安徽医科大学医学心理学系, 合肥 230000
Excitation of the right dorsolateral prefrontal cortex with transcranial direct current stimulation influences response inhibition
Department of Medical Psychology, Anhui Medical University, Hefei 230000, China
收稿日期: 2017-05-29 网络出版日期: 2018-06-01
Received: 2017-05-29 Online: 2018-06-01
拟观察经颅直流电刺激作用于右侧背外侧前额叶皮层前后, 被试在停止信号任务中的行为变化。实验共入组34名正常大学生, 被试前后两次随机接受真刺激和伪刺激, 两次刺激间隔7天, 每个被试在接受刺激前后均完成停止信号任务, 并在每次实验前后完成Stroop色词任务、词语流畅性、数字广度任务。结果发现真刺激作用于右侧背外侧前额叶皮层后停止信号反应时显著减小, 但伪刺激条件下没有该趋势。本实验证明了作用于右侧背外侧前额叶皮层的经颅直流电刺激可以调节反应抑制能力, 右侧背外侧前额叶皮层是反应抑制的重要脑区。
拟观察经颅直流电刺激作用于右侧背外侧前额叶皮层前后, 被试在停止信号任务中的行为变化。实验共入组34名正常大学生, 被试前后两次随机接受真刺激和伪刺激, 两次刺激间隔7天, 每个被试在接受刺激前后均完成停止信号任务, 并在每次实验前后完成Stroop色词任务、词语流畅性、数字广度任务。结果发现真刺激作用于右侧背外侧前额叶皮层后停止信号反应时显著减小, 但伪刺激条件下没有该趋势。本实验证明了作用于右侧背外侧前额叶皮层的经颅直流电刺激可以调节反应抑制能力, 右侧背外侧前额叶皮层是反应抑制的重要脑区。
Response inhibition is a cognitive process required to cancel an intended movement and can protect from danger. Functional magnetic resonance imaging (FMRI) studies showed that the dorsolateral prefrontal cortex (dlPFC) is a crucial brain region for response inhibition. Repetitive transcranial magnetic stimulation (rTMS) is a technique that can determine the contribution of specific cortical regions to behavior. Previous studies have found that repetitive transcranial magnetic stimulation of the dlPFC affects response inhibition. In the current study, we used transcranial direct current stimulation (tDCS), a non-invasive, painless brain stimulation technique with no known side effects, to alter neuronal excitability. A number of tDCS studies have suggested that tDCS may affect response inhibition. However, to date, limited work has been done to explore whether tDCS over the right dlPFC could alter response inhibition. Therefore, this study aimed to investigate the anodal stimulus effect of tDCS on response inhibition. We hypothesized that exciting the neural activity of the right dlPFC with anodal tDCS would enhance the ability of response inhibition. A total of 34 healthy subjects (15 males, 19 females) participated in this within-subjects study. Stop-signal task (SST) was established with E-prime software. Participants received both active and sham stimulation on separate days. SST was used to measure the participants’ capacity for response inhibition. In the active stimulation condition, we delivered a 1.5 mA direct current for 25 min (fade-in/fade-out time: 8 s); in the sham condition, we delivered a 1.5 mA direct current for 30 s at the beginning and 30 s at the end of the stimulation time. Anodal and cathodal stimulation electrodes were placed on F4 and FP1, respectively. Participants completed the SST, Stroop color-word matching task, Verbal Fluency test, and Digit Span test before and after the stimulation. We first calculated the mean reaction time (RT)in the go trials and stop-signal delay for each participant using ANALYZE-IT software. To calculate the individual stop-signal reaction time (SSRT), ANALYZE-IT first computes the mean RTs for all trials without a stop signal and then subtracts the mean stop-signal delay from this value. We performed a series of paired samples t-tests to compare the SSRT of each experimental condition with the SSRT of the sham and active conditions. There were no significant differences in SSRT pre-stimulation in sham or active stimulations, indicating equal response inhibition capacity among the participants. Interestingly, the difference in SSRT before and after stimulation was statistically significant in the active condition, t(33) = -2.25, p < 0.05, Cohens d = 0.38. This demonstrates that participants who received anodal stimulation over the right dlPFC had significantly reduced SSRT change scores on the SST compared to participants in the sham condition. This study demonstrated that transcranial electrical stimulation of the right dlPFC can regulate response inhibition, in that anodal stimulation improved participants’ response inhibition. We confirm previous work suggesting that the right dlPFC is an important brain region of response inhibition.
Response inhibition is a cognitive process required to cancel an intended movement and can protect from danger. Functional magnetic resonance imaging (FMRI) studies showed that the dorsolateral prefrontal cortex (dlPFC) is a crucial brain region for response inhibition. Repetitive transcranial magnetic stimulation (rTMS) is a technique that can determine the contribution of specific cortical regions to behavior. Previous studies have found that repetitive transcranial magnetic stimulation of the dlPFC affects response inhibition. In the current study, we used transcranial direct current stimulation (tDCS), a non-invasive, painless brain stimulation technique with no known side effects, to alter neuronal excitability. A number of tDCS studies have suggested that tDCS may affect response inhibition. However, to date, limited work has been done to explore whether tDCS over the right dlPFC could alter response inhibition. Therefore, this study aimed to investigate the anodal stimulus effect of tDCS on response inhibition. We hypothesized that exciting the neural activity of the right dlPFC with anodal tDCS would enhance the ability of response inhibition.
A total of 34 healthy subjects (15 males, 19 females) participated in this within-subjects study. Stop-signal task (SST) was established with E-prime software. Participants received both active and sham stimulation on separate days. SST was used to measure the participants’ capacity for response inhibition. In the active stimulation condition, we delivered a 1.5 mA direct current for 25 min (fade-in/fade-out time: 8 s); in the sham condition, we delivered a 1.5 mA direct current for 30 s at the beginning and 30 s at the end of the stimulation time. Anodal and cathodal stimulation electrodes were placed on F4 and FP1, respectively. Participants completed the SST, Stroop color-word matching task, Verbal Fluency test, and Digit Span test before and after the stimulation.
We first calculated the mean reaction time (RT)in the go trials and stop-signal delay for each participant using ANALYZE-IT software. To calculate the individual stop-signal reaction time (SSRT), ANALYZE-IT first computes the mean RTs for all trials without a stop signal and then subtracts the mean stop-signal delay from this value. We performed a series of paired samples t-tests to compare the SSRT of each experimental condition with the SSRT of the sham and active conditions. There were no significant differences in SSRT pre-stimulation in sham or active stimulations, indicating equal response inhibition capacity among the participants. Interestingly, the difference in SSRT before and after stimulation was statistically significant in the active condition, t(33) = -2.25, p < 0.05, Cohens d = 0.38. This demonstrates that participants who received anodal stimulation over the right dlPFC had significantly reduced SSRT change scores on the SST compared to participants in the sham condition.
This study demonstrated that transcranial electrical stimulation of the right dlPFC can regulate response inhibition, in that anodal stimulation improved participants’ response inhibition. We confirm previous work suggesting that the right dlPFC is an important brain region of response inhibition.
王慧慧, 罗玉丹, 石冰, 余凤琼, 汪凯.
WANG Hui Hui, LUO Yu Dan, SHI Bing, YU Feng Qiong, WANG Kai.
