慢性电刺激诱发大鼠癫痫模型中核磁共振检测信号异常的非对称性与特征性行为发作的关系

本文旨在探讨内嗅皮质（EC）－海马环路在颞叶癫痫发生中的作用,慢性强直电刺激大鼠石背海马（DH－PC）或右中部颞叶新皮质（MTNC）,每日一次（60Hz,2s,0.4-0.6mA),加续7－10d,刺激DHPC（57.4%,8/14只）或MTNC（71．42％,10／14只）均能引起电极对侧出现非对称性脑区核磁共振（T2－WI）信号增强,组织学切片证实与扩大的侧脑室吻合,可能涉及脑帝质结构的损伤,DHPC刺激组大鼠对侧脑扣内务 伴有高频原发性湿狗样抖（WEDS）,MTNC刺激组大鼠对侧脑损伤伴有低频原发性WEDS,后者在第2个刺激日开始出现,持续到第10天以后,所有假电极组无脑区T2-WI稚号和行为改变,我们推测,刺激HPC或MTNC所致癫痫性早期脑损伤具有同一种机制,涉及EC－HPC环路,刺激MTNC时,可能由于EC潜在门控作用,削弱了进出EC－HPC环路通往新皮质的信息流,致使脑损伤明显时行为发作频度低,另外,非对称非脑扣内务 提示了颞叶癫痫的致痫灶的对侧易感特征。     

氟桂利嗪对青霉素致痫大鼠皮层及海马癫痫样放电的影响

目的:观察氟桂利嗪对青霉素致痫大鼠皮层和海马癫痫样放电的影响.方法:选取Wistar大鼠60只制作青霉素致痫模型,在大鼠海马、颞叶、额叶皮层埋置电极,记录氟桂利嗪(20 mg/kg)灌胃后大鼠癫痫样放电的变化.结果:实验组动物皮层及海马癫痫样放电潜伏期明显延长,持续时间缩短,单位时间内癫痫样放电数明显减少,与对照组相比有显著差异.结论:氟桂利嗪具有明显抗癫痫作用,可显著抑制青霉素致痫鼠皮层及海马区癫痫样放电.     

齿状回在慢性电刺激诱发大鼠颞叶癫痫中的可能作用

本文探讨了齿状回（DG）及海马（HPC）在颞叶癫痫发生中的可能作用,分别强直电刺激（60Hz,0.4-0.6mA,2s)大鼠右背侧海马（DHPC）和DG制作慢性癫痫模型,观察大鼠行为,深部电图及脑区T2加权核磁共振成像（T2－WI)的改变,发现DG刺激组大鼠的原发性湿狗样抖频率明显低于HPC刺激组（P＜0．05）,其深部电图脑波的平均最高振幅也明显低于HPC刺激组大鼠（P＜0．05）,而PC电图的电振荡发生率增加,另外,HPC刺激组大鼠呈现T2－WI高信号强度,而DG刺激组大鼠T2－WI信号强度无明显改变（P＜0．05）,结果表明,DG在内嗅皮质（EC）－HPC环路中可能起着某种“过滤器”的作用,限制来自于大脑皮层通过EC到达HPC的神经信息,一旦丧失该作用可以导致HPC的损害并发生颞叶癫痫。     

杏仁核点燃模型癫痫样放电传播途径研究

目的 :探讨杏仁核点燃模型癫痫样放电的传播途径。方法 :选择健康Wistar大鼠 3 0只以电刺激杏仁核的方式制作杏仁核点燃癫痫模型 ,于右侧杏仁核、左侧海马及右侧额叶皮质埋植电极记录脑电活动 ,观察电刺激杏仁核时在杏仁核、海马及额叶皮质出现癫痫样放电的潜伏期、最低刺激强度及癫痫样放电的持续时间。结果 :杏仁核出现癫痫样放电时 ,海马及皮质均未记录到癫痫样放电。而当杏仁核、海马及皮质三处出现癫痫样放电时的最低刺激强度依次增大 ,潜伏期依次延长 ,海马处癫痫样放电的持续时间最长。结论 :杏仁核点燃模型癫痫样放电可能由杏仁核经海马传至皮层 ,海马可能为癫痫样放电传播的重要结构     

