经颅磁刺激对强直迟缓亚型帕金森病患者脑功能网络的影响

目的 重复经颅磁刺激（r TMS）作为一种无创的神经调控技术，对帕金森病（PD）患者的疗效目前尚未完全明确。本文结合临床量表评估、脑电溯源以及脑功能网络以探讨高频r TMS对强直迟缓亚型帕金森病（AR-PD）患者的作用效应。方法 共纳入18例AR-PD患者，利用标准低分辨率电磁断层成像（s LORETA）对脑电信号进行溯源分析，进而通过复杂网络理论构建脑功能网络，从脑区之间协同工作的角度对比分析网络拓扑特征。结果 磁刺激后前额叶、初级运动皮层出现显著性差异（P<0.05）；与运动感觉产生、运动规划和运动执行相关脑区的网络连通性显著增强（P<0.05）且脑功能网络的拓扑特征平均聚类系数的变化与帕金森病统一评定量表评分的变化存在显著相关性（P<0.05）。结论 推测r TMS改善了AR-PD患者在运动感觉产生到运动执行过程中的信息传递能力，本研究可为r TMS对AR-PD患者运动症状的改善作用与感觉运动网络重新整合的关系提供一定的理论依据。     

食物奖赏和渴求行为相关的大鼠左侧眶额叶皮质Delta频段脑电活动(英文）

眶额叶皮质与中脑边缘多巴胺奖赏系统有着复杂的相互纤维联系。先前的研究探讨了药物成瘾过程中眶额叶皮质的脑电活动。在本实验中,将探讨食物奖赏和渴求过程中该皮质的脑电活动。实验采用了两个环境：对照环境和食物刺激相关的环境。首先,训练大鼠在食物刺激相关的环境中吃巧克力花生豆,而后在该环境中设置两种不同的刺激方式：能看到和闻到但不能吃到(渴求实验),或者仍旧可以吃到巧克力花生豆（奖赏实验）;同时进行左侧眶额叶皮质的脑电记录。结果发现,在食物刺激相关的环境中大鼠Delta频段（2－4 Hz）的脑电活动与食物刺激显著相关,此外,与在对照环境中相比,其相对功率在食物渴求时下降而在食物奖赏时升高。本实验表明,食物相关的奖励可以改变大鼠眶额叶皮质的脑电活动,而且,Delta频段的脑电活动能够作为监测该奖励的一个指标。     

神经活性甾体别孕烯醇酮对脑皮质神经元损伤的保护作用

目的：利用N-甲基-D-天门冬氨酸（NMDA）诱发新生小鼠脑皮质神经元损伤模型,探讨神经活性甾体别孕烯醇酮对脑皮质神经元的保护作用及其机制。方法：应用RT-PCR和Western blot法检测别孕烯醇酮对β2-γ-氨基丁酸受体（β2-GABA-R）表达和对蛋白激酶B（PKB,又称为Akt）磷酸化的影响。应用Western blot和DNA-Ladder方法检测NMDA诱发的神经元凋亡及别孕烯醇酮对NMDA诱发凋亡的影响。结果：Western blot和RT-PCR分析表明0.5×10-6mol/L-5×10-6mol/L别孕烯醇酮使Akt磷酸化增加并促进β2-GABA-R mRNA的表达。1×10-6mol/L别孕烯醇酮预处理小鼠脑皮质神经元有抗凋亡作用,但5×10-6mol/L别孕烯醇酮预处理小鼠脑皮质神经元使NMDA诱发的DNA-Ladder减弱明显,并能有效抵抗NMDA诱发的活化型PRAP、Caspase-3、Caspase-9的增加。结论：别孕烯醇酮可通过促进β2-GABA-R表达和增加Akt磷酸化抵抗NMDA诱发的脑皮质神经元凋亡。     

