经颅磁刺激中刺激线圈的仿真研究

目的设计用于经颅磁刺激的线圈,要求能够对大脑皮质进行多点刺激,且具有聚焦性好、制作简单、使用方便等特点。方法利用电磁仿真方法,以圆形线圈和8字形线圈为基础,计算线圈在均匀人体模型中感应电场的分布情况,比较尺寸、绕法对经颅磁刺激线圈的聚焦性和刺激深度的影响。在此基础上设计了一种多圆相切线圈,并计算该线圈在均匀人体和真实头部模型中的电场分布。结果感应电场强度随刺激深度的增加呈指数式衰减。减小圆形线圈的尺寸,会提高聚焦性,同时可减弱感应电场强度。8字形线圈比圆形线圈具有更好的聚焦性,多层绕法综合效果较好。多圆相切线圈具有8字形线圈的优点,且可以进行多点刺激。结论尺寸、绕法等因素对线圈的聚焦性和刺激深度具有重要影响,多圆相切线圈在经颅磁刺激中具有很好的应用前景。真实头部模型仿真,对于线圈的设计和靶区定位具有重要意义。     

毛蕊花糖苷通过调控BDNF-TrkB信号通路改善CUMS大鼠的抑郁样行为

目的:观察毛蕊花糖苷(acteoside)对慢性不可预见性温和应激(chronic unpredictable mild stress,CUMS)大鼠抑郁样行为的影响,并探讨脑源性神经营养因子-原肌球蛋白受体激酶B(brain-derived neurotrophic factor-tropomyosin receptor kinase B,BDNF-TrkB)信号通路在其中的作用机制。方法:采用CUMS结合孤养的方式制备抑郁模型大鼠,成模后随机分为模型组、盐酸氟西汀(20 mg/kg)组和毛蕊花糖苷(30 mg/kg、60 mg/kg和120 mg/kg)组,每组18只,另取18只正常大鼠作为对照组,连续灌胃给药3周。采用强迫游泳实验和糖水偏好实验检测大鼠抑郁样行为的变化;免疫荧光和Western blot法检测大鼠海马BDNF-TrkB信号通路相关蛋白的表达情况;ELISA法检测脑组织中单胺类神经递质5-羟色胺(5-HT)、多巴胺(DA)和去甲肾上腺素(NE)的含量。结果:与对照组比较,模型组大鼠强迫游泳不动时间明显延长,糖水偏好量明显下降,海马BDNF和TrkB的表达均明显降低,脑组织中5-HT、DA和NE含量均显著减少;与模型组比较,盐酸氟西汀组和毛蕊花糖苷各剂量组以上各检测指标均得到显著逆转(P0.05)。结论:毛蕊花糖苷可能通过上调海马BDNF-TrkB信号通路、增加脑内单胺类神经递质含量而改善CUMS大鼠的抑郁样行为。     

经颅磁刺激帕金森病模型大鼠运动皮质兴奋性的研究

目的:探讨经颅磁刺激(transcranial magnetic stimulation,TMS)对帕金森病(Parkinson discase,PD)模型大鼠大脑皮质电生理学的影响,并从电生理角度探讨PD的发病机制.方法:实验分两组,健康SD雄性大鼠40只,随机分为2组:①实验组(PD模型组)26只,②对照组(生理盐水组)14只.采用静息皮层运动阈值(RMT)、中枢传导时间(CMCT)和运动诱发电位(MEP)的波幅(Amp)作为评定大脑皮质兴奋性的指标.结果统计采用SPSS 11.5统计软件处理,P＜0.05为差异有显著意义.结果:术后1周,实验组左下肢RMT、CMCT较对照组降低或缩短(P＜0.05),而Amp无明显变化;实验组自身左右侧比较,左下肢RMT、CMCT较右下肢缩短,Amp增高(P＜0.05);制模前、术后1周、术后3周实验组大鼠左下肢RMT、CMCT进行性降低(P＜0.05);实验组大鼠右下肢与对照组大鼠左侧及右侧下肢RMT、CMCT及Amp比较差异无统计学意义(P＞0.05).结论:PD模型大鼠损毁侧皮层兴奋性增加,且与症状严重程度相关;PD模型大鼠病情越重、病程越长,大脑皮层兴奋性升高更明显.     