跨颅电刺激对大鼠抑郁症的治疗作用

目的：探讨跨颅电刺激对大鼠抑郁症的治疗作用。方法：跨颅电刺激抑郁症大鼠左侧前额叶皮层,敞箱实验测定大鼠行为学变化,荧光法测定单胺类递质含量的变化。结果：跨颅直流电和低频脉冲电刺激后,大鼠敞箱实验中垂直和水平运动得分均较模型组显著升高（P〈0.05）;且大鼠左侧前额叶皮层和海马5-HT、NE含量较模型组显著升高（P〈0.05）,而前额叶皮层DA含量无显著变化（P〉0.05）。结论：直流电和低频脉冲电跨颅刺激左侧前额叶皮层,对抑郁症均有显著治疗作用。     

慢性颞叶癫痫大鼠行为、电图发作和核磁共振研究--海马-内嗅皮质-颞叶新皮质通路

目的和方法：强直电刺激（６０Ｈｚ,０．４￣０．６ｍＡ,２ｓ）左、右侧背侧海马或中部颞叶新皮质制作慢性大鼠癫痫模型,观察大鼠行为、ＥＥＧ、深部电图以及各脑区Ｔ２（质子横向驰豫时间）加权核磁共振成象（Ｔ２－ＭＲＩ）结构改变,研究海马－内嗅皮质－颞叶新皮质、大脑皮层神经通路在诱发颞叶癫痫中的可能作用。结果：右侧海马刺激组的原发性、继发性湿狗样抖动及癫痫“点燃”效应的发生率明显高于左海马和左、右颞叶新皮质     

癫痫发作敏感大鼠前深梨状皮层T区神经病理观察

目的和方法：采用颞叶癫痫红藻氨酸（kainic acid,KA)模型,制备癫痫发作敏感大鼠,并分别以硫瑾染色和GFAP（神经胶质原纤维酸性蛋白,glial fibrilary acidic protein)免疫组化方法检测前深梨状皮层T区（area tempestas,AT)内神经元损伤及星形胶质细胞增生情况,并与经蝎毒（scorpion venom,SV)处理后癫痫发作敏感性明显降低的大鼠进行比较。结果：与对照组比较,癫痫敏感动物前深梨状皮层T区锥体细胞数目明显减少,GFAP免疫反应阳性星形胶质细胞数目明显增加,染色强度明显增强,（P＜0．05）以剂量为100mg/kg/日的蝎毒给予动物连续灌胃三周,可明显降低其癫痫发作敏感性（P＜0．05）,而脑内梨状皮层T区锥体细胞脱失减轻,GPAP免疫反应活性未见明显增强。结论：推测梨状皮层T区硬化（神经元脱失,星形胶质细胞增生肥大）很可能是癫痫发作敏感性长期存在的重要原因。     

重复经颅磁刺激对卒中后抑郁的治疗效果及机制

卒中后抑郁（post-stroke depression,PSD）是并发于脑血管病的一种情感障碍疾病，发病率高，预后差。重复经颅磁刺激（repetitive transcranial magnetic stimulation,r TMS）是通过磁场变化在大脑中产生感应电流来刺激皮层的非创伤性脑刺激技术，是临床上治疗PSD的一种重要非药物治疗方法，可以显著改善PSD患者的抑郁症状。但目前rTMS的作用机制不明确。本文总结了PSD治疗中有效的rTMS刺激方案，并结合PSD的单胺类神经递质相关致病假说及PSD的临床治疗手段，探索了rTMS通过对单胺类神经递质的调控参与PSD治疗的可能机制。rTMS刺激诱导的皮层单胺类递质释放增加、葡萄糖代谢上升、皮层兴奋性增加，提高了单胺类神经递质和脑源性神经营养因子（brain-derived neurotrophic factor,BDNF）水平，进而引发前额叶抑制功能上升、与下游脑区连接改变、脑网络功能的调整，可能是rTMS治疗PSD的重要机制之一。     

