家族性皮质肌阵挛震颤伴癫痫家系的运动皮质兴奋性观察

目的应用经颅磁刺激(TMS)技术研究家族性皮质肌阵挛震颤伴癫痫(FCMTE)患者的运动皮质兴奋性。方法对一FCMTE家系中的4例患者及2例亲属分别测定了静息运动阈值(RMT)、短间隔皮质内抑制(SICI)、皮质内易化(ICF)和长间隔皮质内抑制(LICI)。结果该FCMTE家系中患者的RMT较亲属的RMT略降低,SICI及LICI显示患者的皮质内抑制功能较亲属增强。结论 FCMTE患者皮质神经元膜电位兴奋性增高,而跨突触神经环路的抑制效应代偿性增强。     

低频重复经颅磁刺激对难治性癫发作频率、静息运动阈值、SPECT的影响

目的：观察低频重复经颅磁刺激（rTMS）的抗癫疗效及可能机制。方法：对4例难治性癫患者灶所在脑区给予rTMS治疗（0.5 Hz,45%最大输出强度,每天15串、100次/串、串间隔30 s,连续10 d）,观察治疗前后各3个月患者的临床发作及1 h时长的脑电图癫波数量,并行单光子发射断层摄影（SPECT）和静息运动阈值检查,以观察感兴趣区（ROI）放射线摄取比值的变化和皮质兴奋性改变。结果：4例患者经rTMS治疗后,3例无发作,1例发作1次。脑电图：1例癫波减少了20%;4例静息运动阈值均增高。SPECT：4例均显示rTMS后ROI值进一步降低。结论：低频rTMS对难治性癫有治疗作用,其抗癫作用可能与减少癫灶局部脑血流灌注和增加静息运动阈值有关。     

重复经颅磁刺激对帕金森病运动功能及运动诱发电位的影响

目的:探讨低频重复经颅磁刺激(rTMS)对PD患者运动皮质兴奋性影响的持续效应。方法:对38例PD患者,予0.5Hz rTMS刺激其主要受累肢体对侧的M1Hand(20×80,100%RMT),连续7d。于首次干预前及末次干预后20min、1周及1个月分别评价其临床运动功能和运动诱发电位。结果:低频rTMS干预后,PD患者UPDRS Ⅲ、僵直、运动迟缓评分、计时运动试验及CSP均存在显著时间效应(P<0.001)。结论:低频rTMS可改善PD患者运动迟缓症状,其对运动功能的影响可持续到刺激停止后1个月,与运动皮质兴奋性的改变一致。     

低频重复经颅磁刺激对帕金森病患者运动皮质兴奋性的影响探讨

目的:观察低频重复经颅磁刺激(rTMS)对帕金森病(PD)患者大脑皮质兴奋性的影响,并从电生理角度进一步探索PD的发病机制。方法:用1HzrTMS技术治疗3 0例PD患者共10d ,另选择15例PD患者为假刺激组,15名健康者为对照组。采用静息态阈值(RT)、中枢传导时间(CMCT)、中枢静息期(CSP)和运动诱发电位(MEP)的波幅作为评定大脑皮质兴奋性的指标。结果:①PD患者的RT、CMCT和CSP较正常对照组明显降低或缩短,而MEP波幅无变化。治疗组治疗后RT增加,CMCT和CSP延长接近正常,与对照组比已无显著差别,但假刺激组没有变化。②以强直症状为主和以震颤症状为主的PD患者其RT、CMCT、CSP和MEP波幅无明显差别。③将PD患者按UPDRS评分的不同分为轻、中、重3种,分别就RT、CMCT、CSP和MEP波幅进行比较,其差别无显著性差异。结论:PD患者大脑皮质兴奋性升高,低频rTMS可部分抑制这种改变,但TMS对评定早期PD患者大脑皮质兴奋性尚不敏感。     

重复经颅磁刺激治疗失眠的临床应用

重复经颅磁刺激（rTMS）是在经颅磁刺激（TMS）技术的基础上发展起来的一项新的神经刺 激技术,它利用电磁感应原理,非侵入性地刺激大脑皮层,改变皮层兴奋性而达到治疗作用。近年来, rTMS在失眠的治疗领域得到广泛的研究和临床运用,并取得了一定的疗效,现结合国内外相关文献, 就rTMS 治疗失眠的临床研究现状进行综述。     

5Hz重复经颅磁刺激对抑郁症的治疗作用

目的 观察重复经颅磁刺激（rTMS）对抑郁症的影响.方法 通过对8例患者（男4例,女4例）进行治疗,rTMS对右侧前额叶部位的刺激（每次给予5 Hz,连续4.9 s的刺激;两次刺激间隔30 s,每次治疗10次刺激,每个疗程10次治疗,持续1个月）.结果 治疗后HAMD、CGI评分较治疗前显著下降,差异具有统计学意义（P〈0.01）.结论 每次3～5 min,用5 Hz爆发刺激模式,比常规高频刺激有更好的调节作用,且刺激时间短,刺激量减小,不良反应更小.     

