1 经颅电刺激(Transcranial Electrical Stimulation, TES)
经颅电刺激(Transcranial Electrical Stimulation, TES)技术从提出到应用经历了一段较长的历史。早在1980年, Merton和Morton就提出了无创的经颅电刺激(TES)方法。他们试图通过电流刺激完好的大脑来改变大脑功能, 证实了经颅电刺激作用于枕叶皮层可以引起光幻视现象(Phosphene)。虽然当时的经颅电刺激是非侵入性的, 但由于使用的电流是高压电流, 会引起被试疼痛和头皮肌肉收缩, 所以这个技术在当时没有得到广泛的关注(Merton & Morton, 1980)。直到20世纪90年代, 随着经颅磁刺激技术的流行, 同样非侵入性的电流刺激技术重新进入研究者们的视线。在21 世纪初, Nitsche和Paulus (2000)运用经颅直流电刺激(transcranial direct current stimulation, tDCS)作用于人类的运动皮层, 发现了皮层在微弱的电刺激(≤ 1 mA)前后兴奋性的变化(Nitsche & Paulus, 2000)。从那之后, 由于TES对神经活动进行直接调控的可能性以及它对大脑皮层的无创性, TES成为近十几年来认知神经科学研究中的一个热点。
TES技术的历史较长, 但操作并不复杂。它是通过两个或多个电极, 将特定模式的低强度电流持续作用于大脑皮层, 以调控大脑神经活动。在TES对视觉功能调控的研究中, 一般把主要电极片安放在Oz处, 参考电极于Cz处(见图1a), 常见的电极片面积在25 cm2到35 cm2之间。也有研究者为了提高电流的空间聚焦, 使用9 cm2或更小的电极片。电刺激的电流强度在0.1 mA到2 mA之间, 持续时间一般为3分钟到30分钟。
图1
根据电刺激所使用电流的不同模式, TES主要分为经颅直流电刺激(tDCS), 经颅交流电刺激(transcranial alternating current stimulation, tACS)和经颅随机电刺激(transcranial random noise stimulation, tRNS)。其中研究得比较早、比较多的是tDCS。tDCS使用的电流是直流电, 它起作用的主要参数包括作用位置、电极极性、电流强度和刺激时间, 见图1b。两种极性的TDCS效果通常相反：阳极经颅电刺激(A-tDCS)被认为能够提高大脑皮层的兴奋性, 而阴极经颅电刺激(C-tDCS)则会降低兴奋性。tACS使用的电流为交流电, 它的主要参数为交流电的频率和电流强度, 见图1c。不同频段的tACS被认为与皮层自发的神经振荡相互作用, 从而影响皮层功能(Herrmann, Strüber, Helfrich, & Engel, 2016)。tRNS相比tACS不同的地方在于所使用的交流电频率是在一个范围内随机的。有研究发现, 10分钟的tRNS刺激就能引起长达60分钟的神经兴奋性(Terney, Chaieb, Moliadze, Antal, & Paulus, 2008)。
2 TES与光幻视阈值(Phosphene Threshold, PT)
光幻视是人眼在没有光源刺激的情况下能感受到了光的一种现象。经颅磁刺激(TMS)脉冲传递到大脑皮层的枕叶皮层可以引起视觉的光幻视(Meyer, Diehl, Steinmetz, Britton, & Benecke, 1991)。能引起光幻视的平均TMS强度定义为光幻视阈值(Phosphene Threshold, PT)。PT对于每一个人来说是相对稳定的, 是衡量视觉皮层兴奋性的一个指标(Boroojerdi, Prager, Muellbacher, & Cohen, 2000)。对基于TMS测量的PT的调控, 提示了TES对视觉皮层兴奋性的有效性。TES调控PT的研究, 刺激位置一般是枕叶区, 目前主要结论是TES能够有效调控基于TMS测量的PT值, 但调控效果视TES的类型和参数而定。
tDCS以特定极性的方式有效调控PT。Antal, Kincses, Nitsche和Paulus (2003a)首次考察了tDCS作用于初级视觉皮层的前后对PT的影响。研究中采用5 Hz的短频磁刺激(TMS)作用于被试的初级视觉皮层V1来测试PT。电刺激条件有阴极、阳极和虚假tDCS三种。刺激电极放置在Oz, 参考电极在Cz。9个正常成年被试在接受电刺激前、刺激后、10分钟后和20分钟后4个时间点进行PT测试。结果发现, 在刺激之后和10分钟时, C-tDCS显著提升PT, 而A-tDCS则显著降低了PT。提示C-tDCS降低了皮层兴奋性, 而A-tDCS提高了皮层兴奋性(Antal et al., 2003a)。Antal等人(2003b)还考察了tDCS对移动PT (moving PT)的影响。研究中使用TMS作用于被试左侧或右侧V5测得移动PT。结果发现, 在刺激之后和10分钟时, C-tDCS显著提高而A-tDCS降低了PT。提示tDCS作用于V1能有效调控移动PT(Antal et al., 2003b)。
