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>

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。14,23,34但是, GNG 任务最好以相对较快的速度进行, 以在整个任务中引出优生优育马达响应, 以便在 nogo-a 试验中充分检查抑制控制。35,36从方法论的角度来看, 快节奏的 GNG 任务给在线 fTMS 实验带来了困难, 因为设备电容器需要时间来为下一个刺激脉冲充电。例如, 我们的单相脉冲产生的 tms 设备至少需要4秒的间隔时间, 从而限制快节奏的在线 tms/GNG 实验。此外, 潜在的神经精神或发育障碍会影响儿童完成快节奏的 GNG 任务的能力。斯莱特-Hammel 任务的一个特点是, 它是自我节奏的, 从而允许集成的 TMS 进行在线生理测量。16考克森et al.在健康成人中使用了在线 fTMS/clockhand 的任务, 以显示在停止试验时, 由 SICI 测量的皮质抑制功能更健壮。一个单独的在线 fTMS/SST 研究显示类似的结果, M1 兴奋性下降后, 停止提示成功停止试验。15与考克森 fTMS/S H 协议16相比, 我们进行了两次重大修改。首先, 我们创建了 "赛车" 版本的 S H 停止信号任务, 这是更多的参与儿科参与者。使用这种设计, 通常开发的儿童 (图 3) 和那些有 ADHD (未公布的数据) 能够完成至少120试验。我们建立在在线 fTMS/S H 任务的另一个功能是动态跟踪算法来调整停止信号的定时, 这样在整个实验结束时, 停止试验的成功率是 ~ 50%。这是很重要的, 因为它可以比较的皮质抑制在成功的和不成功的停止试验, 也消除任务的性能作为一个混杂的变数。
该协议中的单脉冲试验允许研究运动准备过程中皮质的兴奋性。然而, 在停止信号响应抑制任务的情况下, 我们也有兴趣量化 M1 SICI 在停止试验。对于 SICI 定量, 阈调节脉冲刺激强度是一个重要的实验参数。先前的研究记录了调节脉冲强度对 SICI 的剂量效应。37,38这些研究表明, 一个更强的条件反射会引出更深刻的 SICI。然而, 我们的实验室历史上使用 60% * RMT 作为调节脉冲强度, 以检测 SICI 差异的儿科病例对照 TMS 研究。19,20由于此调节脉冲强度也会引起显著的 M1 SICI29, 所以我们在这个 fTMS 任务中使用了 60% * RMT 来调节脉冲。
在 SICI 量化中考虑的另一个因素是单脉冲诱发的机电振幅。采用平均单脉冲诱导的 SICI 比值作为计算的分母。这一基线振幅取决于不同的状态, 如休息, 马达观察/图像, 马达准备以及测试脉冲刺激强度。10,39,40在该在线 fTMS/S H 任务中, 与基线 rest 条件相比, 在任务期间, 该工作区的振幅通常是3到4倍 (未显示数据)。在最初的 SICI 研究28中, 作者指出, SICI 是一个更强的测试刺激。然而, 支持这一结论的原始数据并没有显示在手稿中。随后的研究已经检查了一系列的基线休息的幅度 (0.2, 1 和 4 mV), 并表明, 基线机电振幅不影响 SICI。41,42另一项研究考察了运动条件 (静止、同侧/对侧等轴收缩) 和试验脉冲刺激强度 (90-150% * RMT) 对 SICI 的影响。37 SICI 在等距手指收缩时较少, 并随测试脉冲刺激强度而变化。然而, 重复测量方差分析并没有确定条件和测试脉冲刺激强度之间的统计学意义上的相互作用。后的分析表明, SICI 在对侧等距收缩是重要的一系列测试脉冲刺激强度 (110, 120, 130 和140% 的 RMT)。由于儿童的自然高马达阈值33, 它是理想的保持测试脉冲强度尽可能低, 由于潜在的 TMS 硬件限制和参与者的舒适性。由于这些原因, 我们选择 120% * RMT 作为测试脉冲强度。然而, 这个在线的 S-H/TMS 任务可能适用于甚至更年幼的孩子, 我们要降低测试脉冲强度为 105-110% * RMT 未来的实验。
这个协议的一个潜在的限制是, 更强, 更响亮的 TMS 脉冲对儿童的需要可能会影响他们的 S H 任务的表现。此外, TMS 脉冲的平均增加强度也可能扰乱皮层回路, 从而影响反应抑制。另一种可能性是, 更强的脉搏更响亮, 可以分散孩子在任务。对于未来的实验, 这可以通过重新做斯莱特-Hammel 任务与 tms 脉冲传递在类似的强度在一个区域不涉及电机反应抑制, 或使用假 tms 线圈。另一个限制是停止试验的次数很少。这项 fTMS 任务要求参加者完成120项试验, 其中只有30项是停止试验。我们的动态跟踪算法将会导致50% 的成功率;因此, 只有15成功的和15不成功的试验进行分析。如果在这些试验中检测到明显的运动伪影, 则不包括跟踪, 从而减少统计功率。这可能是真实的, 如果数据被表示为每一个试验类型的每个个体的平均的信号强度 (休息, 去, 停止)。使用重复测量的统计模型, 估计试用型的欧洲议员基于所有的试验, 我们已经做了, 可能会允许更有意义的结果。
总之, 我们开发了一种无创的, 耐受性和交互式的定量皮层抑制的方法, 以检测反应抑制任务中的差异。这可以进一步应用到神经精神的条件, 以研究皮质抑制的儿童。在这个 fTMS 协议上有许多扩展方法。最近的研究已经使用双线圈配对脉冲 TMS 范式来研究成人行为任务中的皮质连通性。43,44使用神经导航, 这种方法可以扩展到儿科人群, 以检查前额淋巴结对反应抑制的影响。重复 TMS (刺激) 提供了另一个选项来调节大脑区域, 这对于抑制运动反应至关重要。43,45,46此外, 另一个潜在的未来应用是将该协议与同时脑电图相结合, 以量化 non-M1 地区的 TMS 诱发皮层电位47 , 以表征与运动反应相关的皮质生理抑制.