经颅重频磁刺激对大鼠脑缺血再灌流损伤早期运动皮层兴奋性和神经功能的影响

目的 观察经颅重频磁刺激（rTMS）对大鼠脑缺血再灌流损伤早期运动皮层兴奋性和神经功能的影响。方法测定Wistar大鼠右后肢运动阚值（MT）．制作左侧大脑中动脉栓塞（MCAO）再灌流模型．给予rTMS（1次／d）。再灌流72h处死取脑。比较大鼠MCAO再灌流损伤不同时间MT、神经功能评分，脑梗死体积的变化及rTMS的影响。结果MCAO再灌流损伤使大鼠出现局灶性梗死灶，MT升高；神经功能障碍且其程度随损伤时间延长而愈加明显．表现为功能评分升高；rTMS可改善大鼠MCAO再灌流损伤72h的MT和功能障碍程度。减小梗死体积。尤其改善神经功能障碍的程度与对照组比较差异有显著性（P=0．004）。结论rTMS可能对早期缺血脑组织有保护作用．对缺血性脑卒中有进一步研究、应用前景。     

重复经颅磁刺激治疗帕金森病的临床研究

目的 探讨低频重复经颅磁刺激（rTMS）对帕金森病（PD）的治疗作用。方法 将45例PD患者随机分为治疗组30例，假刺激组15例。治疗组给予频率1Hz、刺激强度为110％静息阈值的rTMS，每日1次，治疗10d，并在治疗后1个月和3个月时随访。采用UPDRS评分、木插板试验、记时运动试验和10m折返运动试验进行疗效评价，评价前患者停服抗PD药物至少12h。结果治疗组治疗结束后UPDRS总分及Ⅰ、Ⅱ和Ⅲ分较治疗前均明显降低（均P〈0.01），患者木插板所用的平均时间明显减少（P〈0．01），记时运动1min平均运动次数明显增加（P〈0．01），行走速度明显增快（P〈0．01），随访3个月仍低于治疗前（P〈0．05）。治疗后3个月生活满意度（L-S1B）无明显变化，而生活质量评分（PDQ）则明显降低（P〈0．05）。假刺激组治疗前后木插板试验、记时运动试验和10m折返运动均无明显变化。结论 低频rTMS可以改善PD患者的临床症状，提高患者生活质量。     

重复经颅磁刺激预处理对毛果芸香碱致痫作用及海马GAD65表达的影响

目的：观察0．5Hz经颅磁刺激预处理对毛果芸香碱致大鼠癫痫作用的影响及可能机制。方法：将大鼠随机分为0．5Hz重复颅磁刺激（rTMS）组和对照组,分别进行连续2周的相应预处理后腹腔注射毛果芸香碱,观察注药后90min内痫性发作潜伏期和痫性发作行为表现。应用免疫组化学方法观察两组大鼠海马区谷氨酸脱羧酶65（GAD65）的表达。结果：①与对照组相比,rTMS组癫痫发作潜伏期明显延长,发作程度显著减轻（均P〈0．05）;②与对照组相比,rTMS组大鼠海马区表达GAD65神经元的数量明显增多（P〈0．05）。结论：0．5HzrTMS预处理有明显抗癫痫作用,而海马区GAD65阳性表达神经元的增加可能是其抗瘸机制之一。     

高低频重复经颅磁刺激治疗卒中后上肢痉挛的对照研究

目的 探讨高、低频重复经颅磁刺激（repetitive transcranial magnetic stimulation,rTMS）大脑初级运动皮层（M1区）治疗卒中后上肢痉挛的临床疗效及差异。      

Depressed intracortical inhibition after long trains of subthreshold repetitive magnetic stimuli at low frequency

