低、高频闭环电刺激对氯化铁癫痫模型大鼠治疗作用的比较

目的探讨低、高频闭环电刺激对氯化铁癫痫模型大鼠的治疗效果。方法给予SD大鼠头颅额、顶、枕部铺设硬膜外电极6枚,用立体定向方法在大鼠感觉运动皮质区注入氯化铁溶液,建立癫痫模型,分别给予低频刺激(1Hz)和高频刺激(100Hz),同时给予8小时脑电监测。分析大鼠8小时内发作总次数和发作总时间。结果低频和高频电刺激均能抑制大鼠的癫痫发作,而高频与低频刺激在治疗效果上无明显统计学差异。结论低频刺激为较佳的刺激方式。     

急性氯化铁癫痫模型大鼠美解眠诱发放电的实验研究

目的 探讨急性氯化铁癫痫模型大鼠在发作间期美解眠诱发试验中的放电特征.方法 给予SD大鼠头颅额、顶、枕部铺设硬膜外电极6枚,用立体定向方法在大鼠感觉运动皮质区注入氯化铁溶液,建立急性癫痫模型,记录脑电24小时,观察在发作间期给予急性氯化铁癫痫模型大鼠腹腔注射美解眠后诱发癫痫发作的脑电情况.结果 美解眠诱发试验中,出现两种不同类型的癫痫发作期脑电,其中一种与急性氯化铁模型的发作期放电相同,另一种与美解眠自身所致癫痫的发作期放电相似.结论 急性氯化铁癫痫模型大鼠在美解眠诱发试验中能够产生原有癫痫发作,但是假阳性率较高;氯化铁致痫大鼠对美解眠的反应性较正常大鼠高.     

颈迷走神经脉冲电刺激对大鼠点燃速度及杏仁核放电的影响

目的　定量研究颈迷走神经刺激对大鼠癫痫形成速度及杏仁核放电的影响。方法　用频率 16 Hz,波宽1.0 ms,串长 10 s,串隔 7min,强度 3.0 m A的恒流脉冲电刺激 18只大鼠的左颈迷走神经 ,同时用强度 0 .4m A的恒流脉冲电诱发刺激大鼠的杏仁核。以 18只仅刺激杏仁核的大鼠作对照 ,观察其癫痫行为及杏仁核放电情况。结果　实验组有 16 / 18只大鼠被点燃 ,对照组有 17/ 18只点燃 ,组间差异无显著性 (P>0 .0 5)。比之于对照组 ,实验组点燃所需杏仁核平均刺激次数及杏仁核平均后放电阈值均显著增高 (P<0 .0 5) ,但杏仁核平均后放电时间两组差异无显著性 (P>0 .0 5)。结论　迷走神经刺激虽最终难以阻断大鼠点燃的发生 ,但可减缓大鼠点燃发生速度 ,提高杏仁核后放电阈值。其抗痫效应可能主要与提高全脑抑制水平 ,抑制痫性放电扩布有关 ,而对痫灶本身放电影响相对较小。     

皮层电刺激定位功能区的有效刺激参数研究

目的 探讨手术治疗中央区癫痫时,皮层电刺激功能区定位的有效刺激参数.方法 回顾性分析2006年10月至2008年3月北京功能神经外科研究所连续收治的21例中央区癫痫患者的临床资料,研究皮层电刺激功能定位时,感觉、运动及后放电阈值之间的差异以及与阈值相关的因素.结果 运动、感觉、后放电的平均阈值分别为:(3.48±0.87)mA、(3.86±1.31)mA和(4.84±1.38)mA.后放电阈值高于运动、感觉阈值(P＜0.05),且与病史呈负线性关系.结论 以频率50 Hz、脉宽0.2 ms、刺激强度8 mA以下等刺激参数行皮层电刺激定位功能区是安全可靠的;皮层功能定位应个体化实施.

Abstract：

Objective The purpose of the study was to investigate the effective parameters of electric cortex stimulation (ECS)for functional brain mapping.Method We collected 21 subjects who underwent epilepsy surgeries consecutively in Beijing Institute of Functional Neurosurgery with the epileptogenic zone located in perirolandic areas from October 2006 to March 2008.With retrospective study, we systematically analyzed the information about threshold of motor and sensory response and afterdischarge.Results The average threshold of motor and sensory response and afterdischarge were (3.48 ± 0.87 ) mA, ( 3.86 ± 1.31 )mA, (4.84 ± 1.38) mA respectively.The average threshold of afterdischarge was higher than that of motor and sensory response.The difference was significant ( P ＜ 0.05 ).The threshold of afterdischarge was in negative linear correlation with illness duration.Conclusions The ECS parameters of 50 Hz, 0.2 ms for functional brain mapping are effective and safety; ECS should be performed respectively.     