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 border="0" cellpadding="0" cellspacing="0" width="772">
	<tbody>
		<tr height="21">
			<td height="21" style="height:21px;width:271px;">Precision Gamepad</td>
			<td style="width:215px;">Logitech</td>
			<td style="width:119px;">G-UG15</td>
			<td style="width:167px;"></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:271px;">Acquisition Interface Model ACQ-16</td>
			<td style="width:215px;">Gould Instrument Systems Inc</td>
			<td>ACQ-16</td>
			<td></td>
		</tr>
		<tr height="42">
			<td height="42" style="height:42px;width:271px;">Micro1401-3 Data Acquisition Unit</td>
			<td style="width:215px;">Cambridge Electronic Design Ltd</td>
			<td style="width:119px;">Not applicable</td>
			<td></td>
		</tr>
		<tr height="42">
			<td height="42" style="height:42px;width:271px;">Signal version 6 software (Windows)</td>
			<td style="width:215px;">Cambridge Electronic Design Ltd</td>
			<td style="width:119px;">Not applicable</td>
			<td></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:271px;">Power base</td>
			<td style="width:215px;">Coulbourn Instruments</td>
			<td style="width:119px;">V15-17</td>
			<td></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:271px;">Bioamplifier with filters</td>
			<td style="width:215px;">Coulbourn Instruments</td>
			<td style="width:119px;">V75-04</td>
			<td></td>
		</tr>
		<tr height="42">
			<td height="42" style="height:42px;width:271px;">Conductor electrode cables (for surface EMG)</td>
			<td style="width:215px;">Coulbourn Instruments</td>
			<td style="width:119px;">V91-33</td>
			<td></td>
		</tr>
		<tr height="24">
			<td height="24" style="height:24px;width:271px;">2002 TMS device</td>
			<td style="width:215px;">The Magstim Company Ltd</td>
			<td style="width:119px;">Not applicable</td>
			<td></td>
		</tr>
		<tr height="24">
			<td height="24" style="height:24px;width:271px;">BiStim2 module</td>
			<td style="width:215px;">The Magstim Company Ltd</td>
			<td style="width:119px;">Not applicable</td>
			<td></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:271px;">90mm circular TMS coil</td>
			<td style="width:215px;">The Magstim Company Ltd</td>
			<td style="width:119px;">Not applicable</td>
			<td></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:271px;">Presentation software (Windows)</td>