OBJECTIVE: Repetitive transcranial magnetic stimulation (rTMS) modulates cortical excitability. These effects outlast the rTMS train, and range from inhibition to facilitation according to the variables used for rTMS. Several studies have demonstrated short and long-term effects on motor evoked potential (MEP) size, whereas the effects on intracortical inhibition (ICI) and facilitation (ICF) are still unclear. We investigated short- (1-15 min), intermediate- (16-30 min), and long-term (6 h) effects on intracortical excitability. METHODS: Fourteen healthy subjects were stimulated with rTMS trains of 900 pulses (1 Hz, 90% resting motor threshold (rMTh)), delivered over the primary motor cortex and the occipital area. MTh, MEP size, silent period, intracortical inhibition at short (ICI) and long inter-stimulus intervals, and ICF were tested before and after rTMS. RESULTS: ICI was reduced 16-30 min after 1 Hz rTMS trains over the primary motor area, whereas the other response variables remained unchanged. The ICI reduction at 16-30 min was reproducible on different days in the same subjects; it was absent at 6 h and after stimulation of the occipital area. CONCLUSIONS: Subthreshold 1 Hz rTMS decreases ICI by reducing the excitability of intracortical inhibitory interneurones or by altering the electrical properties of the facilitatory chain of neurons responsible for the I waves.     

Interhemispheric effects of high and low frequency rTMS in healthy humans.

OBJECTIVE: We investigated whether repetitive transcranial magnetic stimulation (rTMS) applied to the right motor cortex modified the excitability of the unstimulated left motor cortex. METHODS: Interhemispheric effects of 0.5 and 5 Hz subthreshold rTMS over the right motor cortex were examined by single pulse and paired pulse TMS and by transcranial electrical stimulation (TES) applied to the unstimulated left motor cortex. The effects of (a) 1800 pulses real and sham rTMS with 5 Hz, (b) 180 pulses real and sham rTMS with 0.5 Hz and (c) 1800 pulses real rTMS with 0.5 Hz were studied. RESULTS: Following 5 Hz right motor rTMS motor evoked potential (MEP) amplitudes induced by single pulse TMS over the left motor cortex increased significantly. Intracortical inhibition (ICI) and facilitation (ICF) and MEP amplitudes evoked by TES were unchanged. Sham stimulation had no influence on motor cortex excitability. After 180 pulses right motor cortex rTMS with 0.5 Hz a significant decrease of left motor ICF, but no change in single pulse MEP amplitudes was found. A similar trend was observed with 1800 pulses rTMS with 0.5 Hz. CONCLUSIONS: High frequency right motor rTMS can increase left motor cortex excitability whereas low frequency right motor rTMS can decrease it. These effects outlast the rTMS by several minutes. The underlying mechanisms mediating interhemispheric excitability changes are likely to be frequency dependent.     

Changes in motor cortical excitability induced by high-frequency repetitive transcranial magnetic stimulation of different stimulation durations.

OBJECTIVE: To investigate the changes in cortical excitability of the human motor cortex induced by high-frequency repetitive transcranial magnetic stimulation (rTMS) of different stimulation durations. METHODS: Twenty healthy subjects participated in the study. Subjects received 20 trains of 10-Hz rTMS at 80% of the resting motor threshold (RMT) intensity with two different stimulation durations (5 and 1.5s) over the motor hot spot for left first dorsal interosseous (FDI) muscle. Electromyographic responses (motor-evoked potentials, MEPs) to single-pulse stimulation, and intracortical inhibition (ICI) and intracortical facilitation (ICF) by paired-pulse stimulation were measured bilaterally in the relaxed FDI muscles before, immediately after, and 30, 60, 90 and 120 min after rTMS. RESULTS: After 5s of 10-Hz rTMS, the mean amplitude of MEP for the stimulated M1 cortex decreased for up to 90min (P=0.002) and that of the unstimulated M1 cortex decreased for up to 60 min (P=0.008). Enhancement of ICI and suppression of ICF were observed and sustained for more than 90 min in both stimulated (P=0.001) and unstimulated (P=0.003) M1 cortex after 5s of 10-Hz rTMS. After 1.5s of 10-Hz rTMS, the mean amplitude of MEP increased in stimulated cortex for up to 120 min (P=0.005). CONCLUSIONS: With different stimulation durations, high-frequency subthreshold rTMS can produce different patterns of long-lasting changes in corticospinal and intracortical excitability in stimulated and unstimulated motor cortex in healthy subjects. SIGNIFICANCE: The results have important implications for the selection of stimulation parameters other than the frequency of rTMS. The clinical application of rTMS for the purpose of motor enhancement should be considered along with the mechanism of different stimulation parameters.     

Modulation of motor cortical excitability following rapid-rate transcranial magnetic stimulation.