PKCγ免疫反应定位小鼠皮质脊髓束的实验研究

目的探讨显示皮质脊髓束在成年小鼠脑和脊髓中定位分布的简便有效方法。方法运用蛋白激酶Cγ（PKCγ）免疫组织化学染色法,观察成年ICR小鼠脑和脊髓中皮质脊髓束的定位和分布情况。结果PKCγ免疫阳性产物分布于大脑运动皮层第V层锥体细胞胞体和轴突中,锥体细胞的阳性纤维经内囊、中脑大脑脚底、脑桥基底部、下行至延髓锥体中。在延髓下段,PKCγ阳性纤维经锥体交叉后进入对侧脊髓灰质后联合背侧,形成背侧皮质脊髓束,在脊髓白质的后索腹侧深层下行,至骶髓3-4节段以下逐渐消失。在整个脊髓前索和外侧索中未见有PKCγ阳性纤维。结论PKCγ特异地表达于脊髓后索皮质脊髓束中,提示PKCγ免疫组织化学法是一种显示和观察皮质脊髓束精确定位的有效方法。     

血红素氧合酶-1诱导实验性肺炎球菌性脑膜炎皮质非血红素铁增加，但不造成脑过氧化损伤

铁螯合剂去铁敏（DFO）能够抑制实验性肺炎球菌性脑膜炎新生大鼠皮质坏死,表明游离铁可能导致神经元过氧化损伤。本实验探讨肺炎球菌性脑膜炎中皮质铁蛋白和铁稳态的空间、时间变化。结果表明在感染过程中,全脑皮质的非血红素铁增加,特别是在神经细胞集中的皮质第二、第五层和毛细血管内皮细胞。同时,非血红素铁的增加伴随着血红素氧合酶（HO-1）在神经元、     

小脑皮质结构年龄相关变化的研究进展

衰老过程中小脑皮质出现明显的形态学变化,包括体积萎缩、重量减轻、皮层厚度下降、神经元数量减少,树突丢失、细胞超微结构改变、神经递质紊乱以及胶质细胞增生等。神经元数量丢失与结构退变以及神经递质改变可能会导致老年小脑皮质神经环路破坏和信息传输紊乱,与老年个体运动调节功能及运动学习能力下降有关;神经胶质活动增强对维持老年小脑皮质的形态和功能可能起保护作用。     

胎儿视皮质皮质下层含─氧化氮合酶神经元的发育

本文用出生前１７周至３６周胎儿标本１０个,死后４小时内作常规灌注固定,取脑后作视皮质冰冻切片（３０ｕｍ）,用一氧化氮合酶（ＮＯＳ）组织化学法孵育切片２～４小时,在视皮质皮质下层（ＳＰ）可见ＮＯＳ强阳性神经元。这些神经元胞体大小不一、形态各异、突起显示呈高尔基染色外观,部分神经纤维含有膨体和生长锥。２０周以后,从ＳＰ层有ＮＯＳ阳性神经纤维伸入皮质板或白质。随着胎龄增长,ＮＯＳ阳性神经元密度增加,胞体切面积增大,神经元由幼稚趋向成熟。本研究还观察到胎儿ＳＰ内ＮＯＳ阳性神经元可从形态上明显地划分为两个阶段,并推测ＮＯＳ合成的一氧化氮（ＮＯ）在突触建立和修饰、突触间信息传递、传入纤维对靶器官的识别和脑组织局部血流调节等过程中起着重要作用。     

食物奖赏和渴求行为相关的大鼠左侧眶额叶皮质Delta频段脑电活动(英文）

眶额叶皮质与中脑边缘多巴胺奖赏系统有着复杂的相互纤维联系。先前的研究探讨了药物成瘾过程中眶额叶皮质的脑电活动。在本实验中,将探讨食物奖赏和渴求过程中该皮质的脑电活动。实验采用了两个环境:对照环境和食物刺激相关的环境。首先,训练大鼠在食物刺激相关的环境中吃巧克力花生豆,而后在该环境中设置两种不同的刺激方式:能看到和闻到但不能吃到(渴求实验),或者仍旧可以吃到巧克力花生豆(奖赏实验);同时进行左侧眶额叶皮质的脑电记录。结果发现,在食物刺激相关的环境中大鼠 Delta 频段(2-4 Hz)的脑电活动与食物刺激显著相关,此外,与在对照环境中相比,其相对功率在食物渴求时下降而在食物奖赏时升高。本实验表明,食物相关的奖励可以改变大鼠眶额叶皮质的脑电活动,而且,Delta 频段的脑电活动能够作为监测该奖励的一个指标。     