帕金森病模型大鼠经颅磁刺激运动诱发电位皮层阈值的研究

目的:通过对帕金森病(Parkinson disease,PD)模型大鼠经颅磁刺激(transcranial magnetic stimulation,TMS)运动诱发电位(MEP)皮层阈值(cortical threshold,Ct)的研究,以明确PD的Ct测值以及随病情发展的变化情况,以期为PD临床提供电生理学实验研究依据.方法:实验动物为健康的Sprague-Dawley(SD)雄性大鼠40只,随机分为两组:①实验组(PD模型组)28只;②对照组(生理盐水组)12只.选取其右侧中脑黑质致密部(substantia nigra pars compacta,SNc)与腹侧被盖(ventra tegmental area,VTA)作为靶点,实验组注射6-羟基多巴胺(6-OHDA)以制备PD动物模型,对照组注射同等体积的生理盐水用于比较,于制模前、制模后1周、3周分别行双下肢记录的Ct检查.结果统计采用SPSS 11.5统计软件处理,P＜0.05为差异有显著意义.结果:术后1周,实验组在右侧中脑靶点TMS时于左下肢记录到的Ct较对照组降低,具有统计学意义(P＜0.05),实验组自身左右侧TMS-MEP比较,左下肢Ct较右下肢降低(P＜0.05);制模前、术后1周、术后3周实验组大鼠左下肢Ct进行性降低(P＜0.01);实验组大鼠右下肢及对照组大鼠左侧及右侧下肢Ct比较差异无显著意义(P＞0.05).结论:PD模型大鼠损毁侧Ct增加,PD模型大鼠病情越重、病程越长,Ct增加越明显.     

经颅磁刺激和脑电联合作用时电磁场分布的仿真研究

目的：研究分析经颅磁刺激和脑电（TMS-EEG）联合作用时磁感应强度和感应电场强度的分布情况。方法：利用有限元多物理场仿真软件COMSOL,搭建3层同心球人头模型、TMS线圈模型和EEG电极模型,在TMS线圈的作用下,对比分析了有无脑电极时,人头模型当中磁感应强度和感应电场强度的不同。结果：取头部组织几个特殊位置点,放置脑电极后,各点处磁感应强度和感应电场强度均发生变化,磁感应强度最大变化达19.19%,感应电场强度最大变化达75.33%。添加脑电极后,人体头部组织YZ纵切面的最大磁感应强度降低7 mT,最大感应电场强度值降低0.6 V/m。大脑处的三维磁感应强度和感应电场强度均随着深度的增加而逐渐减小,放置脑电极后,脑组织中的最大磁感应强度值减少1.4 mT,最大感应电场强度值减少0.13 V/m。结论：经TMS-EEG联合作用时,在人头皮处放置脑电极会对电磁场的分布产生影响,间接影响TMS的治疗作用。     

经颅磁刺激对帕金森病模型大鼠运动诱发电位潜伏期的研究

目的：通过对帕金森病（PD）模型大鼠经颅磁刺激（TMS）运动诱发电位（MEP）皮层潜伏期（Lat）的测值以了解其随病情发展的变化情况。方法：健康雄性（SD）大鼠40只,随机分为2组：①PD模型组26只,②对照组（生理盐水组）14只。选取右侧黑质致密部（substantia nigra pars compacta,SNc）与中脑腹侧背盖（ventra tegmental area,VTA）为手术靶点,PD模型组注射6一羟基多巴胺（6-OHDA）制备PD动物模型,对照组注射同等体积的生理盐水。于注射前、注射后第1周、第3周末分别行双下肢TMS-MEP检查。结果：术后1周,PD组鼠左下肢Lat较对照组缩短（P〈0．05）,PD组自身左右侧TMS-MEP比较,左下肢Lat较右下肢缩短（P〈0.05）;术前、术后第1周末、术后第3周末PD组大鼠左下肢Lat进行性缩短（P〈0.01）,PD组大鼠右下肢及对照组大鼠左侧及右侧下肢Lat皆无显著变化（P〉0.05）。结论：PD模型大鼠损毁侧皮层兴奋性增加,且与症状严重程度有关。PD模型大鼠病情越重、病程越长,Lat缩短越明显。     

经颅磁刺激中大鼠真实头模型感应电场分布的研究

经颅磁刺激是一种利用时变磁场产生的感应电流刺激大脑的技术,现在已经广泛地应用于精神疾病的治疗及脑功能的研究.本文建立了经颅磁刺激中大鼠真实头模型,并利用有限元方法计算了模型中感应电场的空间分布情况.该模型可用于动物实验方案的设计和实验结果的解释.     