看到红灯信号, 我们停止已经产生的过马路的冲动; 上课铃声响起, 我们抑制从事下一项娱乐活动的想法; 生活中有许多这样的实例, 我们称这种抑制已经形成的动作反应冲动为反应抑制(Andrés, 2003)。反应抑制(response inhabition)是抑制住不符合当前需要的或不恰当的行为反应能力, 并使人们能够对变化的环境做出灵活的、目标指向的行为(Logan & Cowan, 1984), 是执行功能的核心成分。已有的许多反应抑制任务的研究, 均报告了以右半球为主的反应抑制网络(response inhabition network, RIN)的存在, RIN的关键脑区包括：背外侧前额叶皮层、右额下回、右额中回、前扣带皮层等(Menon, 2011; Bari & Robbins, 2013)。
背外侧前额叶皮层(dorsolateral prefrontal cortex, dlPFC)是备受关注的一个区域, 它在反应抑制中的作用正受到越来越多研究者的重视, 已有的神经心理学研究阐明dlPFC 在认知过程中扮演着重要角色, 并与控制执行功能密切相关。如有研究者使用功能磁共振成像(functional magnetic resonance imaging, fMRI)技术对不同版本的Go-Nogo任务操作所激活的脑区进行了定位,他们发现在不同版本的Go-Nogo任务中,背外侧前额叶皮层被显著激活(Casey et al., 1997); 同样有人曾使用fMRI研究了dlPFC在反应抑制中的神经基础, 他们使用测量反应抑制的Go-Nogo任务, 通过屏幕呈现基于图形计算机的视觉刺激, 被试仰卧并通过棱形眼镜观看刺激, 并要求被试对Go刺激做按键反应。实验结果发现, 在Nogo任务中, 右侧dlPFC较左侧激活程度更强(Konishi et al., 1999); 在赌博成瘾患者存在反应抑制能力损毁的基础上, 比较了赌博成瘾患者与正常被试在Go-Nogo任务中的血氧水平依赖(Blood Oxygenation Level Dependent, BOLD)强度, 发现在Nogo情境下, 赌博成瘾患者在双侧dlPFC脑区的血氧水平依赖强度低于正常被试(van Holst, van Holstein, van den Brink, Veltman, & Goudriaan, 2012); 以上研究均表明dlPFC是反应抑制的重要脑区。
根据既往关于dlPFC在反应抑制中发挥重要作用的研究基础, 有研究者采用重复经颅磁刺激(Repetitive Transcranial Magnetic Stimulation, rTMS)技术验证了dlPFC在反应抑制中的作用。他们对健康被试在间隔一天的时间内分别施加高频率真刺激和伪刺激, 观察被试在康纳斯连续性能测试中的行为变化：与伪刺激条件相比, 真刺激条件下被试行为水平有较显著变化, 即反应抑制得到提升(Hwang, Kim, Park, Bang, & Kim, 2010)。这一研究采用脑刺激(brain stimulation)的技术, 来改变目标皮层的活动水平, 从因果关系上探究了目标皮层区域与反应抑制之间的关联。
近些年来, 一种新兴的非侵入性的脑刺激技 术—经颅直流电刺激(transcranial Direct current stimulation, tDCS)进入了研究者的视线。与tDCS直接作用于目标皮层不同的是, rTMS是通过储存大量电荷的电容器在极短时间内放电, 使感应线圈产生磁场, 磁场穿透大脑颅骨并在脑内产生反向感生电流, 最终引起脑功能或皮层可塑性的变化。与rTMS相比, tDCS较好的避免了由于穿透颅骨而可能带来的能量衰减; 其次, 从安全性的角度分析, 关于rTMS研究中的副反应报道略多, 更为严重的甚至会引发癫痫。tDCS仅有偶尔持续时间短暂的轻微刺痛、皮痒, 目前尚无tDCS诱发癫痫的报道, 因此, tDCS是一种比较安全的经颅刺激方式。且相较rTMS, tDCS具有价格低廉、携带方便、操作简单等突出优势。
tDCS是通过海绵电极产生微弱电流直接刺激目标皮层(Palm, Hasan, Strube, & Padberg, 2016), 共包括三种刺激类型：阳极刺激、阴极刺激和伪刺激; 研究者发现阳极刺激能增加皮质兴奋性, 阴极刺激降低皮质兴奋性(Nitsche & Paulus, 2000), 从神经元水平分析tDCS的作用机制发现阳极刺激产生去极化并起兴奋作用, 阴极刺激则产生超级化并起抑制作用。此技术越来越多的被应用在认知神经、临床研究及康复等多个领域, 其中也包括验证dlPFC在反应抑制中的作用, 近年来, 也有许多此领域的研究陆续涌现。如有研究者利用tDCS阴极作用于右侧dlPFC, 观察被试在Go-Nogo任务中的行为变化, 发现其虚报率增高, 提示被试抑制能力降低, 而tDCS阳极作用于右侧dlPFC却未能改善被试抑制能力(Beeli, Casutt, Baumgartner, & Jäncke, 2008); 利用tDCS作用于dlPFC, 采用检索诱导遗忘测试考查被试接受刺激前后的行为变化, 发现阴极刺激能够降低抑制, 以此说明dlPFC脑区的抑制能够降低被试的抑制能力(Penolazzi, Stramaccia, Braga, Mondini, & Galfano, 2014); 使用tDCS激活左侧dlPFC, 并在 Stroop色词任务中发现真刺激组相比于伪刺激组, 反应时间显著降低, 进一步证 实dlPFC是反应抑制的重要脑区(Loftus, Yalcin, Baughman, Vanman, & Hagger, 2015; Brevet-Aeby, Brunelin, Iceta, Padovan, & Poulet, 2016); 在一项对正常人进行的研究中, 研究者使用 tDCS阳极分别作用于右侧dlPFC和左侧dlPFC, 发现在两种刺激下, 被试的反应抑制能力均未能得到提升(Dambacher et al., 2015; Brevet-Aeby et al., 2016)。
到目前为止, tDCS刺激dlPFC改变反应抑制加工的研究仍然较少, 研究结果不一致, 主要归因于以下两方面。首先在目标脑区的选取上存在多样性, 且有关右侧dlPFC在反应抑制中的作用研究较少; 其次, 在研究范式的选择上存在多样性, 研究反应抑制的常用范式包括Stroop色词任务、反向眼跳任务(anti-saccade task)和Go-Nogo任务、停止信号任务(stop-signal task, SST)等。研究指出Stroop色词任务更多反映对分心刺激的注意控制及选择性注意, 因此可能主要与认知抑制相关(Nigg, 2000); 在反向眼跳任务中, 正向眼跳与反向眼跳间产生的潜伏期差异经常为研究者采用, 并作为衡量抑制功能的指标, 但在反向眼跳任务中, 从提示反向眼跳到靶子出现间存在一段准备时间, 由此有研究者质疑该范式对随后抑制功能考察的可靠性; Go-Nogo 任务相比于反向眼跳任务虽然避免了抑制任务前准备时间对随后抑制功能考查的影响, 但有研究者认为Go-Nogo 任务中被试对Nogo 刺激的反应可能是其通过选择性注意机制忽视了Nogo刺激, 而不是被抑制了(Rubia, Smith, Brammer, & Taylor, 2003); 相较反向眼跳任务和Go-Nogo任务, SST只包括Go刺激, 不含Nogo刺激, 因而可能是测量反应抑制能力更为纯净的方法。SST符合赛马模型理论, 赛马模型认为反应抑制和反应是两个相互独立而又相互竞争的加工过程, 先达到反应阈限者决定随后行为(王琰, 蔡厚德, 2010)。SST中包括一个较为重要的行为学指标, 即停止信号反应时(stop-signal reaction time, SSRT)。跟踪法设计的SST中SSRT均值等于Go RT均值减SSD均值。SSRT越短, 反应控制效率越高(王琰, 蔡厚德, 2010)。
最后, 在既往已有的相关研究基础上, 本研究选择了右侧dlPFC脑区, 选用了测量反应抑制能力更为纯净的范式。旨在采用SST, 通过tDCS阳极作用于右侧dlPFC皮层, 观察被试在刺激前后行为学水平上的变化。本研究假设, 阳极刺激右侧dlPFC会提高被试的反应抑制, 表现在行为学水平上即真刺激前后SSRT差值较伪刺激前后有显著差异。
自2016年12月至2017年8月, 排除脑损伤历史、精神类疾病史等, 使用汉密尔顿抑郁(Hamilton Depression Scale, HAMD)、汉密尔顿焦虑量表(Hamilton Anxiety Scale, HAMA), 排除大于7分的志愿者, 共招募34名(15名男性、19名女性)志愿者, 均为安徽医科大学在读学生(本科生、研究生), 平均年龄22.06岁(从19岁~30岁), 平均受教育年限15.68年(从13年~20年), 所有被试均为右利手, 身体健康, 无神经精神类疾病及脑损伤历史, 无癫痫或癫痫家族史, 视力正常或矫正后正常, 参与时完全自愿, 充分尊重被试的个人意愿, 实验开始前均签署实验知情同意书, 实验结束时予以一定的劳务费。
实验采用被试内设计, 即同一被试需间隔7天随机接受两次刺激(一次真刺激、一次伪刺激), 在tDCS刺激前后分别完成SST, 并在每次实验开始前使用HAMA、HAMD测查被试焦虑抑郁水平, 排除焦虑抑郁大于7分的被试; 刺激前后让被试分别完成Stroop色词任务、数字广度任务、词语流畅性, 前测用以确保被试接受真刺激与伪刺激前在执行功能、工作记忆、思维流畅性等方面基线值无差异, 排除个体差异对实验结果的影响; 同时对刺激前后的测试结果加以比较, 用以观察被试在接受刺激后在执行功能、工作记忆和思维流畅性方面的变化。
本研究采用Starlab研发, NE (Neuroeletrics)公司生产的StarStim经颅直流电刺激仪。使用的是面积为35 cm² (5 cm × 7 cm)的海绵电极, 并通过蓝牙信号控制电流刺激强度及类型。根据EEG10-20系统扩展的坐标和相关磁共振成像定位研究(Jurcak, Tsuzuki, & Dan, 2007)。将阳极电极固定放置在头皮F4位置, 阴极电极固定在FP1位置(见图1)。已有的tDCS研究通常刺激时长为5~30 min (Palm et al., 2016), 有研究报告称刺激5 min已经可以观察到相应的刺激效应(Boggio, Zaghi, & Fregni, 2009), 综合考虑到实验时长问题, 因此本研究中真刺激时长设置为25 min, 且出于安全性的考虑, 我们将电流强度设置为1.5 mA。伪刺激条件下, 采用1.5 mA的微弱直流电仅刺激被试30 s (Loftus et al., 2015), 之后停止刺激(但并不将电极拆除, 电极佩戴在被试头皮上时间同样是25 min, 以确保被试不知道接受的是哪种条件刺激)。在每次实验结束后, 我们会询问被试对此次实验的具体感受, 对表示知道刺激类型的被试予以剔除, 被试均报告两次刺激无差异。真刺激和伪刺激条件下, 电流递增和递减的时间均为8 s。
