功能磁共振成像观察补法、泻法针刺足三里穴对大脑作用的中枢机制

目的 用功能磁共振成像(fMRI)方法观察补法和泻法针刺足三里穴对大脑作用的中枢机制. 方法 选取32名健康右利手志愿者,对11名受检者用补法电针刺激右侧足三里穴(ST36)、11名用泻法电针刺激ST36、10名电针刺激右侧足三里穴同一水平向外2～3 cm处.同时行全脑fMRI扫描;用SPM2软件进行图像后处理. 结果 电针结束后5 min,泻法组的脑区激活不明显,而补法组平均信号升高的脑区主要有双侧尾状核头部、丘脑、左侧岛叶、扣带回及小脑齿状核.电针结束后20～30 min期间两组脑区的激活最为明显,均激活左侧的丘脑、中央旁小叶、中央前回、颞中回、额中回、岛叶、双侧尾状核头部、小脑半球、前、后扣带回;两组激活区域大致相同,但补法组激活的脑区范围更广、强度更大.针刺假穴组只激活中央旁小叶及小脑半球. 结论 补、泻手法针刺足三里穴均能激活边缘系统、辅助运动区、灰质结构等脑区,而应用补法能更早、更强烈地激活上述脑区.     

人脑运动皮质对针刺足三里和阳陵泉反应的功能性磁共振成像研究

目的利用功能性磁共振成像(fMRI)技术观察人脑运动皮质对针刺足三里和阳陵泉穴的反应,对针刺神经机制进行初步探讨.方法对20名健康志愿者(正常对照组)和17例左侧中央沟区病变导致运动障碍的患者(运动障碍组)行实时动态fMRI检查.每名志愿者分别接受以下两项任务①右手对指运动,②被针刺右侧足三里和阳陵泉.对激活的运动皮质功能区进行计数.采用SAS软件包作精确概率法比较两项任务激活各运动功能区的概率.运动障碍组均接受针刺任务,观察病变周围fMRI信号变化情况.结果在正常对照组对指任务时,除去1例合作不好外,其余19例激活右侧第一运动皮质区(RMI)8例,右侧运动前区(RPMC)8例,副运动区(SMA)9例,左侧第一运动皮质区(LMI)19例,左侧运动前区(LPMC)9例针刺任务时,除去4例运动图像伪影明显外,其余16例激活RMI 7例,RPMC11例,SMA 9例,LMI11例,LPMC 13例.对指运动激活LMI概率(100%)较针刺(68.75%)高(P<0.05);其余各运动功能区激活概率差异无显著性(P>0.05).运动障碍组接受针刺任务时,在fMRI脑功能图的整个上额叶均可见明显的功能激活区.结论 fMRI证实运动皮质对针刺足三里和阳陵泉穴存在广泛的反应,人脑的这种反应可能为针刺效应的重要机制.磁共振脑功能成像在针刺机制的研究方面具有重要价值.     

The effects of stimulation at acupoint ST36 points against hemorrhagic shock in dogs

The aim of this study is to investigate the effects of electroacupuncturing (EA) zusanli points on levels of basic hemodynamics, lactate, and cytokines in dogs with hemorrhagic shock. Thirty healthy dogs were randomly divided into 5 groups: sham hemorrhagic shocked group, hemorrhagic shocked group, EA group, nonacupuncturing group, and EA after vagotomy group. Zusanli points were electroacupunctured with constant voltage (10-15 V, 30 Hz) for 30 minutes immediately after the shock models were established. Before the stimulation, a blood pressure transducer was implanted into the right femoral artery for continuous recording of mean arterial pressure (MAP), and a 5F Swan-Ganz pediatric catheter was implanted into the pulmonary artery. The levels of serum tumor necrosis factor α (TNF-α) in the femoral artery were detected at 0, 120, and 180 minutes after hemorrhage. The levels of serum lactate in the femoral artery were detected before hemorrhage (−45 minutes), at 0 minute, and at 180 minutes. In the hemorrhagic shocked group, the levels of MAP, cardiac output, cardiac index, central venous pressure, and pulmonary arterial wedge pressure decreased significantly; at the same time, the levels of serum TNF-α and serum lactate increased significantly. There were no differences between these groups and the hemorrhagic group, but they were different from the sham hemorrhagic shocked group. In the EA group, the levels of MAP, cardiac output, cardiac index, central venous pressure, and pulmonary arterial wedge pressure gradually increased, but the content of serum TNF-α and lactate obviously decreased. The results suggested that EA zusanli points produce a protective effect on hemorrhagic shock in dogs.     