物理疗法联合重复经颅磁刺激对慢性脑缺血大鼠认知功能及突触可塑性的影响及机制

目的 探究物理疗法联合重复经颅磁刺激(rTMS)改善慢性脑缺血大鼠认知功能及突触可塑性的影响及作用机制。方法 40只SPF级SD大鼠,随机分为假手术组(Sham)、模型组(Model)、物理治疗组(PT)、rTMS组及PT联合rTMS组(PT+rTMS),每组8只。Morris水迷宫检测大鼠认知功能;HE染色观察大鼠海马区病理损伤,Nissl染色观察大鼠海马神经元损伤;Golgi-Cox染色观察大鼠海马CA1区神经元树突结构和生长情况;Western blot检测海马组织突触可塑性标志物突触素(SYN)、突触后密度蛋白-95(PSD-95)、生长相关蛋白-43(GAP-43)、糖原合成酶激酶-3(GSK-3β)、β-连环蛋白(β-catenin)、磷酸化GSK-3β(p-GSK-3β)、p-β-catenin蛋白表达。结果 与模型组相比,PT、rTMS及PT+rTMS均显著改善慢性脑缺血大鼠认知功能,改善大鼠海马病理损伤和神经元结构,增加海马区神经元数量,增加神经元树突分支数和树突棘密度,增加海马组织SYN、PSD-95、GAP-43蛋白表达;增加β-catenin、p-GSK-3β蛋...     

经颅磁声耦合电刺激技术应用于小鼠的实验研究

研究经颅磁声耦合刺激技术(transcranial magneto-acoustic stimulation,TMAS)在体小动物脑神经刺激效果。搭建了针对小动物模型的TMAS系统。设置TMAS系统参数,对健康鼠及帕金森(parkinson's disease,PD)模型鼠进行经颅聚焦磁声刺激实验,并分析行为学及电生理结果。经过TMAS刺激后,行为学结果表明磁声刺激组小鼠在主动探索学习能力和运动能力显著高于对照组;电生理结果表明TMAS刺激后PD模型鼠海马区黑质神经突触活性提高。实验结果验证了TMAS技术对小鼠脑神经刺激的有效性。该技术的进一步研究将具有更好的应用前景。     

睡眠脑波调制的与常规的重复经颅磁刺激治疗原发性失眠症的脑电图研究

目的：探讨睡眠脑波调制重复经颅磁刺激与常规重复经颅磁刺激在治疗原发性失眠症中的脑电图（EEG）动态特征及其与临床疗效的关系。方法：按完全随机的方法,将126例原发性失眠症患者分为睡眠脑波调制重复经颅磁刺激组（睡磁组）44例、常规重复经颅磁刺激组（常磁组）42例和假磁刺激治疗组（假磁组）40例。每次持续刺激30min,每日1次,疗程10d。分别观察治疗前、治疗10d时和治疗结束后30d时的Krakow睡眠积分（KSS）、EEG及平均α波绝对功率谱的变化。结果：两磁疗组治疗10d时的KSS显著降低（均P〈0．05）,平均α波绝对功率谱显著升高（均P〈0．05）,尤以睡磁组突出,且持续至治疗结束后30d。治疗10d时磁疗患者平均α波绝对功率谱与其KSS呈显著负相关（n=86,r=0．2136,P〈0．05）。结论：睡眠脑波调制重复经颅磁刺激和常规重复经颅磁刺激对原发性失眠症的异常EEG均有显著的良性调节作用,其疗效与提高平均α波功率谱相关,前者优于后者。     