组织学与核磁共振检测大鼠癫痫源性早期脑损伤的跨半球扩布特征

侵性强直电刺激(60Hz,2s)大鼠右侧背海马(hippocampus,DHPC)CAl基树突区,1次/d,连续刺激10d。分别在施加强直电刺激的第2、4、6、8或10d时进行核磁共振成像检测(T2 weighted magnetic resonamce image T2-WI),并对鼠脑进行组织学切片鉴定。结果表明,早期慢性癫痫源性脑损伤的病理性形态特征主要包括：(1)T2-WI检测侧脑室(lateral ventricle,LV)区域信号增强、组织学检测LV扩大和双侧对称性脉络膜丛病理性增生,后两者并非完全平行呈现。(2)组织学切片显示双侧LV扩大面积与T2-WI信号增强区域面积的脑区分布近似。与空白对照组大鼠相比,电刺激2、4、6、8和10d后,T2-WI信号增强区域面积显著增大(P=0．0259;P＝0．0184;P=0．0184;P＝0．0404;P＝0．0259)以及组织学鉴定LV面积增大(P＝0．0210;P＝0．01;P＝0．0100;P=0．0152).(3)定侧分析显示,T2-WI信号增强以及T2-WI信号增强区域面积和组织学鉴定LV面积扩大,在慢性刺激6d时均以植入电极的对侧为主;第10d时均以同侧为主。三项观察结果的一致性证实了癫痫源性早期脑损伤的跨半球动态扩布特征。     

时域相干刺激研究进展

脑深部电刺激已成为许多神经和精神疾病的有效治疗方法。然而,侵入性的电极植入会带来手术并发症的风险,并且刺激靶区在植入后很难改变。经颅磁刺激和经颅电刺激等非侵入性刺激方法为调节大脑功能提供了新的途径。但是,尚未证明这些非侵入性脑刺激方法可以直接调节脑深部神经元活动而不影响皮层神经元。因此,这些方法主要用于调节大脑表层脑区的神经活动。时域相干（temporal interference,TI）刺激是通过两个高频电场相互作用,产生低频包络调节神经活动的一种非侵入式脑深部电刺激的新方法,该方法有望解决无创脑深部刺激的需求。本文首先介绍TI刺激的概念以及安全性,然后阐述TI刺激现有研究中的电场分析方法,并讨论电场分析相关的生理模型建模方法和仿真平台以及TI刺激诱发场分布的研究进展与在动物和人体中的应用进展。最后,本文展望了TI刺激技术未来发展方向,以期为无创脑深部刺激研究提供新的研究思路。     

Cerebral responses of healthy humans to rhythmic transcranial magnetic stimulation of different intensities

The effect of rhythmic transcranial magnetic stimulation (rTMS) of different intensities (single superthreshold rTMS more intense than 1.2 T and subthreshold one with an intensity of 70–80% of the motor threshold) of sagittal premotor cortical areas on the human functional activity was estimated in eight volunteers on the basis of combined EEG, neuropsychological, and hemodynamic examinations. The objectives of the study included the selection of the frequency of activating stimulation and revision of the objective EEG criteria of rTMS efficiency. It has been demonstrated that analysis of the EEG response to photostimulation at different frequencies is efficient in selecting the rTMS frequency. The EEG coherence is one of the most informative characteristics of the rTMS effect on central neurodynamics. The functional effects of stimulation (activating or inhibitory) have been shown to depend on the initial level of intercentral coherent relationships It has been found that rTMS of the sagittal premotor cortex causes definite changes in the functional activity of a healthy brain different from those caused by placebo. These changes are greater in the left hemisphere (in the form of intrahemispheric changes in coherence and depend on the stimulation intensity (superor subthreshold) and the initial state. The vascular factor has been shown to play an important role in the formation of cerebral responses to rTMS.     

Tracking the mind's image in the brain II: transcranial magnetic stimulation reveals parietal asymmetry in visuospatial imagery

The functional relevance of brain activity during visuospatial tasks was investigated by combining functional magnetic resonance imaging with unilateral repetitive transcranial magnetic stimulation (rTMS). The cognitive tasks involved visuospatial operations on visually presented and mentally imagined material ("mental clock task"). While visuospatial operations were associated with activation of the intraparietal sulcus region bilaterally, only the group which received rTMS to the right parietal lobe showed an impairment of performance during and immediately after rTMS. This functional parietal asymmetry might indicate a capacity of the right parietal lobe to compensate for a temporary suppression of the left. This is compatible with current theories of spatial hemineglect and constitutes a constraint for models of distributed information processing in the parietal lobes.     

A Neuronal Network Model for Simulating the Effects of Repetitive Transcranial Magnetic Stimulation on Local Field Potential Power Spectra

Repetitive transcranial magnetic stimulation (rTMS) holds promise as a non-invasive therapy for the treatment of neurological disorders such as depression, schizophrenia, tinnitus, and epilepsy. Complex interdependencies between stimulus duration, frequency and intensity obscure the exact effects of rTMS stimulation on neural activity in the cortex, making evaluation of and comparison between rTMS studies difficult. To explain the influence of rTMS on neural activity (e.g. in the motor cortex), we use a neuronal network model. The results demonstrate that the model adequately explains experimentally observed short term effects of rTMS on the band power in common frequency bands used in electroencephalography (EEG). We show that the equivalent local field potential (eLFP) band power depends on stimulation intensity rather than on stimulation frequency. Additionally, our model resolves contradictions in experiments.     

