这项研究得到了湘雅博爱康复医院的资助。

本研究严格按照国家人体实验标准进行，临床研究经湘雅博爱康复医院伦理协会批准（伦理批准文号：20211223）。儿童的监护人同意参加该培训项目，并签署了知情同意书。2022年2月至2022年12月，在中南大学湘雅博爱康复医院和湘雅医院招募了患有SCP的儿童。
1.实验前的准备工作
<ol><li>为确保学习结果的准确性，应为康复治疗师提供相关培训，并提前评估他们的技能，以确保他们能够在培训中指导孩子。 注意：rTMS 技术人员应经过培训并具备资格，以确保儿童的安全。</li>
	<li>在实验前与父母进行 rTMS 安全性筛查，包括询问他们是否有癫痫发作和服用药物的证据。 注意：药物可以降低癫痫发作阈值。</li>
</ol>2. 招聘
<ol><li>招募临床诊断和分类符合《中国脑瘫康复治疗指南〔2022〕21标准的SCP患儿。<ol><li>确保孩子年龄在 3 到 6 岁之间。</li>
		<li>确保儿童具有 Gesell 发育诊断量表 （GDDS） 适应性行为区域发展商数 （DQ） > 55，以便他们能够积极参与训练。</li>
		<li>确保儿童具有粗大运动功能分类 （GMFCS） I-III。</li>
		<li>确保儿童可以独立行走超过 10 m，也可以使用助行器行走。</li>
	</ol></li>
	<li>排除以下情况：患有其他类型脑瘫的儿童;在研究期间计划进行医疗康复或手术的儿童;患有癫痫、严重智力障碍、视力障碍或注意力缺陷的儿童;植入人工耳蜗或颅内植入物的儿童。</li>
	<li>培训前，从儿童监护人处获得知情同意书，自愿参加该培训计划，每天 1 次，每周 5 天，持续 12 周。</li>
</ol>3.治疗前评估
<ol><li>分析从招募的 SCP 儿童收集的基线数据，包括姓名、性别、年龄、脑瘫痉挛类型、GMFCS、认知水平、踝足矫形器佩戴、既往或现在的医疗治疗和手术史。</li>
	<li>康复评估 注：研究表明，用于评估 SCP 儿童下肢痉挛程度的综合痉挛量表 （CSS） 具有良好的信度和效度22.<ol><li>通过检查下肢跟腱反射、踝跖屈肌群的肌肉张力和踝阵挛来确定痉挛的程度。使用以下评估标准：无痉挛，<7;轻度痉挛，7-9;中度痉挛，10-12;和严重痉挛，13-16。</li>
		<li>根据儿科平衡量表 （PBS）23 评估平衡功能，其中包括 14 个测试项目。每个项目分为五个级别，每个项目 0-4 分，总分 56 分。分数越高，平衡函数越好。 注：PBS以BBS儿童修订版为基础，主要调整测试项目的顺序，缩短保持姿势的时间，明确测试说明。</li>
		<li>根据 10 m 步行速度 （10MWS）24 评估儿童的行走能力。<ol><li>要求儿童在宽 x 长 = 20 cm x 15 m 规格的跑道上尽可能快地行走，独立或佩戴踝足矫形器或使用 GMFCS III 级儿童的助行器。</li>
		</ol></li>
		<li>让孩子从 15 米标记处开始行走;从 12 m 开始计时，在 2 m 处停止以测量中间 10 m 所花费的时间。让孩子连续进行三次 10MWT 测试，并计算步行速度 （m/s）。 注意：根据 GMFCS，儿童的功能水平被评为 I-III，这意味着他们具有一定的站立和行走能力。</li>
		<li>通过在粗大运动功能测量 （GMFM） 中选择 D 区的站立姿势（13 项）和 E 区的步行、跑步和跳跃（24 项）来评估儿童的粗大运动功能水平。根据各项目的完成程度（0-3分）计算分数，得到D区和E区的总分。分数越高，粗大运动功能越好。</li>
		<li>使用公式 （1） 和 （2） 计算有效率，并通过测量治疗前后 GMFM-88E 部分的分数差异来评估粗大运动功能干预的临床有效性。 有效率 （%） = <img alt="Equation 1" src="/files/ftp_upload/66013/66013eq01.jpg" style="margin: auto;"> （1） 有效率率=显著有效率率+有效率率（2）<ol><li>如果有效率为 >50%，则认为结果显著有效。</li>
			<li>如果有效率在 20% 到 50% 之间，则认为结果是有效的。</li>
			<li>如果有效率为 <20%，则认为结果是无效的。</li>
		</ol></li>
	</ol></li>
</ol>4.治疗方法
注意：向儿童的监护人解释培训计划的原则和目标，以及培训过程中可能出现的不利影响和安全问题。
<ol><li>将SCP患儿按数值表法随机分为常规组、rTMS组、AOT组、联合干预组4组（本研究每组16例）。</li>
	<li>确保所有儿童都接受常规康复治疗，并在此基础上给予他们不同的康复治疗措施。传统组不接受其他康复治疗;rTMS组接受rTMS;AOT 组接收 AOT;研究组接受 rTMS 联合 AOT。<ol><li>向受试者儿童的家庭详细解释他们参与传统康复、rTMS、AOT 和联合干预培训计划的可能性。确保研究人员对受试者的分配不知情，并且不参与评估。</li>
		<li>根据这些孩子的录取顺序，生成一个数字列表作为电子表格。按以下方式随机分组：数字 1、5、9......对于普通组;数字 2、6、10......用于rTMS组;数字 3、7、11......用于 AOT 组;和数字 4、8、12......对于联合干预组。为确保隐私，在每次治疗期间，请使用窗帘为每个孩子提供一个单独的空间。</li>
	</ol></li>
	<li>常规康复<ol><li>运动疗法<ol><li>向儿童的监护人解释运动疗法的原理和目的，并告知他们治疗的持续时间为30分钟。</li>
			<li>根据他们的肌肉力量等级，指导孩子进行肌肉力量锻炼，以训练髋外展肌、髋后伸肌和踝背伸肌，每组 10 次，每天 3 组。</li>
			<li>根据孩子的平衡功能水平，指导孩子进行无支撑站立、双脚并拢站立、单腿站立等平衡训练，每次10分钟。</li>
			<li>根据孩子的行走能力，指导孩子进行手拉手、独立行走、越障等步行训练，每次进行10min。</li>
		</ol></li>
		<li>水疗<ol><li>向儿童监护人解释水疗的原理、过程和目的，并告知他们治疗时间为 20 分钟。</li>
			<li>使用儿童专用水疗机时，将水温调节到37-38°C的适当温度。</li>
			<li>请家长帮孩子脱掉衣服，穿上防水泳裤和水疗项圈，然后让他们进入水疗机。</li>
			<li>点击泡泡浴按钮开始治疗，并指导孩子站立、转身和双脚在水中交替走步。</li>
		</ol></li>
		<li>按摩理疗<ol><li>首先让孩子诊断出来。</li>
			<li>向儿童的监护人解释按摩治疗的效果，并告知他们治疗的持续时间为30分钟。</li>
			<li>将孩子置于俯卧位，并沿冠状动脉和膀胱经络的两侧交替捏合和推动技术 5-10 次。</li>
			<li>将孩子置于俯卧位，用拇指末端从上到下按压富图、良丘、祖三里、解西、桦天、成福、五中穴位的穴位。</li>
			<li>将孩子置于仰卧或俯卧位，同时用拇指和其他四个手指交替在股四头肌、腘绳肌和小腿肱三头肌上有节奏地抬起和捏 10-20 次。</li>
		</ol></li>
	</ol></li>
	<li>rTMS系统 注意：从事 rTMS 的物理治疗师首先参加了制造商安排的培训。为了参与者的安全，治疗师或其他受过培训的医疗专业人员必须监督整个治疗过程，并提前通知监护人，rTMS产生的脉搏在撞击头皮时可能会引起暂时和轻微的疼痛以及面部和四肢的轻微抽搐。<ol><li>rTMS患者准备<ol><li>在第一次就诊时，让物理治疗师了解受试者儿童的基本信息和病史。</li>
			<li>向儿童的监护人解释rTMS治疗的过程和可能的反应，并告知他们治疗的持续时间约为30分钟。</li>
			<li>将孩子置于仰卧或坐姿，用医用酒精为他们的手脱脂，并根据他们的头围为他们每个人选择合适的定位帽。将鼻枕线放在参与儿童正中线的定位帽上，将鼻枕线与颞顶线的交叉点置于眉毛和枕后隆突之间的线中点。 注意： 应根据他们的头围选择合适的尺寸。</li>
			<li>将记录电极固定在参与儿童的拇短外展肌的腹肌上，将参比电极固定在拇短外展肌腱上，将底部电极固定在手腕上。</li>
		</ol></li>
		<li>rTMS操作准备<ol><li>在rTMS仪器上启动计算机应用程序，输入参与患儿的基本信息和诊断结果，确定治疗方案。</li>
			<li>刺激线圈是一个圆形风冷线圈，其中心与对侧M1区域重合，对应于已识别的短外展肌。将线圈与头皮成 45° 角放置。 注：定位帽是根据脑电图（EEG）10-20电极排列系统设计的，可以快速定位M1区域。</li>
			<li>选择30%的刺激强度，通过手动单脉冲刺激对侧拇短外展肌对应的M1区域。 注意：在治疗过程中，参与的儿童应保持其姿势，以避免刺激目标的偏差。</li>
			<li>观察运动诱发电位界面图，逐渐降低刺激强度。如果儿童初级运动皮层 （M1） 的连续 10 次刺激中至少有 5 次在对侧拇外展肌中诱导运动电位强度超过 50 mV，则将 RMT 定义为引起这种反应的最小刺激强度（图 1A）。</li>
			<li>点击 确认 按钮，保存RMT记录，然后进入 治疗参数 设置页面。</li>
		</ol></li>
		<li>rTMS治疗<ol><li>使用以下设置对未受损大脑皮层的 M1 区域进行低频刺激：刺激频率 1 Hz，刺激强度 80% RMT，刺激次数 10，刺激时间 10 秒，重复次数 80，脉冲总数 80025,26（见图 1B）。</li>
			<li>使用以下设置对受损大脑皮层的 M1 区域进行高频刺激： 刺激频率 5 Hz，刺激强度 100% RMT，刺激次数 15，刺激时间 3 s，重复次数 80， 脉冲总数 1,20010（见 图 1C）。</li>
			<li>观察参与儿童的反应。例如，如果孩子因头皮跳动而开始哭泣、面部过度抽搐或出现癫痫发作和其他不良反应的迹象，请立即停止治疗。 注意：对于患有痉挛性双瘫/四肢瘫痪的儿童，在受损大脑皮层的两侧交替进行受损大脑皮层的 M1 区域的高频刺激。对于痉挛性偏瘫患者，未受损的大脑皮层的M1区域受到低频刺激，而M1区域的受损大脑皮层受到高频刺激。</li>
		</ol></li>
	</ol></li>
	<li>在线生产技术（AOT） 注意：AOT要求物理治疗师提前对受试者的身体动作进行录像，并监督整个治疗过程的安全性和训练准确性。<ol><li>向儿童监护人说明AOT的原理、过程和注意事项，并告知他们持续时间为30分钟。</li>
		<li>请两位专业物理治疗师从前、侧、后三个不同角度拍摄身体运动视频，设计六种身体动作，以改善下肢平衡和行走功能。<ol><li>第一个动作是从坐姿到站姿：通过抬起骨盆和伸展膝关节，将身体从直立的坐姿向前移动，逐渐转换为站立姿势，然后坐下。连续执行此操作 3 次（图 2A）。</li>
			<li>第二个动作是站立练习：将体重尽可能向左或向右移动，然后回到中立位置。依次执行 3 次（图 2B）。</li>
			<li>第三个动作也是一个站立练习：将体重尽可能向前或向后移动，然后回到中立位置。依次执行3次（图2C）。</li>
			<li>第四个动作也是一个站立练习：将身体尽可能向左或向右旋转，然后回到中立位置。依次执行 3 次（图 2D）。</li>
			<li>第五个动作是站立练习：向左或向右侧身行走，然后回到中立位置。依次执行 3 次（图 2E）。</li>
			<li>第六个动作是站立练习：左右替上下 10 厘米高的台阶。依次执行 3 次（图 2F）。</li>
		</ol></li>
		<li>让孩子们聚集在一个安静的房间里，以舒适的姿势坐在距离 86 英寸电视 5 米的地方。</li>
		<li>让物理治疗师先解释身体动作，这样孩子们就可以集中精力观看视频。</li>
		<li>看完视频后，让孩子们模仿这些动作。</li>
	</ol></li>
</ol>5. 治疗后评估
注意：每位患者的治疗前和治疗后 12 周评估将由同一位儿科康复医生完成。
<ol><li>对四组儿童进行12周的不同康复措施后，由同一位小儿康复医生重新评估CSS、PBS、10 MWS、GMFM和粗大运动功能的临床疗效。</li>
	<li>记录监护人对治疗方案的满意度和反馈情况，包括治疗的享受程度和自我意识的提高情况，以及监护人对继续治疗的愿望和建议。</li>
</ol>6. 统计分析
<ol><li>将人口统计学、CSS、PBS、10 m步行速度（10MWS）、GMFM、有效率（%）等评估数据录入软件进行统计分析。</li>
	<li>使用 χ2 检验或 Fisher 概率精度方法分析计数数据。</li>
	<li>确定数据是否符合正态分布，并将正态分布数据表示为均值±标清。<ol><li>采用重复测量偏差分析进行四组间比较，在混合模型下进行重复测量方差分析，验证各组的结果和变异分数是否与近似正态分布一致。</li>
	</ol></li>
	<li>将时间视为组内因素，将干预视为组间因素。如果这两个因子之间存在任何交互作用，则在 a= 0.05 时检验每个时间点的组间差异。如果没有交互作用效应，则测试主效应。考虑差异在 P < 0.05 时具有统计学显著性。</li>
</ol>