采用E-prime程序在电脑上呈现SST任务, 任务包括199个trial, 实验开始之前, 向被试说清指导语, 并予以练习, 使其充分理解任务内容。开始时, 黑色屏幕中央会先呈现白色圆圈作为注视点, 200~400 ms后圆圈内出现白色朝左或朝右的箭头,作为Go信号(Go Signal),要求被试看到白色箭头快速按键反应, 箭头朝左按“F”键, 朝右按“J”键, 但其中有些白色箭头会变成红色,红色的箭头即为Stop信号(Stop signal),看到箭头变红要求被试抑制住按键冲动(见图2)。
对真伪刺激前后的stroop效应量(stroop色字–stroop字)、数字广度(顺背、倒背)、词语流畅性, 及两种刺激前HAMA、HAMD, 分别使用SPSS 16.0进行配对样本t检验。结果显示真伪刺激前HAMA无显著差异, t(33) = 0.32, p > 0.05; 真伪刺激前HAMD无显著差异, t(33) = 0.49, p >0.05; 真刺激前后数字广度(倒背), t(33) = 2.23, p < 0.05, Cohen’ d = 0.22; 伪刺激前后数字广度(倒背), t(33) = 3.65, p < 0.01, Cohen’ d = 0.48; 真刺激前后词语流畅性, t(33) = 4.86, p < 0.001, Cohen’ d = 0.60; 伪刺激前后词语流畅性, t(33) = 5.75, p < 0.001, Cohen’ d = 0.93; 均有统计学意义, 并达到显著性水平(见表1)。
|组别||M ± SD||t值||p值|
|真刺激前stroop效应量||6.79 ± 4.58||0.49||0.628|
|伪刺激前stroop效应量||7.32 ± 4.67|
|真刺激前后stroop效应量||-0.99 ± 4.52||-1.28||0.209|
|伪刺激前后stroop效应量||-1.36 ± 4.09||-1.93||0.062|
|真刺激前数字广度(顺背)||7.94 ± 0.24||1.44||0.160|
|伪刺激前数字广度(顺背)||8.00 ± 0.00|
|真刺激前后数字广度(顺背)||0.03 ± 1.17||1.00||0.325|
|伪刺激前后数字广度(顺背)||0.00 ± 0.00|
|真刺激前数字广度(倒背)||6.06 ± 0.95||-0.73||0.473|
|伪刺激前数字广度(倒背)||5.94 ± 0.95|
|真刺激前后数字广度(倒背)||0.21 ± 0.54||2.23||0.033|
|伪刺激前后数字广度(倒背)||0.44 ± 0.70||3.65||0.001|
|真刺激前词语流畅性||27.26 ± 5.46||-0.49||0.625|
|伪刺激前词语流畅性||26.79 ± 4.93|
|真刺激前后词语流畅性||3.38 ± 4.06||4.86||0.000|
|伪刺激前后词语流畅性||4.47 ± 4.53||5.75||0.000|
注：每组n = 34
使用ANALYZE-IT分析软件, 计算出SSD和Go RT的均值, 得出SSRT值。
对真刺激前与伪刺激前SSRT值使用SPSS 16.0进行配对样本t检验。结果显示真刺激前SSRT (306.70 ± 44.78 ms)与伪刺激前SSRT (291.57 ± 33.21 ms)无显著差异, t (33) = 1.84, p > 0.05, 说明被试在接受真刺激前与伪刺激前反应抑制无差异。
|组别||M ± SD||t值||p值|
|真刺激前SSRT||306.70 ± 44.78||-2.25||0.031|
|真刺激后SSRT||290.82 ± 40.97|
|伪刺激前SSRT||291.57 ± 33.21||1.99||0.055|
|伪刺激后SSRT||302.13 ± 40.50|
注：每组n = 34
对真刺激前后与伪刺激前后SSRT的差值进行配对样本t检验。结果显示真刺激前后SSRT差值(-15.88 ± 41.11 ms)与伪刺激前后SSRT差值(10.56 ± 30.98 ms)差异显著, t(33) = -3.68, p < 0.01, Cohen’ d =0.73。
本研究通过观察tDCS作用于dlPFC前后, 健康大学生在SST任务中的行为改变。根据实验结果可知, 阳极tDCS真刺激右侧dlPFC后SSRT显著小于伪刺激, 表明tDCS刺激右侧dlPFC可以调节反应抑制能力, 与我们所提出的假设相符, 并进一步证实了dlPFC是反应抑制的重要脑区。
本研究采用tDCS阳极刺激右侧dlPFC后, 被试的停止信号反应时显著缩短。对存在多动症症状的成年人分别施加阳极tDCS刺激左侧dlPFC、阴极tDCS刺激左侧dlPFC, 实验中使用Stroop色词任务和Go-Nogo对被试的行为变化进行测量, 结果发现阳极tDCS作用于左侧dlPFC提高了被试在Go任务中的正确率, 即损毁被试的抑制能力, 而阴极tDCS作用于左侧dlPFC改善了被试的反应抑制(Soltaninejad, Nejati, & Ekhtiari, 2015); 对情感冷漠、缺乏同理心的人群进行阴极tDCS刺激右侧dlPFC, 并使用Go-Nogo任务测量被试的反应抑制, 结果发现此类高分人群在接受刺激后反应抑制得到较好的改善, 表现在行为学水平上即Nogo正确率的提高(Weidacke, Weidemann, Boy, & Johnston, 2016)。因此, 本研究与以往的研究结果均证实了tDCS可以改变被试的反应抑制。对健康成年人进行10 Hz高频经颅磁刺激(high-frequency repetitive transcranial magnetic stimulation, HF-rTMS)分别作用于左侧dlPFC和右侧dlPFC, 并使用负性情感启动任务(Negative Affective Priming task, NAP)量化刺激前后被试对情绪信息抑制的强度, 结果发现HF-rTMS作用于右侧dlPFC后, 被试对负性信息能够进行更为有效的抑制(Leyman, De Raedt, Vanderhasselt, & Baeken, 2009); 强迫症患者的抑制能力存在损伤, 对强迫症患者进行rTMS治疗发现, 采用100%静息运动阈值刺激患者的右侧dlPFC, 能够改善被试的抑制能力(Zhou, Wang, Wang, Li, & Kuang, 2017; Nordmann, Azorina, Langguth, & Schecklmann, 2015)。与本研究结果相一致, 即通过刺激右侧dlPFC能够达到改变反应抑制的目的。目前tDCS作用于右侧dlPFC以观察被试反应抑制变化的研究匮乏, 而本研究将为物理干预技术能够改变反应抑制能力提供了进一步的证据。不同的脑区有着不一样的功能, 不同的任务其加工机制也有所不同, 且脑区皮质兴奋性的改变将会影响被试在行为任务中的表现。在本次实验中, 从反应抑制的心理加工模型-赛马模型看, 阳极刺激后SSRT值的降低, 表明在右侧dlPFC皮层兴奋性提高后, 被试在对停止信号进行抑制时, 反应抑制的加工过程相较反应过程率先达到反应阈限, 从而导致被试成功抑制动作冲动的内在反应时间的缩短(王琰, 蔡厚德, 2010; 方菁, 朱叶, 赵伟, 张蓓, 王湘, 2013)。与以上研究相比, 本研究采用了经典范式SST, 更为纯净的测量了反应抑制能力的变化。
与本实验结果不同的是, 在Davide等人一项研究中, 他们对20名健康成年人(3名男性, 17名女性)进行阳极tDCS作用于右侧dlPFC及阴极tDCS作用于右侧dlPFC, 刺激时长均为20分钟, 刺激结束15分钟后让被试完成SST, 结果显示两种形式的刺激均未改善被试的反应抑制能力(Stramaccia et al., 2015)。首先,这可能与tDCS刺激时长的不同有关, 一篇关于tDCS治疗抑郁症的meta分析指出, tDCS刺激时长会对其作用效果产生显著影响(Meron, Hedger, Garner, & Baldwin, 2015)。在本研究中, 刺激时长为25分钟, 即对右侧dlPFC脑区进行了更为持久的激活, 由此可能导致了右侧dlPFC脑区出现了更为显著的刺激效应, 进而表现在行为学上即SSRT值的降低, 即反应抑制能力的提高; 其次,可能与tDCS刺激后效应维持及消退有关, tDCS刺激后的持续效应与刺激时长、刺激强度有关, 且刺激后效应会随着时间而消退, 但是具体消退模式还不清楚(Nitsche & Paulus, 2000)。相较于Davide等人的研究, 本研究在刺激结束后即刻让被试完成SST, 由此可能导致了两个研究中被试行为学表现上出现差异。与Davide等人的研究相比较, 本研究探索性的研究了tDCS作用于右侧dlPFC对反应抑制改善的即刻效应, 在之后的实验中, 我们将对tDCS效应的持续时间展开进一步的研究。此外, 对健康大学生施加10 Hz、100%静息运动阈值的rTMS作用于左侧dlPFC, 连续7天, 每天1次, 在实验开始及结束时让被试完成Stroop色词任务, 结果发现, 真刺激组被试在Stroop色词任务表现更佳, 即抑制能力得到改善(Li et al., 2017); 采用5 Hz、100%静息运动阈值的rTMS对边缘型人格障碍患者的左侧dlPFC进行刺激, 使用巴拉特冲动性量表对患者的冲动性进行测评, 最后发现, 在接受了15次的rTMS治疗后, 患者在该量表上的得分显著下降, 冲动性降低、抑制能力改善(Reyes-López et al., 2017)。在2017年的一篇meta分析中也提到, Hz-rTMS作用于左侧dlPFC, 能够改善强迫症患者的抑制能力(Zhou et al., 2017)。RIN的关键脑区包括左侧dlPFC, 所以采用rTMS作用于左侧dlPFC, 也能够达到调节被试反应抑制的目的。在今后的实验中, 我们将对左侧dlPFC在反应抑制中的作用进行研究, 进一步探索左右侧dlPFC在反应抑制能力中发挥作用的大小。
此外, Nigg的研究指出Stroop色词任务可能主要与认知抑制相关, 因此更多反映对分心刺激的注意控制及选择性注意, 因此相较Stroop色词任务, SST能够更为有效的测量出反应抑制能力的变化(Nigg, 2000)。一篇meta分析指出, tDCS作用于健康成年人, 并不能改善被试在数字广度和言语流畅性任务中的表现(Horvath, Forte, & Carter, 2015), 与本研究结果相一致。在本研究中, 真刺激与伪刺激后, 被试在数字广度(倒背)及言语流畅性任务中成绩均得到了提升, 介于本实验中被试在tDCS刺激前后完成数字广度和言语流畅性任务, 间隔时间很短, 所以可能出现了练习效应, 由此导致了该实验结果。
人类需要在错综复杂的生活环境中, 对正确的行为做出反应, 并对不正确的或不必要的行为进行抑制, 这样才能适应环境, 更好的做出执行, 并抑制不必要的行为, 进而更好的生存下来, 因此反应抑制能力与我们的生活息息相关。本研究的结果显示, 在神经机制水平上, 右侧dlPFC脑区与反应抑制能力紧密相关。已有的相关临床研究表明, tDCS对抑郁症、癫痫类疾病、脑卒中后神经康复、失语症、帕金森等多种疾病有效。根据此次实验的结果, 提示tDCS在健康人群的执行功能中也有很大的应用价值。相关临床证据表明, 反应抑制能力的缺损存在于多类疾病中, 如强迫症、多动症等。tDCS本身具备的方便、经济、无创、无副作用等优势, 对于提高病患的反应抑制能力将有积极的应用前景。