正常人体针灸效应功能性磁共振成像的研究

目的评价针刺体表穴位对脑部相应区域的功能性磁共振成像(fMRI)表现。方法17例健康志愿者，在1，5TMRI仪上进行针刺足三里(S36)、阳陵泉(G34)的实时动态fMRI检查，观察并分析针刺效果明显者的脑部功能变化情况，判断针刺效果及其意义。结果17例志愿者中13例检查成功，可见躯体感觉运动区(SMC)、运动前区(PMC)、副运动区(SMA)激活明显，额叶前部、扣带回、尾状核头部、豆状核及丘脑、岛叶、岛盖皮质大多有大面积明显激活，小脑和桥脑也可见有激活，在左侧丘脑、SMA、SMC、PMC激活区附近有信号减低的现象，但激活的像素数不多；信号减低区包括两侧额叶内侧面皮质，双侧扣带回前部皮质，两侧海马区，右侧眶回、基底节、尾状核头部等。结论针刺对脑部相关穴位的治疗效应显著，可产生广泛而复杂的脑功能变化，fMRI可清楚显示针刺效应引起的脑部功能变化，是针刺机制及效应良好且直观的评价途径。     

针刺足三里穴对冷应激性溃疡大鼠下丘脑与肾上腺NOS表达的影响

目的研究针刺足三里穴对急性胃溃疡(由冷应激引起)的保护作用，以及冷应激对大鼠下丘脑及肾上腺一氧化氮合成酶(NOS)表达的影响。方法通过计算胃粘膜溃疡指数和应用RT—PCR技术，对大鼠下丘脑、肾上腺NOS的表达情况进行半定量研究。结果实验数据表明，针刺足三里穴可以明显减少溃疡(由冷应激导致)指数；同时发现下丘脑NOS1不参与冷应激溃疡病理过程，针刺足三里穴可在生理范围内上调下丘脑NOS1的表达水平；下丘脑NOS2参与了冷应激溃疡病理过程，针刺足三里穴可下调其表达，减轻病理损害程度；NOS3也参与了冷应激溃疡病理过程，针刺可以下调其表达水平。但下调程度较轻微；肾上腺NOS1及NOS3表达水平在应激过程中增高，针刺只能抑制NOS1表达，肾上腺NOS2不参与该应激过程。结论针刺对冷应激溃疡具有一定的保护作用，该保护作用是通过生理性上调下丘脑NOS1表达、下调NOS2及NOS3病理性高表达以及抑制肾上腺NOS1表达而实现的。     

人脑对事件相关食物视觉刺激反应的功能磁共振成像的初步研究

目的通过功能磁共振成像(fMRI)初步研究人脑对事件相关食物视觉刺激反应.方法本研究利用fMRI技术具有时间分辨率高、对人体无创并且可以对单例数据处理分析的优势,采用平面回波成像(EPI)序列,检测在饥饿状态下,人脑对事件相关食物视觉刺激反应.实验中2名健康志愿受试者,选择事件相关任务模式禁食12 h后扫描.扫描的同时接受随机播放的食物图片、非食物图片和空白模糊图片的视觉刺激.用SPM 2软件处理功能成像数据,对由三类图片所引发的感兴趣区(ROI)做相关t检验统计.结果与食物渴求相关的脑区分布在杏仁核、眶额皮质以及枕叶皮质,与既往的正电子放射扫描成像(PET)实验结果相符.结论确定与食物渴求相关的奖赏通路,对于了解人类在饥饿状态下对食物渴求的复杂认知规律,为进一步寻找有效调控人类摄食行为的手段有重要意义.     