OBJECTIVE: To investigate the effect of high frequency rTMS (25 Hz at 90-100% of resting motor threshold) on the excitability of the motor cortex of healthy human subjects. METHODS: Resting and active motor threshold, MEP recruitment curve (I/O curve), short interval intracortical inhibition (SICI) and facilitation (ICF), and the duration of the silent period (SP) were tested in the right first dorsal interosseous muscle (FDI) before and twice after the end of 1500 pulses in 16 normal young adult male volunteers. RESULTS: Twenty-five Hertz rTMS decreased motor thresholds, reduced the duration of the silent period and had a tendency to increase the slope of the I/O curve. Most of these effects lasted for the duration of the two post-testing sessions (at least 30 min) and had returned to normal by 2h. There were no significant effects on SICI/ICF. CONCLUSION: Twenty-five Hertz rTMS can produce a long lasting increase in cortical excitability in healthy subjects. SIGNIFICANCE: This method may prove useful for the study of normal human physiology and for therapeutic manipulation of brain plasticity.     

Dual modulating effects of amphetamine on neuronal excitability and stimulation-induced plasticity in human motor cortex.

OBJECTIVES: The objective of the present study is to test the modulating effects of dextro-amphetamine (d-AMP) on excitability and stimulation-induced plasticity in human motor cortex. METHODS: Transcranial magnetic stimulation (TMS) was used to measure motor threshold, motor evoked potential (MEP) size and paired-pulse intracortical facilitation (ICF) in the biceps muscle of 7 healthy subjects before and after two different experimental manipulations: temporary forearm ischemic nerve block (INB) alone, or INB plus 0.1 Hz repetitive TMS (INB+rTMS) of the motor cortex contralateral to INB. Both manipulations were run after treatment with 10mg of d-AMP or placebo (PBO). RESULTS: In the PBO experiments, INB alone had no significant effect on MEP size or ICF, while INB+rTMS produced long-lasting (>60 min) increases. Compared with PBO, d-AMP led to a short-lasting ( approximately 10 min) increase in MEP size in the INB alone experiment, but suppressed the long-lasting increases of MEP size and ICF in the INB+rTMS experiment. CONCLUSIONS: The present findings suggest that d-AMP increases neuronal excitability but suppresses long-lasting stimulation-induced plasticity in human motor cortex. These dual effects may be relevant when using d-AMP to modulate human cortex function.     

Modification of cortical excitability induced by gabapentin: a study by transcranial magnetic stimulation

Transcranial magnetic stimulation (TMS) was employed before and after a single dose of gabapentin to evaluate how this drug affects the activity of excitatory and inhibitory circuits within the motor cortex. Eleven healthy volunteers were studied. For the evaluation of cortical excitability, the following parameters were taken into account: resting and active motor threshold (RMT, AMT); cortical silent period (CSP); and intracortical inhibition (ICI) and facilitation (ICF). Peripheral silent period (PSP) was also detected. All parameters were measured before and 3 and 24 hours after 800 mg gabapentin was administered in a single oral dose. Gabapentin deepened the ICI and suppressed the ICF at 3 h but not at 5 h after dosing. We conclude that, in the normal human brain, gabapentin may act on intracortical excitability by shifting the balance towards less excitation and more inhibition. Received: 30 March 2001 / Accepted in revised form: 17 May 2001     

Decreased corticospinal excitability after subthreshold 1 Hz rTMS over lateral premotor cortex

OBJECTIVE: To study whether trains of subthreshold 1 Hz repetitive transcranial magnetic stimulation (rTMS) over premotor, prefrontal, or parietal cortex can produce changes in excitability of motor cortex that outlast the application of the train. BACKGROUND: Prolonged 1 Hz rTMS over the motor cortex can suppress the amplitude of motor-evoked potentials (MEP) for several minutes after the end of the train. Because TMS can produce effects not only at the site of stimulation but also at distant sites to which it projects, the authors asked whether prolonged stimulation of sites distant but connected to motor cortex can also lead to lasting changes in MEP. METHODS: Eight subjects received 1500 magnetic stimuli given at 1 Hz over the left lateral frontal cortex, the left lateral premotor cortex, the hand area of the left motor cortex, and the left anterior parietal cortex on four separate days. Stimulus intensity was set at 90% active motor threshold. Corticospinal excitability was probed by measuring the amplitude of MEP evoked in the right first dorsal interosseous muscle by single suprathreshold stimuli over the left motor hand area before, during, and after the conditioning trains. RESULTS: rTMS over the left premotor cortex suppressed the amplitude of MEP in the right first dorsal interosseous muscle. The effect was maximized (approximately 50% suppression) after 900 pulses and outlasted the full train of 1500 stimuli for at least 15 minutes. Conditioning rTMS over the other sites did not modify the size of MEP. A control experiment showed that left premotor cortex conditioning had no effect on MEP evoked in the left first dorsal interosseous muscle. CONCLUSIONS: Subthreshold 1 Hz rTMS of the left premotor cortex induces a short-lasting inhibition of corticospinal excitability in the hand area of the ipsilateral motor cortex. This may provide a model for studying the functional interaction between premotor and motor cortex in healthy subjects and patients with movement disorders.     

