1、 何谓经颅磁刺激？何谓经颅磁刺激？transcranial magnetic stimulation （TMS）Baker 于1985年首先创立的一种电生理技术 利用磁线圈的时变电流产生时变脉冲磁场，作用于大脑皮层产生感应电流来改变皮层神经细胞的动作电位，从而影响神经活动和脑内代谢的磁刺激技术 具有非侵入性、无痛、穿透力强、安全可靠、操作简便等优点 正电子发射断层扫描（正电子发射断层扫描（PET）功能核磁共振功能核磁共振（fMRI）脑磁图（脑磁图（MEG）经颅磁刺激（经颅磁刺激（TMS）TMS是在一组高压大容量的电容上充电，用电子开关向磁场刺激线圈放电，在0.2毫秒内流过数千安培的脉冲电流，瞬
2、时功率达到几十兆瓦，线圈产生的脉冲磁场峰值可达14T，强大的瞬变磁场可以毫无损耗地穿过颅骨，根据电磁感应原理，在线圈下的颅内大脑皮质产生反向感应电流，刺激局部大脑神经细胞，引起兴奋和抑制，产生一系列生理生化反应。可引起多种神经递质的释放（多巴胺、5-羟基氨、谷氨酸等）并调制受体的敏感性；TMS对即早基因即早基因（immediate early genes）表达的影响,TMS引起皮质较广泛的c-fos、c-jun基因表达增加，转录因子CREB磷酸化、mRNA表达增加；通过改变脑血流、代谢，及内分泌功能而发挥作用；高频rTMS，可使神经元兴奋性增加，低频刺激则有抑制作用。刺激脉冲分类 单脉冲经颅磁
3、刺激（single-pulse TMS，sTMS）双脉冲经颅磁刺激（paired pulse TMS，pTMS）重复性经颅磁刺激（repetitive transcranial magnetic stimulation，rTMS）刺激频率分类 低频（5HZ）高频（5HZ）MEP是用磁（或电）刺激运动皮质或其传出通路，在刺激点下方通路及效应器所记录到的电反应。MEP可较为客观地反映运动皮质的兴奋性，定量评估中枢运动传导功能。在皮质神经元至脊髓前角运动神经元通路上任何部位的损害均可导致MEP的异常，表现为阈值、潜伏期及中枢运动传导时间的改变。阈值（阈值（motor threshold）MEP波幅波
4、幅 皮质潜伏期（皮质潜伏期（cortical latency，CL）皮质静止期（皮质静止期（cortical silent period，CSP）中枢运动传导时间（中枢运动传导时间（CMCT）突触的修剪和精化突触的修剪和精化 生后第生后第12年神经突触过度生成；生后第年神经突触过度生成；生后第2年直年直至青春期中期，过多的突触将被修剪，代之以至青春期中期，过多的突触将被修剪，代之以功能依赖的突触联系的精化。功能依赖的突触联系的精化。视皮层的突触修剪精化过程较运动皮层早。视皮层的突触修剪精化过程较运动皮层早。Johnston MV.Injury and plasticity in the dev
5、eloping brain.Exp Neurol,2003(184):S37S41.脑回化脑回化 随神经发育，脑回外形也将发生改变；脑回化的个体发育主要在新生儿期，脑回发育成熟对TMS-MEP的影响可在生后6周出现。Armstrong E,Schleicher A,Omran H,Curtis M,Zilles K.The ontogeny of human gyrification.Cereb Cortex 1995;5:5663.白质的髓鞘化白质的髓鞘化 皮质脊髓束的髓鞘化主要在生后第2年完成，而皮层下及胼胝体白质的髓鞘化较晚，直至成人期早期尚未完成。脑白质髓鞘化的顺序：从下向上，从后向前
6、，由中央白质向周边白质，最后为皮层下白质。线圈直径线圈直径头围大小头围大小Interestingly,despite the smaller head circumferences in children,brain volume in humans remains remarkably similar from 6 years of age onwards with only a small reduction in volume for infants and children under 6 years of age(Bartholomeusz et al.,2002).不同年龄儿童TM
7、S-MEP相关指数的特点 特殊疾病的研究 Cerebral palsy hemiplegia ADHD Rett syndrome Epilepsy Freidreich ataxia Pelizaeus-Merzbacher disease adrenoleukodystrophy三、三、TMS技术在儿童神经康技术在儿童神经康复领域的研究复领域的研究 阈值 10岁儿童MEP阈值较成人高，到青春期降至成人水平；(Garvey et al.,2003；Moll et al.,1999；Nezu et al.,1997)儿童与成人一致，静息阈值较易化后的运动阈值高；(Garvey et al.,2
8、003)6岁的儿童，静息下即使以最大刺激强度也可能引不出可靠的MEP；(Koh and Eyre,1988)而在靶肌肉兴奋下，即使是新生儿MEP亦可引出(Eyre et al.,2001)MEP threshold was obtained using a focal coil both when the target muscle(first dorsal interosseus FDI)was at rest(RMT)and when there was background muscle activation(AMT).Percentage of maximum stimulator i
