这项研究由国家心理健康研究所 (R01MH095014) 资助。

这项议定书得到了辛辛那提儿童医院医疗中心和约翰霍普金斯机构审查委员会的批准, 作为对儿童和成人的最低风险研究。单和配对脉冲 TMS 被认为是安全的儿童2岁以上的每一个国际专家共识。24在向家长/监护人和参与人解释 TMS 的潜在风险后, 如果他们同意继续进行此项研究, 则签署同意和同意表格。
1. 筛选和介绍
<ol><li>使用标准化的问卷调查 TMS 禁忌症的屏幕主题。25
</li>
	<li>演示 TMS 是如何通过在操作者自己的前臂上提供一个磁性脉冲来工作的。</li>
	<li>在参与者的前臂上提供一个 TMS 脉冲, 这样他/她就能感觉到脉搏。</li>
	<li>将耳塞放在参加者的耳中, 以便进行听力保护。</li>
</ol>2. 表面肌电信号的设置和手定位
<ol><li>有主题绑架主导食指, 以确定第一次背间肌 (FDI)。将负电极置于 FDI 的腹部, 然后将正极电极放在 2nd和 3rd掌 (mcp) 接头和 5th mcp 接头上的接地电极之间。</li>
	<li>将参与者的手放在手臂和双手的尺面上, 完全放在枕头上, 不需要进行反重力工作 (图 1)。</li>
	<li>当第三第五手指弯曲时, 让参与者扩展占主导地位的食指。然后将游戏控制器垫放在枕头上, 这样食指就可以放在赛车的按钮上。这种手的立场的理由是, GO 行动要求外国直接投资的激活, 以解除该按钮的食指。因此, 记录肌电图追踪的主要外国直接投资将探讨 M1 兴奋性和抑制的 GO 和停止试验分别。</li>
</ol>3. 基线 TMS 数据采集
<ol><li>设置记录参数的录音-低和高通滤波器的100和1000赫兹, 采样率2赫。</li>
	<li>获得基线 tms 测量使用90毫米圆形 tms 线圈定位到头骨上方与手柄指向枕在最佳位置和方向, 以生产一个在正确的外国直接投资按标准议定书.26此线圈的位置和方向应产生一个诱导后向前电流超过 M1。<ol>
<li>在热点定位后, 使用蜡铅笔标记头皮位置, 以确保 TMS 脉冲传递发生在同一皮层区域。</li>
	</ol>
</li>
	<li>执行二十项试验27基线单脉冲 (sp) TMS 诱导外国直接投资欧洲议员在休息时用两只手的强度120% 的 RMT。</li>
	<li>执行二十试验的基线配对脉冲 TMS 措施 M1 短间隔皮质抑制 (SICI) 在休息使用间刺激间隔 3 ms, 60% * rmt 作为调理脉冲强度和 120% rmt 作为测试脉冲强度量化 M1抑制 GABAA-能神经元活动。28,29,30将基线测量的跨试验间隔设置为6±0.3 秒。</li>
</ol>4. S H 行为任务
<ol><li>在显示器前面直接显示赛车的响应抑制任务。开始实验的第一个训练对象的行为任务。告诉主题, 在按钮被按下主食指 (图 2A) 后, 显示器左侧的汽车将开始移动。</li>
	<li>告诉与会者, GO 试验的目标是在屏幕上的垂直线上显示的距离, 但在800毫秒目标之前举起手指。屏幕将显示 "良好的工作", 如果手指升降机发生在700和800毫秒, 否则它将显示 "过早" 或 "为时已晚"。参加练习10去试。</li>
	<li>为停止任务提供培训, 告诉参与者第二组试验涉及汽车随机停在800毫秒目标之前。<ol>