tACS在特定频率时能够有效调控PT。Kanai, Paulus和Walsh (2010)考察了tACS对视觉皮层兴奋性的影响。研究中在使用不同频率的tACS (5, 10, 20和40 Hz)刺激于枕叶区时, 采用单脉冲TMS测量PT。结果发现, 20 Hz的tACS在刺激过程中降低了PT, 即提高了视觉皮层的兴奋性, 其他频率的tACS对PT没有影响(Kanai et al., 2010)。
3 TES与视野(Visual Field, VF)
视野是指人的头部和眼球不动的情况下, 眼睛观看正前方物体时所能看得见的空间范围, 是一项基本的视觉功能(Smythies, 1996)。一般通过静态视野计和动态视野计来测量视野。视觉通路上任何一处病变都会导致视野缺损(Kasten et al., 1999)。视野缺损是指视野范围内普遍或局部的视敏度的缺失, 可能表现为视力减退、视物不清、偏盲等。TES用于研究视野恢复的主要针对人群是视野缺损病人, 目前主要的结论是TES能够有效增大视野缺损病人的视野范围, 但不同刺激模式的效果不一样。
3.1 TDCS与VF
tDCS结合恢复训练能有效促进视野缺损病人的视野恢复。Ela B. Plow等人首先考察了TDCS结合视觉恢复治疗(Vision Restoration Therapy, VRT)对中风后偏盲病人视野恢复的作用。病人接受3个月的视觉恢复治疗训练, 每周3天, 每天2次, 每次30分钟。实验组病人在接受VRT训练时同时接受A-tDCS。刺激电极位于Oz, 参考电极位于Cz, 电流强度为2 mA。控制组病人在训练时接受虚假电刺激。训练前后用高分辨率视野计进行测试。结果发现接受A-TDCS的病人的视野相比控制组恢复得更好 (Plow, Obretenova, Fregni, Pascual-Leone, & Merabet, 2012; Plow et al., 2011; Plow, Obretenova, Jackson, & Merabet, 2012)。Alber, Moser, Gall和Sabel (2017)考察了tDCS结合视觉恢复训练对大脑后动脉中风病人视野恢复的效果。7个同侧偏盲病人接受66 (±50)天的视觉恢复训练, 其中有10天在训练时接受20分钟的A-tDCS刺激。电极位置于O1或O2, 参考电极位于Cz。7个损伤时长和程度与实验组的7人相匹配的病人作为控制组, 仅接受一般训练。结果发现, 实验组相比控制组, 病人视野范围恢复的效果更好(Alber et al., 2017)。
tDCS能够有效影响正常人周边视野的阈值。Costa等人(2015a)考察了tDCS对正常人中央和周边视野的影响。实验采用被试内设计, 15个正常被试先后接受3个tDCS的刺激条件：阳极电刺激、阴极电刺激和假刺激, 每个刺激条件之间间隔1周。刺激作用期间完成视野测量任务。结果发现tDCS降低了周边视野的阈值, 但对中心视野没有显著的影响(Costa, Gualtieri et al., 2015a)。
3.2 tACS与VF
tACS能够有效提升视野受损病人的视野范围。tACS对视野恢复的研究, 刺激位置主要在眼球的外周位置。Sabel等人(2011)通过双盲、随机、控制组的实验设计, 考察了重复性经眼眶交流电刺激(repetitive transorbital alternating current stimulation, rtACS)对视神经损伤病人的视野恢复效果。4个rtACS的电极片放在左右眼球的上、下位置, 参考电极位于右臂手腕处。电流强度是为每个人刚好能够被引起光幻视的值(≤ 1 mA), 刺激时间为10天, 每天40分钟。实验组12个视神经受损病人在刺激前后完成中心视野(Central visual fields)的高分辨率视野测试任务。结果发现, 相比于控制组, 实验组显著提高了病人的视野范围(Sabel et al., 2011)。这一结果在之后的446个神经损伤病人的临床观察研究中得到验证(Fedorov et al., 2011)。随后的研究也发现这种视野范围的提升, 跟视觉功能问卷得分的提高是相关的, 提示视野恢复也能够有效提升病人视功能相关的生活质量(Gall et al., 2011)。