丘脑底核电刺激对癫痫大鼠模型基底节神经元放电的影响

目的应用不同频率的电刺激海人酸模型癫痫大鼠STN核,观察STN核以及SNr(黑质网状部)神经元细胞在刺激后放电频率的变化,研究电刺激STN对STN内神经元和SNr神经元放电的影响,探讨STN-DBS治疗癫痫的作用机制。方法10只癫痫大鼠为实验组,另10只正常大鼠作为对照组。参照大鼠立体定向图谱,将记录的玻璃微电极和刺激电极分别插入STN、SNr核团内,刺激频率分为三组,分别为30 Hz、130 Hz、260 Hz。通过单神经元放电细胞外记录方法分别于高频刺激前后记录脑内核团神经元放电情况,分析神经元在STN-HFS刺激前和刺激时放电改变情况。结果正常大鼠的STN及SNr神经元放电与癫痫模型大鼠相比,两者放电频率不存在显著性差异,对放电模式的分析发现两者也无明显差异(P>0.05)。癫痫大鼠的STN及SNr神经元在30 Hz的刺激过程中放电频率多数没有明显变化。随着放电频率的增加两种神经元在电刺激后多数神经元放电明显受到抑制。在130 Hz和260 Hz组,受抑制的神经元较30 Hz组明显增加,具有显著性差异(P<0.05)。结论本研究证实高频电刺激STN明显抑制了STN和SNr神经元的兴奋性,其效果与频率是相...     

白细胞介素-6对皮质发育障碍大鼠痫性放电的影响

目的采用多电极皮层脑电监测技术,通过局部给药的方式,观察白细胞介素-6(IL-6)对大鼠皮质发育障碍(MCD)痫性放电的影响。方法建立液氮皮层冰冻MCD模型:对新出生的SD大鼠进行脑皮质板局部冰冻损伤。模型建立后通过形态学、行为学等进行评价。手术前1 w对MCD模型小鼠进行皮层脑电埋置。术后1 w所有实验大鼠随机分成匹罗卡品组、匹罗卡品加IL-6组。模型诱导组大鼠氯化锂腹腔注射(180 mg/kg),20 h后给予硫酸阿托品1 mg/kg腹腔注射,30 min后再给予20 mg/kg匹罗卡品腹腔注射。模型诱导加IL-6组增加IL-6局部注射。注射前先进行30 min的基线监测,注射后直接进行电生理检测。监测完毕对动物行为学以及相关如潜伏期、持续时间等电生理指标进行分析。结果所有实验组大鼠注射匹鲁卡品后随即出现眨眼、节律性咀嚼、节律性点头,约30 min后出现Ⅳ级以上发作。但是IL-6注射组动作明显减轻,出现时间较晚。电生理结果显示,与模型诱导组相比(25.93±1.33)min,模型诱导加IL-6注射组表现为潜伏期明显延长(31.05±2.35)min,两组潜伏期发作时间有明显差异(P0.01);与模型诱导组相比[(34.58±1.02)s],模型诱导加IL-6注射组表现为放电持续时间明显减少[(17.75±1.94)s],两组时间有明显差异(P0.01);与模型诱导组相比[(28.83±4.26)次],模型诱导加IL-6注射组表现为自发性癫痫放电次数明显减少[(12.00±3.03)次],两组时间有明显差异(P0.01)。结论 IL-6明显减少痫性放电阈值,减少放电持续时间,可能对癫痫发作有一定的保护作用。     

海马电刺激对耐药性颞叶癫痫大鼠CA1区神经元钠通道电流的影响

目的 建立多药耐药性颞叶癫痫模型,以海马CA1区锥体细胞钠通道电流的变化为观察指标,探讨海马电刺激治疗耐药性颞叶癫痫的可能机制.方法 选用Wistar大鼠80只制作慢性杏仁核点燃癫痫模型,制作成功后用经典抗癫痫药苯妥英钠和苯巴比妥进行筛选,根据癫痫大鼠对药物的反应区别出耐药癫痫大鼠及药物敏感大鼠,将筛选出的耐药性癫痫大鼠分为海马刺激组(n=6)及耐药对照组(n=6),用膜片钳全细胞记录模式观察海马电刺激后脑细胞钠通道电流的变化.结果 进行海马电刺激2周后,刺激杏仁核诱发的癫痫发作明显减轻,海马刺激组与耐药对照组Racine分级分别为(2.32±0.38)级和(4.45±0.42)级,差异具有统计学意义(t=84.600,P=0.000),后放电各项参数也明显改善,膜片钳全细胞记录结果表明,海马刺激组钠通道电流峰值及激活曲线向去极化方向偏移,失活曲线向超极化方向偏移,海马刺激组钠通道失活后恢复时间[(17.9±0.6)s]较耐药对照组[(16.3±0.3)s]明显延长(t=-25.420,P=0.000).结论 海马电刺激可以抑制钠通道电流,其治疗耐药性癫痫的作用可能是通过抑制钠通道电流而降低脑细胞兴奋性,从而减少癫痫性电活动的产生而实现的.     