大鼠躯体感觉皮质即早基因c-fos表达的研究

选择性地对大鼠单根触须刺激后,通过原位杂交组织化学检测相应的躯体感觉皮质内即早基因c-fos的表达、局部定位以及与刺激强度的关系。结果表明,触须的刺激导致了相应皮质内即早基因c－fos表达增加。脑皮质第4层基因表达最明显。且基因表达量与刺激强度成正比。从脑皮质细胞组成方面证实了c-fos表达主要在皮质第4层的星形细胞;在最强的刺激后,星形细胞邻近的神经元也被标记上了。结果提示：感觉输入可影响即早基因c-fos的表达,即早基因的表达受神经元活动的调节,这种基因调节是神经元整体功能所必需的一部分。     

猫小脑皮质浦肯野细胞超微结构的年龄相关变化

目的比较观察青年猫（1-3岁）和老年猫（12-13岁）小脑皮质浦肯野细胞（Purkinje cell,PC）的超微结构,探讨其年龄相关变化的生理意义。方法常规电镜包埋、切片、染色,透射电镜下观察并拍照。结果老年组PC粗面内质网碎裂,核糖体解离;线粒体膨解,嵴减少;高尔基复合体扁平囊扩张,极性退化;脂褐素聚积;膜性髓样结构与空泡变性出现;核膜内陷,染色质固缩;生物膜系统结构破坏等。结论衰老过程中细胞器结构退化可能影响老年PC物质合成、能量供应、信息传递及神经元的结构稳定,导致衰老PC死亡,推测与老年个体运动调节和运动学习等小脑功能退化有重要联系。     

Transcranial magnetic stimulation: a primer

Transcranial magnetic stimulation (TMS) is a technique for noninvasive stimulation of the human brain. Stimulation is produced by generating a brief, high-intensity magnetic field by passing a brief electric current through a magnetic coil. The field can excite or inhibit a small area of brain below the coil. All parts of the brain just beneath the skull can be influenced, but most studies have been of the motor cortex where a focal muscle twitch can be produced, called the motor-evoked potential. The technique can be used to map brain function and explore the excitability of different regions. Brief interference has allowed mapping of many sensory, motor, and cognitive functions. TMS has some clinical utility, and, because it can influence brain function if delivered repetitively, it is being developed for various therapeutic purposes.     

Can ultrasound be used to stimulate nerve tissue?

Background  

The stimulation of nerve or cortical tissue by magnetic induction is a relatively new tool for the non-invasive study of the brain and nervous system. Transcranial magnetic stimulation (TMS), for example, has been used for the functional mapping of the motor cortex and may have potential for treating a variety of brain disorders.     

The effect of skilled motor training on corticomotor control of back muscles in different presentations of low back pain

Transcranial magnetic stimulation (TMS) has revealed differences in the motor cortex (M1) between people with and without low back pain (LBP). There is potential to reverse these changes using motor skill training, but it remains unclear whether changes can be induced in people with LBP or whether this differs between LBP presentations. This study (1) compared TMS measures of M1 (single and paired-pulse) and performance of a motor task (lumbopelvic tilting) between individuals with LBP of predominant nociceptive (n = 9) or nociplastic presentation (n = 9) and pain-free individuals (n = 16); (2) compared these measures pre- and post-training; and (3) explored correlations between TMS measures, motor performance, and clinical features. TMS measures did not differ between groups at baseline. The nociplastic group undershot the target in the motor task. Despite improved motor performance for all groups, only MEP amplitudes increased across the recruitment curve and only for the pain-free and nociplastic groups. TMS measures did not correlate with motor performance or clinical features. Some elements of motor task performance and changes in corticomotor excitability differed between LBP groups. Absence of changes in intra-cortical TMS measures suggests regions other than M1 are likely to be involved in skill learning of back muscles.     