痉挛性脑瘫儿童联合干预训练 

提交人无需声明任何利益冲突。

对于患有SCP的儿童，γ和α神经元的活动增加会导致皮质脊髓束输入受到抑制，从而导致肌肉紧张增加，称为痉挛。由于肢体痉挛会显著影响SCP患儿下肢运动功能的发展，因此减少痉挛是重要的训练目标之一。目前，采用逐步治疗策略来缓解痉挛状态，包括康复护理、物理治疗、骨科支具应用、肉毒杆菌毒素注射27、药物治疗和手术干预28。在这项研究中，使用运动疗法、水疗、按摩疗法和 rTMS 等康复技术来缓解 SCP 患儿的痉挛。 表2 显示，联合干预组的CSS评分比其他3组有更大的提高，表明rTMS和AOT联合干预在缓解SCP患儿痉挛状态方面效果更好。Rajak et al.12 提出，增加 rTMS 治疗的频率有助于减少 CP 儿童的肌肉痉挛并促进运动功能的发展。Gupta等29 用rTMS分别用5 Hz和10 Hz治疗脑瘫患者20 d，刺激大脑运动皮层，结果显示rTMS治疗的肌肉张力明显低于常规组。这一发现与本研究的结果一致，其中实验组的CSS得分明显优于其他三组儿童。
在接受rTMS治疗之前，有必要首先测量儿童的运动阈值，以确定他们的治疗强度。对于痉挛性偏瘫患儿，首先评估健康侧，然后评估患侧。健康侧的运动阈值用于确定治疗强度。在rTMS治疗过程中，应正确佩戴定位帽，线圈刺激中心应与线圈确定的固定点重合，线圈应与头皮成45°放置。在这项研究中，选择 M1 区域作为刺激部位，以改善下肢运动障碍。频率为1 Hz的低频刺激可以减少脑血流量和刺激侧的兴奋性，增加对侧的兴奋性。频率为5 Hz的高频刺激可直接提高受刺激侧的皮质兴奋性。目的是达到更好的半球间抑制效果，低频和高频交替刺激有利于运动功能的恢复。
AOT 代表了一种很有前途的脑瘫干预方法，它恢复了受损的大脑网络以重建运动功能，作为物理治疗的辅助手段15,30。根据这一机制，学者们探索了AOT与约束诱导疗法6、全身振动训练31和脑机接口系统32在脑瘫康复中的协同作用。AOT必须向观察者展示有意义的动作，并要求孩子具有一定的认知能力来模仿视频中的动作。AOT 的关键点是观察，而不是动作的执行。由于平衡障碍会影响SCP儿童的独立行走和日常活动，因此提高他们的平衡控制能力尤为重要。这项研究纳入了涉及功能性运动的 AOT 计划，以增强下肢平衡和行走能力。孩子们聚精会神地观看视频，物理治疗师向他们讲述了视频中呈现的动作的更多细节，并指导和监督孩子们正确地进行动作。在培训期间，物理治疗师需要向儿童阐明运动细节，并采取激励措施以确保自发参与。AOT由于操作简单，在脑瘫患儿的远程康复环境中取得了良好的治疗效果33。因此，我们鼓励家长进行密集的居家训练，以提高训练效果。同时，训练效果与患者在观察和/或执行运动时坚持的训练计划密切相关。根据观察培训资源所付出的不同关注程度，将产生不同的学习和绩效结果34.Kim等人[35]在比较短期和长期AOT干预的结果时发现没有实质性差异。
本研究在常规康复的基础上，分别采用常规康复措施、rTMS、AOT和rTMS联合干预4种不同干预方式对SCP患儿粗大运动功能的影响，探讨联合干预是否具有协同效应。表3、表4和表5说明，治疗12周后，各组PBS、10MWS和GMFM评分均有所改善。然而，与传统干预组、rTMS 和 AOT 组相比，联合干预组在 PBS、10MWS 和 GMFM 评分方面表现出最显着的提高。此外，其粗大运动功能有效率也明显更高。表6显示，联合干预组粗大运动功能有效率为87.50%，超过常规组（25.00%）、rTMS组（62.50%）和AOT组（68.75%）（χ2=13.850，P=0.003），表明rTMS和AOT联合干预对改善SCP患儿运动功能更有效。调控机制可能是：首先，rTMS位点是大脑皮层下肢运动区的M1区域，靠近AOT激活MNS的区域。运动观察和执行通过 MNS36 加强了运动皮层和 M1 区域之间的联系。其次，Sun等37证实，rTMS通过向目标大脑区域施加磁场来调节目标大脑皮层的兴奋性，从而产生感应电流，感应电流可以沿着皮质脊髓束和周围运动神经传播，导致肌肉反应，促进肢体运动功能的恢复。AOT可以通过首先观察视频为儿童提供预期的动作体验和准备，并在执行相同任务时促进任务依赖的神经元网络活动38。第三，rTMS 刺激侧运动皮质区域通过感应电流诱导皮层下回路的跨突触激活，从而减少运动和肌肉痉挛活动以建立正确的运动模式39.AOT程序的动作视频可以反复观察，同时通过重复执行程序40来增强运动记忆并促进大脑皮层重塑。联合干预可以协同调节皮层活动，增加运动皮层的兴奋性和运动单元的募集，减少痉挛和肌肉反射亢进，增强相互互动的效果。由于这些原因，rTMS与AOT联合可能具有协同作用，以优化神经可塑性变化并改善运动功能恢复。
rTMS 和 AOT 的联合成为 SCP 患儿下肢功能障碍个体化康复的有效策略，可改善平衡和运动功能。这项研究也存在缺点：由于未使用假 rTMS 条件，因此 rTMS 可能存在安慰剂效应。该研究中使用的大多数评估方法都是康复评估量表，没有应用神经生理学、脑电图或功能性 MRI 等影像学的客观评估。此外，为了获得rTMS治疗和AOT的标准化治疗参数或确定治疗效果，需要进行大规模、长期的临床研究和随机对照试验，并进行客观的神经生理学或影像学评估。

脑性瘫痪1 型 （CP） 是儿童中最常见的致残性疾病之一，是一组由发育中的胎儿和婴儿非进行性脑损伤引起的持续性综合征，包括中枢性运动障碍、姿势异常和行动不便。目前，全球约有1700万儿童患有脑瘫2，其中中国的病例超过500万。在各种形式的脑瘫中，痉挛性脑瘫（SCP）约占80%3。患有SCP的儿童患有脑损伤，导致肌肉痉挛、感觉功能下降、肌肉协调受损和平衡能力下降，所有这些都阻碍了独立行走和日常活动。目前用于增强SCP儿童粗大运动功能的康复措施包括核心稳定性训练4、任务导向训练5、约束诱导运动疗法6和镜像视觉反馈疗法7等活动。这些措施可以通过改善外周器官的功能，自下而上调节和重塑中枢神经系统，从而改善儿童的临床症状。 
经颅磁刺激 （TMS）8,9 是一种无痛、非侵入性且安全的治疗方法。rTMS是指在发出单一命令后，以相等的时间间隔连续释放刺激，这是常规重复刺激模式之一。它基于电磁感应和电磁转换的原理，通过刺激线圈施加瞬态电流，形成脉冲磁场穿透颅骨，产生感应电流，刺激神经元，触发一系列生理生化反应。rTMS 已被应用于神经系统疾病的监测、评估和治疗，为探索大脑的结构和功能提供了一种新的方法10。现有研究11,12 表明 rTMS 对脑瘫儿童的肢体痉挛和运动功能具有不同的治疗效果。此外，rTMS治疗结合其他康复技术的效果更为明显。
AOT 是一种利用镜像神经元系统 （MNS） 建立运动学习和记忆的康复方法13,14。AOT的本质是让观察者仔细观察视频中的动作，然后尽力模仿他们所观察到的。观察过程可能会触发称为 MNS 的神经网络中的激活，类似于当一个人亲自参与执行这些动作时发生的激活15，这为 AOT 提供了神经生理学基础。AOT 已显示出在改善运动障碍患者的运动技能方面取得成功，在脑瘫患者的中风恢复和上肢运动功能恢复方面产生了积极成果16,17。
我们之前的研究发现，基于镜像神经元系统的AOT可以有效提高脑瘫儿童的平衡和行走能力18。此外，研究19 表明，rTMS可以改善SCP患儿的肌肉痉挛、运动和步态，但应用于脑瘫患儿的rTMS治疗标准尚未统一，探索rTMS不同参数对CP患儿的影响，提供个性化、精准的治疗标准是一个亟待解决的问题。我们相信，将rTMS与AOT相结合有潜力发展成为一种有价值的脑瘫神经康复物理治疗策略。rTMS 和 AOT 都刺激了 SCP20 儿童的大脑皮层，从而有助于粗大运动功能的发育。本研究旨在了解rTMS和AOT的联合治疗是否比常规治疗或单独使用rTMS或AOT能取得更大的协同效应。