<li>告诉孩子, 当汽车随机停止时, 不要举起手指, 把食指放在按钮上。为了在这些停止试验中获得成功, 手指必须保持在按钮上, 直到检查标记被编程为在每次试验开始后出现1000毫秒。通知参与者, 如果出现停止信号, 并且在检查器标记前举起手指, 则会显示 "太早" 消息。告诉孩子在成功停止试验后会显示一个 "伟大的" 消息。</li>
		<li>让孩子练习10停止试验。 注意: 该程序具有动态跟踪算法。在训练后的实际实验中, 第一个停止信号发生在500毫秒. 如果参与者没有停止试验, 那么下一站试验将更容易 (即停止信号将从800毫秒目标转移50毫秒)。然而, 如果停止试验是成功的, 那么下一站试验将更加困难 (即停止信号将转移50毫秒对目标)。这一动态跟踪过程确保在整个实验结束时, 大约50% 的停止试验将是成功的, 而另一半则是失败的试验。停止信号被编程, 以调整在300和700毫秒后开始试用。</li>
	</ol>
</li>
	<li>在参与者练习只进行仅限和停止的试验后, 告诉他们下一个练习块包含了 "go 和停止" 试验的混合。让孩子做20试验混合去和停止作为最后的做法。</li>
</ol>5. 在线 S/TMS 实验
<ol><li>在开始线上/TMS 实验之前, 提醒参与者加合物 (向下推) 主导的食指开始试验, 绑架 (解除) 手指去试验和保持手指在按钮停止试验。在每次试验中, 选择食指内收来启动和维持汽车运动, 因为在 TMS 脉冲 (图 2A 和 2B) 时, 第一个背间骨间 (外国直接投资) 肌肉, 即肌电铅被放置, 将休息, 从而减少了外国直接投资追踪中运动伪影的可能性。</li>
	<li>告诉参与者, TMS 脉冲将在 S H 任务期间交付。指导的主题, 将有3块在线 S-H TMS 试验 (3 去: 1 停止试验比率)。 注: 在 GO 试验期间, TMS 脉冲被编程在每次试验开始后650毫秒交付。这个时间的选择是根据先前的 TMS 研究表明, 增加 M1 兴奋性与运动准备可以在这个范围内捕获。10为停止试验, TMS 脉冲被交付150毫秒在中止信号以后。在成功的停止试验中, 食指不解除按钮因此捕获的 M1 兴奋性反映了与反应抑制有关的皮层活动, 而不是运动的准备或执行。</li>
	<li>将 90 mm 圆形线圈放在顶点上, 使用先前的蜡笔标记优先激发主导 M1, 并将调节脉冲强度设置为 60% * rmt, 并将脉冲测试到 120% * rmt。开始在线/TMS 实验。需要孩子完成120试验的时间一般是30-40 分钟。</li>
</ol>6. 赛车斯莱特-Hammel 行为数据
<ol><li>对于 GO 试验, 将反应时间确定为相对于每个试验开始时的指举时间。平均每块。对于停止试验, 指举时间决定成功, 而汽车停止信号时间 (即停止信号延迟;SSD) 是从试验开始到汽车随机停止点的时间间隔。由于动态跟踪过程, 停止信号时间收敛到50% 成功/失败平均。</li>
	<li>计算停止信号反应时间 (SSRT) 减去平均停车时间从平均的手指升降机时间在 go 试验 (SSRT = 平均去反应时间-平均停止信号时间 [即 SSD])。平均所有的 SSD 按块和计算每块 SSRT。</li>
</ol>7. TMS 数据处理
<ol><li>在每个试验中量化 TMS 使用峰值峰值振幅测量毫伏。在 TMS 脉冲之前排除对运动工件的试验 (肌电图面积大于70伏超过100毫秒)。</li>
</ol>

