Cerebral mechanism of puncturing at He-Mu point combination for functional dyspepsia:study protocol for a randomized controlled parallel trial

Acupuncture is widely used to treat functional dyspepsia with satisfactory outcomes. Combination of the He and Mu acupoints is commonly used and has a synergistic effect on functional dyspepsia;however, its underlying mechanisms remain unclear.Therefore, a ran-domized controlled parallel clinical trial is currently underway at Chengdu University of Traditional Chinese Medicine, China.This trial is designed to explore the efficacy of and central responses to the He-Mu point combination in patients with functional dyspepsia using functional magnetic resonance imaging. A total of 105 patients with functional dyspepsia will be allocated into 3 groups:the low-He point group (puncturing at Zusanli (ST36)), Mu point group (puncturing at Zhongwan (CV12)), and He-Mu point combination group (puncturing at ST36 and CV12). Every participant will receive 20 sessions of manual acupuncture for 4 weeks.The needles will be inserted perpen-dicularly to a depth of 1 to 2 cun.The angle of rotation and twisting will range from 90 to 180 degrees, while lifting and thrusting will range from 0.3 to 0.5 cm.The various manipulations will be performed 60 to 90 times per minute.The needles will remain in place for 30 minutes, during which manipulation will be applied every 10 minutes. Magnetic resonance imaging will be performed before and after 20 sessions of acupuncture.The primary outcome is symptom improvement according to the Chinese version of the Nepean Dyspepsia Index. Secondary outcomes include the Leeds dyspepsia questionnaire, Self-Rating Anxiety Scale, Self-Rating Depression Scale, Beck Anxiety Inventory, Beck Depression Inventory, and visual analogue scale scores before and after 10 and 20 sessions of acupuncture. Needle sensa-tion and adverse events will be used to assess the therapeutic effects.This study will promote more widespread awareness of the benefits of acupoint combination in the clinical setting and provide a further explanation of the neuromechanism by which acupuncture at the He-Mu point combination for functional dyspepsia. Registration:Chinese Clinical Trial Registry, ChiCTR-IOR-15006402.     

不同穴位皮部浅刺与常规针刺在fMRI脑功能成像中的差异

Few studies have examined the effects of different stimuli at a single acupoint using functional magnetic resonance imaging.The present study applied acupuncture at the Neiguan(PC 6),Waiguan(SJ 5),Zhigou(SJ 6) and Yanglingquan(GB 34) acupoints in healthy volunteers.fMRI was used to examine the activation of brain areas in response to different types of acupuncture(cutaneous or routine acupuncture) at each acupoint.There were no significant differences in the distribution of activation in the regions of interest between cutaneous and routine acupuncture at the Neiguan,Waiguan,and Zhigou acupoints,but some differences were observed between the two methods of acupuncture at the Yanglingquan acupoint.There were no significant differences in the intensity of induced activation between cutaneous and routine acupuncture at the Neiguan,Zhigou and Yanglingquan acupoints,but the activation intensity in the right cerebellum induced by routine acupuncture at the Waiguan acupoint was greater than that induced by cutaneous acupuncture.Results confirmed that cutaneous and routine acupuncture at the Neiguan,Waiguan,Zhigou and Yanglingquan acupoints activated different functional brain areas,and caused activation of different intensities in some areas.     

Brain functional changes in facial expression recognition in patients with major depressive disorder before and after antidepressant treatment A functional magnetic resonance imaging study

Functional magnetic resonance imaging was used during emotion recognition to identify changes in functional brain activation in 21 first-episode, treatment-naive major depressive disorder patients before and after antidepressant treatment. Following escitalopram oxalate treatment, patients exhibited decreased activation in bilateral precentral gyrus, bilateral middle frontal gyrus, left middle temporal gyrus, bilateral postcentral gyrus, left cingulate and right parahippocampal gyrus, and increased activation in right superior frontal gyrus, bilateral superior parietal lobule and left occipital gyrus during sad facial expression recognition. After antidepressant treatment, patients also exhibited decreased activation in the bilateral middle frontal gyrus, bilateral cingulate and right parahippocampal gyrus, and increased activation in the right inferior frontal gyrus, left fusiform gyrus and right precuneus during happy facial expression recognition. Our experimental findings indicate that the limbic-cortical network might be a key target region for antidepressant treatment in major depressive disorder.     