经皮电针刺激正常人耳甲迷走神经的功能MRI脑效应研究

目的探讨耳甲迷走神经刺激术的脑通路,为耳迷走神经刺激调制孤束核-边缘叶脑网络假说提供证据。材料与方法随机录用16名健康志愿者,参加经皮电刺激右耳甲部迷走神经分布区（t VNS）,以同侧上耳舟部刺激为对照,记录刺激的耳部感觉,观察全脑6 min扫描的Bold-f MRI信号变化,分析脑功能激活特点,应用SPM8处理f MRI数据。结果两组电流、感觉频率及强度未见明显区别。经皮电刺激耳甲部t VNS正常人激发了左侧孤束核及边缘叶脑区广泛而较强的负激活效应,局限性激活位于体感区及岛叶等,而对照部产生了右侧三叉神经核等脑干核团负激活及脑部体感区明显的激活现象。结论经皮电刺激迷走神经产生了孤束核-边缘叶脑网络的调制效应,为经皮电刺激耳甲部迷走神经治疗抑郁症等脑中枢机制打下基础。     

Brain activation in response to bladder filling and simultaneous stimulation of the dorsal clitoral nerve--an fMRI study in healthy women

AIMS: Using functional magnetic resonance imaging (fMRI) we investigated the cortical and subcortical representations during bladder filling and the effect of simultaneous stimulation of the dorsal clitoral nerve on these cortical and subcortical structures. METHODS: After approval of the local ethics committee, 8 healthy females were included. Prior to scanning, subjects were catheterized and the bladder was filled until first desire to void occurred. In a block design protocol we performed repetitive manual bladder filling (FILLING) and emptying of additional 80 ml saline, alternating with rest conditions (REST) of constant bladder volume. The protocol was repeated with simultaneous stimulation of the dorsal clitoral nerve during the filling periods (COMBINED). Activation maps were calculated by means for 3 different contrasts: 1) FILLING>REST, 2) COMBINED>REST and 3) FILLING>COMBINED. RESULTS: A group analysis of contrast 1) showed activation of the right prefrontal and orbitofrontal cortices, the insula bilaterally, the left precuneus, the parietal operculum bilaterally, the cerebellum bilaterally (q(FDR)< or =0.001), the right anterior cingulate gyrus (q(FDR)< or =0.005) and the right anterior mid pons (q(FDR)< or =0.05). Contrast 2) showed activation in the right frontal area, the left insula, the parietal operculum bilaterally and the left cerebellum (q(FDR)< or =0.001). Deactivations were found in the middle frontal gyrus bilaterally and the post- and paracentral gyri bilaterally. Contrast 3) revealed stronger activation during FILLING in the bilateral frontal and prefrontal areas, the right anterior cingulated gyrus, and the right putamen (q(FDR)< or =0.05). Only the right insula showed stronger activation during the COMBINED condition. CONCLUSION: Simultaneous dorsal clitoral nerve stimulation during bladder filling reduced the activation of certain cortical areas suggesting a neuromodulatory effect of this stimulation on supraspinal centres involved in lower urinary tract control.     

An integrated model of the human ventilatory control system: the response to hypoxia

The mathematical model of the respiratory control system described in a previous companion paper is used to analyse the ventilatory response to hypoxic stimuli. Simulation of long‐lasting isocapnic hypoxia at normal alveolar PCO₂ (40 mmHg=5·33 kPa) shows the occurrence of a biphasic response, characterized by an initial peak and a subsequent hypoxic ventilatory decline (HVD). The latter is about as great as 2/3 of the initial peak and can be mainly ascribed to prolonged neural hypoxia. If isocapnic hypoxia is performed during hypercapnia (PACO₂=48 mmHg =6·4 kPa), the ventilatory response is stronger and HVD is minimal (about 1/10–1/5 of the initial peak). During poikilocapnic hypoxia, ventilation exhibits smaller changes compared with the isocapnic case, with a rapid return toward baseline within a few minutes. Moreover, a significant undershoot occurs at the termination of the hypoxic period. This undershoot may lead to apnea and to a transient destabilization of the control system if the peripheral chemoreflex gain and time delay are twofold greater than basal.     