本研究虽然为右侧dlPFC在反应抑制中的作用提供了重要证据, 但介于在本研究中并未对左侧dlPFC在反应抑制中发挥的作用做探讨, 所以无法说明左右侧dlPFC在反应抑制中哪一侧起了更大的作用, 为了进一步探究以上的问题, 将来的研究方向可进一步研究阳极tDCS作用于左侧dlPFC对于反应抑制的影响, 并结合神经电生理技术、功能磁共振成像等技术, 更为深入综合的探究反应抑制的神经机制。其次, 本研究样本量较小, 且招募的被试均是安徽医科大学在校学生, 从而使本研究结果推论到其他群体中缺乏可信度, 因此, 在今后的研究中, 我们将就此方面做出改善, 增大样本量, 以及丰富群体的多样性。
Frontal cortex as the central executive of working memory: Time to revise our view,
For historical reasons (Bianchi, 1895; Harlow, 1968; Luria, 1966; Shallice, 1982), a specific link between the central executive of working memory and the frontal cortex was originally suggested by Baddeley (1986). This review discusses the evidence against such a univocal link. Two executive processes investigated in neuropsychology are discussed: inhibition (WCST, Stroop, proactive interference, go-no go, Stop signal and the Hayling test) and dual-task management. The evidence reviewed demonstrates (i) that executive processes involve links between different brain areas, not exclusively with the frontal cortex, (ii) that patients with no evidence of frontal damage present with executive deficits, and (iii) that patients with frontal lesions do not always show executive deficits. In conclusion, this review suggests that it is time for a more dynamic and flexible view of the neural substrate of executive processes to be considered. It also confirms, as recently suggested by Baddeley (1996, 1998a, 1998b), that the study of frontal patients cannot be used as a primary source of evidence to understand CE functions.
Negative correlation between right prefrontal activity during response inhibition and impulsiveness: A fMRI study,
Behavioral disinhibition in Go/No–Go task is thought to be associated with impulsiveness in humans. Recent imaging studies showed that neural circuits involving diverse areas of the frontal cortex and other association cortex sites such as the parietal cortex are implicated in the inhibition of response during No–Go trials. The aim of the present study was to investigate the association between regional cerebral activation during No–Go trials and impulsiveness. Seventeen righthanded healthy volunteers participated in the study. We used functional magnetic resonance imaging to measure the brain activation during a Go/No–Go task. The Barratt Impulsiveness Scale, 11 th version (BIS–11) was used to measure impulsiveness. Activated regions included the right middle frontal gyrus and the inferior parietal lobe, which is consistent with previous neuroimaging studies. A negative correlation was observed between the motor impulsiveness of BIS–11 and No–Gorelated activation in the right dorsolateral prefrontal cortex (RDLPFC). Our results suggest that the RDLPFC is the area most sensitive to differences in individual motor impulsiveness and its activity may be an indicator of the individual capacity for response inhibition.
Inhibition and impulsivity: Behavioral and neural basis of response control,
Abstract In many circumstances alternative courses of action and thoughts have to be inhibited to allow the emergence of goal-directed behavior. However, this has not been the accepted view in the past and only recently has inhibition earned its own place in the neurosciences as a fundamental cognitive function. In this review we first introduce the concept of inhibition from early psychological speculations based on philosophical theories of the human mind. The broad construct of inhibition is then reduced to its most readily observable component which necessarily is its behavioral manifestation. The study of 'response inhibition' has the advantage of dealing with a relatively simple and straightforward process, the overriding of a planned or already initiated action. Deficient inhibitory processes profoundly affect everyday life, causing impulsive conduct which is generally detrimental for the individual. Impulsivity has been consistently linked to several types of addiction, attention-deficit/hyperactivity disorder, mania and other psychiatric conditions. Our discussion of the behavioral assessment of impulsivity will focus on objective laboratory tasks of response inhibition that have been implemented in parallel for humans and other species with relatively few qualitative differences. The translational potential of these measures has greatly improved our knowledge of the neurobiological basis of behavioral inhibition and impulsivity. We will then review the current models of behavioral inhibition along with their expression via underlying brain regions, including those involved in the activation of the brain's emergency 'brake' operation, those engaged in more controlled and sustained inhibitory processes and other ancillary executive functions. Copyright 漏 2013. Published by Elsevier Ltd.