不同参数的rtACS效果不一样：方波重复交流电刺激(Square-rtACS)的效果优于正弦重复交流电刺激(Sinus-rtACS)。Gall等人(2013a)考察了Sinus-rtACS对视野范围的影响, 并与他先前的square-rtACS的研究结果做对比。36个视野缺损的被试分实验组和控制组, 接受共10天, 每天25到40分钟的电刺激或虚假刺激, 在刺激前后完成高分辨率的视野测试。结果发现, Sinus-rtACS对视野范围的提升仅在被试内统计中显著, 在被试间不显著, 提升幅度相比Square-rtACS要小(Gall, Bola, et al., 2013a)。
rtACS对视野缺损病人的视野恢复效果相对稳定。Gall等人(2013b)把98个视觉神经损伤病人分层随机分配到rtACS实验组和控制组。被试在刺激前后以及两个月之后接受视野测试。结果发现, 实验组相比控制组, 视野恢复效果要好, 并且提升效果能保持至少2个月(Gall, Federov, et al., 2013b)。Gall等人(2016)通过随机、双盲、控制组实验考察了rtACS对偏盲病人(partially blind patients)的视野范围的提升。结果发现实验组相比控制组视野提升了范围(24%), 并且视野提升的效果至少保持了2个月(Gall et al., 2016)。
4 TES与对比敏感度(Contrast Sensitivity, CS)
最初探索TES对视觉皮层兴奋性的调控是从tDCS调控对比敏感度开始的, 刺激电极位置常为初级视皮层V1的Oz, 参考电极为Cz。目前tDCS对CS的调控效果的结论主要是A-tDCS能提高被试的对比敏感度, C-tDCS的作用相反, 但也有研究发现不一致的结果。
Antal等人率先在2001年考察了TDCS对正常人的对比度阈值的调控作用。刺激条件有阳极、阴极。结果发现C-tDCS在作用期间和10分钟后都显著提高了被试的对比度阈值, 而A-TDCS对比敏感度没有影响(Antal, Nitsche, & Paulus, 2001)。Spiegel, Byblow, Hess和Thompson (2013)考察了tDCS对弱视成年人的对比敏感度的影响。实验采用被试内设计, 13个弱视被试先后接受阳极和阴极2个TDCS条件。在电刺激进行之前、期间和之后测试被试的对比敏感度。结果发现C-TDCS降低了弱视成年人好眼的对比敏感度, A-tDCS提高了8个(总13个)弱视成年人弱视眼的对比敏感度(Spiegel et al., 2013)。Ding等人(2016)考察了tDCS对弱视成年人的对比敏感度和视觉诱发电位的影响。实验组21个弱视被试和控制组的27个正常成年人, 先后接受3个tDCS条件：阳极、阴极和虚假刺激条件。结果发现A-tDCS提高了弱视成年人弱视眼的对比敏感度, 并且提高了视觉诱发电位振幅; C-tDCS的效果则相反(Ding et al., 2016)。Reinhart, Xiao, McClenahan和Woodman (2016)考察了tDCS对成年人空间视知觉的影响。刺激电极位置为P1/P2, 参考电极位于对侧脸颊。结果发现A-tDCS有效提高了被试的中央视力, 并且提高了被试在高空间频率下的对比敏感度(Reinhart et al.,2016)。Costa等人(2015b)考察了tDCS对成年人的对比敏感度和视觉诱发电位的影响。电极片面积为25 cm2, 电刺激强度为1.5 mA, 刺激时间为30分钟。结果发现tDCS对对比敏感度没有调控作用(Costa, Hamer, et al., 2015b)。Richard, Johnson, Thompson和Hansen (2015)考察了tDCS对成年人在4个空间频率下的对比敏感度的影响。实验采用被试内设计, 26个本科生先后接受2个tDCS条件：阳极和阴极刺激条件。条件之间间隔至少48小时。结果发现C-tDCS提高, A-tDCS降低了空间频率为8cpd的对比敏感度(Richard et al., 2015)。目前对于tDCS对CS调控结论不一的情况尚未有合理的解释, 可能是因为在不同的研究中使用的电极片面积的不同, 导致相近电流强度下头皮所承受的电流密度其实不一样。电刺激的时长也可能是导致刺激效果差异的因素, 作用时长和效果之间也可能不是简单的线性关系。
5 TES与视觉运动知觉(Visual Motion Perception)
视觉运动知觉(visual motion perception)是指视觉系统对物体运动的知觉能力。在TES对运动知觉影响的研究中, 电极刺激位置在V5或M1, 参考电极位于Cz。目前的结论主要是A-tDCS能有效增强视觉运动的信号, C-tDCS能降低信号的背景噪音的激活水平。