An integrated model of the human ventilatory control system: the response to hypercapnia

This work presents a mathematical model of the human respiratory control system, based on physiological knowledge. It includes three compartments for gas storage and exchange (lungs, brain tissue and other body tissues), and various kinds of feedback mechanisms. These comprehend peripheral chemoreceptors in the carotid body, central chemoreceptors in the medulla and a central ventilatory depression. The latter acts by reducing the response of the central neural system to the afferent peripheral chemoreceptor activity during prolonged hypoxia of the brain tissue. Furthermore, the model considers local blood flow adjustments in response to O₂ and CO₂ arterial pressure changes. In this study, the model has been validated by simulating the response to square changes in alveolar PCO₂, performed at different constant levels of alveolar PO₂. A good agreement with data reported in the literature has been checked. Subsequently, a sensitivity analysis on the role of the main feedback mechanisms on ventilation response to CO₂ has been performed. The results suggest that the ventilatory response to CO₂ challenges during hyperoxia can be almost completely ascribed to the central chemoreflex, while, during normoxia, the peripheral chemoreceptors provide a modest contribution too. By contrast, the response to hypercapnic stimuli during hypoxia involves a complex superimposition among different factors with disparate dynamics. Hence, results suggest that the ventilatory response to hypercapnia during hypoxia is more complex than that provided by simple empirical models, and that discrimination between the central and peripheral components based on time constants may be misleading.     

电针足三里穴后脑功能磁共振成像显示不同脑区的激活变化

目的:传统医学认为针刺足三里可补气、抗衰老。应用脑功能磁共振成像客观观察电针刺激足三里穴对各认知功能相关脑区活动情况的影响。方法:观察于2004-03/10在首都医科大学宣武医院神经内科完成。纳入标准:年龄在50～60岁之间,性别不限,饮食规律,无精神或神经系统疾病史且自愿参加本研究的健康人。排除标准:MRI确定患有其他疾病者及接受过针刺治疗者。共有3人符合以上标准,男1人,女2人。通过脑功能磁共振成像技术观察电针刺激志愿者右侧下肢足三里穴引起中枢神经系统不同脑区的功能变化,一次脑功能磁共振成像扫描给予间断电针刺激3次,采用静息-刺激交替模式。结果:进入结果分析保持为3人。电针刺激足三里穴主要引起两侧前额叶和颞叶的神经功能变化,左侧脑部激活较右侧表现明显,具体为左侧颞上回、颞中回、颞下回激活,右侧颞中回激活。此外,左侧脑干有少量激活,其他脑区无明显激活。结论:电针刺激足三里穴能激活前额叶和颞叶等与认知功能有关的脑区。     

基于脑fMRI技术针刺支沟穴特异性及脑网络的研究进展

支沟穴临床疗效显著且应用普遍,但其针刺作用机制尚不完全清楚,功能磁共振成像(functional magnetic resonance imaging,fMRI)技术已成为研究针刺作用脑神经机制的重要手段.经过查询、整理应用脑fMRI技术研究针刺支沟穴的相关文献得知,针刺支沟穴特异性激活脑区与主管胃肠道疾病相关脑区结构...     