GluR2Q在下丘脑乳头体上核内过度表达对于大鼠颞叶癫痫脑电的影响

目的 探讨下丘脑乳头体内兴奋性刺激对于颞叶癫痫脑电变化的影响。方法 利用HVJ－脂质体转染法在下丘脑乳头体内转染兴奋性氨基酸受体亚基GluR2Q，研究其对于海人酸（kainic acid,KA)诱发的癫痫模型脑电变化的影响。结果 GluR1Q基因转染组大鼠癫痫连续性放电的开始时间明显早于KA对照组，且持续时间较KA对照组明显延长。结论 下丘脑内GluR2Q基因转染能提高其兴奋性，并促进癫痫波在海马内的传播。     

迷走神经、躯体神经与运动皮质电刺激对戊四氮点燃大鼠惊厥行为的影响

目的 探讨迷走神经、躯体神经(坐骨神经、三叉神经)与运动皮质电刺激对戊四氮点燃大鼠惊厥行为的影响是否存在差异.方法 分别剥离大鼠迷走神经、坐骨神经(三叉神经不予以剥离)和建立运动皮质电刺激模型,给予上述4种电刺激后腹腔注射戊四氮50 mg/kg,观察大鼠行为学的变化.结果 对照组在注射戊四氮后9只大鼠(9/10)出现Racine分级Ⅳ～Ⅴ级惊厥发作,迷走神经、坐骨神经、三叉神经刺激后大鼠惊厥发作均不同程度减轻(Ⅰ～Ⅲ级发作大鼠分别为5、6、5只),但给运动皮质电刺激后大鼠无惊厥行为.当实验鼠的皮质、海马出现病理改变(实验鼠已成为癫(癎)模型)时,再给同剂量戊四氮点燃时,相同参数的运动皮质电刺激则不能抑制大鼠的惊厥行为,反而出现Ⅳ～Ⅴ级发作(10/10).结论 在生理性状态下4种电刺激方法在行为学上均可不同程度抑制戊四氮诱发的惊厥发作,以皮质电刺激效果最好,然而当鼠脑内的癫(癎)灶形成且处于病理状态下时此种效果消失.     

癫痫与皮质扩散性抑制相关性研究进展

皮质扩散性抑制是神经元集体去极化在大脑皮质中传播的病理去极化波,沿大脑皮质缓慢传播,可短暂性抑制脑电活动,与多种发作性脑病相关。皮质扩散性抑制与痫样放电是共同发生的电生理现象,引起皮质扩散性抑制的因素亦可诱发癫痫发作;抑制皮质扩散性抑制的发生、传播可改变癫痫发作阈值,减少癫痫发作,二者相互联系、相互影响。本文综述癫痫与皮质扩散性抑制的相关性研究进展,以提高临床对二者相关性的认识。     

Electric stimulation on human cortex suppresses fast cortical activity and epileptic spikes

Summary:  Purpose: To investigate underlying mechanisms and adequate parameters for electric cortical stimulation to inhibit epileptic focus in humans.
Methods: A patient with intractable partial epilepsy had subdural electrodes implanted for preoperative evaluation. Cortical functional mapping was performed by using 50-Hz alternating square pulse of 0.3-ms duration, 1 to 7 mA, within 5 s. Spike frequency and electrocorticogram (ECoG) power spectra were compared before and after the stimulation when epileptic focus and distant area were stimulated. A similar comparison also was performed in low-frequency stimulation of 0.9 Hz applied for 15 min.
Results: Interictal spikes were reduced after electric cortical stimulation of the epileptic area at a frequency of 50 Hz as well as 0.9 Hz, with concomitant decrease in the electrographic fast activities at 50-Hz stimulation.
Conclusions: These data suggest that electric cortical stimulation at both high and low frequency has a suppressive effect on epileptic activities in human cortex, possibly through distinct mechanisms.     