Remodeling of motor cortex function in acute cerebral infarction patients following human urinary kallidinogenase A functional magnetic resonance imaging evaluation after 6 months

A total of 29 patients were treated within 48 hours after acute subcortical cerebral infarction with Xuesaitong or Xuesaitong plus human urinary kallidinogenase for 14 days.Neurological deficits,activity of daily living,and evaluations of distal upper limb motor functions at the 6-month follow-up showed that patients treated with Xuesaitong plus human urinary kallidinogenase recovered better than with Xuesaitong alone.In addition,functional MRI revealed that activation sites were primarily at the ipsilesional side of injury in all patients.Human urinary kallidinogenase induced hyperactivation of the ipsilesional primary sensorimotor cortex,premotor cortex,supplementary motor area,and contralesional posterior parietal cortex.Results showed that human urinary kallidinogenase improved symptoms of neurological deficiency by enhancing remodeling of long-term cortical motor function in patients with acute cerebral infarction.     

弥散张量纤维素成像三维重建皮质脊髓束定位脑初级运动功能区

Functional MRI (fMRI) is widely used as a non-invasive method for the evaluation of pre-operation motor function.However,patients with cortical function impairment,such as those with hemiparesis,can rarely achieve hand clenching,a typical fMRI task for central sulcus identification,and the method is also of limited use in uncooperative children.Thus,it is important to develop a new method for identifying primary motor areas (PMA) in such individuals.This study used corticospinal tractography to identify the PMA in 20 patients with deep-seated brain tumor.Two regions of interest were set within the brainstem for corticospinal tract (CST) fiber tracking:one at the level of the pons and the other at the level of the cerebral peduncle.The CST fiber tracking results and fMRI activation signals were merged with three-dimensional anatomic MRI findings.The consistency of identifying the PMA by CST and fMRI was analyzed.fMRI activation signals were distributed mainly in the contralateral central sulcus around the omega-shaped hand knob.The CST consistently propagated from the pons and cerebral peduncle to the suspected PMA location.There was a good correlation between CST fiber tracking results and fMRI activation signals in terms of their abilities to identify the PMA.The differences between fMRI and CST fiber tracking findings may result from our functional task,which consisted only of hand movements.Our results indicate that diffusion tensor imaging is a useful brain mapping technique for identifying the PMA in paralyzed patients and uncooperative children.     

Modulatory effects of acupuncture on brain networks in mild cognitive impairment patients

Functional magnetic resonance imaging has been widely used to investigate the effects of acupuncture on neural activity. However, most functional magnetic resonance imaging studies have focused on acute changes in brain activation induced by acupuncture. Thus, the time course of the therapeutic effects of acupuncture remains unclear. In this study, 32 patients with amnestic mild cognitive impairment were randomly divided into two groups, where they received either Tiaoshen Yizhi acupuncture or sham acupoint acupuncture. The needles were either twirled at Tiaoshen Yizhi acupoints, including Sishencong(EX-HN1), Yintang(EX-HN3), Neiguan(PC6), Taixi(KI3), Fenglong(ST40), and Taichong(LR3), or at related sham acupoints at a depth of approximately 15 mm, an angle of ± 60°, and a rate of approximately 120 times per minute. Acupuncture was conducted for 4 consecutive weeks, five times per week, on weekdays. Resting-state functional magnetic resonance imaging indicated that connections between cognition-related regions such as the insula, dorsolateral prefrontal cortex, hippocampus, thalamus, inferior parietal lobule, and anterior cingulate cortex increased after acupuncture at Tiaoshen Yizhi acupoints. The insula, dorsolateral prefrontal cortex, and hippocampus acted as central brain hubs. Patients in the Tiaoshen Yizhi group exhibited improved cognitive performance after acupuncture. In the sham acupoint acupuncture group, connections between brain regions were dispersed, and we found no differences in cognitive function following the treatment. These results indicate that acupuncture at Tiaoshen Yizhi acupoints can regulate brain networks by increasing connectivity between cognition-related regions, thereby improving cognitive function in patients with mild cognitive impairment.     