Modulating presence and impulsiveness by external stimulation of the brain,
Background "The feeling of being there" is one possible way to describe the phenomenon of feeling present in a virtual environment and to act as if this environment is real. One brain area, which is hypothesized to be critically involved in modulating this feeling (also called presence) is the dorso-lateral prefrontal cortex (dlPFC), an area also associated with the control of impulsive behavior. Methods In our experiment we applied transcranial direct current stimulation (tDCS) to the right dlPFC in order to modulate the experience of presence while watching a virtual roller coaster ride. During the ride we also registered electro-dermal activity. Subjects also performed a test measuring impulsiveness and answered a questionnaire about their presence feeling while they were exposed to the virtual roller coaster scenario. Results Application of cathodal tDCS to the right dlPFC while subjects were exposed to a virtual roller coaster scenario modulates the electrodermal response to the virtual reality stimulus. In addition, measures reflecting impulsiveness were also modulated by application of cathodal tDCS to the right dlPFC. Conclusion Modulating the activation with the right dlPFC results in substantial changes in responses of the vegetative nervous system and changed impulsiveness. The effects can be explained by theories discussing the top-down influence of the right dlPFC on the "impulsive system".
Modulation of emotions associated with images of human pain using anodal transcranial direct current stimulation (tDCS),
Viewing images of other humans in pain elicits a variety of responses including distress, anxiety, and a sensation that is similar to pain. We aimed to evaluate whether transcranial direct current stimulation (tDCS) could be effective in modulating the emotional aspects of pain as to further explore mechanisms of tDCS in pain relief. Twenty-three healthy subjects rated images with respect to unpleasantness and discomfort/pain (baseline), and then received stimulation with tDCS under four different conditions of stimulation: anodal tDCS of the left primary motor cortex (M1), dorsolateral prefrontal cortex (DLPFC), occipital cortex (V1); and sham tDCS. The order of conditions was randomized and counterbalanced across subjects. During each stimulation session (after 3 min of stimulation), subjects were shown a new set of aversive images and were again asked to rate the images with respect to unpleasantness and discomfort/pain. The results showed that ratings of unpleasantness and discomfort/pain were significantly decreased during DLPFC tDCS only, as compared to baseline and sham tDCS. The other conditions of stimulation (M1 and V1 tDCS) did not result in any significant changes. These results support the notion that DLPFC is a critical area for the emotional processing of pain and also suggests that DLPFC may be a potential target of stimulation for alleviation of pain with a significant emotional-affective component. Our results also suggest that the mechanism of tDCS in modulating emotional pain involve pathways that are independent of those modulating the somatosensory perception of pain.
Prefrontal cortex and impulsivity: Interest of noninvasive brain stimulation,
The data led us to consider new therapeutic alternatives in impulsive disorders by modulating prefrontal cortex activity through NIBS.
A developmental functional MRI study of prefrontal activation during performance of a Go-No-Go task,
This study examines important developmental differences in patterns of activation in the prefrontal cortex during performance of a Go-No-Go paradigm using functional magnetic resonance imaging (fMRI). Eighteen subjects (9 children and 9 adults) were scanned using gradient echo, echo planar imaging during performance of a response inhibition task. The results suggest four general findings. First, the location of activation in the prefrontal cortex was not different between children and adults, which is similar to our earlier pediatric fMRI results of prefrontal activation during a working memory task (Casey et al., 1995). Second, the volume of activation was significantly greater for children relative to adults. These differences in volume of activation were observed predominantly in the dorsal and lateral prefrontal cortices. Third, although inhibitory processes have typically been associated with more ventral or orbital frontal regions, the current study revealed activation that was distributed across both dorsolateral and orbitofrontal cortices. Finally, consistent with animal and human lesion studies, activity in orbital frontal and anterior cingulate cortices correlated with behavioral performance (i.e., number of false alarms). These results further demonstrate the utility of this methodology in studying pediatric populations.
No effects of bilateral tDCS over inferior frontal gyrus on response inhibition and aggression,
Response inhibition is defined as the capacity to adequately withdraw pre-planned responses. It has been shown that individuals with deficits in inhibiting pre-planned responses tend to display more aggressive behaviour. The prefrontal cortex is involved in both, response inhibition and aggression. While response inhibition is mostly associated with predominantly right prefrontal activity, the neural components underlying aggression seem to be left-lateralized. These differences in hemispheric dominance are conceptualized in cortical asymmetry theories on motivational direction, which assign avoidance motivation (relevant to inhibit responses) to the right and approach motivation (relevant for aggressive actions) to the left prefrontal cortex. The current study aimed to directly address the inverse relationship between response inhibition and aggression by assessing them within one experiment. Sixty-nine healthy participants underwent bilateral transcranial Direct Current Stimulation (tDCS) to the inferior frontal cortex. In one group we induced right-hemispheric fronto-cortical dominance by means of a combined right prefrontal anodal and left prefrontal cathodal tDCS montage. In a second group we induced left-hemispheric fronto-cortical dominance by means of a combined left prefrontal anodal and right prefrontal cathodal tDCS montage. A control group received sham stimulation. Response inhibition was assessed with a go/no-go task (GNGT) and aggression with the Taylor Aggression Paradigm (TAP). We revealed that participants with poorer performance in the GNGT displayed more aggression during the TAP. No effects of bilateral prefrontal tDCS on either response inhibition or aggression were observed. This is at odds with previous brain stimulation studies applying unilateral protocols. Our results failed to provide evidence in support of the prefrontal cortical asymmetry model in the domain of response inhibition and aggression. The absence of tDCS effects might also indicate that the methodological approach of shifting cortical asymmetry by means of bilateral tDCS protocols has failed.
Stop signal task and the related models of response inhibiton
停止信号任务(Stop Signal Task)是研究反应抑制的常用实验范式之一,近年来被广泛运用于认知神经科学、心理病理学等研究领域。本文详细介绍了经典停止信号任务的实验过程、评价指标,重点阐述了与此任务相关的反应抑制理论模型——独立竞争模型,并提出该范式存在的问题,为停止信号任务范式的完善与推广提供了基础。
停止信号任务(Stop Signal Task)是研究反应抑制的常用实验范式之一,近年来被广泛运用于认知神经科学、心理病理学等研究领域。本文详细介绍了经典停止信号任务的实验过程、评价指标,重点阐述了与此任务相关的反应抑制理论模型——独立竞争模型,并提出该范式存在的问题,为停止信号任务范式的完善与推广提供了基础。
Quantitative review finds no evidence of cognitive effects in healthy populations from single-session transcranial direct current stimulation (tDCS),
Abstract BACKGROUND: Over the last 15-years, transcranial direct current stimulation (tDCS), a relatively novel form of neuromodulation, has seen a surge of popularity in both clinical and academic settings. Despite numerous claims suggesting that a single session of tDCS can modulate cognition in healthy adult populations (especially working memory and language production), the paradigms utilized and results reported in the literature are extremely variable. To address this, we conduct the largest quantitative review of the cognitive data to date. METHODS: Single-session tDCS data in healthy adults (18-50) from every cognitive outcome measure reported by at least two different research groups in the literature was collected. Outcome measures were divided into 4 broad categories: executive function, language, memory, and miscellaneous. To account for the paradigmatic variability in the literature, we undertook a three-tier analysis system; each with less-stringent inclusion criteria than the prior. Standard mean difference values with 95% CIs were generated for included studies and pooled for each analysis. RESULTS: Of the 59 analyses conducted, tDCS was found to not have a significant effect on any - regardless of inclusion laxity. This includes no effect on any working memory outcome or language production task. CONCLUSION: Our quantitative review does not support the idea that tDCS generates a reliable effect on cognition in healthy adults. Reasons for and limitations of this finding are discussed. This work raises important questions regarding the efficacy of tDCS, state-dependency effects, and future directions for this tool in cognitive research. Copyright 2015 Elsevier Inc. All rights reserved.