Low-intensity repetitive transcranial magnetic stimulation decreases motor cortical excitability in humans.

Repetitive transcranial magnetic stimulation of the motor cortex (rTMS) can be used to modify motor cortical excitability in human subjects. At stimulus intensities near to or above resting motor threshold, low-frequency rTMS (approximately 1 Hz) decreases motor cortical excitability, whereas high-frequency rTMS (5-20 Hz) can increase excitability. We investigated the effect of 10 min of intermittent rTMS on motor cortical excitability in normal subjects at two frequencies (2 or 6 Hz). Three low intensities of stimulation (70, 80, and 90% of active motor threshold) and sham stimulation were used. The number of stimuli were matched between conditions. Motor cortical excitability was investigated by measurement of the motor-evoked potential (MEP) evoked by single magnetic stimuli in the relaxed first dorsal interosseus muscle. The intensity of the single stimuli was set to evoke baseline MEPs of approximately 1 mV in amplitude. Both 2- and 6-Hz stimulation, at 80% of active motor threshold, reduced the magnitude of MEPs for approximately 30 min (P < 0.05). MEPs returned to baseline values after a weak voluntary contraction. Stimulation at 70 and 90% of active motor threshold and sham stimulation did not induce a significant group effect on MEP magnitude. However, the intersubject response to rTMS at 90% of active motor threshold was highly variable, with some subjects showing significant MEP facilitation and others inhibition. These results suggest that, at low stimulus intensities, the intensity of stimulation may be as important as frequency in determining the effect of rTMS on motor cortical excitability.     

Modulation of learning and hippocampal, neuronal plasticity by repetitive transcranial magnetic stimulation (rTMS)

The influence of high-frequency repetitive transcranial magnetic stimulation (rTMS) on learning process in mice and on neuronal excitability of the hippocampal tissue obtained from stimulated animals were investigated. While the stimulation with rTMS at higher frequency (15 Hz) improved animals' performance in novel object recognition test (NOR), lower frequency (1 and 8 Hz) impaired the memory. The effect was observed when evaluated immediately after rTMS exposure and declined with time. In parallel to the results of behavioral test, there was a significant enhancement of the synaptic efficiency expressed as of the long-term potentiation (LTP) recorded from hippocampal slices prepared from the animals exposed to 15 Hz rTMS. The stimulation with 1 and 8 Hz had no influence on the magnitude of LTP. Our results demonstrate that rTMS modifies mechanisms involved in memory formation. The effects of rTMS in vivo are preserved and expressed in the hippocampus tested in vitro.     

The influence of low-frequency left prefrontal repetitive transcranial magnetic stimulation on memory for words but not for faces

Brain imaging studies suggest localization of verbal working memory in the left dorsolateral prefrontal cortex (DLPFC) while face processing and memory is localized in the inferior temporal cortex and other brain areas. The goal of this study was to assess the effect of left DLPFC low-frequency repetitive transcranial magnetic stimulation (rTMS) on verbal recall and face recognition. The study revealed a significant decrease of free recall in word encoding under rTMS (110% of motor threshold, 0.9 Hz) in comparison with sham stimulation (p=0.03), while no significant difference was found with facial memory tests. Our findings support the essential role of the left DLPFC in word but not facial memory and confirm the content specific arrangement of cortical areas involved in semantic memory. As a non-invasive tool, rTMS is useful for cognitive brain mapping and the functional localization of the category specific memory system.     

帕金森病合并抑郁与脑血流灌注的关系及经颅磁刺激的影响

目的：应用CT灌注成像技术观察帕金森病合并抑郁患者局灶脑血流灌注的特点,进一步探讨抑郁症发生与脑血流的关系.方法：将41例帕金森患者根据是否合并抑郁症分为帕金森病组22例、帕金森病合并抑郁症者为抑郁组19例、其中抑郁组分为经颅磁刺激（rTMS）治疗前组、治疗后组,3组均进行CT局部脑血流灌注显像,半定量分析各脑区血流灌注情况.结果：帕金森合并抑郁症组患者双侧额叶、颞叶和基底节的脑血流量测定（CBF）较帕金森病组显著下降（P＜0.05）;抑郁组左、右侧脑血流低灌注存在不对称性,左侧额叶、顶叶的CBF较右侧显著下降（P＜0.01）;rTMS治疗后脑血流灌注较治疗前改善,HAMD评分改善（P＜0.05）.结论：帕金森患者存在局灶性脑血流灌注降低,合并抑郁症患者额、顶叶下降更明显,经颅磁刺激治疗后脑血流低灌注改善.     