Widespread functional connectivity and fMRI fluctuations in human visual cortex in the absence of visual stimulation

To what extent does the visual system's activity fluctuate when no sensory stimulation is present? Here, we studied this issue by examining spontaneous fluctuations in BOLD signal in the human visual system, while subjects were placed in complete darkness. Our results reveal widespread slow fluctuations during such rest periods. In contrast to stimulus-driven activity, during darkness, functionally distinct object areas were fluctuating in unison. These fMRI fluctuations became rapidly spatially de-correlated (39% drop in correlation level, P < 0.008) during visual stimulation. Functional connectivity analysis revealed that the slow spontaneous fluctuations during rest had consistent and specific neuro-anatomical distribution which argued against purely hemodynamic noise sources. Control experiments ruled out eye closure, low luminance and mental imagery as the underlying sources of the spontaneous fluctuations. These results demonstrate that, when no stimulus is present, sensory systems manifest a robust level of slow organized fluctuation patterns.     

人类大脑皮层对人物肖像和风景识别的fMRI研究

目的探讨人类大脑对物体的识别功能区集中在大脑皮层的位置.方法使用了三种黑白图片:人物肖像、自然风景和打乱的图片给9例均为右利手的正常人观看,同时用1.5 T MRI仪采集实验对象的解剖像、三维全脑结构像和功能像.实验结果用功能神经成像分析软件 (AFNI)进行数据处理及分析.结果在腹侧颞叶(梭状回)后部存在两个相邻的区域分别对风景和人物敏感,其中靠内侧的区域对风景刺激的反应更强烈,靠外侧的区域则对人物刺激的反应更强;而且风景相关区域和人物相关区域呈现出从内侧到外侧的一种渐变过渡的分布.结论尽管参与人物视觉加工的脑区和参与风景视觉加工的脑区对不同的两种刺激的反应强度有所不同,但两个脑区并不截然分开,而是连续分布并相互重叠的.     

针刺联合语言康复训练治疗脑卒中失语症的疗效及功能性磁共振成像研究

目的 利用血氧水平依赖性功能性磁共振成像(BOLD-fMRI)技术观察脑卒中失语症患者针刺联合语言康复训练治疗前和治疗后语言中枢激活脑区的变化,并比较单纯语言康复训练与联合治疗两种任务态下患者的言语功能恢复情况及激活脑区功能性磁共振成像(fMRI)差异.方法 选取20例脑卒中失语症患者,所有患者均为右利手,按随机数字表法将其分为单一治疗组和联合治疗组,每组10例.单一治疗组采用语言康复训练,联合治疗组在此基础上增加针刺治疗,分别于入院当日及治疗1个月后采用BOLD-fMRI技术对患者的中枢激活脑区进行评定,并于治疗1个月后应用汉语失语成套测验(ABC)评价患者的言语功能恢复情况.结果 治疗过程中,单一治疗组有1例患者再发脑卒中,未能复查fMRI.治疗后,单一治疗组和联合治疗组的有效率分别为55.56％和100.00％,联合治疗组言语功能恢复状况优于单一治疗组(P＜0.05).单一治疗组和联合治疗组患者的激活体素和激活强度变化与组内治疗前比较,差异均有统计学意义(P＜0.05),其中联合治疗组右侧激活脑区明显多于左侧,且其激活脑区较单一治疗组更为显著、广泛(P＜0.05),主要包括双侧额叶、楔叶、后扣带回、舌回、枕叶、胼胝体压部、小脑半球,左侧中央前后回、中央旁小叶、颞叶、角回、楔前叶,右侧海马、海马旁回.结论 针刺联合语言康复训练可引起患者相应脑功能激活区产生变化,而这些特异性激活区可能与患者的言语功能恢复有关.     