<table><tbody><tr><td>K6 multimedia scene interactive training system</td><td>Hunan Le Jiekang technology Co., LTD</td><td></td><td>Program implementation</td></tr><tr><td>KLW-SLL type spa machine for children</td><td>Nanjing Kanglongwei Technology Industrial Co., LTD</td><td></td><td>Conventional therapy</td></tr><tr><td>Pulse magnetic field stimulator model YRD CCY-II</td><td>Shenzhen Yingzhi technology Co., LTD</td><td></td><td>Program implementation</td></tr><tr><td>SPSS26 software</td><td>IBM</td><td></td><td>Statistic analysis</td></tr></tbody></table>

repeated transcranial magnetic stimulation combined with action observation training in children with spastic cerebral palsy

本研究介绍了一项使用 2 x 2 因子设计的随机对照试验的结果，比较了重复经颅磁刺激 （rTMS） 和动作观察训练 （AOT） 干预方法对痉挛性脑瘫 （SCP） 儿童痉挛状态、平衡功能和运动功能的影响。该研究旨在调查两种干预措施的组合是否比单独治疗或传统治疗产生更大的改善。
本研究对象患儿按照随机数表随机分为常规组、rTMS组、AOT组、联合干预组4组。四组患儿均接受常规康复治疗，在此基础上给予不同治疗方案的康复治疗方案。常规组无其他治疗，rTMS组接受rTMS，AOT组接受AOT，联合干预组接受rTMS和AOT联合干预。他们每周接受 5 天的培训，持续 12 周。在训练计划开始时和完成 12 周的治疗时评估了痉挛、平衡功能、步行能力和粗大运动功能评分的变化。
共有 64 名患有 SCP 的儿童完成了这项研究，并对他们的结果进行了分析。实验组总粗大运动功能效率为87.50%，明显高于常规组的25.00%、rTMS组的62.50%和AOT组的68.75%。初步结果表明，rTMS和AOT联合干预能有效改善儿童的平衡功能和运动功能，且联合干预的治疗效果优于常规治疗、rTMS或AOT单独使用。最后，明确了联合干预的临床疗效和最佳治疗参数，为治疗师为SCP患儿进行下肢功能康复提供临床依据。