Stimulus intensity and coil characteristics influence the efficacy of rTMS to suppress cortical excitability.

OBJECTIVE: Low-frequency repetitive transcranial magnetic stimulation (rTMS) can reduce cortical excitability. Here we examined whether inhibitory after effects of low-frequency rTMS are influenced by stimulus intensity, the type of TMS coil and re-afferent sensory stimulation. METHODS: In fifteen healthy volunteers, we applied 900 biphasic pulses of 1Hz rTMS to the left primary motor cortex (M1) at an intensity that was 10% below or 15% above resting motor threshold. For rTMS, we used two different figure-of-eight shaped coils (Magstim or Medtronic coil) attached to the same stimulator. We recorded motor evoked potentials (MEPs) evoked with the same set-up used for rTMS (MEP-rTMS) before and twice after rTMS. Using a different TMS setup, we also applied monophasic pulses to the M1 in order to assess the effects of rTMS on corticospinal excitability, intracortical paired-pulse excitability and the duration of the cortical silent period (CSP). In a control experiment, the same measurements were performed after 15min of 1Hz repetitive electrical nerve stimulation (rENS) of the right ulnar nerve. RESULTS: Analysis of variance revealed an interaction between intensity, coil and time of measurement (p<0.035), indicating that the effect of 1Hz rTMS on MEP-rTMS amplitude depended on the intensity and the type of coil used for rTMS. Suppression of corticospinal excitability was strongest after suprathreshold 1Hz rTMS with the Medtronic coil (p<0.01 for both post-rTMS measurements relative to pre-intervention baseline). Regardless of the type of coil, suprathreshold but not subthreshold rTMS transiently prolonged the CSP and attenuated paired-pulse facilitation. Suprathreshold 1Hz rENS also induced a short-lasting inhibition of MEP-rTMS. CONCLUSIONS: Both the stimulation intensity and the type of TMS coil have an impact on the after effects of 1Hz rTMS. Re-afferent feedback activation may at least in part account for the stronger suppression of corticospinal excitability by suprathreshold 1Hz rTMS. SIGNIFICANCE: These data should be considered when rTMS is used as a therapeutic means.     

经颅重复磁刺激对人脑皮层兴奋性的影响

目的　研究经颅重复磁刺激（rTMS）对人脑运动皮层兴奋性的影响。方法　5Hz×30次或15Hz×30次rTMS,以相当于120%静止运动阈值的强度,作用于12名青壮年志愿者,并利用成对的条件-检测刺激方法检验rTMS对皮层内抑制（ICI）及皮层内易化（ICF）的影响。结果　15HzrTMS显著抑制ICI达3.4min,兴奋ICF达1.5min,而运动阈值仅被降低约30s。5HzrTMS仅显著抑制ICI30s,而对ICF及运动阈值无影响。结论　高频阈上rTMS能一过性抑制皮层内抑制环路并提高皮层内兴奋性环路的活动。     

Determining optimal rTMS parameters through changes in cortical inhibition

ObjectivesEvidence shows that repetitive transcranial magnetic stimulation (rTMS) changes cortical inhibition (CI) and excitability and that these changes may relate to its therapeutic effects. This study aimed to investigate the effects of differing durations or ‘doses’ of rTMS on cortical inhibition and excitability in healthy subjects.MethodsFour different experiments were conducted: 1 session of 1200 pulses of 1 or 20 Hz active or sham rTMS; 10 sessions of 1 or 20 Hz active or sham rTMS, 1200 pulses/session; 1 session of 3600 pulses of 1 or 20 Hz active or sham rTMS; 1 session of 6000 pulses of 20 Hz active or sham rTMS. Measures of cortical inhibition and excitability included short-interval intracortical inhibition, long interval cortical inhibition, cortical silent period (CSP), motor evoked potential amplitude, resting motor threshold and intracortical facilitation.ResultsOnly 6000 pulses of 20 Hz rTMS lead to a significant lengthening of the CSP and therefore potentiation of CI. There were no changes to excitability measures.ConclusionOnly high frequency rTMS potentiated CI. Longer treatment durations are required to produce such changes.SignificanceStudies investigating the therapeutic effects of rTMS may benefit from extended dosing with increased number of pulses per session. CSP lengthening may be used to guide treatment response.     

Motor cortical excitability studied with repetitive transcranial magnetic stimulation in patients with Huntington's disease.