Sustained brain activation supporting stop-signal task performance,
Stop-signal paradigms operationalize a basic test of goal-directed behaviour whereby an overarching stop goal that is performed intermittently must be maintained throughout ongoing performance of a reaction time go task (go goal). Previous studies of sustained brain activation during stop-signal task performance in humans did not observe activation of the dorsolateral prefrontal cortex (DLPFC) that, in concert with the parietal cortex, is known to subserve goal maintenance. Here we explored the hypothesis that a DLPFC and parietal network has a key role in supporting ongoing stop-signal task performance. We used a blocked functional magnetic resonance imaging design that included blocks of trials containing typical stop-signal paradigm stimuli that were performed under three conditions: Stop condition, which required reaction time responding to go stimuli and inhibition of cued responses upon presentation of a stop signal; Go condition, identical except that the tone was ignored; and Passive condition, which required only quiescent attention to stimuli. We found that, whereas a distributed corticothalamic network was more active in Stop compared with Go, only the right DLPFC and bilateral parietal cortex survived after masking that contrast with Stop compared with Passive. These findings indicate that sustained activation of a right dominant frontoparietal network supports stop goal processes during ongoing performance of the stop-signal task.
Acute high-frequency rTMS of the left dorsolateral prefrontal cortex and attentional control in healthy young men,
Previous studies have shown that high-frequency repetitive transcranial magnetic stimulation (rTMS) over the dorsolateral prefrontal cortex induces neuromodulation in prefrontal and striatal regions. We hypothesized that high-frequency rTMS over the dorsolateral prefrontal cortex would influence attentional control, which has been associated with neural activity in the same region. Seventeen healthy young men volunteered to participate in a sham-controlled rTMS study. Participants received both rTMS and sham stimulation on separate days and the Conners' continuous performance test was used to assess response inhibition and attentional vigilance. Results indicated that participants showed fewer commission errors during trials after rTMS as compared with sham stimulation, at longer interstimulus intervals (ISIs), which suggests that high-frequency rTMS may have the potential to improve response inhibition. This finding contributes to the understanding of the relationship between the dorsolateral prefrontal cortex and attentional control and suggests possible therapeutic applications for high-frequency rTMS.
10/20, 10/10, and 10/5 systems revisited: Their validity as relative head- surface-based positioning systems,
With the advent of multi-channel EEG hardware systems and the concurrent development of topographic and tomographic signal source localization methods, the international 10/20 system, a standard system for electrode positioning with 21 electrodes, was extended to higher density electrode settings such as 10/10 and 10/5 systems, allowing more than 300 electrode positions. However, their effectiveness as relative head-surface-based positioning systems has not been examined. We previously developed a virtual 10/20 measurement algorithm that can analyze any structural MR head and brain image. Extending this method to the virtual 10/10 and 10/5 measurement algorithms, we analyzed the MR images of 17 healthy subjects. The acquired scalp positions of the 10/10 and 10/5 systems were normalized to the Montreal Neurological Institute (MNI) stereotactic coordinates and their spatial variability was assessed. We described and examined the effects of spatial variability due to the selection of positioning systems and landmark placement strategies. As long as a detailed rule for a particular system was provided, it yielded precise landmark positions on the scalp. Moreover, we evaluated the effective spatial resolution of 329 scalp landmark positions of the 10/5 system for multi-subject studies. As long as a detailed rule for landmark setting was provided, 241 scalp positions could be set effectively when there was no overlapping of two neighboring positions. Importantly, 10/10 positions could be well separated on a scalp without overlapping. This study presents a referential framework for establishing the effective spatial resolutions of 10/20, 10/10, and 10/5 systems as relative head-surface-based positioning systems.
Common inhibitory mechanism in human inferior prefrontal cortex revealed by event- related functional MRI,
Abstract Inhibition of an ongoing reaction tendency for adaptation to changing environments is a major function of the human prefrontal cortex. This function has been investigated frequently using the go/no-go task and set-shifting tasks such as the Wisconsin Card Sorting Test (WCST). Studies in humans and monkeys suggest the involvement of the dorsolateral prefrontal cortex in the two task paradigms. However, it remains unknown where in the dorsolateral prefrontal cortex this function is localized, whether a common inhibitory mechanism is used in these task paradigms and how this inhibitory function acts on two different targets, i.e. the go response in the go/no-go task and the cognitive set in the WCST. In the go/no-go task of this study, subjects were instructed to either respond (go trial) or not respond (no-go trial), depending on the cue stimulus presented. The signals of functional MRI (fMRI) related to the inhibitory function should be transient by nature. Thus, we used the temporal resolution of fMRI (event-related fMRI) by which transient signals in go and no-go trials can be analysed separately and compared with each other. We found a focus that showed transient no-go dominant activity in the posterior part of the inferior frontal sulcus in the right hemisphere. This was true irrespective of whether the subjects used their right or left hands. These results suggest that the transient activation in the right inferior prefrontal area is related to the neural mechanism underlying the response inhibition function. Furthermore, this area was found to be overlapped spatially with the area that was activated transiently during cognitive set shifting in the WCST. The transient signals in the go/no-go task peaked 5 s after the transient expression of the inhibitory function, and the transient signals in the WCST peaked 7s after the transient expression, reflecting different durations of neuronal activity in the two inhibitory task paradigms. These results imply that the right inferior prefrontal area is commonly involved in the inhibition of different targets, i.e. the go response during performance of the go/no-go task and the cognitive set during performance of the WCST.
Influence of high-frequency repetitive transcranial magnetic stimulation over the dorsolateral prefrontal cortex on the inhibition of emotional information in healthy volunteers,
Abstract BACKGROUND: Evidence suggests that repetitive transcranial magnetic stimulation (rTMS) over the left dorsolateral prefrontal cortex (DLPFC) might be a promising new treatment procedure for depression. However, underlying working mechanisms of this technique are yet unclear. Multiple sessions of rTMS may--apart from the reported antidepressant effects--cause primary improvements in attentional control over emotional information, modulated by changes in cortical brain excitability within stimulated prefrontal regions. METHOD: In two experiments, we examined the temporary effects of high-frequency (HF) rTMS (10 Hz) applied over the left and right DLPFC on the attentional processing of emotional information and self-reported mood within samples of healthy volunteers. RESULTS: The present study showed that one session of HF-rTMS over the right DLPFC produces instant impairments in the ability to inhibit negative information, in line with a characteristic cognitive vulnerability found in depressive pathology, whereas HF-rTMS of the left DLPFC did not lead to significant changes in attentional control. These effects could not be attributed to mood changes. CONCLUSIONS: The findings of the present study may suggest a specific involvement of the right DLPFC in the attentional processing of emotional information.
The effects of high-frequency rTMS over the left DLPFC on cognitive control in young healthy participants,
A large body of evidence suggests that repetitive transcranial magnetic stimulation (rTMS) is clinically effective in treating neuropsychiatric disorders and multiple sessions are commonly used. However, it is unknown whether multiple sessions of rTMS improve cognitive control, which is a function of the neural circuitry of the left dorsolateral prefrontal cortex (DLPFC)-cingulate cortex in healthy individuals. In addition, it is still unclear which stages of neural processing are altered by rTMS. In this study, we investigated the effects of high-frequency rTMS on cognitive control and explored the time course changes of cognitive processing after rTMS using event-related potentials (ERPs). For seven consecutive days, 25 young healthy participants underwent one 10-Hz rTMS session per day in which stimulation was applied over the left DLPFC, and a homogeneous participant group of 25 individuals received a sham rTMS treatment. A Stroop task was performed, and an electroencephalogram (EEG) was recorded. The results revealed that multiple sessions of rTMS can decrease reaction time (RTs) under both congruent and incongruent conditions and also increased the amplitudes of both N2 and N450 compared with sham rTMS. The negative correlations between the mean amplitudes of both N2 and N450 and the RTs were found, however, the latter correlation were restricted to incongruent trials and the correlation was enhanced significantly by rTMS. This observation supports the view that high-frequency rTMS over the left DLPFC can not only recruit more neural resources from the prefrontal cortex by inducing an electrophysiologically excitatory effect but also enhance efficiency of resources to deploy for conflict resolution during multiple stages of cognitive control processing in healthy young people.