Compensatory recombination phenomena of neurological functions in central dysphagia patients

We speculate that cortical reactions evoked by swallowing activity may be abnormal in patients with central infarction with dysphagia. The present study aimed to detect functional imaging features of cerebral cortex in central dysphagia patients by using blood oxygen level-dependent functional magnetic resonance imaging techniques. The results showed that when normal controls swallowed, primary motor cortex(BA4), insula(BA13), premotor cortex(BA6/8), supramarginal gyrus(BA40), and anterior cingulate cortex(BA24/32) were activated, and that the size of the activated areas were larger in the left hemisphere compared with the right. In recurrent cerebral infarction patients with central dysphagia, BA4, BA13, BA40 and BA6/8 areas were activated, while the degree of activation in BA24/32 was decreased. Additionally, more areas were activated, including posterior cingulate cortex(BA23/31), visual association cortex(BA18/19), primary auditory cortex(BA41) and parahippocampal cortex(BA36). Somatosensory association cortex(BA7) and left cerebellum in patients with recurrent cerebral infarction with central dysphagia were also activated. Experimental findings suggest that the cerebral cortex has obvious hemisphere lateralization in response to swallowing, and patients with recurrent cerebral infarction with central dysphagia show compensatory recombination phenomena of neurological functions. In rehabilitative treatment, using the favorite food of patients can stimulate swallowing through visual, auditory, and other nerve conduction pathways, thus promoting compensatory recombination of the central cortex functions.     

Functional magnetic resonance imaging evaluation of brain function reorganization in cerebral stroke patients after constraint-induced movement therapy

In this study, stroke patients received constraint-induced movement therapy for 3 weeks. Before and after constraint-induced movement therapy, the flexibility of their upper limbs on the affected side was assessed using the Wolf motor function test, and daily use of their affected limbs was assessed using the movement activities log, and cerebral functional reorganization was assessed by functional magnetic resonance imaging. The Wolf motor function test score and the movement activities log quantity and quality scores were significantly increased, while action performance time in the Wolf motor function test was significantly decreased after constraint-induced movement therapy. By functional magnetic resonance imaging examination, only scattered activation points were visible on the affected side before therapy. In contrast, the volume of the activated area was increased after therapy. The activation volume in the sensorimotor area was significantly different before and after therapy, and the activation area increased and appeared adjusted. In addition to the activated area around the lesions being decreased, there were also some new activated areas, including the supplementary movement area, premotor area and the ipsilateral sensorimotor area. Our findings indicate that constraint-induced movement therapy significantly improves the movement ability and daily use of the affected upper limbs in stroke patients and promotes cerebral functional reorganization.     

Dynamic functional connectivity analysis of Taichong (LR3) acupuncture effects in various brain regions

The present study conducted a multi-scale dynamic functional connectivity analysis to evaluate dynamic behavior of acupuncture at Taichong (LR3) and sham acupoints surrounding Taichong. Results showed differences in wavelet transform coherence characteristic curves in the declive, precuneus, postcentral gyrus, supramarginal gyrus, and occipital lobe between acupuncture at Taichong and acupuncture at sham acupoints. The differences in characteristic curves revealed that the specific effect of acupuncture existed during the post-acupuncture rest state and lasted for 5 minutes.     

Serum anti-aquaporin 4 antibody in neuromyelitis patients is not correlated with the length of injured spinal cord segments

Clinical information and serum samples of 20 neuromyelitis patients and 30 patients with multiple sclerosis were collected in this study. The expression of anti-aquaporin 4 antibody in the serum of all patients was detected with an indirect immunofluorescence assay, using human embryonic kidney 293 cell line that stably express human-derived aquaporin 4 as a substrate. The characteristics of head and spinal magnetic resonance imaging were also observed in patients who had neuromyelitis and were positive for anti-aquaporin 4 antibody. Results showed that the expression of anti-aquaporin 4 antibody was significantly different between multiple sclerosis patients and neuromyelitis patients. There were 13 out of 20 neuromyelitis patients (including high-risk syndrome) that were positive for anti-aquaporin 4 antibody. The magnetic resonance imaging examinations of the head and spinal cord found that among the 13 positive patients, nine cases showed normal cerebral hemisphere and optic nerve, two cases had optic nerve changes, and one case had an atypical lesion in the brain. All 30 multiple sclerosis patients were negative for this antibody. The experimental findings indicate that patients with neuromyelitis optica had more than three lesioned segments in the spinal cord by magnetic resonance imaging, and the segment length of the injured spinal cord was not associated with the titer of aquaporin 4 antibody in neuromyelitis patients.     