Antal等人(2004a)考察了tDCS对视觉-运动追踪任务学习的影响。实验中刺激位置在V5, M1和V1, 参考电极位于Cz。刺激条件有两种：阳极刺激和阴性刺激。被试在接受电刺激时完成一个视觉运动的追踪任务。结果发现在知觉学习发生的早期阶段, 只有在A-tDCS作用于V5或M1时有促进作用。C-tDCS对学习没有影响。作用于V1脑区对这个学习任务没有影响(Antal, Nitsche, Kincses, et al., 2004a)。Antal等人(2004b)考察了tDCS对视觉-运动追踪任务表现的影响, 发现只有在C-tDCS作用于V5的时候, 追踪任务的成绩得到了提升, 作用于其他脑区时对任务没有影响。另外研究者还发现, 只有在有随机点背景的条件下, C-tDCS作用于V5时的任务表现是提升的。这些结果说明V5在复杂的运动知觉中可能的重要作用, 提示C-tDCS的作用可能是降低了噪音的影响(Antal, itsche, Kruse, et al., 2004b)。Battaglini, Noventa和Casco (2017)考察了阳极和阴性tDCS作用于V5对视觉运动知觉任务的影响。实验设计是被试间设计, 15个被试接受阴性直流电刺激, 15个被试接受阳极TDCS; 刺激位置在左侧V5。结果提示阳极和阴性tDCS作用于V5时影响的是不同的两个参数：相比虚假电刺激, C-tDCS降低了噪音激活水平, 表现为在低一致性水平下被试任务成绩的提高, 提示A-tDCS提升的是信号的识别能力(Battaglini et al., 2017)。对于A-tDCS能够增强视觉运动信号的结论在对枕叶病变被试的研究中得到验证。Olma等人(2013)考察了tDCS对枕叶缺血性病变被试的视觉运动知觉的影响。电刺激条件为阳极电刺激与虚假刺激, 刺激位置为初级视觉皮层, 电流强度为1.5 mA, 刺激时间为连续5天, 每天刺激时长为20分钟, 被试的任务是判断两次出现的随机点运动方向是否一致。结果发现A-tDCS提高了病人视觉运动方向辨别的成绩, 并且这种提升保持了14天甚至更长时间(Olma et al., 2013)。
6 TES与视知觉学习(Visual Perceptual Learning)
知觉学习是指由于训练或者经验引起的长期而稳定的对某些刺激的知觉能力的提升(Gibson, 1963)。视知觉学习揭示了视觉皮层拥有自发的神经可塑性的能力, 能够引起短期、甚至更持久的突触连接强度的改变(Sherman & Spear, 1982)。目前TES对视觉知觉学习的研究, 主要结论是TES能够促进知觉学习的效果, 但不同模式的影响效果不一样。
A-tDCS能够促进知觉学习, C-tDCS对学习没有影响。Antal等人(2004a)考察了tDCS对视觉运动学习的影响。刺激位置是V5, 初级运动皮层(M1)和初级视觉皮层(V1)。刺激条件是阳极和阴性的tDCS。在被试完成知觉学习任务的同时接受刺激10分钟结果发现, 当阳极刺激于V5或者M1时, 视觉追踪任务的学习得到了提升, 而C-tDCS对学习效果没有作用(Antal, Nitsche, Kincses, et al., 2004a)。Sczesny-Kaiser等人(2016)考察了tDCS对正常成年人视觉知觉学习的影响同时测量了V1的兴奋性。实验是双盲的被试内设计, 实验条件有阳极, 阴性和虚假刺激3个。30个成年被试在完成视觉方向辨别的学习任务时, 接受20分钟的tDCS。4天知觉学习的前后测量配对刺激视觉诱发电位(paired stimulation-visual evoked potential, ps-VEP)和PT。结果发现, 相比虚假刺激条件, A-tDCS促进了知觉学习, 也提高了ps-VEP, 提示A-tDCS刺激之后提高了皮层的兴奋性。C-tDCS对知觉学习和PT都没有影响(Sczesny-Kaiser et al., 2016)。
高频段的tRNS对知觉学习有一定促进作用。Fertonani, Pirulli和Miniussi (2011)考察了不同TES模式对视知觉学习的影响。实验是被试间的实验设计, 正式实验中有84个成年被试, 被分为6组。刺激位置为初级视觉皮层, 刺激条件一共6个：高频tRNS (100~640 Hz)、低频tRNS (0.1~100 Hz)、阳极tDCS、阴极tDCS、虚假刺激和刺激位置于Cz的高频tRNS控制条件。结果发现, 作用于初级视觉皮层的高频tRNS能够显著提升方向辨别学习任务的表现(Fertonani et al., 2011)。
7 TES调控视觉功能小结
用TES直接对视觉基本功能进行调控的研究中, 不同的电刺激模式, 以及电刺激的不同参数对调控效果的影响是不一样的(见表1)。
表1 TES对视觉功能的影响
| 研究 | 功能 | 电极 位置 | 强度 (mA) | 时长 (min) | 次数 | 主要结论 |
|---|---|---|---|---|---|---|
| Antal et al. (2003a) | PT | Oz, Cz | 1.0 | 10 | 1 | C-tDCS作用后及10分钟后显著提升PT, 而A-tDCS则显著降低了PT |