腹膜腔给予SAHA通过上调大麻素受体1的表达改善大鼠骨癌痛的研究

目的:观察腹膜腔给予辛二酰苯胺异羟肟酸(suberoylanilide hydroxamic acid,SAHA)对于骨癌痛(cancer-induced bone pain,CIBP)模型大鼠脊髓背角内大麻素受体1(cannabinoid-like receptor 1,CB1R)表达的影响。方法:将健康雌性SD大鼠随机分为4组:Sham+saline组、CIBP 7 d+saline组、CIBP 14 d+saline组、CIBP 14d+SAHA组。后三组动物胫骨内注射Walker 256乳腺癌肿瘤细胞制作骨癌痛模型。CIBP+SAHA组术后第1 d开始每日连续腹膜腔给予50 mg/kg SAHA至第14 d。利用机械刺激法连续观察各组大鼠的痛行为变化。应用免疫组织化学染色和Western Blot方法观察大鼠腰膨大节段脊髓背角内CB1R的表达情况。结果:自术后第7 d开始,与假手术组相比,CIBP组大鼠机械性缩足阈值(paw withdrawal threshold,PWT)明显下降(P0.01),这种变化一直持续到至少术后第14 d。从术后第1~14 d连续腹膜腔内给予SAHA能明显缓解大鼠机械性痛敏(P0.05)。免疫荧光组织化学染色显示:CB1R主要表达于脊髓背角浅层,CIBP组大鼠脊髓内CB1R表达上调,而腹膜腔内给予SAHA后可进一步促进脊髓背角内CB1R的上调。Western Blot结果显示:与对照组相比,造模后第7d和14 d脊髓背角内CB1R表达上调(P0.05)。与骨癌痛相比,从术后第1~14 d连续腹膜腔给予SAHA能明显促进脊髓背角内CB1R的表达(P0.05)。结论:在骨癌痛状态下,大鼠脊髓背角内CB1R表达增加,可能与体内内源性镇痛系统的激活有关,但此时与对照组相比,上调的CB1R不足以发挥镇痛效果;而腹膜腔内给予SAHA后,脊髓背角内CB1R受体表达进一步上调,从而发挥其镇痛效果。     

枫叶黄酮对老年痴呆动物模型的抗氧化作用及分子机制

目的:构建β淀粉样蛋白1-42(Aβ1-42)联合D-半乳糖(D-gal)致痴呆模型,探讨枫叶黄酮抗氧化作用的分子机制。方法:36只成年雄性Sprague Dawley(SD)大鼠随机分为3组:假手术组、模型组、治疗组。采用侧脑室注射β淀粉样蛋白1-42(Aβ1-42)联合腹腔注射D半乳糖(D-gal)构建SD大鼠痴呆模型后经枫叶黄酮治疗,采用Morris水迷宫实验(MWM)检测大鼠学习记忆能力;用化学比色法检测大脑皮质丙二醛(MDA)和内源性巯醇抗氧化物(酶):谷胱甘肽还原酶(glutathione reductase,GR)、谷胱甘肽(glutathione,GSH)、谷胱甘肽过氧化酶(glutathione peroxidase,GSH-PX)、超氧化物歧化酶(superoxide dismutase,SOD)的含量;免疫印迹法检测大脑皮质中丝裂原活化蛋白激酶(mitogen-activated protein kinase,MAPK)家族相关蛋白:细胞外信号调节蛋白激酶(extra-cellular signal-regulated protein kinase,ERK)、p38、c-Jun氨基末端激酶(c-Jun N-terminal kinase,JNK)的磷酸化水平。结果:模型组与假手术组比较:大鼠的逃避潜伏期明显延长(P<0.05),在第Ш象限逗留的时间明显减少(P<0.05),跨越平台次数明显减少(P<0.05);大脑皮质MDA含量增加(P<0.05),GR、GSH-PX的含量降低(P<0.05);p38、JNK磷酸化增强,ERK磷酸化水平降低。而枫叶黄酮治疗后:大鼠逃避潜伏期明显缩短(P<0.05),在第Ⅲ象限逗留的时间明显增加(P<0.05),跨越平台次数明显增加(P<0.05);大脑皮质MDA含量降低(P<0.05),GR、GSH-PX的含量升高(P<0.05);p38、JNK磷酸化被抑制,ERK的磷酸化增加。结论:枫叶黄酮能改善学习记忆能力,对抗大鼠神经系统衰老。其作用可能是通过上调痴呆模型大鼠大脑皮质内源性巯醇抗氧化物(酶)GR和GSH-PX的含量,抑制p38、JNK磷酸化并增强ERK磷酸化而实现的。     

Altered CB1 receptor and endocannabinoid levels precede motor symptom onset in a transgenic mouse model of Huntington's disease