本文介绍了64例SCP患儿（补充表S1 和 补充文件1）的结果，他们按照数字表法随机分为4组，给予不同的康复措施，为期12周。在整个过程中，参与的儿童均未出现头痛、头晕、癫痫发作等不良反应。
四组儿童的人口统计数据如 表1所示。治疗前，脑瘫的性别比、年龄、痉挛性类别、GMFCS、GDDS发育商数（GDDS DQ）、辅助器具（踝足矫形器或助行器）使用情况差异均无统计学意义（ 均P > 0.05）。
 表2比较了4组患儿在12周治疗前后的CSS评分。训练12周后，4组CCS评分均显著下降，其中联合干预组的变化明显大于其他3组。时间效应、组间交互作用效应、交互作用效应均显著（P < 0.05），组间效应不显著（P > 0.05）。
4组患者12周训练前后的PBS、10MWS、GMFM得分见 表3、 表4、 表5。与训练前评分相比，治疗后4组PBS、10MWS、GMFM评分均显著提高，其中联合干预组评分提高幅度最大。时间效应、组间交互作用效应、交互作用效应均显著（P < 0.05），组间效应不显著（P > 0.05）。
表6显示了所有四组儿童对粗大运动功能的临床影响。联合干预组粗大运动功能总有效率为87.50%，明显高于其余3组（rTMS组62.50%，AOT组68.75%，常规组25.00%）（χ2=13.850，P=0.003）。 
<img alt="Figure 1" class="xfigimg" src="/files/ftp_upload/66013/66013fig01.jpg"> 图 1：M1 区域的刺激。 （A） 阈值确定：当对侧 M1 区域对应于拇外展肌时测量 RMT 值，该区域用单脉冲刺激以产生运动诱发电位。（B）对未受损大脑皮层M1区的低频刺激：刺激频率为1Hz，刺激强度为80%RMT，刺激次数为10次，刺激时间持续10 s，重复次数为80次，脉冲总数为800次。（C）损伤大脑皮层M1区高频刺激：刺激频率为5 Hz，刺激强度为100% RMT，刺激次数为15次，刺激时间持续3 s，重复次数为80次，脉冲总数为1200次。 <a href="https://www-jove-com.remotexs.ntu.edu.sg/files/ftp_upload/66013/66013fig01large.jpg" target="_blank">请点击这里查看此图的较大版本.</a>
<img alt="Figure 2" class="xfigimg" src="/files/ftp_upload/66013/66013fig02.jpg"> 图2：动作观察训练。 （A） 第一乐章：从坐到停的转换。（B） 第二乐章：左/右体重移动。（C）第三乐章：来回体重移动。（D）第四乐章：左/右身体旋转。（E） 第五乐章：左/右行走。（F） 第六乐章：交替上下步。 <a href="https://www-jove-com.remotexs.ntu.edu.sg/files/ftp_upload/66013/66013fig02large.jpg" target="_blank">请点击这里查看此图的较大版本.</a>
<table border="1" fo:keep-together.within-page="1" fo:keep-with-next.within-page="always"><tbody><tr><td colspan="10">（n= 64，x±s）</td>
		</tr><tr><td colspan="3">项目</td>
			<td colspan="2">常规组</td>
			<td>rTMS集团</td>
			<td>AOT集团</td>
			<td>联合干预组</td>
			<td>χ2 /F</td>
			<td>P</td>
		</tr><tr><td colspan="3">数量 （n）</td>
			<td colspan="2">16</td>
			<td>16</td>
			<td>16</td>
			<td>16</td>
			<td></td>
			<td></td>
		</tr><tr><td colspan="3">性别比例（男性/女性）</td>
			<td colspan="2">10/6</td>
			<td>10/6</td>
			<td>13/3</td>
			<td>9/7</td>
			<td>2.494</td>
			<td>0.476</td>
		</tr><tr><td colspan="3">年龄（岁）</td>
			<td colspan="2">4.44±0.80</td>
			<td>4.74±0.68</td>
			<td>4.71±0.54</td>
			<td>4.63±0.68</td>
			<td>0.654</td>
			<td>0.683</td>
		</tr><tr><td colspan="3">痉挛性脑瘫的分类（痉挛性半腿麻痹/痉挛性浸渍腿/痉挛性四肢瘫痪）</td>
			<td colspan="2">02-07-2007</td>
			<td>5/10/1</td>
			<td>6/9/1</td>
			<td>5/10/1</td>
			<td>2.105</td>
			<td>0.945</td>
		</tr><tr><td colspan="3">全球绿色监测燃料烃 （n） （I/II/III 级）</td>
			<td colspan="2">7/3/6</td>
			<td>6/5/5</td>
			<td>8/5/3</td>
			<td>8/5/3</td>
			<td>2.750</td>
			<td>0.868</td>
		</tr><tr><td colspan="3">GDDS 数据索引</td>
			<td colspan="2">70.06±10.25</td>
			<td>70.13±9.44</td>
			<td>71.56±12.58</td>
			<td>69.25±6.89</td>
			<td>0.148</td>
			<td>0.931</td>
		</tr><tr><td colspan="3">辅助设备的使用 （n） 是/否</td>
			<td colspan="2"> 5/11</td>
			<td>3/13</td>
			<td>3/13</td>
			<td>4/12</td>
			<td>1.780</td>
			<td>0.699</td>
		</tr></tbody></table>表1：四组儿童基本信息比较（n = 64，x ± s）。 *单因素方差分析。培训前，在性别比例、年龄、脑瘫痉挛类别、GMFCS、GDDS发育商数（GDDS DQ）和辅助设备（踝足矫形器或助行器）的使用方面没有显著差异，表明具有可比性。缩写：GMFCS=粗大运动功能分类;GDDS DQ = Gesell 发育诊断时间表发育商。
<table border="1" fo:keep-together.within-page="1" fo:keep-with-next.within-page="always"><tbody><tr><td colspan="3">群</td>
			<td>数量 （n）</td>
			<td>以前</td>
			<td>后</td>
			<td>F</td>
			<td>P</td>
		</tr><tr><td colspan="3">常规组</td>
			<td>16</td>
			<td>10.63±1.67</td>
			<td>10.19±1.76</td>
			<td></td>
			<td></td>
		</tr><tr><td colspan="3">rTMS集团</td>
			<td>16</td>
			<td>10.88±1.41</td>
			<td>9.75±1.13</td>
			<td></td>
			<td></td>
		</tr><tr><td colspan="3">AOT集团</td>
			<td>16</td>
			<td>10.75±1.13</td>
			<td>9.75±1.00</td>
			<td></td>
			<td></td>
		</tr><tr><td colspan="3">联合干预组</td>
			<td>16</td>
			<td>10.69±1.01</td>
			<td>8.88±1.02</td>
			<td></td>
			<td></td>
		</tr><tr><td colspan="3">组因素</td>
			<td></td>
			<td></td>
			<td></td>
			<td>0.774</td>
			<td>0.513</td>
		</tr><tr><td colspan="3">时间因素</td>
			<td></td>
			<td></td>
			<td></td>
			<td>228.261</td>
			<td><0.001</td>
		</tr><tr><td colspan="3">组因素 * 时间因素</td>
			<td></td>
			<td></td>
			<td></td>
			<td>15.217</td>
			<td><0.001</td>
		</tr></tbody></table>表 2：四组儿童 CSS 分数的比较 （n = 64， x ± s）。 处理后重复测量方差分析结果显示，时间效应、组间交互效应、交互作用效应显著（P < 0.05），组间效应不显著（P > 0.05）。缩写：CSS = 综合痉挛量表;rTMS = 重复经颅磁刺激;AOT = 动作观察训练。
<table border="1" fo:keep-together.within-page="1" fo:keep-with-next.within-page="always"><tbody><tr><td colspan="3">群</td>
			<td>数量 （n）</td>
			<td>以前</td>
			<td>后</td>
			<td>F</td>
			<td>P</td>
		</tr><tr><td colspan="3">常规组</td>
			<td>16</td>
			<td>28.25±9.38</td>
			<td>31.13±9.22</td>
			<td></td>
			<td></td>
		</tr><tr><td colspan="3">rTMS集团</td>
			<td>16</td>
			<td>29.44±10.05</td>
			<td>35.56±9.82</td>