			<td style="width:215px;">Neurobehavioral Systems Inc</td>
			<td style="width:119px;">Not applicable</td>
			<td></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:271px;">Windows computer</td>
			<td style="width:215px;"></td>
			<td style="width:119px;">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协。还探讨了这些变量之间的相互作用。这一分析表明, 年龄是唯一的变量, 对 SSRT (p = 0.005) 有显著的影响。
TMS 神经数据的特点是使用峰值至峰值作为回归分析的相关变量。在运动准备过程中, M1 的兴奋性在实际运动发生前增加。TMS 的研究表明, 这种兴奋性增加发生在肌肉收缩前 100-140 毫秒。10,11,31,32在这项任务中, tms 脉冲和指举成功的停止试验之间的时间总是大于150毫秒 (即最新可能的 tms 脉冲发生在 850 ms 和手指升降机发生 > 1000 毫秒后启动试验)。在我们的分析, 我们有兴趣比较皮质兴奋性和抑制相关的运动反应抑制。因为我们有兴趣比较所有的三不同的任务条件 (GO, 成功的停止, 失败的停止), 我们分析的数据从试验时, TMS 脉冲和手指升降机之间的时间是至少150毫秒, 因为在这个时间框架之外的信号幅度不受运动准备。10,11,31,因此, 32此时间延迟不包括在回归模型中作为协。对于我们的回归模型, 我们把年龄作为一个协, 因为它影响了童年时期的机电振幅。33独立于模型的类变量包括性、站点、试验块、TMS 脉冲条件 (单对配对脉冲) 和试验条件 (GO、成功停止、失败停止)。主要的相互作用的兴趣是在 TMS 脉冲条件和试验条件, 因为我们感兴趣的是如何 M1 兴奋性 (单脉冲 tms) 和抑制 (配对脉冲 tms) 不同的任务条件之间的差异。
对于机电系统的振幅, 回归模型中的独立变量性、位置和试块不显著。在回归模型中, 年龄并不显著, 协 (p = 0.28)。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。图 3使用从回归模型计算的具有代表标准错误的误差线的最小平方均值估计, 在不同的试验条件下显示具有代表性的神经数据。在三任务条件之间, 对单脉冲机电振幅的所有配对明智的比较是微不足道的 (假发现率 [罗斯福] 调整了 p > 0.05)。然而, 对于抑制成对脉冲的欧洲议员, GO 与失败停止之间的区别 (罗斯福调整的 p = 0.009) 和成功与失败的中止 (罗斯福调整的 p = 0.03) 是重要的。在 GO 和成功停止试验之间的配对脉冲的不同幅度的比较并不显著 (罗斯福调整 p = 0.56)。
<img alt="Figure 1" class="xfigimg" src="/files/ftp_upload/56789/56789fig1.jpg"> 图 1: 赛车 S H 任务中的手和手指位置双手枕在枕头上。占主导地位的食指是延长和休息在游戏控制器按钮。占主导地位的食指压低按钮, 并激活每个试验。<a href="//cloudflare-jove-com.remotexs.ntu.edu.sg/files/ftp_upload/56789/56789fig1large.jpg" target="_blank">请单击此处查看此图的较大版本.</a>
<img alt="Figure 2" class="xfigimg" src="/files/ftp_upload/56789/56789fig2v2.jpg"> 图 2: 试用示意图。 (A) 试用示意图。在一个按钮上占主导地位的食指, 激活汽车在屏幕上移动。预计参加者将在试验开始后的 700-800 毫秒之间举起手指, 以阻止汽车接近, 但在800毫秒目标之前。TMS 脉冲被给在650毫秒在试验开始之后。 (B) 在 GO 试验中穿插的是停止试验, 在这期间, 参与者被指示防止手指抬起以响应停止信号 (即汽车在800毫秒大关前的某个时刻突然停止)。TMS 脉冲被交付了150毫秒在中止信号以后。<a href="//cloudflare-jove-com.remotexs.ntu.edu.sg/files/ftp_upload/56789/56789fig2v2large.jpg" target="_blank">请单击此处查看此图的较大版本.</a>
<img alt="Figure 3" class="xfigimg" src="/files/ftp_upload/56789/56789fig3.jpg"> 图3。在赛车的任务中的振幅.M1 单和配对脉冲 tms 测量的毫伏振幅 (在不同的条件下) 为这个在线的 S H/tms 任务 (去, 成功的中止, 失败的中止) 被绘。利用回归分析计算出的最小二乘估计值。误差线表示从回归模型计算出的标准误差。<a href="//cloudflare-jove-com.remotexs.ntu.edu.sg/files/ftp_upload/56789/56789fig3large.jpg" target="_blank">请单击此处查看此图的较大版本.</a>