| Kanai et al. (2010) | PT | Oz, Cz | 0.75 | 5~8 | 1 | 20 Hz tACS在作用中降低了PT |
| Plow et al. (Plow et al., 2011, Plow, Obretenova, Fregni, et al., 2012; Plow, Obretenova, Jackson,et al., 2012) | VF | Oz, Cz | 2 | 30 | 72 | 接受A-tDCS的病人的视野 相比控制组恢复得更好 |
| Costa et al. (2015a) | VF | Oz, Cz | 1.5 | ≤25 | 1 | A-tDCS作用时降低了周边视野的阈值 |
| Alber et al. (2017) | VF | O1/O2, Cz | 2 | 20 | 10 | 接受A-tDCS的病人的视野 相比控制组恢复得更好 |
| Sabel et al. (2011) | VF | 眼球四周 | <1 | 40 | 10 | r-tACS实验组相比控制组显著提高了视野范围 |
| Fedorov et al. (2011) | VF | 眼球四周 | <1 | 25~40 | 10 | r-tACS实验组相比控制组显著提高了视野范围 |
| Gall et al. (2013a) | VF | 眼球四周 | <1 | 25~40 | 10 | r-tACS实验组相比控制组显著提高了视野范围 |
| Gall et al. (2016) | VF | 眼球四周 | <1 | 25~50 | 10 | r-tACS实验组相比控制组显著提高了视野范围 |
| Antal et al. (2001) | CS | Oz, Cz | 1.0 | 7 | 1 | C-tDCS作用时及之后10分钟降低CS |
| Spiegel et al. (2013) | CS | Oz, Cz | 2.0 | 15 | 1 | C-tDCS降低了弱视患者好眼的CS |
| Costa et al. (2015b) | CS | Oz, Cz | 1.5 | 30 | 1 | 没有影响 |
| Richard et al. (2015) | CS | Oz, Cz | 2.0 | 21.05±2.74 | 1 | C-tDCS提高, A-tDCS降低空间频率为8cpd时的CS |
| Ding et al. (2016) | CS | Oz, Cz | 2.0 | 20 | 1 | A-tDCS提高了弱视眼的CSF. |
| Reinhart et al. (2016) | CS | P1/P2, 对侧脸颊 | 2.0 | 20 | 1 | A-tDCS提高了半球对侧的高频CSF |
| Antal et al. (2004a) | VMP | V5/M1, Cz | 1.0 | 10 | 1 | A-tDCS作用于V5, M1促进了视觉追踪任务表现 |
| Antal et al. (2004b) | VMP | V5, Cz | 1.0 | 7 | 1 | C-tDCS作用于V5时提高了随机点背景条件的任务表现 |
| Olma et al. (2013) | VMP | V1, Cz | 1.5 | 20 | 5 | A-tDCS提高了运动方向辨别成绩 |
| Battaglini et al. (2017) | VMP | V5, Cz | 1.5 | 12 | 1 | A-tDCS提高了任务表现, C-tDCS提高了在低一致性水平下的成绩 |
| Antal et al. (2004a) | PL | V5/M1, Cz | 1.0 | 10 | 1 | A-tDCS作用于V5, M1在学习早期阶段促进了视觉追踪任务表现 |
| Fertonani et al. (2011) | PL | V1, Cz | 1.5 | 22 | 1 | 作用于V1的hf-tRNS能够显著提升方向辨别学习任务的表现 |
| Sczesny-Kaiser et al. (2016) | PL | Oz, Cz | 1.0 | 20 | 4 | A-tDCS作用于V1促进了知觉学习 |
注：PT, Phosphene Threshold, 光幻视阈值; VF, Visual Field, 视野; CS, Contrast Sensitivity, 对比敏感度; VMP, Visual Motion Perception, 视觉运动知觉; PL, Perceptual Learning, 知觉学习。
