, forty healthy volunteers were recruited, in which more than 40 minutes of repeated acupuncture stimulation was implemented at acupoint Zhusanli (ST36). Three runs of acupuncture fMRI datasets were acquired, with each run consisting of two blocks of acupuncture stimulation. Besides general linear model (GLM) analysis, the cumulative effects of acupuncture were analyzed with analysis of covariance (ANCOVA) to find the association between the brain response and the cumulative duration of acupuncture stimulation in each stimulation block. The experimental results showed that the brain response in the initial stage was the strongest although the brain response to acupuncture was time-variant. In particular, the brain areas that were activated in the first block and the brain areas that demonstrated cumulative effects in the course of repeated acupuncture stimulation overlapped in the pain-related areas, including the bilateral middle cingulate cortex, the bilateral paracentral lobule, the SII, and the right thalamus. Furthermore, the cumulative effects demonstrated bimodal characteristics, i.e. the brain response was positive at the beginning, and became negative at the end. It was suggested that the cumulative effect of repeated acupuncture stimulation was consistent with the characteristic of habituation effects. This finding may explain the neurophysiologic mechanism underlying acupuncture analgesia.

Brain responses to acupuncture are probably dependent on the brain functional status.

In recent years, neuroimaging studies of acupuncture have explored extensive aspects of brain responses to acupuncture in finding its underlying mechanisms. Most of these studies have been performed on healthy adults. Only a few studies have been performed on patients with diseases. Brain responses to acupuncture in patients with the same disease at different pathological stages have not been explored, although it may be more important and helpful in uncovering its underlying mechanisms. In the present study, we used fMRI to compare brain responses to acupuncture in patients with Bell's palsy at different pathological stages with normal controls and found that the brain response to acupuncture varied at different pathological stages of Bell's palsy. The brain response to acupuncture decreased in the early stages, increased in the later stages, and nearly returned to normal in the recovered group. All of the changes in the brain response to acupuncture could be explained as resulting from the changes in the brain functional status. Therefore, we proposed that the brain response to acupuncture is dependent on the brain functional status, while further investigation is needed to provide more evidence in support of this proposition.

Hyperglycaemia exacerbates choroidal neovascularisation in mice via the oxidative stress-induced activation of STAT3 signalling in RPE cells.

Choroidal neovascularisation (CNV) that occurs as a result of age-related macular degeneration (AMD) causes severe vision loss among elderly patients. The relationship between diabetes and CNV remains controversial. However, oxidative stress plays a critical role in the pathogenesis of both AMD and diabetes. In the present study, we investigated the influence of diabetes on experimentally induced CNV and on the underlying molecular mechanisms of CNV. CNV was induced via photocoagulation in the ocular fundi of mice with streptozotocin-induced diabetes. The effect of diabetes on the severity of CNV was measured. An immunofluorescence technique was used to determine the levels of oxidative DNA damage by anti-8-hydroxy-2-deoxyguanosine (8-OHdG) antibody, the protein expression of phosphorylated signal transducer and activator of transcription 3 (p-STAT3) and vascular endothelial growth factor (VEGF), in mice with CNV. The production of reactive oxygen species (ROS) in retinal pigment epithelial (RPE) cells that had been cultured under high glucose was quantitated using the 2',7'-dichlorofluorescein diacetate (DCFH-DA) method. p-STAT3 expression was examined using Western blot analysis. RT-PCR and ELISA processes were used to detect VEGF expression. Hyperglycaemia exacerbated the development of CNV in mice. Oxidative stress levels and the expression of p-STAT3 and VEGF were highly elevated both in mice and in cultured RPE cells. Treatment with the antioxidant compound N-acetyl-cysteine (NAC) rescued the severity of CNV in diabetic mice. NAC also inhibited the overexpression of p-STAT3 and VEGF in CNV and in RPE cells. The JAK-2/STAT3 pathway inhibitor AG490 blocked VEGF expression but had no effect on the production of ROS in vitro. These results suggest that hyperglycaemia promotes the development of CNV by inducing oxidative stress, which in turn activates STAT3 signalling in RPE cells. Antioxidant supplementation helped attenuate the development of CNV. Thus, our results reveal a potential strategy for the treatment and prevention of diseases involving CNV.

[Study on inter-individual variability of cerebral response to acupuncture with fMRI].