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<li>Wessel, J. R. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/pubmed?term=((Prepotent+motor+activity+and+inhibitory+control+demands+in+different+variants+of+the+go%2Fno-go+paradigm%5BTitle%5D)+AND+%22Psychophysiology%22%5BJournal%5D)">Prepotent motor activity and inhibitory control demands in different variants of the go/no-go paradigm.</a> Psychophysiology. , (2017).</li>
<li>Garavan, H., Ross, T. J., Stein, E. A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/pubmed?term=((Right+hemispheric+dominance+of+inhibitory+control%3A+an+event-related+functional+MRI+study%5BTitle%5D)+AND+%22Proc+Natl+Acad+Sci+U+S+A%22%5BJournal%5D)">Right hemispheric dominance of inhibitory control: an event-related functional MRI study.</a> Proc Natl Acad Sci U S A. 96 (14), 8301-8306 (1999).</li>
<li>Garry, M. I., Thomson, R. H. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/pubmed?term=((The+effect+of+test+TMS+intensity+on+short-interval+intracortical+inhibition+in+different+excitability+states%5BTitle%5D)+AND+%22Exp+Brain+Res%22%5BJournal%5D)">The effect of test TMS intensity on short-interval intracortical inhibition in different excitability states.</a> Exp Brain Res. 193 (2), 267-274 (2009).</li>
<li>Chen, R., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/pubmed?term=((Intracortical+inhibition+and+facilitation+in+different+representations+of+the+human+motor+cortex%5BTitle%5D)+AND+%22J+Neurophysiol%22%5BJournal%5D)">Intracortical inhibition and facilitation in different representations of the human motor cortex.</a> J Neurophysiol. 80 (6), 2870-2881 (1998).</li>
<li>van der Kamp, W., Zwinderman, A. H., Ferrari, M. D., van Dijk, J. G. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/pubmed?term=((Cortical+excitability+and+response+variability+of+transcranial+magnetic+stimulation%5BTitle%5D)+AND+%22J+Clin+Neurophysiol%22%5BJournal%5D)">Cortical excitability and response variability of transcranial magnetic stimulation.</a> J Clin Neurophysiol. 13 (2), 164-171 (1996).</li>
<li>Williams, J., Pearce, A. J., Loporto, M., Morris, T., Holmes, P. S. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/pubmed?term=((The+relationship+between+corticospinal+excitability+during+motor+imagery+and+motor+imagery+ability%5BTitle%5D)+AND+%22Behav+Brain+Res%22%5BJournal%5D)">The relationship between corticospinal excitability during motor imagery and motor imagery ability.</a> Behav Brain Res. 226 (2), 369-375 (2012).</li>
<li>Roshan, L., Paradiso, G. O., Chen, R. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/pubmed?term=((Two+phases+of+short-interval+intracortical+inhibition%5BTitle%5D)+AND+%22Exp+Brain+Res%22%5BJournal%5D)">Two phases of short-interval intracortical inhibition.</a> Exp Brain Res. 151 (3), 330-337 (2003).</li>
<li>Sanger, T. D., Garg, R. R., Chen, R. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/pubmed?term=((Interactions+between+two+different+inhibitory+systems+in+the+human+motor+cortex%5BTitle%5D)+AND+%22J+Physiol%22%5BJournal%5D)">Interactions between two different inhibitory systems in the human motor cortex.</a> J Physiol. 530 (Pt 2), 307-317 (2001).</li>
<li>Picazio, S., Ponzo, V., Koch, G. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/pubmed?term=((Cerebellar+Control+on+Prefrontal-Motor+Connectivity+During+Movement+Inhibition%5BTitle%5D)+AND+%22Cerebellum%22%5BJournal%5D)">Cerebellar Control on Prefrontal-Motor Connectivity During Movement Inhibition.</a> Cerebellum. 15 (6), 680-687 (2016).</li>
<li>Picazio, S., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/pubmed?term=((Prefrontal+control+over+motor+cortex+cycles+at+beta+frequency+during+movement+inhibition%5BTitle%5D)+AND+%22Curr+Biol%22%5BJournal%5D)">Prefrontal control over motor cortex cycles at beta frequency during movement inhibition.</a> Curr Biol. 24 (24), 2940-2945 (2014).</li>
<li>Obeso, I., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/pubmed?term=((Stimulation+of+the+pre-SMA+influences+cerebral+blood+flow+in+frontal+areas+involved+with+inhibitory+control+of+action%5BTitle%5D)+AND+%22Brain+Stimul%22%5BJournal%5D)">Stimulation of the pre-SMA influences cerebral blood flow in frontal areas involved with inhibitory control of action.</a> Brain Stimul. 6 (5), 769-776 (2013).</li>
<li>Ficarella, S. C., Battelli, L. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/pubmed?term=((The+critical+role+of+the+dorsal+fronto-median+cortex+in+voluntary+action+inhibition%3A+A+TMS+study%5BTitle%5D)+AND+%22Brain+Stimul%22%5BJournal%5D)">The critical role of the dorsal fronto-median cortex in voluntary action inhibition: A TMS study.</a> Brain Stimul. 10 (3), 596-603 (2017).</li>
<li>Cash, R. F., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/pubmed?term=((Characterization+of+Glutamatergic+and+GABAA-Mediated+Neurotransmission+in+Motor+and+Dorsolateral+Prefrontal+Cortex+Using+Paired-Pulse+TMS-EEG%5BTitle%5D)+AND+%22Neuropsychopharmacology%22%5BJournal%5D)">Characterization of Glutamatergic and GABAA-Mediated Neurotransmission in Motor and Dorsolateral Prefrontal Cortex Using Paired-Pulse TMS-EEG.</a> Neuropsychopharmacology. 42 (2), 502-511 (2017).</li>
</ol>