9、ntensity is represented on the Y axis.Age group is represented on the X axis.Group 1=6 to 7 year old children(n=5);Group 2=8 to 9 year old children(n=8);Group 3=10 to 11 year old children(n=10);Group 4=12 to 13 year old children(n=8);Group 5=adults(n=9).Open boxes represent RMT,hatched boxes represe
10、nt AMT.Error bars represent 1 standard deviation from the mean.Note that thresholds get lower with age and that,for all age groups,lower stimulation intensities are required to obtain the AMT.From Garvey MA&Gilbert DL,Transcranial Magnetic Stimulation in Children,Eur J Paediatr Neurol 2004;8:719.静息下
11、与易化的CMCT的发育规律不同，35岁易化下的CMCT达到成熟；静息下的CMCT则到青春期早期亦未成熟。(Eyre et al.,1991；Fietzek et al.,2000；Kohand Eyre,1988；Mller et al.,1994)学龄前儿童的“latency jump”是成人的4倍；(Abbruzzese and Trompetto,2002；Rossini et al.,1994).CSP的个体化发育体现皮质抑制性神经元和胼胝体体部白质髓鞘化的程度；学龄前儿童CSP缺失，直至67岁才可始见确定的CSP；(Heinen et al.,1998b)67岁阶段与成熟相比较，CS
12、P潜伏期延长而时程缩短，此后几年中潜伏期逐渐缩短，而时程逐渐增加，至青春期早期达到成熟水平。(Garvey et al.,2003)The figure shows three EMG tracings of the iSP from a 7 year old boy(upper),a 12 year old girl(middle),and a 22 year old man(lower).Maturation of the Ipsilateral Silent PeriodJulia Vry,et al.Exp Brain Res,2008(186):611-618.平均年龄平均年龄11.
13、9 2.1岁，岁，GMFCS level 1:n=3,2:n=2,3:n=6,4:n=4,5:n=0English-language studies using rTMS in persons under the age of 18,yielding 6 published reports.Because rTMS is typically delivered at or above 1 Hz for psychiatric indications,our search was confined to these frequencies.Also included are studies in
14、volving rTMS above 1 Hz for non-psychiatric indications.Articles were retrieved from the MEDLINE database.There were 19 reported subjects under age 18 who have been administered rTMS at a frequency above 1 Hz:10 for major depression,5 for spastic cerebral palsy and 4 for epilepsia partialis continua
15、.We found that most subjects responded favorably to rTMS and no adverse events have been reported.However data are insufficient for drawing firm conclusions about safety and efficacy.Further studies of rTMS as a treatment for adolescent depression are warranted.rTMS for adolescents:Safety and efficacy considerations.Douglas DAgati,et al.Psychiatry Research,2010(177):280-285.