The impact of transcranial direct current stimulation on inhibitory control in young adults,
Abstract BACKGROUND: There is increasing evidence that the dorso-lateral prefrontal cortex (DLPFC), a brain region related to reward and motivational processes, is involved in effective response inhibition and that decreased activity in this region coincides with reduced inhibitory capacity. Using transcranial direct current stimulation (tDCS) to manipulate cortical activation, this study examined whether cross-hemispheric tDCS over the DLPFC affected performance on an inhibitory control task. METHODS: Neurologically intact participants performed a modified Stroop color-word matching task before and after completing one of two tDCS conditions; (1) anodal stimulation over the left DLPFC or (2) sham tDCS. RESULTS: There was a statistically significant effect of tDCS condition on Stroop reaction time (RT) pre-post tDCS change scores. Participants who received anodal stimulation over the left DLPFC demonstrated statistically significant faster RT change scores on the Stroop items compared to participants in the sham condition. Although errors on Stroop incongruent items decreased before and after receiving the tDCS treatment, there were no significant differences in errors on Stroop items between the anodal stimulation over left DLPFC and sham tDCS conditions. Anodal tDCS, which is known to elevate neural excitation, may have enhanced activation levels in the left DLPFC and minimized impairment of inhibitory control, resulting in better task performance. CONCLUSIONS: Current findings provide preliminary evidence that increased excitation of the left DLPFC improves inhibitory control and are a step toward understanding the potential of tDCS for moderating deficits in inhibitory control.
On the ability to Inhibit thought and action: A theory of an act of control,
Large-scale brain networks and psychopathology: A unifying triple network model,
The science of large-scale brain networks offers a powerful paradigm for investigating cognitive and affective dysfunction in psychiatric and neurological disorders. This review examines recent conceptual and methodological developments which are contributing to a paradigm shift in the study of psychopathology. I summarize methods for characterizing aberrant brain networks and demonstrate how network analysis provides novel insights into dysfunctional brain architecture. Deficits in access, engagement and disengagement of large-scale neurocognitive networks are shown to play a prominent role in several disorders including schizophrenia, depression, anxiety, dementia and autism. Synthesizing recent research, I propose a triple network model of aberrant saliency mapping and cognitive dysfunction in psychopathology, emphasizing the surprising parallels that are beginning to emerge across psychiatric and neurological disorders.
Transcranial direct current stimulation (tDCS) in the treatment of depression: Systematic review and meta-analysis of efficacy and tolerability,
tDCS may be efficacious for treatment of MDE. The data do not support the use of tDCS in treatment-resistant depression, or as an add-on augmentation treatment. Larger studies over longer treatment periods are needed.
On inhibition/disinhibition in developmental psychopathology: Views from cognitive and personality psychology and a working inhibition taxonomy,
Disinhibition is a common focus in psychopathology research. However, use of inhibition models often is piecemeal, lacking an overarching taxonomy of inhibitory processes. The author organizes key concepts and models pertaining to different kinds of inhibitory control from the cognitive and temperament/personality literatures. Within the rubrics of executive inhibitory processes, motivational inhibitory processes, and automatic attentional inhibition processes, 8 kinds of inhibition are distinguished. Three basic temperament traits may address key executive and motivational inhibitory processes. Future developmental psychopathology research should be based on a systematic conceptual taxonomy of the kinds of inhibitory function relevant to a given disorder. Such an approach can clarify which inhibition distinctions are correct and which inhibition deficits go with which disorders.
Excitability changes induced in the human motor cortex by weak transcranial direct current stimulation,
A systematic review of non-motor rTMS induced motor cortex plasticity,
Motor cortex excitability can be measured by single- and paired-pulse transcranial magnetic stimulation (TMS). Repetitive transcranial magnetic stimulation (rTMS) can induce neuroplastic effects in stimulated and in functionally connected cortical regions. Due to its ability to non-invasively modulate cortical activity, rTMS has been investigated for the treatment of various neurological and psychiatric disorders. However, such studies revealed a high variability of both clinical and neuronal effects induced by rTMS. In order to better elucidate this meta-plasticity, rTMS-induced changes in motor cortex excitability have been monitored in various studies in a pre-post stimulation design. Here, we give a literature review of studies investigating motor cortex excitability changes as a neuronal marker for rTMS effects over non-motor cortical areas. A systematic literature review in April 2014 resulted in 29 articles in which motor cortex excitability was assessed before and after rTMS over non-motor areas. The majority of the studies focused on the stimulation of one of three separate cortical areas: the prefrontal area (17 studies), the cerebellum (8 studies), or the temporal cortex (3 studies). One study assessed the effects of multi-site rTMS. Most studies investigated healthy controls but some also stimulated patients with neuropsychiatric conditions (e.g., affective disorders, tinnitus). Methods and findings of the identified studies were highly variable showing no clear systematic pattern of interaction of non-motor rTMS with measures of motor cortex excitability. Based on the available literature, the measurement of motor cortex excitability changes before and after non-motor rTMS has only limited value in the investigation of rTMS related meta-plasticity as a neuronal state or as a trait marker for neuropsychiatric diseases. Our results do not suggest that there are systematic alterations of cortical excitability changes during rTMS treatment, which calls into question the practice of re-adjusting the stimulation intensity according to the motor threshold over the course of the treatment.
tDCS for the treatment of depression: A comprehensive review,
Abstract Transcranial direct current stimulation (tDCS) has been investigated for the treatment of major depressive disorders in recent years. Here, we review the implications of current research for the clinical use of tDCS in the treatment of major depressive disorder. Meta-analyses, randomized, placebo-controlled clinical trials, open-label trials, case reports and review articles were identified through a systematic search of the literature database of the National Institutes of Health (USA). Available articles were evaluated with regard to their clinical relevance. Results of tDCS efficacy are inconsistent due to the small sample sizes, the heterogeneous patient samples and the partially high treatment resistance in some studies. Overall, tDCS has very low side effects. Meta-analyses suggest some efficacy of tDCS in the treatment of acute depressive disorder with moderate effect size, and low efficacy in treatment-resistant depression. A general statement about the efficacy of tDCS as a therapeutic tool in major depression seems to be premature. tDCS is considered as a safe therapeutic option and is associated with only minor side effects. The effectiveness of tDCS decreases with resistance to treatment. Psychotropic drugs may attenuate or amplify its effects. The use of 2 mA current strength over 20 min per day over a short time span can be considered as safe.
Human memory retrieval and inhibitory control in the brain: Beyond correlational evidence,
Abstract Retrieving information from long-term memory can result in the episodic forgetting of related material. One influential account states that this retrieval-induced forgetting (RIF) phenomenon reflects inhibitory mechanisms called into play to decrease retrieval competition. Recent neuroimaging studies suggested that the prefrontal cortex, which is critically engaged in inhibitory processing, is also involved in retrieval competition situations. Here, we used transcranial direct current stimulation (tDCS) to address whether inhibitory processes could be causally linked to RIF. tDCS was administered over the right dorsolateral prefrontal cortex during the retrieval-practice phase in a standard retrieval-practice paradigm. Sixty human participants were randomly assigned to anodal, cathodal, or sham-control groups. The groups showed comparable benefits for practiced items. In contrast, unlike both the sham and anodal groups, the cathodal group exhibited no RIF. This pattern is interpreted as evidence for a causal role of inhibitory mechanisms in episodic retrieval and forgetting.
Clinical improvement in patients with borderline personality disorder after treatment with repetitive transcranial magnetic stimulation: Preliminary results, doi:
Abstract Objective:: Current treatment of borderline personality disorder (BPD) consists of psychotherapy and pharmacological interventions. However, the use of repetitive transcranial magnetic stimulation (rTMS) could be beneficial to improve some BPD symptoms. The objective of this study was to evaluate clinical improvement in patients with BPD after application of rTMS over the right or left dorsolateral prefrontal cortex (DLPFC). Method:: Twenty-nine patients with BPD from the National Institute of Psychiatry, Mexico, were randomized in two groups to receive 15 sessions of rTMS applied over the right (1 Hz, n=15) or left (5 Hz, n=14) DLPFC. Improvement was measured by the Clinical Global Impression Scale for BPD (CGI-BPD), Borderline Evaluation of Severity Over Time (BEST), Beck Depression Inventory (BDI), Hamilton Anxiety Rating Scale (HAM-A), and Barratt Impulsiveness Scale (BIS). Results:: Intragroup comparison showed significant (p < 0.05) reductions in every psychopathologic domain of the CGI-BPD and in the total scores of all scales in both groups. Conclusions:: Both protocols produced global improvement in severity and symptoms of BPD, particularly in impulsiveness, affective instability, and anger. Further studies are warranted to explore the therapeutic effect of rTMS in BPD. Clinical trial registration:: NCT02273674 .