作者没有什么可透露的。

该协议是一种新的儿童友好的方法结合停止信号任务和 TMS 检查事件相关的皮层抑制。临床观察的运动抑制缺损和不良表现的停止信号任务已经证明在许多神经精神条件。3相对较少的调查人员使用在线 fTMS 来检查在反应抑制任务中皮质的兴奋性和抑制。一些团体已成功地使用 TMS 在 GNG 任务, 以显示不同的皮质生理在儿童和成人。14,23<su...

反应抑制是有选择地防止那些不必要的行动, 可能干扰预期的功能目标的能力。1皮质-纹网络在反应抑制中处于重要的作用, 随着儿童的成熟而逐渐变得更有效, 但在许多神经精神状态 (如注意缺陷多动症 (ADHD), 学习障碍, 强迫症和精神分裂症。2,3马达响应抑制可以通过不同的行为范式进行检查, 如 Go/nogo-a (GNG) 和停止信号任务 (SST)。1,单独的4行为数据不提供有关可能可修改的、可量化的生物机制的信息。本研究的首要目标是建立一个儿童友好的方法来评估运动皮层的生理反应抑制执行期间, 为了开发一个基于大脑的定量生物标志物的神经基质的这项任务。此类生物标记物可广泛应用于神经行为疾病的预后或治疗预测研究。
为此, 调查人员选择并修改了斯莱特-Hammel (S H) 任务5。这是一个停止信号任务, 要求参与者抑制内部生成的预编程操作。这个自我节奏的任务包括去和停止试验。go 试验是由受试者按下按钮并保持压力而启动的, 指示将手指从按钮 (即 GO 动作) 中抬离, 但在800毫秒目标之前。在最初的范例中, 时间是用快速旋转的手在时钟上表示的。停止试验随机穿插在 go 试验期间, 该人必须抑制预先计划的 go 动作 (即防止指举)。停止信号任务更困难, 因为受试者必须在预编程 GO 信号的上下文中抑制响应, 而在 GNG 任务中, 决定是启动还是不启动没有预先命令的操作。6此外, 通过停止信号任务来研究响应抑制可能更准确, 因为在 GNG 任务中, 信号与响应之间的一致相关性可能导致自动抑制。7自动抑制的理论是, 信号和响应之间的一致映射 (即 go 信号总是导致 go 响应, 反之亦然) 导致在整个实验过程中进行自动处理, 以便停止试验通过内存检索进行部分处理, 绕过某些执行控制。8,9
经颅磁刺激 (TMS) 是一种非侵入性的技术, 可用于测量皮质生理。使用单和配对脉冲刺激模式, 可以量化皮质兴奋性和抑制。虽然大多数发表的 TMS 研究调查皮层生理学在休息, 一些小组已经检查皮层兴奋性/抑制在心理准备的行动10和在不同的认知状态, 可能反映在电机皮质生理学。11,12,13,14此功能性 tms (fTMS) 方法需要在线 tms 测量, 而参与者则执行行为任务, 从而允许您探测与高时间分辨率相关的状态依赖性皮层变化。以这种方式提供神经变化的实时信息, 可拓宽电机控制的生理研究15,16和神经精神状态17,18, 19,20。
先前的 fTMS 研究使用 GNG14和 SST 任务15、16、21, 探讨了健康成人的反应抑制皮层机制。此外, 一项研究表明, 在 fTMS/GNG 实验中, 单剂量的哌改变了健康成人的运动皮层生理。22到目前为止, 有两组已发表儿科 fTMS 研究使用 GNG 任务, 以表征 ADHD 患者的皮质生理的23和妥瑞症17。目前没有发表的 fTMS 研究利用 SST 在儿科人口。
fTMS 研究的一个关键问题, 比单独的 TMS 研究更大的程度, 是肌肉伪迹。标准的表面肌电图 (肌电信号) 测量的振幅和潜伏期的运动诱发电位 (机电) 不能被污染的肌肉神器。因此, 例如, 为了研究在反应时间研究中的运动准备的皮层变化, TMS 脉冲必须精确地定时发生在 GO 信号之后, 但在个体的反应时间之前。因此, 在任何任务, 这是至关重要的, 以确保 TMS 脉冲发生的时候, 电机的反应还没有开始, 和参与者是舒适的, 能够保持相关的肌肉休息。这可能是异常的问题与动孩子谁可能自然地有外来的运动和谁可能保持他们的胳膊和手紧张在整个反应时间游戏。
本研究的目的是开发一个 Hammel 的, 适合于研究初级运动皮层 (M1) 生理学的斯莱特-海温的版本。这项任务应该是 1) 容易理解的儿童, 2) 相对容易完成的儿童和 3) 与在线 TMS 兼容。

<table><tbody><tr><td>Precision Gamepad</td><td>Logitech</td><td>G-UG15</td><td></td></tr><tr><td>Acquisition Interface Model ACQ-16</td><td>Gould Instrument Systems Inc</td><td>ACQ-16</td><td></td></tr><tr><td>Micro1401-3 Data Acquisition Unit</td><td>Cambridge Electronic Design Ltd</td><td>Not applicable</td><td></td></tr><tr><td>Signal version 6 software (Windows)</td><td>Cambridge Electronic Design Ltd</td><td>Not applicable</td><td></td></tr><tr><td>Power base</td><td>Coulbourn Instruments</td><td>V15-17</td><td></td></tr><tr><td>Bioamplifier with filters</td><td>Coulbourn Instruments</td><td>V75-04</td><td></td></tr><tr><td>Conductor electrode cables (for surface EMG)</td><td>Coulbourn Instruments</td><td>V91-33</td><td></td></tr><tr><td>200&lt;sup&gt;2&lt;/sup&gt; TMS device</td><td>The Magstim Company Ltd</td><td>Not applicable</td><td></td></tr><tr><td>BiStim&lt;sup&gt;2&lt;/sup&gt; module</td><td>The Magstim Company Ltd</td><td>Not applicable</td><td></td></tr><tr><td>90mm circular TMS coil</td><td>The Magstim Company Ltd</td><td>Not applicable</td><td></td></tr><tr><td>Presentation software (Windows)</td><td>Neurobehavioral Systems Inc</td><td>Not applicable</td><td></td></tr><tr><td>Windows computer</td><td></td><td>Not applicable</td><td></td></tr></tbody></table>

online transcranial magnetic stimulation protocol for measuring cortical physiology associated with response inhibition