不同频率重复经颅磁刺激治疗脑卒中后失语症的效果观察

目的:探讨不同频率重复经颅磁刺激(Repeated transcranial magnetic stimulation,r TMS)治疗脑卒中后失语症的临床效果。方法:选取2015年10月至2018年10月我院收治的脑卒中后失语症患者80例,采用随机数字表法将患者分为两组,低频组患者给予低频r TMS治疗,高频组患者给予高频r TMS治疗。比较两组患者治疗后的西方失语成套测验(Western Aphasia Battery,WAB)各项评分,治疗前后日常生活交流能力检查(Communicative abilities in daily living test,CADL)评分、视图命名得分及命名反应时间的变化。结果:治疗后,两组患者的自发语言、听理解、命名、复述和失语商(Aphasia quotient,AQ)评分比较均无统计学差异(P0.05);两组CADL评分和视图命名得分均较治疗前显著升高(P0.05),但两组间比较无统计学差异(P0.05);两组命名反应时间均较治疗前显著缩短,且高频组显著短于低频组(P0.05)。结论:高频r TMS与低频r TMS均可显著改善脑卒中后失语症患者的自发语言、听理解、命名、复述及日常生活交流能力,但高频r TMS在缩短命名反应时间方面具有更好的效果。     

MRI-guided dmPFC-rTMS as a Treatment for Treatment-resistant Major Depressive Disorder

Here we outline the protocol for magnetic resonance imaging (MRI) guided repetitive transcranial magnetic stimulation (rTMS) to the dorsal medial prefrontal cortex (dmPFC) in patients with major depressive disorder (MDD). Technicians used a neuronavigation system to process patient MRIs to generate a 3-dimensional head model. The head model was subsequently used to identify patient-specific stimulatory targets. The dmPFC was stimulated daily for 20 sessions. Stimulation intensity was titrated to address scalp pain associated with rTMS. Weekly assessments were conducted on the patients using the Hamilton Rating Scale for Depression (HamD₁₇) and Beck Depression Index II (BDI-II). Treatment-resistant MDD patients achieved significant improvements on both HAMD and BDI-II. Of note, angled, double-cone coil rTMS at 120% resting motor threshold allows for optimal stimulation of deeper midline prefrontal regions, which results in a possible therapeutic application for MDD. One major limitation of the rTMS field is the heterogeneity of treatment parameters across studies, including duty cycle, number of pulses per session and intensity. Further work should be done to clarify the effect of stimulation parameters on outcome. Future dmPFC-rTMS work should include sham-controlled studies to confirm its clinical efficacy in MDD.     

Brain lipid changes after repetitive transcranial magnetic stimulation: potential links to therapeutic effects?

Repetitive transcranial magnetic stimulation (rTMS) is increasingly used in the management of neurologic disorders such as depression and chronic pain, but little is known about how it could affect brain lipids, which play important roles in membrane structure and cellular functions. The present study was carried out to examine the effects of rTMS on brain lipids at the individual molecular species level using the novel technique of lipidomics. Rats were subjected to high frequency (15 Hz) stimulation of the left hemisphere with different intensities and pulses of rTMS. The prefrontal cortex, hippocampus and striatum were harvested 1 week after rTMS and lipid profiles analyzed by tandem mass spectrometry. rTMS resulted in changes mainly in the prefrontal cortex. There were significant alterations in plasmalogen phosphatidylethanolamines, phosphatidylcholines, and increases in sulfated galactosylceramides or sulfatides. Plasmalogen species with long chain polyunsaturated fatty acids (PUFAs) showed decrease in abundance together with corresponding increase in lysophospholipid species suggesting endogenous release of long chain fatty acids such as docosahexaenoic acid (DHA) in brain tissue. The hippocampus showed no significant changes, whilst changes in the striatum were often opposite to that of the prefrontal cortex. It is postulated that changes in brain lipids may underlie some of the clinical effects of rTMS.