			<td></td>
			<td></td>
		</tr><tr><td colspan="3">AOT集团</td>
			<td>16</td>
			<td>29.25±9.84</td>
			<td>35.94±8.62</td>
			<td></td>
			<td></td>
		</tr><tr><td colspan="3">联合干预组</td>
			<td>16</td>
			<td>29.81±11.59</td>
			<td>41.88±8.03</td>
			<td></td>
			<td></td>
		</tr><tr><td colspan="3">组因素</td>
			<td></td>
			<td></td>
			<td></td>
			<td>1.12</td>
			<td>0.348</td>
		</tr><tr><td colspan="3">时间因素</td>
			<td></td>
			<td></td>
			<td></td>
			<td>371.208</td>
			<td><0.001</td>
		</tr><tr><td colspan="3">组因素 * 时间因素</td>
			<td></td>
			<td></td>
			<td></td>
			<td>27.954</td>
			<td><0.001</td>
		</tr></tbody></table>表 3：四组儿童 PBS 评分的比较 （n = 64， x ± s）。 处理后重复测量方差分析结果显示，时间效应、组间交互效应、交互作用效应显著（P < 0.05），组间效应不显著（P > 0.05）。缩写：PBS = Pediatric Balance Scale;rTMS = 重复经颅磁刺激;AOT = 动作观察训练。
<table border="1" fo:keep-together.within-page="1" fo:keep-with-next.within-page="always"><tbody><tr><td colspan="3">群</td>
			<td>数量 （n）</td>
			<td>以前</td>
			<td>后</td>
			<td>F</td>
			<td>P</td>
		</tr><tr><td colspan="3">Conventiona 集团</td>
			<td>16</td>
			<td>1.02±0.14</td>
			<td>1.10±0.16</td>
			<td></td>
			<td></td>
		</tr><tr><td colspan="3">rTMS集团</td>
			<td>16</td>
			<td>0.98±0.18</td>
			<td>1.15±0.16</td>
			<td></td>
			<td></td>
		</tr><tr><td colspan="3">AOT集团</td>
			<td>16</td>
			<td>0.99±0.12</td>
			<td>1.15±0.09</td>
			<td></td>
			<td></td>
		</tr><tr><td colspan="3">联合干预组</td>
			<td>16</td>
			<td>1.02±0.15</td>
			<td>1.24±0.11</td>
			<td></td>
			<td></td>
		</tr><tr><td colspan="3">组因素</td>
			<td></td>
			<td></td>
			<td></td>
			<td>0.946</td>
			<td>0.424</td>
		</tr><tr><td colspan="3">时间因素</td>
			<td></td>
			<td></td>
			<td></td>
			<td>501.551</td>
			<td><0.001</td>
		</tr><tr><td colspan="3">组因素 * 时间因素</td>
			<td></td>
			<td></td>
			<td></td>
			<td>19.275</td>
			<td><0.001</td>
		</tr></tbody></table>表 4：四组儿童 （n = 64， x ± s） 中 10MWS 分数的比较。 处理后重复测量方差分析结果显示，时间效应、组间交互效应、交互作用效应显著（P < 0.05），组间效应不显著（P > 0.05）。缩写：10MWS = 10 m 步行速度;rTMS = 重复经颅磁刺激;AOT = 动作观察训练。
<table border="1" fo:keep-together.within-page="1" fo:keep-with-next.within-page="always"><tbody><tr><td colspan="3">群</td>
			<td>数量 （n）</td>
			<td>以前</td>
			<td>后</td>
			<td>F</td>
			<td>P</td>
		</tr><tr><td colspan="3">Conventiona 集团</td>
			<td>16</td>
			<td>46.63±20.05</td>
			<td>54.00±22.19</td>
			<td></td>
			<td></td>
		</tr><tr><td colspan="3">rTMS集团</td>
			<td>16</td>
			<td>48.94±19.96</td>
			<td>61.94±20.61</td>
			<td></td>
			<td></td>
		</tr><tr><td colspan="3">AOT集团</td>
			<td>16</td>
			<td>50.25±15.25</td>
			<td>63.63±16.40</td>
			<td></td>
			<td></td>
		</tr><tr><td colspan="3">联合干预组</td>
			<td>16</td>
			<td>50.94±18.43</td>
			<td>75.69±17.86</td>
			<td></td>
			<td></td>
		</tr><tr><td colspan="3">组因素</td>
			<td></td>
			<td></td>
			<td></td>
			<td>1.300</td>
			<td>0.283</td>
		</tr><tr><td colspan="3">时间因素</td>
			<td></td>
			<td></td>
			<td></td>
			<td>502.502</td>
			<td><0.001</td>
		</tr><tr><td colspan="3">组因素 * 时间因素</td>
			<td></td>
			<td></td>
			<td></td>
			<td>31.184</td>
			<td><0.001</td>
		</tr></tbody></table>表 5：四组儿童 GMFM 评分的比较 （n = 64， x ± s）。 处理后重复测量方差分析结果显示，重复测量方差分析结果显示，时间效应以及组间和时间间的交互效应显著（P < 0.05），组间效应不显著（P > 0.05）。缩写：GMFM=粗大运动功能测量;rTMS = 重复经颅磁刺激;AOT = 动作观察训练。
<table border="1" fo:keep-together.within-page="1" fo:keep-with-next.within-page="always"><tbody><tr><td colspan="3">群</td>
			<td>数</td>
			<td>明显有效</td>
			<td>有效</td>
			<td>无效</td>
			<td>有效率</td>
		</tr><tr><td colspan="3">常规组</td>
			<td>16</td>
			<td>1</td>
			<td>3</td>
			<td>12</td>
			<td>25.00%</td>
		</tr><tr><td colspan="3">rTMS集团</td>
			<td>16</td>
			<td>3</td>
			<td>7</td>
			<td>6</td>
			<td>62.50%</td>
		</tr><tr><td colspan="3">AOT集团</td>
			<td>16</td>
			<td>2</td>
			<td>9</td>
			<td>5</td>
			<td>68.75%</td>
		</tr><tr><td colspan="3">联合干预组</td>
			<td>16</td>
			<td>7</td>
			<td>7</td>
			<td>2</td>
			<td>87.50%</td>
		</tr><tr><td colspan="3">χ2</td>
			<td></td>
			<td></td>
			<td></td>
			<td></td>
			<td>13.850</td>
		</tr><tr><td colspan="3">P</td>
			<td></td>
			<td></td>
			<td></td>
			<td></td>
			<td>0.003</td>
		</tr><tr><td colspan="8">缩写：rTMS=重复经颅磁刺激;AOT = 动作观察训练。</td>
		</tr></tbody></table>表6：所有四组儿童的粗大运动功能比较（n [%]）。 缩写：rTMS=重复经颅磁刺激;AOT = 动作观察训练。
补充档案1：病人的病例信息。 患者接受rTMS联合AOT治疗。治疗12周后，比较治疗前后各项评价指标数据，确定联合干预对患者粗大运动功能的临床效果。 <a href="https://www-jove-com.remotexs.ntu.edu.sg/files/ftp_upload/66013/Case%20information%20of%20Shu%20XX.pdf" target="_blank">请点击这里下载此文件。</a>
补充表S1：患者数据。<a href="https://www-jove-com.remotexs.ntu.edu.sg/files/ftp_upload/66013/66013_S1.xlsx" target="_blank">请点击这里下载此文件。</a>