我们描述了一个可重现的, 有利于儿童的马达反应抑制任务的发展, 适合在线经颅磁刺激 (TMS) 表征的初级运动皮质 (M1) 兴奋性和抑制。运动反应抑制防止不必要的行为, 并在几个神经精神条件异常。TMS 是一种非侵入性的技术, 可以量化 M1 的兴奋性和抑制使用单和配对脉冲协议, 可以精确计时研究皮质生理与高时间分辨率。我们修改了原来的斯莱特-Hammel (S H) 停止信号任务, 创建一个 "赛车" 版本与 TMS 脉冲时间锁定的内部试验事件。这项任务是自我节奏, 每个试验启动后, 一个按钮推动赛车向 800 ms 目标。去试验需要一个手指升降机来阻止赛车就在这个目标。随机穿插是停止试验 (25%) 在这期间, 动态调整停止信号提示主题, 以防止手指举升。对于 GO 试验, TMS 脉冲被交付了在650毫秒在试验以后开始;然而, 对于停止试验, TMS 脉冲发生150毫秒后停止信号。TMS 脉冲的计时根据脑电图 (eeg) 研究在停止信号任务期间在这些时间范围显示事件相关的变化决定。这项任务在两个研究站点 (n=38) 的3块中进行了研究, 我们记录了行为表现和事件相关的运动诱发电位。采用回归建模的方法, 利用年龄作为多独立变量的协 (性别、研究部位、阻滞、TMS 脉冲条件 [单-对配对脉冲]、试验条件 [GO、成功停止、失败停止]) 来分析机电环境的振幅。分析表明, TMS 脉冲条件 (p < 0.0001) 及其与试验条件 (p = 0.009) 的相互作用是显著的。这个在线的 S-H/tms 范例的未来应用包括增加同时脑电图采集来测量 TMS 诱发的脑电图电位。一个潜在的限制是, 在儿童, TMS 脉冲声音可能会影响行为任务的表现。

回归分析是使用商业统计软件包来分别分析行为和神经数据的。代表性数据从23典型地开发的孩子从辛辛那提和15从巴尔的摩 (25 男性, 13 女性)。年龄没有区别在站点之间 (10.3 ±1.3 年为辛辛那提并且10.4 ±1.2 年为巴尔的摩; t 测试 p = 0.74)
我们使用回归模型来分析 SSRT 与性别、地点 (辛辛那提 vs 巴尔的摩) 和试验块作为独立变量的?...

Watch this Scientific Journal Video about Online Transcranial Magnetic Stimulation Protocol for Measuring Cortical Physiology Associated with Response Inhibition at JoVE.com

Online Transcranial Magnetic Stimulation Protocol for Measuring Cortical Physiology Associated with Response Inhibition

我们描述了一个实验过程, 以量化的兴奋性和抑制的主要运动皮层在电机响应抑制任务, 利用经颅磁刺激在整个过程中停止信号的任务。

在线经颅磁刺激测量与反应抑制相关的皮质生理

We describe the development of a reproducible, child-friendly motor response inhibition task suitable for online Transcranial Magnetic Stimulation (TMS) ...

online-transcranial-magnetic-stimulation-protocol-for-measuring

Research

JoVE Journal

Neuroscience

9.1K 次观看.  University of Cincinnati. 我们描述了一个实验过程, 以量化的兴奋性和抑制的主要运动皮层在电机响应抑制任务, 利用经颅磁刺激在整个过程中停止信号的任务。

视频: Online Transcranial Magnetic Stimulation Protocol for Measuring Cortical Physiology Associated with Response Inhibition

Transcranial Magnetic Stimulation for Investigating Causal Brain-behavioral Relationships and their Time Course

Transcranial magnetic stimulation (TMS) is a safe, non-invasive brain stimulation technique that uses a strong electromagnet in order to temporarily disrupt information processing in a brain region, generating a short-lived &#8220;virtual lesion.&#8221; Stimulation that interferes with task performance indicates that the affected brain region is necessary to perform the task normally. In other words, unlike neuroimaging methods such as functional magnetic resonance imaging (fMRI) that indicate correlations between brain and behavior, TMS can be used to demonstrate causal brain-behavior relations. Furthermore, by varying the duration and onset of the virtual lesion, TMS can also reveal the time course of normal processing. As a result, TMS has become an important tool in cognitive neuroscience. Advantages of the technique over lesion-deficit studies include better spatial-temporal precision of the disruption effect, the ability to use participants as their own control subjects, and the accessibility of participants. Limitations include concurrent auditory and somatosensory stimulation that may influence task performance, limited access to structures more than a few centimeters from the surface of the scalp, and the relatively large space of free parameters that need to be optimized in order for the experiment to work. Experimental designs that give careful consideration to appropriate control conditions help to address these concerns. This article illustrates these issues with TMS results that investigate the spatial and temporal contributions of the left supramarginal gyrus (SMG) to reading.

Transcranial magnetic stimulation (TMS) is a technique for non-invasively disrupting neural information processing and measuring its effect on behavior. When TMS interferes with a task, it indicates that the stimulated brain region is necessary for normal task performance, allowing one to systematically relate brain regions to cognitive functions.

经颅磁刺激对调查因果脑 - 行为关系及其时间进程

Transcranial magnetic stimulation (TMS) is a safe, non-invasive brain stimulation technique that uses a strong electromagnet in order to temporarily ...