目前tDCS对基本视觉功能的研究相比其他电刺激模式要多, tDCS可能是以极性特异的方式调控基本视功能的。A-tDCS最初在对运动皮层的研究中发现能够提高运动皮层的兴奋性, 而C-tDCS能够降低皮层兴奋性, 这一结论在对初级视觉皮层的研究中也同样适用。研究者们用A-tDCS作用于V1, 发现A-tDCS能够调节TMS诱发的光幻视阈值, 促进视野损伤病人的视野恢复, 提高正常人和弱视人群的对比敏感度, 促进对刺激运动信号的识别等, 提示我们A-tDCS确实能够某种程度上提高大脑皮层的兴奋性, 而C-tDCS则降低兴奋性。在部分研究中, 也有研究者发现了不一致的结论, 提示电流极性不是单独起作用, 而是与电刺激所使用的电流强度和刺激时间等因素共同起作用的。在结论不一致的研究中, 电刺激时长都长于20分钟, 提示我们在固定电流强度的情况下刺激时长不适过长, 否则有可能会对皮层产生损伤, 甚至得到相反的调控效果。电刺激对正常人群和弱视人群的作用效果可能是不一样的。在指定的刺激参数条件下, 电刺激的作用次数会影响刺激的效果和维持的时间长短。在单次刺激的研究中, 很多研究没有发现显著的调控效果。考虑到大脑是一个相对稳定的一个系统, 可能对来自外部的微弱电流有一定的抵抗作用, 所以单次刺激有时候对皮层的调节作用并不能及时反映在行为的测量上。而在多次电刺激的研究中, 实验组效果相比控制组提升很多。总体来说, 提示tDCS在起作用的参数设定下, 多次少量的电刺激对调控的效果可能比较好, 对于具体视觉功能的优化参数有待更多这方面的研究。
tACS被认为是以频率特定的方式调控基本视觉功能的。在过去的几年中, 脑电图(EEG)和脑磁图的(MEG)记录探讨了特定频段的神经振荡的功能作用。tACS在刺激期间与大脑自发的神经振荡产生交互, 通过影响神经振荡达到影响基本视觉功能。在对基本视觉功能的研究中, 不同频段的tACS有不同的调控效果。在对PT的调控中, 只有20 Hz对PT有影响。在对视野缺损的恢复研究中, 5到30 Hz的rtACS的多次刺激对视野恢复有促进作用。
tACS的电流强度也关乎到对皮层振荡的调控。Moliadze, Atalay, Antal和Paulus (2012)发现初级运动皮层的兴奋性跟tACS电流强度之间存在非线性关系。他们利用140 Hz的tACS作用于初级运动皮层, 当电流强度为0.2 mA时对皮层是抑制的作用, 电流强度为0.6到0.8 mA没有影响, 但电流提高到1 mA时, 发现tACS对皮层有兴奋作用, 提示抑制和兴奋神经元对交流电有不同的敏感度。当电流在某个强度区间时, 它们之间对皮层的影响相互抵消(Moliadze, Atalay, Antal, & Paulus, 2012)。在此之前, Antal等人(2008)就结合EEG和tACS进行了研究。研究中tACS的电流强度为0.4 mA, 频段有5个水平：1、10、15、30、45 Hz。可能由于所使用tACS的电流强度太低, 结果发现tACS没有引起EEG的变化(Antal et al., 2008)。
8 TES的生理机制
TES在不同的电流模式下, 起作用的主要参数并不一致, 对应的神经机制可能也是不同的。
目前对TDCS的神经生物机制已有一些初步的结论：tDCS可能与谷氨酸、γ-氨基丁酸能、多巴胺能、5-羟色胺和胆碱能活性的调节有关。从细胞水平而言, tDCS能够引起大脑皮层的兴奋性, 可能是微弱电流使得神经元细胞极化或去极化, 即阳极电刺激使得神经元细胞去极化, 阴极电刺激使得神经元细胞极化(Liebetanz, Nitsche, Tergau, & Paulus, 2002)。神经元放电阈值的改变是神经元兴奋性的改变的基础。从分子水平而言, 研究发现阻断钙离子通道和钠离子通道能消除A-tDCS的刺激效果, 而γ-氨基丁酸能激动剂和NMAD受体激动剂能够促进A-DCS的刺激效果(Stagg & Nitsche, 2011)。NMDA受体拮抗剂则能够消除A-tDCS和C-tDCS的刺激效果, 提示NMAD受体在tDCS效果中可能扮演重要的角色(Chaieb, Antal, & Paulus, 2015)。也有fMRI研究认为tDCS的作用可能是提高了血脉舒张的程度(Alekseichuk, Diers, Paulus, & Antal, 2016)。
对tDCS的神经机制的研究多是来自运动皮层, 然而研究发现, 在使用同样刺激参数的情况下, tDCS对视觉皮层的调控作用和效果的持续时间, 与运动皮层并不完全相同(Antal, Kincses, Nitsche, Bartfai, & Paulus, 2004)。而在初级运动皮层和视觉皮层之间, 皮层连接的差异、神经元细胞膜特性的差异、以及受体表达的差异, 都可能是引起tDCS刺激后的效应差异的因素(Medeiros et al., 2012)。