Right inferior prefrontal cortex mediates response inhibition while mesial prefrontal cortex is responsible for error detection,
Inhibitory control and error detection are among the highest evolved human self-monitoring functions. Attempts in functional neuroimaging to effectively isolate inhibitory motor control from other cognitive functions have met with limited success. Different brain regions in inferior, mesial, and dorsolateral prefrontal cortices and parietal and temporal lobes have been related to inhibitory control in go/no-go and stop tasks. The widespread activation reflects the fact that the designs used so far have comeasured additional noninhibitory cognitive functions such as selective attention, response competition, decision making, target detection, and inhibition failure. Here we use rapid, mixed trial, event-related functional magnetic resonance imaging to correlate brain activation with an extremely difficult situation of inhibitory control in a challenging stop task that controls for noninhibitory functions. The difficulty of the stop task, requiring withholding of a triggered motor response, was assured by an algorithm that adjusted the task individually so that each subject only succeeded on half of all stop trials, failing on the other half. This design allowed to elegantly separate brain activation related to successful motor response inhibition and to inhibition failure or error detection. Brain activation correlating with successful inhibitory control in 20 healthy volunteers could be isolated in right inferior prefrontal cortex. Failure to inhibit was associated with activation in mesial frontopolar and bilateral inferior parietal cortices, presumably reflecting an attention network for error detection.
Effect of anodal and cathodal transcranial direct current stimulation on DLPFC on modulation of inhibitory control in ADHD,
The purpose of this study was to improve the inhibitory control functions through transcranial direct current stimulation (tDCS) in adolescents with ADHD symptoms.Twenty high school students with ADHD symptoms participated in this single-blinded, crossover, sham-controlled study. All the participants were tested during the application of Stroop and Go/No-Go tasks that is used to measure inhibitory control, using 1.5 mA of tDCS for 15 min over the left dorsolateral prefrontal cortex (DLPFC).Anodal stimulation on left DLPFC had no effect on interference inhibition during the Stroop task and increased the proportion of correct responses in the "Go stage" of the Go/No-Go test compared with sham condition. Cathodal stimulation on the left DLPFC increased the inhibition accuracy in the inhibition stage during Go/No-Go task in comparison with sham.tDCS over the left DLPFC of adolescents who suffer from ADHD symptoms can improve inhibitory control in prepotent response inhibition.
Assessing the effects of tDCS over a delayed response inhibition task by targeting the right inferior frontal gyrus and right dorsolateral prefrontal cortex,
Abstract Many situations in our everyday life call for a mechanism deputed to outright stop an ongoing course of action. This behavioral inhibition ability, known as response stopping, is often impaired in psychiatric conditions characterized by impulsivity and poor inhibitory control. Transcranial direct current stimulation (tDCS) has recently been proposed as a tool for modulating response stopping in such clinical populations, and previous studies in healthy humans have already shown that this noninvasive brain stimulation technique is effectively able to improve response stopping, as measured in a stop-signal task (SST) administered immediately after the stimulation. So far, the right inferior frontal gyrus (rIFG) has been the main focus of these attempts to modulate response stopping by the means of noninvasive brain stimulation. However, other cortical areas such as the right dorsolateral prefrontal cortex (rDLPFC) have been implicated in inhibitory control with other paradigms. In order to provide new insight about the involvement of these areas in response stopping, in the present study, tDCS was delivered to 115 healthy subjects, using five stimulation setups that differed in terms of target area (rIFG or rDLPFC) and polarity of stimulation (anodal, cathodal, or sham). The SST was performed 15 min after the offset of the stimulation. Consistently with previous studies, only anodal stimulation over rIFG induced a reliable, although weak, improvement in the SST, which was specific for response stopping, as it was not mirrored in more general reaction time measures.
Response inhibition during cue reactivity in problem gamblers: An fmri study,
Disinhibition over drug use, enhanced salience of drug use and decreased salience of natural reinforcers are thought to play an important role substance dependence. Whether this is also true for pathological gambling is unclear. To understand the effects of affective stimuli on response inhibition in problem gamblers (PRGs), we designed an affective Go/Nogo to examine the interaction between response inhibition and salience attribution in 16 PRGs and 15 healthy controls (HCs). Four affective blocks were presented with Go trials containing neutral, gamble, positive or negative affective pictures. The No-Go trials in these blocks contained neutral pictures. Outcomes of interest included percentage of impulsive errors and mean reaction times in the different blocks. Brain activity related to No-Go trials was assessed to measure response inhibition in the various affective conditions and brain activity related to Go trials was assessed to measure salience attribution. PRGs made fewer errors during gamble and positive trials than HCs, but were slower during all trials types. Compared to HCs, PRGs activated the dorsolateral prefrontal cortex, anterior cingulate and ventral striatum to a greater extent while viewing gamble pictures. The dorsal lateral and inferior frontal cortex were more activated in PRGs than in HCs while viewing positive and negative pictures. During neutral inhibition, PRGs were slower but similar in accuracy to HCs, and showed more dorsolateral prefrontal and anterior cingulate cortex activity. In contrast, during gamble and positive pictures PRGs performed better than HCs, and showed lower activation of the dorsolateral and anterior cingulate cortex. This study shows that gambling-related stimuli are more salient for PRGs than for HCs. PRGs seem to rely on compensatory brain activity to achieve similar performance during neutral response inhibition. A gambling-related or positive context appears to facilitate response inhibition as indicated by lower brain activity and fewer behavioural errors in PRGs.
Mental processing models and neural mechanisms for response inhibition
Cathodal tDCS improves task performance in participants high in Coldheartedness,
The current results demonstrate the utility of tDCS as a tool to assess how differences in cortical responsivity are associated with specific personality traits. Additionally, this study represents the first investigation into the influence of psychopathic traits on tDCS effects on dlPFC, and we observed beneficial changes in response inhibition as a result of, especially, cathodal stimulation in participants scoring high on Coldheartedness.
An updated meta-analysis: Short-term therapeutic effects of repeated transcranial magnetic stimulation in treating obsessive-compulsive disorder,
Abstract BACKGROUND: This study was conducted to evaluate the short-term therapeutic effects of using repeated transcranial magnetic stimulation (rTMS) to treat obsessive-compulsive disorder (OCD) and to examine potential influencing factors. METHOD: We searched the PubMed, EMBASE, CENTRAL, Wanfang, CNKI, and Sinomed databases on September 18, 2016 and reviewed the references of previous meta-analyses. Sham-controlled, randomized clinical trials using rTMS to treat OCD were included. Hedge's g was calculated for the effect size. Subgroup analyses and univariate meta-regressions were conducted. RESULTS: Twenty studies with 791 patients were included. A large effect size (g=0.71; 95%CI, 0.55-0.87; P<0.001) was found for the therapeutic effect. Targeting the supplementary motor area (SMA) (g=0.56; 95%CI, 0.12-1.01; P<0.001), left dorsolateral prefrontal cortex (DLPFC) (g=0.47; 95%CI, 0.02-0.93; P=0.02), bilateral DLPFC (g=0.65; 95%CI, 0.38-0.92; P<0.001) and right DLPFC (g=0.93; 95%CI, 0.70-1.15; P<0.001), excluding the orbitofrontal cortex (OFC) (g=0.56; 95%CI, -0.05-1.18; P=0.07), showed significant improvements over sham treatments. Both low-frequency (g=0.73; 95%CI, 0.50-0.96; P<0.001) and high-frequency (g=0.70; 95%CI, 0.51-0.89; P<0.001) treatments were significantly better than sham treatments, with no significant differences between the effects of the two frequencies. The subgroup analyses indicated that patients who were non-treatment resistant, lacked concurrent major depressive disorder (MDD) and received threshold-intensity rTMS showed larger therapeutic effects than the corresponding subgroups. The subgroup analysis according to sham strategy showed that tilted coils yielded larger effects than sham coils. Meta-regression analyses revealed that none of the continuous variables were significantly associated with the therapeutic effects. LIMITATIONS: Only short-term therapeutic effects were assessed in this study. CONCLUSIONS: Based on this study, the short-term therapeutic effects of rTMS are superior to those of sham treatments. The site of stimulation, stimulation frequency and intensity and sham condition were identified as potential factors modulating short-term therapeutic effects. The findings of this study may inspire future research. Copyright 漏 2017 Elsevier B.V. All rights reserved.
版权所有 © 《心理学报》编辑部