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

Nanyang Technological University

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

A Novel Approach for Documenting Phosphenes Induced by Transcranial Magnetic Stimulation

Stimulation of the human visual cortex produces a transient perception of light, known as a phosphene. Phosphenes are induced by invasive electrical stimulation of the occipital cortex, but also by non-invasive Transcranial Magnetic Stimulation (TMS)1 of the same cortical regions. The intensity at which a phosphene is induced (phosphene threshold) is a well established measure of visual cortical excitability and is used to study cortico-cortical interactions, functional organization 2, susceptibility to pathology 3,4 and visual processing 5-7. Phosphenes are typically defined by three characteristics: they are observed in the visual hemifield contralateral to stimulation; they are induced when the subject s eyes are open or closed, and their spatial location changes with the direction of gaze 2. Various methods have been used to document phosphenes, but a standardized methodology is lacking. We demonstrate a reliable procedure to obtain phosphene threshold values and introduce a novel system for the documentation and analysis of phosphenes. We developed the Laser Tracking and Painting system (LTaP), a low cost, easily built and operated system that records the location and size of perceived phosphenes in real-time. The LTaP system provides a stable and customizable environment for quantification and analysis of phosphenes.

Phosphenes are transient percepts of light that can be induced by applying Transcranial Magnetic Stimulation (TMS) to visually sensitive regions of cortex. We demonstrate a standard protocol for determining the phosphene threshold value and introduce a novel method for quantifying and analyzing perceived phosphenes.

一个新颖的方法记录经颅磁刺激诱发幻视

Stimulation of the human visual cortex produces a transient perception of light, known as a phosphene. Phosphenes are induced by invasive electrical ...

科研

神经科学

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 ...

TMS: Using the Theta-Burst Protocol to Explore Mechanism of Plasticity in Individuals with Fragile X Syndrome and Autism

Fragile X Syndrome (FXS), also known as Martin-Bell Syndrome, is a genetic abnormality found on the X chromosome.1,2 Individuals suffering from FXS display abnormalities in the expression of FMR1 - a protein required for typical, healthy neural development.3 Recent data has suggested that the loss of this protein can cause the cortex to be hyperexcitable thereby affecting overall patterns of neural plasticity.4,5
In addition, Fragile X shows a strong comorbidity with autism: in fact, 30% of children with FXS are diagnosed with autism, and 2 - 5% of autistic children suffer from FXS.6
Transcranial Magnetic Stimulation (a non-invasive neurostimulatory and neuromodulatory technique that can transiently or lastingly modulate cortical excitability via the application of localized magnetic field pulses 7,8) represents a unique method of exploring plasticity and the manifestations of FXS within affected individuals. More specifically, Theta-Burst Stimulation (TBS), a specific stimulatory protocol shown to modulate cortical plasticity for a duration up to 30 minutes after stimulation cessation in healthy populations, has already proven an efficacious tool in the exploration of abnormal plasticity.9,10 
Recent studies have shown the effects of TBS last considerably longer in individuals on the autistic spectrum - up to 90 minutes.11 This extended effect-duration suggests an underlying abnormality in the brain's natural plasticity state in autistic individuals - similar to the hyperexcitability induced by Fragile X Syndrome.
In this experiment, utilizing single-pulse motor-evoked potentials (MEPs) as our benchmark, we will explore the effects of both intermittent and continuous TBS on cortical plasticity in individuals suffering from FXS and individuals on the Autistic Spectrum.

In this article, we examine the effects of Theta-Burst TMS stimulation on cortical plasticity in individuals suffering from Fragile X syndrome and individuals on the autistic spectrum.

TMS:使用的Theta突发协议，以探索个人与脆性X综合征与孤独症的可塑性Mechasnism

Fragile X Syndrome (FXS), also known as Martin-Bell Syndrome, is a genetic abnormality found on the X chromosome.1,2 Individuals suffering from FXS ...

State-Dependency Effects on TMS:  A Look at Motive Phosphene Behavior

Transcranial magnetic stimulation (TMS) is 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.1,2 Within the field of TMS, the term state dependency refers to the initial, baseline condition of the particular neural region targeted for stimulation. As can be inferred, the effects of TMS can (and do) vary according to this primary susceptibility and responsiveness of the targeted cortical area.3,4,5

In this experiment, we will examine this concept of state dependency through the elicitation and subjective experience of motive phosphenes. Phosphenes are visually perceived flashes of small lights triggered by electromagnetic pulses to the visual cortex. These small lights can assume varied characteristics depending upon which type of visual cortex is being stimulated. In this particular study, we will be targeting motive phosphenes as elicited through the stimulation of V1/V2 and the V5/MT+ complex visual regions.6

In this article, we examine the effects of visually relevant state dependency on TMS induced motive phosphenic presentations.