捻转和非捻转刺激太溪穴后脑激活状态的功能磁共振成像研究

目的：观察功能磁共振成像了解捻转刺激太溪穴和非捻转刺激所引起的脑激活区状态。 方法：纳入健康青年志愿者12名,选取右侧太溪穴,采用组块刺激模式,静息阶段与刺激阶段交替出现,重复3次,分为3个组块。刺激为手法捻转行针或非捻转,非捻转即手放在针柄,但不进行任何操作。扫描后图像使用SPM2进行后处理。 结果：捻转刺激太溪穴主要激活了右侧颞上回BA22,左侧的额中回BA46,其次为左右顶叶的中央后回BA2,BA3,左额叶的额下回BA45和左顶叶的顶下小叶BA40;而非捻转刺激则没有激活。 结论：捻转刺激太溪穴和非捻转刺激的激活不同,与本经相关的经络、脏腑联系密切相关。     

The salient characteristics of the central effects of acupuncture needling: limbic-paralimbic-neocortical network modulation

Human and animal studies suggest that acupuncture produces many beneficial effects through the central nervous system. However, the neural substrates of acupuncture actions are not completely clear to date. fMRI studies at Hegu (LI4) and Zusanli (ST36) indicated that the limbic system may play an important role for acupuncture effects. To test if this finding applies to other major classical acupoints, fMRI was performed on 10 healthy adults during manual acupuncture at Taichong (LV3), Xingjian (LV2), Neiting (ST44), and a sham point on the dorsum of the left foot. Although certain differences could be observed between real and sham points, the hemodynamic response (BOLD signal changes) and psychophysical response (sensory experience) to acupuncture were generally similar for all four points. Acupuncture produced extensive deactivation of the limbic-paralimbic-neocortical system. Clusters of deactivated regions were seen in the medial prefrontal cortex (frontal pole, pregenual cingulate), the temporal lobe (amygdala, hippocampus, and parahippocampus) and the posterior medial cortex (precuneus, posterior cingulate). The sensorimotor cortices (somatosensory cortices, supplementary motor cortex), thalamus and occasional paralimbic structures such as the insula and anterior middle cingulate cortex showed activation. Our results provide additional evidence in support of previous reports that acupuncture modulates the limbic-paralimbic-neocortical network. We hypothesize that acupuncture may mediate its antipain, antianxiety, and other therapeutic effects via this intrinsic neural circuit that plays a central role in the affective and cognitive dimensions of pain as well as in the regulation and integration of emotion, memory processing, autonomic, endocrine, immunological, and sensorimotor functions.     

Effects of acupuncture at Sibai （ST 2） acupoint on neuronal discharge in rat nucleus tractus solitarius