科研

行为学

Combining Transcranial Magnetic Stimulation and fMRI to Examine the Default Mode Network

The default mode network is a group of brain regions that are active when an individual is not focused on the outside world and the brain is at "wakeful rest."1,2,3 It is thought the default mode network corresponds to self-referential or "internal mentation".2,3
It has been hypothesized that, in humans, activity within the default mode network is correlated with certain pathologies (for instance, hyper-activation has been linked to schizophrenia 4,5,6 and autism spectrum disorders 7 whilst hypo-activation of the network has been linked to Alzheimer's and other neurodegenerative diseases 8). As such, noninvasive modulation of this network may represent a potential therapeutic intervention for a number of neurological and psychiatric pathologies linked to abnormal network activation. One possible tool to effect this modulation is Transcranial Magnetic Stimulation: a non-invasive neurostimulatory and neuromodulatory technique that can transiently or lastingly modulate cortical excitability (either increasing or decreasing it) via the application of localized magnetic field pulses.9
In order to explore the default mode network's propensity towards and tolerance of modulation, we will be combining TMS (to the left inferior parietal lobe) with functional magnetic resonance imaging (fMRI). Through this article, we will examine the protocol and considerations necessary to successfully combine these two neuroscientific tools.

In this article, we examine the methodology and considerations relevant to the combination of TMS and fMRI to examine the effects of brain stimulation on the default network.

结合经颅磁刺激和功能磁共振成像检查默认模式网络

The default mode network is a group of brain regions that are active when an individual is not focused on the outside world and the brain is at "wakeful ...

神经科学

Intracortical Inhibition Within the Primary Motor Cortex Can Be Modulated by Changing the Focus of Attention

It is well recognized that an external focus (EF) compared with an internal focus (IF) of attention improves motor learning and performance. Studies have indicated benefits in accuracy, balance, force production, jumping performance, movement speed, oxygen consumption, and fatiguing task. Although behavioral outcomes of using an EF strategy are well explored, the underlying neural mechanisms remain unknown. A recent TMS study compared the activity of the primary motor cortex (M1) between an EF and an IF. More precisely, this study showed that, when adopting an EF, the activity of intracortical inhibitory circuits is enhanced.
On the behavioral level, the present protocol tests the influence of attentional foci on the time to task failure (TTF) when performing submaximal contractions of the first dorsal interosseous (FDI). Additionally, the current paper describes two TMS protocols to assess the influence of attentional conditions on the activity of cortical inhibitory circuits within the M1. Thus, the present article describes how to use single-pulse TMS at intensities below the motor threshold (subTMS) and paired-pulse TMS, inducing short-interval intracortical inhibition (SICI) when applied to the M1. As these methods are assumed to reflect the responsiveness of GABAergic inhibitory neurons, without being affected by spinal reflex circuitries, they are well suited to measuring the activity of intracortical inhibitory circuits within the M1.
The results show that directing attention externally improves motor performance, as participants were able to prolong the time to task failure. Moreover, the results were accompanied by a larger subTMS-induced electromyography suppression and SICI when adopting an EF compared to an IF. As the level of cortical inhibition within the M1 was previously demonstrated to influence motor performance, the enhanced inhibition with an EF might contribute to the better movement efficiency observed in the behavioral task, indicated by a prolonged TTF with an EF.

Using two different transcranial magnetic stimulation (TMS) protocols, this manuscript describes how to measure and compare cortical inhibition within the primary motor cortex when adopting different attentional foci.

通过改变注意力的焦点, 可以调节皮质在初级运动皮层内的抑制

It is well recognized that an external focus (EF) compared with an internal focus (IF) of attention improves motor learning and performance. Studies have ...

Continuous Theta Burst Stimulation of the Posterior Medial Frontal Cortex to Experimentally Reduce Ideological Threat Responses

Decades of behavioral science research have documented functional shifts in attitudes and ideological adherence in response to various challenges, but little work to date has illuminated the neural mechanisms underlying these dynamics. This paper describes how continuous theta burst transcranial magnetic stimulation may be employed to experimentally assess the causal contribution of cortical regions to threat-related ideological shifts. In the example protocol provided here, participants are exposed to a threat prime-an explicit reminder of their own inevitable death and bodily decomposition-following a downregulation of the posterior medial frontal cortex (pMFC) or a sham stimulation. Next, disguised within a series of distracter tasks, participants' relative degree of ideological adherence is assessed-in the present example, with regard to coalitional prejudice and religious belief. Participants for whom the pMFC has been downregulated exhibit less coalitionally biased responses to an immigrant critical of the participants' national in-group, and less conviction in positive afterlife beliefs (i.e., God, angels, and heaven), despite having recently been reminded of death. These results complement prior findings that continuous theta burst stimulation of the pMFC influences social conformity and sharing and illustrate the feasibility of investigating the neural basis of high-level social cognitive shifts using transcranial magnetic stimulation.

Threats reliably evoke shifts in high-level ideological investment, but little work to date has explored the neural mechanisms underlying these dynamics. This paper describes how continuous theta burst transcranial magnetic stimulation may be employed to test the contribution of the posterior medial frontal cortex (and/or other regions) to threat-related ideological shifts.

连续θ爆刺激后内侧额叶皮层实验降低意识形态威胁反应

Decades of behavioral science research have documented functional shifts in attitudes and ideological adherence in response to various challenges, but ...