依赖国家对TMS的:一看动机幻视行为

Transcranial magnetic stimulation (TMS) is a non-invasive neurostimulatory and neuromodulatory technique that can transiently or lastingly modulate ...

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 ...

Effects of Transcranial Alternating Current Stimulation on the Primary Motor Cortex by Online Combined Approach with Transcranial Magnetic Stimulation

Transcranial Alternating Current Stimulation (tACS) is a neuromodulatory technique able to act through sinusoidal electrical waveforms in a specific frequency and in turn modulate ongoing cortical oscillatory activity. This neurotool allows the establishment of a causal link between endogenous oscillatory activity and behavior. Most of the tACS studies have shown online effects of tACS. However, little is known about the underlying action mechanisms of this technique because of the AC-induced artifacts on Electroencephalography (EEG) signals. Here we show a unique approach to investigate online physiological frequency-specific effects of tACS of the primary motor cortex (M1) by using single pulse Transcranial Magnetic Stimulation (TMS) to probe cortical excitability changes. In our setup, the TMS coil is placed over the tACS electrode while Motor Evoked Potentials (MEPs) are collected to test the effects of the ongoing M1-tACS. So far, this approach has mainly been used to study the visual and motor systems. However, the current tACS-TMS setup can pave the way for future investigations of cognitive functions. Therefore, we provide a step-by-step manual and video guidelines for the procedure.

Transcranial Alternating Current Stimulation (tACS) allows the modulation of cortical excitability in a frequency-specific fashion. Here we show a unique approach which combines online tACS with single pulse Transcranial Magnetic Stimulation (TMS) in order to "probe" cortical excitability by means of Motor Evoked Potentials.

经颅磁刺激在线联合方法对经颅交流电刺激对原发性运动皮层的影响

Transcranial Alternating Current Stimulation (tACS) is a neuromodulatory technique able to act through sinusoidal electrical waveforms in a specific ...

Chronic Transcranial Electrical Stimulation and Intracortical Recording in Rats

Transcranial electrical stimulation (TES) is a powerful and relatively simple approach to diffusely influence brain activity either randomly or in a closed-loop event-triggered manner. Although many studies are focusing on the possible benefits and side-effects of TES in healthy and pathologic brains, there are still many fundamental open questions regarding the mechanism of action of the stimulation. Therefore, there is a clear need for a robust and reproducible method to test the acute and the chronic effects of TES in rodents. TES can be combined with regular behavioral, electrophysiological, and imaging techniques to investigate neuronal networks in vivo. The implantation of transcranial stimulation electrodes does not impose extra constraints on the experimental design while it offers a versatile, flexible tool to manipulate brain activity. Here we provide a detailed, step-by-step protocol to fabricate and implant transcranial stimulation electrodes to influence brain activity in a temporally constrained manner for months.

This detailed protocol describes transcranial stimulation electrode placement on the temporal bone in order to investigate the short- and long-term effects of transcranial electrical stimulation in freely moving rats.

大鼠慢性经颅电刺激及 Intracortical 记录

Transcranial electrical stimulation (TES) is a powerful and relatively simple approach to diffusely influence brain activity either randomly or in a ...

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 ...

Stimulation Location Determination using a 3D Digitizer with High-Definition Transcranial Direct Current Stimulation

The abundance of neuroimaging data and rapid development of machine learning has made it possible to investigate brain activation patterns. However, causal evidence of brain area activation leading to a behavior is often left missing. Transcranial direct current stimulation (tDCS), which can temporarily alter brain cortical excitability and activity, is a noninvasive neurophysiological tool used to study causal relationships in the human brain. High-definition transcranial direct current stimulation (HD-tDCS) is a noninvasive brain stimulation (NIBS) technique that produces a more focal current compared to conventional tDCS. Traditionally, the stimulation location has been roughly determined through the 10-20 EEG system, because determining precise stimulation points can be difficult. This protocol uses a 3D digitizer with HD-tDCS to increase accuracy in determination of stimulation points. The method is demonstrated using a 3D digitizer for more accurate localization of stimulation points in the right temporo-parietal junction (rTPJ).

Presented here is a protocol to achieve higher accuracy in determination of stimulation location combining a 3D digitizer with high-definition transcranial direct current stimulation.

使用具有高清晰度颅内直接电流刺激的 3D 数字化仪确定刺激位置

The abundance of neuroimaging data and rapid development of machine learning has made it possible to investigate brain activation patterns. However, ...

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 ...