作者聚焦： 重复经颅磁刺激结合脑瘫的运动观察

痉挛型脑瘫（SCP）患儿因脑皮层运动区域损伤，出现肢体痉挛、运动障碍、姿势异常等症状，导致无法正常站立和行走。因此，缓解SCP患儿肢体痉挛和增强粗大运动功能已成为重要的治疗目标。

反复经颅磁刺激联合动作观察训练治疗儿童痉挛性脑瘫

This study presents the results of a randomized controlled trial utilizing a 2 x 2 factorial design, comparing the effects of repeated transcranial ...

这项研究是脑瘫在儿童中实际应用的产物。而投资案例中，重复经颅磁刺激结合运动观察训练对粗大运动功能恢复的临床疗效。重复经颅磁刺激是治疗脑瘫患儿的重要成果，在进行运动观察训练时，能有效缓解特异性，增强运动功能。与单独使用一种治疗相比，rTMS联合AOT干预可以达到更好的临床疗效。在这项研究中，使用了运动、水疗、按摩等常规治疗，以及重复经颅磁刺激疗法、运动观察训练和重复经颅磁刺激疗法结合运动观察训练、康复技术。

repeated-transcranial-magnetic-stimulation-combined-with-action

Nanyang Technological University

Research

JoVE Journal

Medicine

Repeated Transcranial Magnetic Stimulation Combined with Action Observation Training in Children with Spastic Cerebral Palsy

910 次观看.  Xiangya Boai Rehabilitation Hospital. 这项研究是脑瘫在儿童中实际应用的产物。而投资案例中，重复经颅磁刺激结合运动观察训练对粗大运动功能恢复的临床疗效。重复经颅磁刺激是治疗脑瘫患儿的重要成果，在进行运动观察训练时，能有效缓解特异性，增强运动功能。与单独使用一种治疗相比，rTMS联合AOT干预可以达到更好的临床疗效。在这项研究中，使用了运动、水疗、按摩等常规治疗，以及重复经颅...

视频: 作者聚焦： 重复经颅磁刺激结合脑瘫的运动观察

Corticospinal Excitability Modulation During Action Observation

This study used the transcranial magnetic stimulation/motor evoked potential (TMS/MEP) technique to pinpoint when the automatic tendency to mirror someone else's action becomes anticipatory simulation of a complementary act. TMS was delivered to the left primary motor cortex corresponding to the hand to induce the highest level of MEP activity from the abductor digiti minimi (ADM; the muscle serving little finger abduction) as well as the first dorsal interosseus (FDI; the muscle serving index finger flexion/extension) muscles. A neuronavigation system was used to maintain the position of the TMS coil, and electromyographic (EMG) activity was recorded from the right ADM and FDI muscles. Producing original data with regard to motor resonance, the combined TMS/MEP technique has taken research on the perception-action coupling mechanism a step further. Specifically, it has answered the questions of how and when observing another person's actions produces motor facilitation in an onlooker's corresponding muscles and in what way corticospinal excitability is modulated in social contexts.

Single-pulse transcranial magnetic stimulation over the primary motor cortex, neuronavigation, and registration of electromyographic activity of hand muscles were used in this study to explore corticospinal excitability while participants were observing action sequences.