Brain State-dependent Brain Stimulation with Real-time Electroencephalography-Triggered Transcranial Magnetic Stimulation

The effect of a stimulus to the brain depends not only on the parameters of the stimulus but also on the dynamics of brain activity at the time of the stimulation. The combination of electroencephalography (EEG) and transcranial magnetic stimulation (TMS) in a real-time brain state-dependent stimulation system allows the study of relations of dynamics of brain activity, cortical excitability, and plasticity induction. Here, we demonstrate a newly developed method to synchronize the timing of brain stimulation with the phase of ongoing EEG oscillations using a real-time data analysis system. This real-time EEG-triggered TMS of the human motor cortex, when TMS is synchronized with the surface EEG negative peak of the sensorimotor &#181;-alpha (8-14 Hz) rhythm, has shown differential corticospinal excitability and plasticity effects. The utilization of this method suggests that real-time information about the instantaneous brain state can be used for efficacious plasticity induction. Additionally, this approach enables personalized EEG-synchronized brain stimulation which may lead to the development of more effective therapeutic brain stimulation protocols.

This paper describes real-time electroencephalography-triggered transcranial magnetic stimulation to study and modulate human brain networks.

脑状态依赖性脑刺激与实时脑脑图触发颅内磁刺激

The effect of a stimulus to the brain depends not only on the parameters of the stimulus but also on the dynamics of brain activity at the time of the ...

The Use of Magnetic Resonance Spectroscopy as a Tool for the Measurement of Bi-hemispheric Transcranial Electric Stimulation Effects on Primary Motor Cortex Metabolism

Transcranial direct current stimulation (tDCS) is a neuromodulation technique that has been increasingly used over the past decade in the treatment of neurological and psychiatric disorders such as stroke and depression. Yet, the mechanisms underlying its ability to modulate brain excitability to improve clinical symptoms remains poorly understood 33. To help improve this understanding, proton magnetic resonance spectroscopy (1H-MRS) can be used as it allows the in vivo quantification of brain metabolites such as &#947;-aminobutyric acid (GABA) and glutamate in a region-specific manner 41. In fact, a recent study demonstrated that 1H-MRS is indeed a powerful means to better understand the effects of tDCS on neurotransmitter concentration 34. This article aims to describe the complete protocol for combining tDCS (NeuroConn MR compatible stimulator) with 1H-MRS at 3 T using a MEGA-PRESS sequence. We will describe the impact of a protocol that has shown great promise for the treatment of motor dysfunctions after stroke, which consists of bilateral stimulation of primary motor cortices 27,30,31. Methodological factors to consider and possible modifications to the protocol are also discussed.

This article aims to describe a basic protocol for combining transcranial direct current stimulation (tDCS) with proton magnetic resonance spectroscopy (1H-MRS) measurements to investigate the effects of bilateral stimulation on primary motor cortex metabolism.

磁共振波谱的用途，用于对初级运动皮层新陈代谢双半球经颅电刺激效果的测量工具一

Transcranial direct current stimulation (tDCS) is a neuromodulation technique that has been increasingly used over the past decade in the treatment of ...

Combined Transcranial Magnetic Stimulation and Electroencephalography of the Dorsolateral Prefrontal Cortex

Transcranial magnetic stimulation (TMS) is a non-invasive method that produces neural excitation in the cortex by means of brief, time-varying magnetic field pulses. The initiation of cortical activation or its modulation depends on the background activation of the neurons of the cortical region activated, the characteristics of the coil, its position and its orientation with respect to the head. TMS combined with simultaneous electrocephalography (EEG) and neuronavigation (nTMS-EEG) allows for the assessment of cortico-cortical excitability and connectivity in almost all cortical areas in a reproducible manner. This advance makes nTMS-EEG a powerful tool that can accurately assess brain dynamics and neurophysiology in test-retest paradigms that are required for clinical trials. Limitations of this method include artifacts that cover the initial brain reactivity to stimulation. Thus, the process of removing artifacts may also extract valuable information. Moreover, the optimal parameters for dorsolateral prefrontal (DLPFC) stimulation are not fully known and current protocols utilize variations from the motor cortex (M1) stimulation paradigms. However, evolving nTMS-EEG designs hope to address these issues. The protocol presented here introduces some standard practices for assessing neurophysiological functioning from stimulation to the DLPFC that can be applied in patients with treatment resistant psychiatric disorders that receive treatment such as transcranial direct current stimulation (tDCS), repetitive transcranial magnetic stimulation (rTMS), magnetic seizure therapy (MST) or electroconvulsive therapy (ECT).

The protocol presented here is for TMS-EEG studies utilizing intracortical excitability test-retest design paradigms. The intent of the protocol is to produce reliable and reproducible cortical excitability measures for assessing neurophysiological functioning related to therapeutic interventions in the treatment of neuropsychiatric diseases such as major depression.

侧前额叶皮质联合经颅磁刺激与脑电图的研究

Transcranial magnetic stimulation (TMS) is a non-invasive method that produces neural excitation in the cortex by means of brief, time-varying magnetic ...