OBJECTIVE: Effects of inter-individual variability on fMRI of acupuncture were observed and the possible influencing factors were further analyzed. METHODS: Twenty-six healthy volunteers were selected. And acupuncture was applied at Zusanli (ST 36) on the left side with even manipulation. The same experimental designation and data collecting reference were adopted to collect functional data. Then, the same data processing method was applied for analyzing individual data. Data which did not confirm with data analyzing qualification were rejected. The 26 individual data which met the requirement were taken randomly for 5 times according to the principle of random group division. Five groups named with A, B, C, D and E were thus generated with 11 samples in each. Images were processed with the AFNI software for every group, and the activated brain areas were revealed. RESULTS: Activated areas in the brain were observed in all the 5 groups, and the results vary a lot among different groups. Decreased signals of activated brain areas were observed in group C, while increased signals were seen in group D. Partial increasing and partial decreasing signals appeared in the other 3 groups. Compared with other groups, group D demonstrated totally different activated areas. The rate of difference among different groups is 46.7%-100.0%, and most of the differences were over half of the activated areas. CONCLUSION: Under the pre-requisites of strict control of experimental designation, acupuncture method, data collecting and processing, great differences have been found in the activated areas of the brain. It indicates that obvious individual differences existes in the activated areas of the brain with acupuncture. And the difference may greatly influence the researching result of fMRI as well as conclusions of those results.

Acupuncture inhibits cue-induced heroin craving and brain activation.

Previous research using functional MRI has shown that specific brain regions associated with drug dependence and cue-elicited heroin craving are activated by environmental cues. Craving is an important trigger of heroin relapse, and acupuncture may inhibit craving. In this study, we performed functional MRI in heroin addicts and control subjects. We compared differences in brain activation between the two groups during heroin cue exposure, heroin cue exposure plus acupuncture at the Zusanli point (ST36) without twirling of the needle, and heroin cue exposure plus acupuncture at the Zusanli point with twirling of the needle. Heroin cue exposure elicited significant activation in craving-related brain regions mainly in the frontal lobes and callosal gyri. Acupuncture without twirling did not significantly affect the range of brain activation induced by heroin cue exposure, but significantly changed the extent of the activation in the heroin addicts group. Acupuncture at the Zusanli point with twirling of the needle significantly decreased both the range and extent of activation induced by heroin cue exposure compared with heroin cue exposure plus acupuncture without twirling of the needle. These experimental findings indicate that presentation of heroin cues can induce activation in craving-related brain regions, which are involved in reward, learning and memory, cognition and emotion. Acupuncture at the Zusanli point can rapidly suppress the activation of specific brain regions related to craving, supporting its potential as an intervention for drug craving.

[Study on the relative specificity of the heart and lung meridians in brain with fMRI].

OBJECTIVE: To study the central modulation mechanism on the relative specificity of the Heart and Lung Meridians and to provide the experimental evidence for deeply study on correlation between meridian-viscera and brain. METHODS: Ten healthy students in Anhui College of TCM were chosen and a modified block design was adopted. After 32 time points of resting and 32 of rotation needling, then 48 of resting and 32 stimulating, and 16 resting time points, functional imagings were collected at last. All the process would last for 10 min 44 sec. Acupuncture work was finished by one acupuncturist with extensive experience by acupuncture at the left Shenmen (HT 7) or Taiyuan (LU 8) with the disposable sterile stainless steel needle, and uniform reinforcing-reducing method was used with frequency of 1 Hz and depth of 1.0 cm. After the experiment, the sensation of acupuncture and the other feeling or psychic process were inquired and recorded detailedly. These data were analyzed by AFNI software. RESULTS: Acupuncture at Taiyuan (LU 8) could excite the contralateral frontal lobe, apical lobe, cerebral ganglion, VI, VIII areas and inferior semilunar lobule of cerebellum, and restrain bilateral callosal gyrus and homolateral gyrus rectus. Acupuncture at Shenmen (HT 7) could excite the contralateral IV-VIII areas of cerebellum, and homolateral VI, VII areas of cerebellum, and restrain parts of homolateral apical lobe. CONCLUSION: Acupuncture at Shenmen (HT 7) of the Heart Meridian and Taiyuan (LU 8) of the Lung Meridian can excite or restrain different brain areas, indicating that there are relatively specific corresponding brain areas for the Heart Meridian and Lung Meridian.