Effects of low frequency and low intensity repetitive paired pulse stimulation of the primary motor cortex.

OBJECTIVE: Following a previous report [Bestmann et al. Clin Neurophysiol 2004;115:755-64] that pairs of subthreshold pulses of transcranial magnetic stimulation (TMS) can show temporal summation, we explored whether repeated application of pairs of stimulation could produce long-lasting after effects on the excitability of the human motor cortex. METHODS: Twelve healthy subjects received 25 min repetitive paired pulse magnetic stimulation (paired rTMS) given at a frequency of about 0.6 Hz over the left primary motor cortex (500 paired stimuli in total). The interval between the paired stimuli was 3 ms and the intensity of both stimuli was 80% of active motor threshold. The resting and active motor threshold, MEP recruitment curve, short interval intracortical inhibition (SICI) and facilitation, and the duration of the cortical silent period (SP) were tested for the right first interosseous muscle (FDI) before and two times after the end of 25 min paired rTMS. RESULTS: Prolonged subthreshold paired rTMS produced a significant decrease in excitability in the corticospinal projection to FDI: resting motor threshold was significantly increased and MEP recruitment was significantly decreased, SICI was significantly increased at 2 and 4 ms and the SP was significantly increased in duration. CONCLUSIONS: Prolonged low frequency paired rTMS at subthreshold intensity can modulate cortical excitability by producing inhibitory effects that outlast the period of stimulation.     

Heightened seizure susceptibility associated with brain dermoid cyst and the administration of human chorionic gonadotropin (hCG)

It is known that the intramuscular injection of human chorionic gonadotropin (hCG) lowers the threshold for motor evoked responses (MEPs) in the first dorsal interosseous (FDI) muscle to transcranial magnetic stimulation (TMS) in humans. We describe the case of a patient with a clinically silent left-sided nasofrontal dermoid cyst who, while being treated with hCG/LH for hypogonadotropic hypogonadism, presented with simple partial seizures, ipsilateral to the cyst, with secondary generalization. Motor cortex excitability was studied by single and paired TMS and MEPs were recorded from FDI. Resting motor threshold (RMT), active motor threshold (AMT), MEP size, intracortical inhibition (ICI) and intracortical facilitation (ICF) were tested during and after suspension of hormonal therapy. RMT and AMT were lower, MEP size was larger, ICI was decreased while ICF was slightly diminished during treatment. Overall, this indicated a reduced intracortical inhibition during hormonal therapy. It is concluded that treatment with hCG/LH may favour seizure onset in the presence of potentially epileptogenic lesions such as an intracranial dermoid cyst.     

Subthreshold low frequency repetitive transcranial magnetic stimulation selectively decreases facilitation in the motor cortex.

OBJECTIVE: To investigate the modulatory effect of a subthreshold low frequency repetitive transcranial magnetic stimulation (rTMS) train on motor cortex excitability. METHODS: The study consisted of two separate experiments. Subjects received a 10 min long subthreshold 1 Hz rTMS train. In the first experiment, (single pulse paradigm), cortical excitability was assessed by measuring the amplitude of motor evoked potentials (MEPs) before and after the rTMS train. In the second experiment, a paired pulse paradigm was employed. RESULTS: Corticospinal excitability, as measured by the MEP amplitude, was reduced by the rTMS train (experiment 1), with a significant effect lasting for about 10 min after the train completion. There was notable inter-individual as well as intra-individual variability in the effect. rTMS produced a significant decrease in intra-cortical facilitation as measured by the paired pulse paradigm (experiment 2). This effect lasted for up to 15 min following the train. Intra-cortical inhibition was not significantly affected. CONCLUSIONS: Subthreshold low frequency rTMS depresses cortical excitability beyond the duration of the train. This effect seems primarily due to cortical dysfacilitation. These results have implications on the therapeutic use of rTMS.