BACKGROUND： Electrophysiology can prove the integration of afferent information from the stomach meridian of Foot-Yangming in the nucleus tractus solitarius （NTS） and objectively describe the specific association between meridian vessels and Zang Fu organs. OBJECTIVE： To investigate the effects of afferent information from acupuncture at Sibai （ST 2） acupoint on neuronal discharge in rat NTS. DESIGN, TIME AND SETFING： A randomized, controlled, animal experiment was performed at the Key Laboratory of Meridian-Vessels and Zang Fu Organs, Traditional Chinese Medicine University of Hunan, State Administration of Traditional Chinese Medicine, and Key Laboratory of Acupuncture, Moxibustion, and the Biological Information of Hunan Higher Education Institutes, between December 2005 and October 2008. MATERIALS： A total of 52 Sprague Dawley rats, of either gender, aged 4 months, were included in this study. Acupuncture needles of 0.32 mm （diameter） x 40 mm （length） were used. METHODS： An extracellular recording protocol was applied. The Sibai （ST 2） acupoint in the stomach meridian of Foot-Yangming was used as an acupuncture point （acupoint）. Simultaneously, Dicang （ST 4） and Neiting （ST 44） acupoints in the stomach meridian of Foot-Yangming, Quanliao （S118） acupoint in the small intestine meridian of Hand-Taiyang, and a non-acupoint lateral to Sibai （ST 2） acupoint, were selected as controls. The Sibai （ST 2） acupoint was stimulated for 30 seconds by hand acupuncture through twirling and rotating, to determine the neurons responding to body surface stimulation in the NTS. MAIN OUTCOME MEASURES： Frequency of responding NTS neurons after acupuncture at four acupoints including Sibai （ST 2）, Dicang （ST 4）, Neiting （ST 44） and Quanliao （SI 18） and one non-acupoint. RESULTS： The frequency of responding NTS neurons was significantly higher after acupuncture at Sibaithan at control sites including the Dicang （ST 4）, Neiting （ST 44） and Quanliao （S118） acupoints and at the non-acupoint （P 〈 0.01）. The frequency of responding NTS neurons at Dicang （ST 4） and Quanliao （SI 18） was significantly higher than at Quanliao （SI 18） and the non-acupoint （P 〈 0.05）. The rate of frequency change of responding NTS neurons for the Sibai （ST 2）, Dicang （ST 4）, Neiting （ST 44）, and Quanliao （S118） acupoints as well as the non-acupoint was （35.08±4.80） %, （28.25± 5.46） %, （27.57± 4.87） %, （20.02 ±4.23） %, and （18.55 ±2.49） % respectively. Simultaneously, significant differences existed between Sibai （ST 2） and the other acupoints （P 〈 0.05 or P〈 0.01）. CONCLUSION： Compared with the Dicang （ST 4） and Neiting （ST 44） acupoints in the stomach meridian of Foot-Yangming, Quanliao （SI 18） acupoint in the small intestine meridian of Hand-Taiyang, and the non-acupoint lateral to Sibai （ST 2） acupoint, the Sibai （ST 2） acupoint in the stomach meridian of Foot- Yangming is more closely related to the NTS. In the stomach meridian of Foot- Yangming, afferent information is different in distant and near Shu acupoints, indicating that each Shu acupoint has its own specificity.     

Acupuncture at Waiguan (TE5) influences activation/deactivation of functional brain areas in ischemic stroke patients and healthy people A functional MRI study

In the present study, 10 patients with ischemic stroke in the left hemisphere and six healthy controls were subjected to acupuncture at right Waiguan (TE5). In ischemic stroke subjects, functional MRI showed enhanced activation in Broadmann areas 5, 6, 7, 18, 19, 24, 32, the hypothalamic inferior lobe, the mamillary body, and the ventral posterolateral nucleus of the left hemisphere, and Broadmann areas 4, 6, 7, 18, 19 and 32 of the right hemisphere, but attenuated activation of Broadmann area 13, the hypothalamic inferior lobe, the posterior lobe of the tonsil of cerebellum, and the culmen of the anterior lobe of hypophysis, in the left hemisphere and Broadmann area 13 in the right hemisphere. In ischemic stroke subjects, a number of deactivated brain areas were enhanced, including Broadmann areas 6, 11, 20, 22, 37, and 47, the culmen of the anterior lobe of hypophysis, alae lingulae cerebella, and the posterior lobe of the tonsil of cerebellum of the left hemisphere, and Broadmann areas 8, 37, 45 and 47, the culmen of the anterior lobe of hypophysis, pars tuberalis adenohypophyseos, inferior border of lentiform nucleus, lateral globus pallidus, inferior temporal gyrus, and the parahippocampal gyrus of the right hemisphere. These subjects also exhibited attenuation of a number of deactivated brain areas, including Broadmann area 7. These data suggest that acupuncture at Waiguan specifically alters brain function in regions associated with sensation, vision, and motion in ischemic stroke patients. By contrast, in normal individuals, acupuncture at Waiguan generally activates brain areas associated with insomnia and other functions.     