tACS主要起作用的可能是电流的频率。由于皮层的神经振荡被认为跟人类的认知功能紧密关联, tACS被认为能够通过特定频率的交流电跟脑自发的神经振荡相互作用, 调节神经自发振荡的幅度和强度, 从而达到调控行为表现的目的(Zaehle, Rach, & Herrmann, 2010)。Zaehle等人(2010)利用alpha频段的tACS作用于被试, 在刺激前后3分钟测量每个人的离线EEG。发现在tACS (电流强度为1120 ± 489 µA)之后, alpha频段的功率谱得到了显著的提升(Zaehle et al., 2010)。之后Neuling, Rach和Herrmann (2013)重复了这个结果, 并且发现alpha频段功率谱的提升在刺激结束之后至少能维持30分钟(Neuling, Rach, & Herrmann, 2013)。
9 总结与展望
TES的优点主要是安全和能够主动控制皮层兴奋性。第一, TES是安全的刺激技术。尽管之前有一个与tDCS相关的癫痫发作案例, 但因果关系尚未清楚。并且Liebetanz等人在2006年通过大鼠癫痫模型发现阳极tACS并没有改变癫痫发作的阈值(Liebetanz et al., 2006)。而Matsumoto等人在2017年的综述文章中总结了tACS和tDCS的副作用, 结论为在传统的刺激参数下tDCS和tACS对成人和儿童, 健康被试和病人都是安全的(Matsumoto & Ugawa, 2017)。第二, TES能够主动控制皮层兴奋性。tACS为揭开皮层定位和功能之间的因果关系提供了可能性(Stonkus, Braun, Kerlin, Volberg, & Hanslmayr, 2016)。
TES的缺点在于所使用电流在作用于皮层时的空间聚焦不够精确, 即空间分辨率低。在tDCS研究中, 电流通过头皮到达皮层, 电流的溃散导致了空间聚焦程度的降低。针对这个问题, 已有部分研究者使用高分辨率的经颅直流电刺激(high definition-tDCS), 即利用多个小电极片(1cm2)作用于选定区域, 提高作用电流的聚焦程度(Villamar et al., 2013)。
成年人的视觉皮层仍然具有一定的可塑性, 反映在基本视觉功能在一定程度上能够被调控。经颅电刺激作为一种新兴的无创的脑皮层刺激手段, 提供了一种可能的调节视觉基本功能的手段。本文总结了关于TES调控视觉功能的研究现状, 包括光幻视阈值、视野、对比敏感度、视觉运动、视知觉学习、视觉诱发电位等。
TES对视觉功能的调控有利于临床上改善视觉功能受损的个体的加工, 这就需要在机制上和参数标准化及稳定性(可重复性)上有突破。未来的研究需要考虑以下几个方向：1)经颅电刺激效果的优化参数。如何找到最佳的参数作用于皮层, 以获得最优化的调控效果, 是临床和基础研究工作者都关注的问题。2)经颅电刺激的神经生物学基础。目前我们对TES作用于人类皮层时及之后的生理变化需要更进一步的了解。
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Repetitive transcranial direct current stimulation induced excitability changes of primary visual cortex and visual learning effects-A pilot study
Organization of visual pathways in normal and visually deprived cats
DOI:10.1152/physrev.1982.62.2.738
URL
PMID:6280221
[本文引用: 1]
Physiol Rev. 1982 Apr;62(2):738-855. Research Support, U.S. Gov't, P.H.S.; Review
A note on the concept of the visual field in neurology, psychology, and visual neuroscience
DOI:10.1068/p250369
URL
PMID:8804101
[本文引用: 1]
Some current confusions in visual neuroscience and psychology over the use of the terms 'visual field', 'field of vision', 'stimulus field', and topographic 'brain maps' are reviewed. These are often used as synonyms, whereas they refer to quite different things. A plea is made that visual scientists should use these terms correctly to avoid conceptual and engineering confusion.