OBJECTIVE: TMS techniques have provided controversial information on motor cortical function in Huntington's disease (HD). We investigated the excitability of motor cortex in patients with HD using repetitive transcranial magnetic stimulation (rTMS). METHODS: Eleven patients with HD, and 11 age-matched healthy subjects participated in the study. The clinical features of patients with HD were evaluated with the United Huntington's Disease Rating Scale (UHDRS). rTMS was delivered with a Magstim Repetitive Magnetic Stimulator through a figure-of-8 coil placed over the motor area of the first dorsal interosseus (FDI) muscle. Trains of 10 stimuli were delivered at 5 Hz frequency and suprathreshold intensity (120% resting motor threshold) with the subjects at rest and during voluntary contraction of the target muscle. RESULTS: In healthy subjects at rest, rTMS produced motor evoked potentials (MEPs) that increased in amplitude over the course of the trains. Conversely in patients, rTMS left the MEP size almost unchanged. In both groups, during voluntary contraction rTMS increased the silent period (SP) duration. CONCLUSIONS: Because rTMS modulates motor cortical excitability by activating cortical excitatory and inhibitory interneurons these findings suggest that in patients with HD the excitability of facilitatory intracortical interneurones is decreased. SIGNIFICANCE: We suggest that depressed excitability of the motor cortex in patients with HD reflects a disease-related weakening of cortical facilitatory mechanisms.     

Motor cortex dysfunction revealed by cortical excitability studies in Parkinson's disease: influence of antiparkinsonian treatment and cortical stimulation.

Single or paired pulse paradigms of transcranial magnetic stimulation (TMS) provide several parameters to test motor cortex excitability, such as motor threshold (MT), motor evoked potential (MEP) amplitude, electromyographic silent period to cortical stimulation (CSP) and intracortical facilitation (ICF) or inhibition (ICI). Various changes in TMS parameters, revealing motor cortex dysfunction, were found in patients with Parkinson's disease (PD). For instance, low MT and increased MEP size disclosed an enhanced corticospinal motor output at rest, while reduced ICF and failure of MEP size increase during contraction suggested defective facilitatory cortical inputs, particularly for movement execution. Inhibitory cortical pathways were also found less excitable at rest (reduced ICI) and sometimes during contraction (shortened CSP). By restoring cortical inhibition, dopaminergic drugs and deep brain stimulation probably overcome the difficulty to focus neuronal activity onto the appropriate network required for a specific motor task. The application of repetitive TMS trains over motor cortical areas also showed some effect on cortical excitability, opening perspectives to consider the motor cortex as a target for therapeutic neuromodulation in PD. However, systematic studies of cortical excitability remained to be performed in large series of patients with PD, taking into account disease stage, clinical symptoms and medication influence.     

Assessment of cortical excitability using threshold tracking techniques

Conventional paired-pulse transcranial magnetic stimulation (TMS) techniques of assessing cortical excitability are limited by fluctuations in the motor evoked potential (MEP) amplitude. The aim of the present study was to determine the feasibility of threshold tracking TMS for assessing cortical excitability in a clinical setting and to establish normative data. Studies were undertaken in 26 healthy controls, tracking the MEP response from abductor pollicis brevis. Short-interval intracortical inhibition (SICI) occurred up to an interstimulus interval (ISI) of 7-10 ms, with two distinct peaks evident, at ISIs of < or =1 and 3 ms, followed by intracortical facilitation to an ISI of 30 ms. Long-interval intracortical inhibition (LICI) occurred at ISIs of 50-300 ms, peaking at 150 ms. The present study has confirmed the effectiveness of the threshold tracking TMS technique in reliably and reproducibly measuring cortical excitability. Simultaneous assessment of upper and lower motor neuronal function with threshold tracking techniques may help to determine the site of disease onset and patterns of progression in neurodegenerative diseases.     

High-frequency and brief-pulse stimulation pulses terminate cortical electrical stimulation-induced afterdischarges

Brief-pulse stimulation at 50 Hz has been shown to terminate afterdischarges observed in epilepsy patients. However, the optimal pulse stimulation parameters for terminating cortical electrical stimulation-induced afterdischarges remain unclear. In the present study, we examined the effects of different brief-pulse stimulation frequencies (5, 50 and 100 Hz) on cortical electrical stimulation-induced after-discharges in 10 patients with refractory epilepsy. Results demonstrated that brief-pulse stimulation could terminate cortical electrical stimulation-induced afterdischarges in refractory epilepsy patients. In conclusion, (1) a brief-pulse stimulation was more effective when the afterdischarge did not extend to the surrounding brain area. (2) A higher brief-pulse stimulation frequency (especially 100 Hz) was more likely to terminate an afterdischarge. (3) A low current intensity of brief-pulse stimulation was more likely to terminate an afterdischarge.     

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.