Ontogeny of atrial natriuretic factor (ANF) binding in various areas of the rat brain

In order to evaluate the possibility that ANF might be associated with brain maturation, we have studied the distribution of ANF binding sites as a function of brain development in the rat. Using in vitro autoradiography, we have observed that ANF binding first appeared before the 13th day of foetal life. In some brain structures, the changes in ANF binding concentration and distribution were dramatic during maturation. In 13-day old foetus, specific ANF binding was observed in cerebral cortex and olfactory bulb. On the 17th day of foetal life, two labeled layers were observed in the cerebral cortex: the basal layer (cortical plate) and the superficial layer. With further development, the ANF binding of the cortical plate decreased whereas the labeling increased in the superficial layer so that 9 days after birth a strong labeling was observed in the superficial layer of the cortex. Thereafter the density of ANF binding rapidly diminished and almost no specific labeling could be detected in the cortex of adult animals. In the hippocampus and amygdaloid complex, ANF binding was first detected at birth and increased rapidly in the following days to reach maximal concentration 5 days after birth. Then, the binding gradually decreased with age and completely disappeared in adult animals. In some other structures, such as the habenula, cerebellum, thalamus and some hypothalamic nuclei, the specific ANF binding appeared around the time of birth, increased until adulthood was reached, and then remained stable. These results indicate that ANF binding sites are transiently associated with some brain structures during maturation and suggest that ANF might be involved in brain development.     

Activation of olfactory and trigeminal cortical areas following stimulation of the nasal mucosa with low concentrations of S(-)-nicotine vapor--an fMRI study on chemosensory perception

Applied to the nasal mucosa in low concentrations, nicotine vapor evokes odorous sensations (mediated by the olfactory system) whereas at higher concentrations nicotine vapor additionally produces burning and stinging sensations in the nose (mediated by the trigeminal system). The objective of this study was to determine whether intranasal stimulation with suprathreshold concentrations of S(-)-nicotine vapor causes brain activation in olfactory cortical areas or if trigeminal cortical areas are also activated. Individual olfactory detection thresholds for S(-)-nicotine were determined in 19 healthy occasional smokers using a computer-controlled air-dilution olfactometer. Functional magnetic resonance images were acquired using a 1.5T MR scanner with applications of nicotine in concentrations at or just above the individual's olfactory detection threshold. Subjects reliably perceived the stimuli as being odorous. Accordingly, activation of brain areas known to be involved in processing of olfactory stimuli was identified. Although most of the subjects never or only rarely observed a burning or painful sensation in the nose, brain areas associated with the processing of painful stimuli were activated in all subjects. This indicates that the olfactory and trigeminal systems are activated during perception of nicotine and it is not possible to completely separate olfactory from trigeminal effects by lowering the concentration of the applied nicotine. In conclusion, even at low concentrations that do not consistently lead to painful sensations, intranasally applied nicotine activates both the olfactory and the trigeminal system.     

Needling at the Waiguan (SJ5) in healthy limbs deactivated functional brain areas in ischemic stroke patients A functional magnetic resonance imaging study

Deactivation is common in cerebral functional imaging. However, the physiological mechanisms responsible for this phenomenon remain poorly understood. The present study analyzed 12 ischemic stroke patients, who were randomly assigned to two groups: one group underwent sham needling and true needling at the Waiguan (SJ 5) in the healthy upper limb and the other group underwent sham and true needling at a sham point. Functional magnetic resonance imaging results showed no activation points in brain tissues fo...     

Cortical brain responses during passive nonpainful median nerve stimulation at low frequencies (0.5-4 Hz): an fMRI study

Previous findings have shown that the human somatosensory cortical systems that are activated by passive nonpainful electrical stimulation include the contralateral primary somatosensory area (SI), bilateral secondary somatosensory area (SII), and bilateral insula. The present study tested the hypothesis that these areas have different sensitivities to stimulation frequency in the condition of passive stimulation. Functional MRI (fMRI) was recorded in 24 normal volunteers during nonpainful electrical median nerve stimulations at 0.5, 1, 2, and 4 Hz repetition rates in separate recording blocks in pseudorandom order. Results of the blood oxygen level-dependent (BOLD) effect showed that the contralateral SI, the bilateral SII, and the bilateral insula were active during these stimulations. As a major finding, only the contralateral SI increased its activation with the increase of the stimulus frequency at the mentioned range. The fact that nonpainful median-nerve electrical stimuli at 4 Hz induces a larger BOLD response is of interest both for basic research and clinical applications in subjects unable to perform cognitive tasks in the fMRI scanner.