应用功能性磁共振成像技术探讨针刺三阴交穴对脑功能的调节作用

目的观察手捻针刺三阴交穴对脑组织功能性磁共振成像（fMRI）的影响，分析针刺三阴交穴对大脑不同区域功能的调节作用，从现代科学角度对针刺三阴交穴的可能作用机理进行初步探讨。方法应用磁共振成像系统，对8名健康右利手志愿者接受针刺右侧三阴交穴期间的功能活动进行全脑扫描，获得针刺三阴交穴的脑功能激活图。8名自愿者的数据经过空间平滑、头动矫正等处理后进行平均化，通过反卷积计算每个体素的信号改变，定义P〈0．001为差异具有统计学意义。结果针刺右侧三阴交穴可激活左右额内侧回、右额中回、左额下回、双侧中央旁小叶、左右中央前回、左右中央后回、左侧顶下小叶、双侧楔前叶、右颞中回、右扣带回、右扣带后回、双侧颞上回、双侧颞横回、双侧岛叶和双侧丘脑。结论针刺三阴交穴可激活额、顶、颞叶皮质以及扣带回、楔前叶、岛叶、丘脑，可能是其治疗泌尿、生殖、消化系统疾病和下肢神经痛、瘫痪，以及改善精神和睡眠状态的作用机制。针刺三阴交穴能引起双侧特定脑皮质的反应，进一步证实穴位与脑皮质相应代表区之间存在相关性。     

Source of nonlinearity of the BOLD response revealed by simultaneous fMRI and NIRS

The nonlinearity of the blood oxygenation level-dependent (BOLD) response to stimuli of different duration, particularly those of short duration, has been well studied by functional magnetic resonance imaging (fMRI). This nonlinearity is assumed to be due to neural adaptation and the nonlinearity of the response in the oxygen extraction fraction (OEF); the latter has not been examined quantitatively in humans. To evaluate how the OEF response contributes to the nonlinearity of the BOLD response to neural activity, we used simultaneous fMRI and near-infrared spectroscopy (NIRS). The responses to visual stimuli of four different durations were measured as changes in the BOLD signal and the NIRS-derived hemoglobin concentrations. The hemodynamic response nonlinearity was quantified using an impulse response function model with saturation nonlinearity scaling in the response amplitude, assuming that the unknown neural adaptation parameters varied within a physiologically feasible range. Independent of the degree of neural adaptation, the BOLD response consistently showed saturation nonlinearity similar to that of the OEF response estimated from the NIRS measures, the nonlinearity of which was greater than that of the response in the total hemoglobin concentration representing the cerebral blood volume (CBV). We also found that the contribution of the OEF response to the BOLD response was four to seven times greater than the contribution of the CBV response. Thus, we conclude that the nonlinearity of the BOLD response to neural activity originates mainly from that of the OEF response.     

Attenuation of brain response to heroin correlates with the reinstatement of heroin-seeking in rats by fMRI

Thirty male Sprague-Dawley rats were divided into two groups and trained to self-administer either saline (n = 14) or heroin (0.1 mg/kg per injection, n = 16) for 10-12 days until a stable self-administration (SA) behavior was achieved. After 8-9 days of withdrawal, each group was divided into two subgroups for reinstatement tests and functional magnetic resonance image (fMRI) scanning, respectively, to determine the neural correlates of the reinstatement of heroin-seeking behavior. For reinstatement testing, heroin-SA rats (n = 10) displayed robust reinstatement of drug-seeking behavior triggered by an acute heroin priming injection, whereas saline control rats (n = 8) did not show such a behavioral response. Regional positive or negative blood oxygen level-dependent (BOLD) signals, induced by heroin priming injection, were observed in both groups of rats during fMRI scanning. However, such heroin-induced positive BOLD signal primarily in the prefrontal cortex and parietal cortex was significantly attenuated in heroin-SA rats (n = 6) when compared to saline control rats (n = 6). Similarly, the heroin-induced negative BOLD signal in the subcortical regions, such as in the nucleus accumbens and hippocampus, was also significantly attenuated in both signal intensity and number of brain voxels activated in heroin-SA rats. These data demonstrate that heroin-induced reinstatement of drug-seeking behavior coincides with a significant, enduring reduction in opiate-induced brain activity in heroin-SA rats, suggesting a possible role of opiate tolerance in mediating reinstatement of drug-seeking behavior.