Measuring and Manipulating Functionally Specific Neural Pathways in the Human Motor System with Transcranial Magnetic Stimulation

Understanding interactions between brain areas is important for the study of goal-directed behavior. Functional neuroimaging of brain connectivity has provided important insights into fundamental processes of the brain like cognition, learning, and motor control. However, this approach cannot provide causal evidence for the involvement of brain areas of interest. Transcranial magnetic stimulation (TMS) is a powerful, noninvasive tool for studying the human brain that can overcome this limitation by transiently modifying brain activity. Here, we highlight recent advances using a paired-pulse, dual-site TMS method with two coils that causally probes cortico-cortical interactions in the human motor system during different task contexts. Additionally, we describe a dual-site TMS protocol based on cortical paired associative stimulation (cPAS) that transiently enhances synaptic efficiency in two interconnected brain areas by applying repeated pairs of cortical stimuli with two coils. These methods can provide a better understanding of the mechanisms underlying cognitive-motor function as well as a new perspective on manipulating specific neural pathways in a targeted fashion to modulate brain circuits and improve behavior. This approach may prove to be an effective tool to develop more sophisticated models of brain-behavior relations and improve diagnosis and treatment of many neurological and psychiatric disorders.

This article describes new approaches to measure and strengthen functionally specific neural pathways with transcranial magnetic stimulation. These advanced noninvasive brain stimulation methodologies can provide new opportunities for the understanding of brain-behavior relations and development of new therapies to treat brain disorders.

利用颅内磁刺激测量和操纵人体运动系统中功能特定的神经通路

Understanding interactions between brain areas is important for the study of goal-directed behavior. Functional neuroimaging of brain connectivity has ...

Conventional and Threshold-Tracking Transcranial Magnetic Stimulation Tests for Single-handed Operation

Most single-pulse transcranial magnetic stimulation (TMS) parameters (e.g., motor threshold, stimulus-response function, cortical silent period) are used to examine corticospinal excitability. Paired-pulse TMS paradigms (e.g., short- and long-interval intracortical inhibition (SICI/LICI), short-interval intracortical facilitation (SICF), and short- and long-latency afferent inhibition (SAI/LAI)) provide information about intracortical inhibitory and facilitatory networks. This has long been done by the conventional TMS method of measuring changes in the size of the motor-evoked potentials (MEPs) in response to stimuli of constant intensity. An alternative threshold-tracking approach has recently been introduced whereby the stimulus intensity for a target amplitude is tracked. The diagnostic utility of threshold-tracking SICI in amyotrophic lateral sclerosis (ALS) has been shown in previous studies. However, threshold-tracking TMS has only been used in a few centers, in part due to the lack of readily available software but also perhaps due to uncertainty over its relationship to conventional single- and paired-pulse TMS measurements.
A menu-driven suite of semi-automatic programs has been developed to facilitate the broader use of threshold-tracking TMS techniques and to enable direct comparisons with conventional amplitude measurements. These have been designed to control three types of magnetic stimulators and allow recording by a single operator of the common single- and paired-pulse TMS protocols.
This paper shows how to record a number of single- and paired-pulse TMS protocols on healthy subjects and analyze the recordings. These TMS protocols are fast and easy to perform and can provide useful biomarkers in different neurological disorders, particularly neurodegenerative diseases such as ALS.

We present a suite of standardized single- and paired-pulse transcranial magnetic stimulation (TMS) recording protocols, with options for conventional amplitude measurements and threshold-tracking. This program can control three different types of magnetic stimulators and is designed to enable all tests to be performed conveniently by a single operator.

单手操作的常规和阈值跟踪经颅磁刺激测试

Most single-pulse transcranial magnetic stimulation (TMS) parameters (e.g., motor threshold, stimulus-response function, cortical silent period) are used ...

Measuring Contralateral Silent Period Induced by Single-Pulse Transcranial Magnetic Stimulation to Investigate M1 Corticospinal Inhibition

Contralateral silent period (cSP) is a period of suppression in the background electrical muscle activity captured by electromyography (EMG) after a motor evoked potential (MEP). To obtain this, an MEP is elicited by a suprathreshold transcranial magnetic stimulation (TMS) pulse delivered to the primary motor cortex (M1) of the target muscle selected, while the participant provides a standardized voluntary target muscle contraction. The cSP is a result of inhibitory mechanisms that occur after the MEP; it provides a broad temporal assessment of spinal inhibition in its initial ~50 ms, and cortical inhibition after. Researchers have tried to better understand the neurobiological mechanism behind the cSP to validate it as a potential diagnostic, surrogate, and predictive biomarker for different neuropsychiatric diseases. Therefore, this article describes a method to measure M1 cSP of lower and upper limbs, including a selection of target muscle, electrode placement, coil positioning, method of measuring voluntary contraction stimulation, intensity setup, and data analysis to obtain a representative result. It has the educational objective of giving a visual guideline in performing a feasible, reliable, and reproducible cSP protocol for lower and upper limbs and discussing practical challenges of this technique.

Contralateral silent period (cSP) assessment is a promising biomarker to index cortical excitability and treatment response. We demonstrate a protocol to assess cSP intended for studying M1 corticospinal inhibition of upper and lower limbs.

测量单脉冲经颅磁刺激诱导的对侧沉默期以研究M1皮质脊髓抑制

Contralateral silent period (cSP) is a period of suppression in the background electrical muscle activity captured by electromyography (EMG) after a motor ...