行动观察期间皮质脊体兴奋调节

This study used the transcranial magnetic stimulation/motor evoked potential (TMS/MEP) technique to pinpoint when the automatic tendency to mirror someone ...

科研

行为学

Modeling Stroke in Mice - Middle Cerebral Artery Occlusion with the Filament Model

Stroke is among the most frequent causes of death and adult disability, especially in highly developed countries. However, treatment options to date are very limited. To meet the need for novel therapeutic approaches, experimental stroke research frequently employs rodent models of focal cerebral ischaemia. Most researchers use permanent or transient occlusion of the middle cerebral artery (MCA) in mice or rats.
Proximal occlusion of the middle cerebral artery (MCA) via the intraluminal suture technique (so called filament or suture model) is probably the most frequently used model in experimental stroke research. The intraluminal MCAO model offers the advantage of inducing reproducible transient or permanent ischaemia of the MCA territory in a relatively non-invasive manner. Intraluminal approaches interrupt the blood flow of the entire territory of this artery. Filament occlusion thus arrests flow proximal to the lenticulo-striate arteries, which supply the basal ganglia. Filament occlusion of the MCA results in reproducible lesions in the cortex and striatum and can be either permanent or transient. In contrast, models inducing distal (to the branching of the lenticulo-striate arteries) MCA occlusion typically spare the striatum and primarily involve the neocortex. In addition these models do require craniectomy. In the model demonstrated in this article, a silicon coated filament is introduced into the common carotid artery and advanced along the internal carotid artery into the Circle of Willis, where it blocks the origin of the middle cerebral artery. In patients, occlusions of the middle cerebral artery are among the most common causes of ischaemic stroke. Since varying ischemic intervals can be chosen freely in this model depending on the time point of reperfusion, ischaemic lesions with varying degrees of severity can be produced. Reperfusion by removal of the occluding filament at least partially models the restoration of blood flow after spontaneous or therapeutic (tPA) lysis of a thromboembolic clot in humans.
In this video we will present the basic technique as well as the major pitfalls and confounders which may limit the predictive value of this model.

Filamentous occlusion of the Middle cerebral artery is a common model for studying ischemic stroke in mice.

建模在小鼠体内的行程 - 中东与灯丝模型大脑中动脉闭塞

Stroke is among the most frequent causes of death and adult disability, especially in highly developed countries. However, treatment options to date are ...

医学

Utilizing Transcranial Magnetic Stimulation to Study the Human Neuromuscular System

Transcranial magnetic stimulation (TMS) has been in use for more than 20 years 1, and has grown exponentially in popularity over the past decade. While the use of TMS has expanded to the study of many systems and processes during this time, the original application and perhaps one of the most common uses of TMS involves studying the physiology, plasticity and function of the human neuromuscular system. Single pulse TMS applied to the motor cortex excites pyramidal neurons transsynaptically 2 (Figure 1) and results in a measurable electromyographic response that can be used to study and evaluate the integrity and excitability of the corticospinal tract in humans 3. Additionally, recent advances in magnetic stimulation now allows for partitioning of cortical versus spinal excitability 4,5. For example, paired-pulse TMS can be used to assess intracortical facilitatory and inhibitory properties by combining a conditioning stimulus and a test stimulus at different interstimulus intervals 3,4,6-8. In this video article we will demonstrate the methodological and technical aspects of these techniques. Specifically, we will demonstrate single-pulse and paired-pulse TMS techniques as applied to the flexor carpi radialis (FCR) muscle as well as the erector spinae (ES) musculature. Our laboratory studies the FCR muscle as it is of interest to our research on the effects of wrist-hand cast immobilization on reduced muscle performance6,9, and we study the ES muscles due to these muscles clinical relevance as it relates to low back pain8. With this stated, we should note that TMS has been used to study many muscles of the hand, arm and legs, and should iterate that our demonstrations in the FCR and ES muscle groups are only selected examples of TMS being used to study the human neuromuscular system.

Transcranial magnetic stimulation (TMS) is a non-invasive tool to gain insight on the physiology and function of the human nervous system. Here, we present our TMS techniques to study cortical excitability of the upper limb and lumbar musculature.

利用经颅磁刺激，以研究人类的神经肌肉系统

Transcranial magnetic stimulation (TMS) has been in use for more than 20 years 1, and has grown exponentially in popularity over the past decade.  While ...

Eye Tracking Young Children with Autism

The rise of accessible commercial eye-tracking systems has fueled a rapid increase in their use in psychological and psychiatric research. By providing a direct, detailed and objective measure of gaze behavior, eye-tracking has become a valuable tool for examining abnormal perceptual strategies in clinical populations and has been used to identify disorder-specific characteristics1, promote early identification2, and inform treatment3. In particular, investigators of autism spectrum disorders (ASD) have benefited from integrating eye-tracking into their research paradigms4-7. Eye-tracking has largely been used in these studies to reveal mechanisms underlying impaired task performance8 and abnormal brain functioning9, particularly during the processing of social information1,10-11. While older children and adults with ASD comprise the preponderance of research in this area, eye-tracking may be especially useful for studying young children with the disorder as it offers a non-invasive tool for assessing and quantifying early-emerging developmental abnormalities2,12-13. Implementing eye-tracking with young children with ASD, however, is associated with a number of unique challenges, including issues with compliant behavior resulting from specific task demands and disorder-related psychosocial considerations. In this protocol, we detail methodological considerations for optimizing research design, data acquisition and psychometric analysis while eye-tracking young children with ASD. The provided recommendations are also designed to be more broadly applicable for eye-tracking children with other developmental disabilities. By offering guidelines for best practices in these areas based upon lessons derived from our own work, we hope to help other investigators make sound research design and analysis choices while avoiding common pitfalls that can compromise data acquisition while eye-tracking young children with ASD or other developmental difficulties.

Eye tracking has long been used to study gaze patterns in typically-developing individuals, but recent technological advancements have made its use with clinical populations, including autism, more feasible. While eye-tracking young children with autism can offer insight into early symptom manifestations, it involves methodological challenges. Suggestions for best practices are provided.

自闭症幼儿的眼动追踪

The rise of accessible commercial eye-tracking systems has fueled a rapid increase in their use in psychological and psychiatric research. By providing a ...

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 ...

神经科学

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

We describe the development of a reproducible, child-friendly motor response inhibition task suitable for online Transcranial Magnetic Stimulation (TMS) characterization of primary motor cortex (M1) excitability and inhibition. Motor response inhibition prevents unwanted actions and is abnormal in several neuropsychiatric conditions. TMS is a non-invasive technology that can quantify M1 excitability and inhibition using single- and paired-pulse protocols and can be precisely timed to study cortical physiology with high temporal resolution. We modified the original Slater-Hammel (S-H) stop signal task to create a &#34;racecar&#34; version with TMS pulses time-locked to intra-trial events. This task is self-paced, with each trial initiating after a button push to move the racecar towards the 800 ms target. GO trials require a finger-lift to stop the racecar just before this target. Interspersed randomly are STOP trials (25%) during which the dynamically adjusted stop signal prompts subjects to prevent finger-lift. For GO trials, TMS pulses were delivered at 650 ms after trial onset; whereas, for STOP trials, the TMS pulses occurred 150 ms after the stop signal. The timings of the TMS pulses were decided based on electroencephalography (EEG) studies showing event-related changes in these time ranges during stop signal tasks. This task was studied in 3 blocks at two study sites (n=38) and we recorded behavioral performance and event-related motor-evoked potentials (MEP). Regression modelling was used to analyze MEP amplitudes using age as a covariate with multiple independent variables (sex, study site, block, TMS pulse condition [single- vs. paired-pulse], trial condition [GO, successful STOP, failed STOP]). The analysis showed that TMS pulse condition (p&#60;0.0001) and its interaction with trial condition (p=0.009) were significant. Future applications for this online S-H/TMS paradigm include the addition of simultaneous EEG acquisition to measure TMS-evoked EEG potentials. A potential limitation is that in children, the TMS pulse sound could&#160;affect behavioral task performance.