Huntington's disease (HD) is an inherited neurodegenerative disease characterised by cell dysfunction and death in the basal ganglia and cortex. Currently there are no effective pharmacological treatments available. Loss of cannabinoid CB1 receptor ligand binding in key brain regions is detected early in HD in human postmortem tissue [Glass M, Dragunow M, Faull RL (2000) The pattern of neurodegeneration in Huntington's disease: a comparative study of cannabinoid, dopamine, adenosine and GABA(A) receptor alterations in the human basal ganglia in Huntington's disease. Neuroscience 97:505–519]. In HD transgenic mice environmental enrichment upregulates the CB1 receptors and slows disease progression [Glass M, van Dellen A, Blakemore C, Hannan AJ, Faull RL (2004) Delayed onset of Huntington's disease in mice in an enriched environment correlates with delayed loss of cannabinoid CB1 receptors. Neuroscience 123:207–212]. These findings, combined with data from lesion studies have led to the suggestion that activation of cannabinoid receptors may be protective. However, studies suggest that CB1 mRNA may be decreased early in the disease progression in HD mice, making this a poor drug target. We have therefore performed a detailed analysis of CB1 receptor ligand binding, protein, gene expression and levels of endocannabinoids just prior to motor symptom onset (12 weeks of age) in R6/1 transgenic mice. We demonstrate that R6/1 mice exhibit a 27% decrease in CB1 mRNA in the striatum compared to wild type (WT). Total protein levels, determined by immunohistochemistry, are not significantly different to WT in the striatum or globus pallidus, but are significantly decreased by 19% in the substantia nigra. CB1 receptor ligand binding demonstrates significant but small decreases (<20%) in all basal ganglia regions evaluated. The levels of the endocannabinoid 2-arachidonoyl glycerol are significantly increased in the cortex (147%) while anandamide is significantly decreased in the hippocampus to 67% of WT. Decreases are also apparent in the ligand binding of neuronal D1 and D2 dopamine receptors co-located with CB1, while there is no change in GABA_A receptor ligand binding. These results suggest that in this R6/1 mouse colony at 12 weeks there are only very small changes in CB1 protein and receptors and thus this would be an appropriate time point to evaluate therapeutic interventions.     

Dopaminergic signaling in prefrontal cortex contributes to the antidepressant effect of electroacupuncture: An iTRAQ-based proteomics analysis in a rat model of CUMS

Electroacupuncture (EA) is used as an adjunctive treatment for depression. This study was conducted to evaluate the efficacy and mechanisms of EA in the depressive rat model induced by chronic unpredictable mild stress (CUMS) in male adult Wistar rats. The underlying mechanisms were explored by using isobaric tags for relative and absolute quantitation (iTRAQ)-based proteomic analysis of the proteins in the prefrontal cortex (PFC), and observing the number of the PFC neurons stained with hematoxylin and eosin (H&E) and synaptic morphological changes under transmission electron microscopy (TEM). The results showed that EA plus paroxetine (EA + Par) for 1 week significantly relieved depression-like anhedonia symptoms and improved anxiety-like behavior, accompanied by the improvements in synaptic morphology and a significant increase of PFC neurons. Moreover, EA or paroxetine alone significantly alleviated anhedonia symptoms after 2 weeks of intervention. Additionally, iTRAQ analysis showed that dopaminergic signaling was significantly altered in CUMS rats after 1 week of EA treatment. As the critical enzyme of this pathway, aromatic-l -amino-acid decarboxylase (DDC) was significantly upregulated after the treatment with EA + Par for 1 week. These findings suggested that the dopaminergic signaling pathway in PFC may be involved in the antidepressant mechanisms of EA.     

ASIC1a和TASKs在大鼠癫痫持续状态模型中的作用

目的:探讨酸敏感离子通道1a(ASIC1a)、弱内向整流钾通道相关的酸敏感钾通道1和3(TASK-1和TASK-3)在大鼠癫痫持续状态(SE)中的表达及其在癫痫持续状态中的作用。方法:成年雄性SD大鼠随机分为对照组(control)和SE组,应用氯化锂-匹罗卡品诱导SE模型,采用real time RT-PCR和Western Blot技术分别检测海马组织ASIC1a、TASK-1和TASK-3在SE后0、1、2和3 h mRNA、蛋白表达水平,应用膜片钳技术观察SE后ASIC1a、TASK-1和TASK-3对海马CA1区锥体神经元兴奋性的影响。结果:在mRNA水平,与control组相比,SE组ASIC1a在2和3 h、TASK-1在1 h、TASK-3在3 h时间点表达显著减少。在蛋白水平,与control组相比,SE组ASIC1a、TASK-1和TASK-3在3 h时间点表达均显著降低。与SE control组相比,给予ASIC1a抑制剂后动作电位(AP)的频率明显降低,给予TASK-1和TASK-3抑制剂后,AP的频率均显著增加。结论:SE后大鼠海马区ASIC1a、TASK-1...     