Systematic assessment of training-induced changes in corticospinal output to hand using frameless stereotaxic transcranial magnetic stimulation

Measuring changes in the characteristics of corticospinal output has become a critical part of assessing the impact of motor experience on cortical organization in both the intact and injured human brain. In this protocol we describe a method for systematically assessing training-induced changes in corticospinal output that integrates volumetric anatomical MRI with transcranial magnetic stimulation (TMS). A TMS coil is sited to a target grid superimposed onto a 3D MRI of cortex using a stereotaxic neuronavigation system. Subjects are then required to exercise the first dorsal interosseus (FDI) muscle on two different tasks for a total of 30 min. The protocol allows for reliably and repeatedly detecting changes in corticospinal output to FDI muscle in response to brief periods of motor training.     

Electronically switchable sham transcranial magnetic stimulation (TMS) system

Transcranial magnetic stimulation (TMS) is increasingly being used to demonstrate the causal links between brain and behavior in humans. Further, extensive clinical trials are being conducted to investigate the therapeutic role of TMS in disorders such as depression. Because TMS causes strong peripheral effects such as auditory clicks and muscle twitches, experimental artifacts such as subject bias and placebo effect are clear concerns. Several sham TMS methods have been developed, but none of the techniques allows one to intermix real and sham TMS on a trial-by-trial basis in a double-blind manner. We have developed an attachment that allows fast, automated switching between Standard TMS and two types of control TMS (Sham and Reverse) without movement of the coil or reconfiguration of the setup. We validate the setup by performing mathematical modeling, search-coil and physiological measurements. To see if the stimulus conditions can be blinded, we conduct perceptual discrimination and sensory perception studies. We verify that the physical properties of the stimulus are appropriate, and that successive stimuli do not contaminate each other. We find that the threshold for motor activation is significantly higher for Reversed than for Standard stimulation, and that Sham stimulation entirely fails to activate muscle potentials. Subjects and experimenters perform poorly at discriminating between Sham and Standard TMS with a figure-of-eight coil, and between Reverse and Standard TMS with a circular coil. Our results raise the possibility of utilizing this technique for a wide range of applications.     

How Thoughts Give Rise to Action - Conscious Motor Intention Increases the Excitability of Target-Specific Motor Circuits

The present study shows evidence for conscious motor intention in motor preparation prior to movement execution. We demonstrate that conscious motor intention of directed movement, combined with minimally supra-threshold transcranial magnetic stimulation (TMS) of the motor cortex, determines the direction and the force of resulting movements, whilst a lack of intention results in weak and omni-directed muscle activation. We investigated changes of consciously intended goal directed movements by analyzing amplitudes of motor-evoked potentials of the forearm muscle, flexor carpi radialis (FCR), and extensor carpi radialis (ECR), induced by transcranial magnetic stimulation over the right motor cortex and their motor outcome. Right-handed subjects were asked to develop a strong intention to move their left wrist (flexion or extension), without any overt motor output at the wrist, prior to brain stimulation. Our analyses of hand acceleration and electromyography showed that during the strong motor intention of wrist flexion movement, it evoked motor potential responses that were significantly larger in the FCR muscle than in the ECR, whilst the opposite was true for an extension movement. The acceleration data on flexion/extension corresponded to this finding. Under no-intention conditions again, which served as a reference for motor evoked potentials, brain stimulation resulted in undirected and minimally simultaneous extension/flexion innervation and virtually no movement. These results indicate that conscious intentions govern motor function, which in turn shows that a neuronal activation representing an “intention network” in the human brain pre-exists, and that it functionally represents target specific motor circuits. Until today, it was unclear whether conscious motor intention exists prior to movement, or whether the brain constructs such an intention after movement initiation. Our study gives evidence that motor intentions become aware before any motor execution.     