We describe an experimental procedure to quantify excitability and inhibition of primary motor cortex during a motor response inhibition task by using Transcranial Magnetic Stimulation throughout the course of a Stop Signal Task.

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) ...

The Combined Use of Transcranial Direct Current Stimulation and Robotic Therapy for the Upper Limb

Neurologic disorders such as stroke and cerebral palsy are leading causes of long-term disability and can lead to severe incapacity and restriction of daily activities due to lower and upper limb impairments. Intensive physical and occupational therapy are still considered main treatments, but new adjunct therapies to standard rehabilitation that may optimize functional outcomes are being studied.
Transcranial direct current stimulation (tDCS) is a noninvasive brain stimulation technique that polarizes underlying brain regions through the application of weak direct currents through electrodes on the scalp, modulating cortical excitability. Increased interest in this technique can be attributed to its low cost, ease of use, and effects on human neural plasticity. Recent research has been performed to determine the clinical potential of tDCS in diverse conditions such as depression, Parkinson&#39;s disease, and motor rehabilitation after stroke. tDCS helps enhance brain plasticity and seems to be a promising technique in rehabilitation programs.
A number of robotic devices have been developed to assist in the rehabilitation of upper limb function after stroke. The rehabilitation of motor deficits is often a long process requiring multidisciplinary approaches for a patient to achieve maximum independence. These devices do not intend to replace manual rehabilitation therapy; instead, they were designed as an additional tool to rehabilitation programs, allowing immediate perception of results and tracking of improvements, thus helping patients to stay motivated.
Both tDSC and robot-assisted therapy are promising add-ons to stroke rehabilitation and target the modulation of brain plasticity, with several reports describing their use to be associated with conventional therapy and the improvement of therapeutic outcomes. However, more recently, some small clinical trials have been developed that describe the associated use of tDCS and robot-assisted therapy in stroke rehabilitation. In this article, we describe the combined methods used in our institute for improving motor performance after stroke.

The combined use of transcranial direct current stimulation and robotic therapy as an add-on for conventional rehabilitation therapy may result in improved therapeutic outcomes due to modulation of brain plasticity. In this article, we describe the combined methods used in our institute for improving motor performance after stroke.

经颅直流电刺激与上肢机器人治疗的联合应用

Neurologic disorders such as stroke and cerebral palsy are leading causes of long-term disability and can lead to severe incapacity and restriction of ...

Non-Invasive Modulation and Robotic Mapping of Motor Cortex in the Developing Brain

Mapping the motor cortex with transcranial magnetic stimulation (TMS) has potential to interrogate motor cortex physiology and plasticity but carries unique challenges in children. Similarly, transcranial direct current stimulation (tDCS) can improve motor learning in adults but has only recently been applied to children. The use of tDCS and emerging techniques like high&#8211;definition tDCS (HD-tDCS) require special methodological considerations in the developing brain. Robotic TMS motor mapping may confer unique advantages for mapping, particularly in the developing brain. Here, we aim to provide a practical, standardized approach for two integrated methods capable of simultaneously exploring motor cortex modulation and motor maps in children. First, we describe a protocol for robotic TMS motor mapping. Individualized, MRI-navigated 12x12 grids centered on the motor cortex guide a robot to administer single-pulse TMS. Mean motor evoked potential (MEP) amplitudes per grid point are used to generate 3D motor maps of individual hand muscles with outcomes including map area, volume, and center of gravity. Tools to measure safety and tolerability of both methods are also included. Second, we describe the application of both tDCS and HD-tDCS to modulate the motor cortex and motor learning. An experimental training paradigm and sample results are described. These methods will advance the application of non-invasive brain stimulation in children.

We demonstrate protocols for the modulation (tDCS, HD-tDCS) and mapping (robotic TMS) of the motor cortex in children.

发育中大脑运动皮质的非侵入性调制和机器人映射

Mapping the motor cortex with transcranial magnetic stimulation (TMS) has potential to interrogate motor cortex physiology and plasticity but carries ...

联合周围神经刺激和可控脉搏参数 TMS

Combined Peripheral Nerve Stimulation and Controllable Pulse Parameter Transcranial Magnetic Stimulation to Probe Sensorimotor Control and Learning

Skilled motor ability depends on efficiently integrating sensory afference into the appropriate motor commands. Afferent inhibition provides a valuable tool to probe the procedural and declarative influence over sensorimotor integration during skilled motor actions. This manuscript describes the methodology and contributions of short-latency afferent inhibition (SAI) for understanding sensorimotor integration. SAI quantifies the effect of a convergent afferent volley on the corticospinal motor output evoked by transcranial magnetic stimulation (TMS). The afferent volley is triggered by the electrical stimulation of a peripheral nerve. The TMS stimulus is delivered to a location over the primary motor cortex that elicits a reliable motor-evoked response in a muscle served by that afferent nerve. The extent of inhibition in the motor-evoked response reflects the magnitude of the afferent volley converging on the motor cortex and involves central GABAergic and cholinergic contributions. The cholinergic involvement in SAI makes SAI a possible marker of declarative-procedural interactions in sensorimotor performance and learning. More recently, studies have begun manipulating the TMS current direction in SAI to tease apart the functional significance of distinct sensorimotor circuits in the primary motor cortex for skilled motor actions. The ability to control additional pulse parameters (e.g., the pulse width) with state-of-the-art controllable pulse parameter TMS (cTMS) has enhanced the selectivity of the sensorimotor circuits probed by the TMS stimulus and provided an opportunity to create more refined models of sensorimotor control and learning. Therefore, the current manuscript focuses on SAI assessment using cTMS. However, the principles outlined here also apply to SAI assessed using conventional fixed pulse width TMS stimulators and other forms of afferent inhibition, such as long-latency afferent inhibition (LAI).

作者聚焦： 结合周围神经刺激和可控脉搏参数经颅磁刺激以探测感觉运动控制和学习  

Short-latency afferent inhibition (SAI) is a transcranial magnetic stimulation protocol to probe sensorimotor integration. This article describes how SAI can be used to study the convergent sensorimotor loops in the motor cortex during sensorimotor behavior.

结合周围神经刺激和可控脉搏参数经颅磁刺激探测感觉运动控制和学习

Skilled motor ability depends on efficiently integrating sensory afference into the appropriate motor commands. Afferent inhibition provides a valuable ...

反复经颅磁刺激联合动作观察训练治疗儿童痉挛性脑瘫

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经颅直流电刺激与上肢机器人治疗的联合应用

发育中大脑运动皮质的非侵入性调制和机器人映射

结合周围神经刺激和可控脉搏参数经颅磁刺激探测感觉运动控制和学习

结合周围神经刺激和可控脉搏参数经颅磁刺激探测感觉运动控制和学习