昆明山海棠对胶原诱导型关节炎大鼠的作用及可能机制

探讨昆明山海棠(THH)对胶原诱导型关节炎(CIA)大鼠的作用及可能机制。取60只大鼠随机分6组,建立CIA大鼠模型,分别采用不同剂量的THH每天灌胃1次,连续30d。动态观察关节炎指数(AI)及关节的病理改变,用RT-PCR及免疫组化法分别检测HIF-1αmRNA及其蛋白的表达。结果显示,THH可明显抑制CIA大鼠的足爪肿胀,减轻滑膜增殖及炎症反应,降低HIF-1α表达,其中以中剂量THH的治疗效果最佳。以上结果表明THH治疗CIA大鼠具有明显疗效,其作用机制可能与降低外周血以及滑膜组织内的HIF-1α的表达有关。     

The rat exposure test: a model of mouse defensive behaviors

In order to facilitate behavioral, and potentially pharmacological, analyses of risk assessment behaviors in mice, a rat exposure test (RET) was devised and evaluated. This test provides a home chamber connected via a tunnel to a rat (predator) exposure area. Familiar substrate is provided to permit burying, and mouse subjects are habituated to the apparatus prior to exposure to an amphetamine-activated rat. In comparison to toy-rat-exposed controls, rat-exposed BALB/c mice showed significantly more risk assessment [stretch attend posture (SAP) and stretch approach], freezing, and avoidance (time in the home chamber), and less time in contact with the wire mesh screen between itself and the threat stimulus. When BALB/c, C57BL/6, CD-1, and Swiss-Webster mice were compared in this test, the two inbred strains (BALB/c and C57BL/6) tended to show more extreme values of particular defensive behaviors, compared to the two outbred strains (Swiss-Webster and CD-1). C57BL/6 mice showed more avoidance and higher levels of SAP, freezing, and burying than BALB/c and more than one or both outbred strains as well. BALB/c mice showed little defensive burying, both in comparison to toy-exposed controls (Experiment 1), and in comparison to the three other strains in Experiment 2. These findings are somewhat at variance with characterizations of anxiety in C57BL/6 and BALB/c mice, based on tests utilizing novel areas and noxious stimuli, suggesting strain differences in defensiveness to such stimuli, compared to antipredator defense levels. Nonetheless, with the exception of burying in BALB/c mice, all strains showed all defensive behaviors measured to the rat stimulus. In particular, SAP levels were substantial in all strains tested, suggesting the usefulness of this test in assessment of the role of risk assessment in defense.     

Paired-pulse rTMS at trans-synaptic intervals increases corticomotor excitability and reduces the rate of force loss during a fatiguing exercise of the hand

Previous studies have shown that the motor evoked potential (MEP) amplitude increases as force declines during a fatiguing muscle contraction, indicating that there is an increase in corticomotor excitability. In spite of this there is a progressive reduction in voluntary motor drive, as shown by an increase in the interpolated twitch force as fatigue develops. The aim of this study was to determine whether, by further increasing corticomotor excitability using a paired-pulse rTMS protocol designed to induce I-wave facilitation (iTMS), force loss during a sustained voluntary contraction could be reduced. We designed a cross-over study incorporating a 15-min period of iTMS (ISI 1.5 ms; 0.2 Hz; ∼AMT), following which MEP amplitude (first dorsal interosseous muscle) increased to 194 ± 38% of baseline (P < 0.05), compared to a control period of stimulation that did not increase MEP amplitude (single-pulse TMS; 0.2 Hz; ∼ 1.2 AMT). Eight right-handed healthy subjects received both iTMS and control stimulation, in a randomized order, a week apart. We measured percentage force loss at the end of a 10-s maximum right hand key-pinch task, and compared force loss before and after stimulation. There was an improvement in task performance following iTMS, with a reduction in force loss compared to pre-stimulation baseline (11.3 ± 2.0 vs. 17.6 ± 2.4%; post vs. pre; P < 0.05). There was no significant difference in force loss before and after control stimulation. The results indicate that by increasing corticomotor excitability using paired-pulse rTMS at trans-synaptic intervals, maximum voluntary force can be sustained at a higher level during a brief fatiguing maximal voluntary contraction.