精准定位脑刺激对运动功能调控研究进展

脑刺激是神经科学研究的重要手段,传统的经颅磁刺激和经颅电刺激等脑刺激方法尽管能调控运动功能(包括减轻运动性障碍疾病的运动障碍、提高运动能力等),但存在空间分辨率低且无法刺激深部脑组织的局限性.近年来迅速发展的深部脑刺激(deep brain stimulation,DBS)、光遗传学、经颅超声刺激(transcranial ultrasound stimulation,TUS)、时间干涉(temporal interference,TI)等精准定位脑刺激方法,具有空间分辨率高、可聚焦深部脑组织等优点.本文综述了上述几种脑刺激方法的原理、特点,对运动功能调控的研究进展,以及面临的挑战和发展前景,从而为神经科学研究提供更好的研究工具,为临床实践提供更多的干预治疗手段.     

创伤后应激障碍的经颅磁刺激研究进展

创伤后应激障碍会损伤记忆、注意和执行等认知功能,引起异常的脑活动及脑区间功能连接.尽管药物治疗和心理干预能够取得一定的治疗效果,但存在药物副作用和起效延迟等问题.经颅磁刺激作为新的创伤后应激障碍干预手段受到越来越多的关注.本文通过综述经颅磁刺激干预创伤后应激障碍以及调控认知功能和脑活动的相关研究,系统探讨了创伤后应激障碍干预中经颅磁刺激模式、刺激靶点和疗效评估等问题,并提出未来借助更有效的技术手段进行定位、建立全面有效的评估体系和结合新的记忆理论探索具有长期临床改善效果的干预方案.     

Effects of high frequency electromagnetic field (EMF) emitted by mobile phones on the human motor cortex

We investigated whether the pulsed high frequency electromagnetic field (EMF) emitted by a mobile phone has short term effects on the human motor cortex. We measured motor evoked potentials (MEPs) elicited by single pulse transcranial magnetic stimulation (TMS), before and after mobile phone exposure (active and sham) in 10 normal volunteers. Three sites were stimulated (motor cortex (CTX), brainstem (BST) and spinal nerve (Sp)). The short interval intracortical inhibition (SICI) of the motor cortex reflecting GABAergic interneuronal function was also studied by paired pulse TMS method. MEPs to single pulse TMS were also recorded in two patients with multiple sclerosis showing temperature dependent neurological symptoms (hot bath effect). Neither MEPs to single pulse TMS nor the SICI was affected by 30 min of EMF exposure from mobile phones or sham exposure. In two MS patients, mobile phone exposure had no effect on any parameters of MEPs even though conduction block occurred at the corticospinal tracts after taking a bath. As far as available methods are concerned, we did not detect any short-term effects of 30 min mobile phone exposure on the human motor cortical output neurons or interneurons even though we can not exclude the possibility that we failed to detect some mild effects due to a small sample size in the present study. This is the first study of MEPs after electromagnetic exposure from a mobile phone in neurological patients.     

Transcranial magnetic stimulation intensities in cognitive paradigms

Background

Transcranial magnetic stimulation (TMS) has become an important experimental tool for exploring the brain''s functional anatomy. As TMS interferes with neural activity, the hypothetical function of the stimulated area can thus be tested. One unresolved methodological issue in TMS experiments is the question of how to adequately calibrate stimulation intensities. The motor threshold (MT) is often taken as a reference for individually adapted stimulation intensities in TMS experiments, even if they do not involve the motor system. The aim of the present study was to evaluate whether it is reasonable to adjust stimulation intensities in each subject to the individual MT if prefrontal regions are stimulated prior to the performance of a cognitive paradigm.

Methods and Findings

Repetitive TMS (rTMS) was applied prior to a working memory task, either at the ‘fixed’ intensity of 40% maximum stimulator output (MSO), or individually adapted at 90% of the subject''s MT. Stimulation was applied to a target region in the left posterior middle frontal gyrus (pMFG), as indicated by a functional magnetic resonance imaging (fMRI) localizer acquired beforehand, or to a control site (vertex). Results show that MT predicted the effect size after stimulating subjects with the fixed intensity (i.e., subjects with a low MT showed a greater behavioral effect). Nevertheless, the individual adaptation of intensities did not lead to stable effects.

Conclusion

Therefore, we suggest assessing MT and account for it as a measure for general cortical TMS susceptibility, even if TMS is applied outside the motor domain.