Anodal transcranial direct current stimulation transiently improves contrast sensitivity and normalizes visual cortex activation in individuals with amblyopia
Physiological basis of transcranial direct current stimulation
Since the rediscovery of transcranial direct current stimulation (tDCS) about 10 years ago, interest in tDCS has grown exponentially. A noninvasive stimulation technique that induces robust excitability changes within the stimulated cortex, tDCS is increasingly being used in proof-of-principle and stage IIa clinical trials in a wide range of neurological and psychiatric disorders. Alongside these clinical studies, detailed work has been performed to elucidate the mechanisms underlying the observed effects. In this review, the authors bring together the results from these pharmacological, neurophysiological, and imaging studies to describe their current knowledge of the physiological effects of tDCS. In addition, the theoretical framework for how tDCS affects motor learning is proposed.
Probing the causal role of prestimulus interregional synchrony for perceptual integration via tACS
DOI:10.1038/srep32065 URL [本文引用: 1]
Increasing human brain excitability by transcranial high-frequency random noise stimulation
For >20 years, noninvasive transcranial stimulation techniques like repetitive transcranial magnetic stimulation (rTMS) and direct current stimulation (tDCS) have been used to induce neuroplastic-like effects in the human cortex, leading to the activity-dependent modification of synaptic transmission. Here, we introduce a novel method of electrical stimulation: transcranial random noise stimulation (tRNS), whereby a random electrical oscillation spectrum is applied over the motor cortex. tRNS induces consistent excitability increases lasting 60 min after stimulation. These effects have been observed in 80 subjects through both physiological measures and behavioral tasks. Higher frequencies (100 640 Hz) appear to be responsible for generating this excitability increase, an effect that may be attributed to the repeated opening of Na+ channels. In terms of efficacy tRNS appears to possess at least the same therapeutic potential as rTMS/tDCS in diseases such as depression, while furthermore avoiding the constraint of current flow direction sensitivity characteristic of tDCS.
Technique and considerations in the use of 4x1 ring high-definition transcranial direct current stimulation (HD-tDCS)
Transcranial alternating current stimulation enhances individual alpha activity in human EEG
Abstract Non-invasive electrical stimulation of the human cortex by means of transcranial direct current stimulation (tDCS) has been instrumental in a number of important discoveries in the field of human cortical function and has become a well-established method for evaluating brain function in healthy human participants. Recently, transcranial alternating current stimulation (tACS) has been introduced to directly modulate the ongoing rhythmic brain activity by the application of oscillatory currents on the human scalp. Until now the efficiency of tACS in modulating rhythmic brain activity has been indicated only by inference from perceptual and behavioural consequences of electrical stimulation. No direct electrophysiological evidence of tACS has been reported. We delivered tACS over the occipital cortex of 10 healthy participants to entrain the neuronal oscillatory activity in their individual alpha frequency range and compared results with those from a separate group of participants receiving sham stimulation. The tACS but not the sham stimulation elevated the endogenous alpha power in parieto-central electrodes of the electroencephalogram. Additionally, in a network of spiking neurons, we simulated how tACS can be affected even after the end of stimulation. The results show that spike-timing-dependent plasticity (STDP) selectively modulates synapses depending on the resonance frequencies of the neural circuits that they belong to. Thus, tACS influences STDP which in turn results in aftereffects upon neural activity.The present findings are the first direct electrophysiological evidence of an interaction of tACS and ongoing oscillatory activity in the human cortex. The data demonstrate the ability of tACS to specifically modulate oscillatory brain activity and show its potential both at fostering knowledge on the functional significance of brain oscillations and for therapeutic application.
