发育中大脑运动皮质的非侵入性调制和机器人映射
1Department of Neurosciences,University of Calgary, 2Hotchkiss Brain Institute,University of Calgary, 3Cumming School of Medicine,University of Calgary, 4Department of Pediatrics,University of Calgary, 5Alberta Children’s Hospital Research Institute,University of Calgary, 6Faculty of Medicine and Dentistry,University of Alberta, 7Department of Clinical Neurosciences,University of Calgary
Summary
我们演示了儿童运动皮层的调制(tDCS、HD-tDCS)和映射(机器人TMS)的协议。
Abstract
使用颅内磁刺激(TMS)绘制运动皮层具有质疑运动皮层生理和可塑性的潜力,但对儿童具有独特的挑战。同样,颅内直流刺激(tDCS)可以改善成人的运动学习,但最近才应用于儿童。使用tDCS和新兴技术,如高清晰度tDCS(HD-tDCS),需要特殊的方法学考虑在发展中的大脑。机器人TMS运动映射可能赋予映射独特的优势,特别是在正在发育的大脑。在这里,我们的目标是为两种能够同时探索儿童运动皮层调制和运动图的集成方法提供实用、标准化的方法。首先,我们描述了机器人TMS电机映射的协议。以运动皮层为中心的个性化 MRI 导航 12×12 网格引导机器人管理单脉冲 TMS。每个网格点的平均电机唤起电位 (MEP) 振幅用于生成单个手部肌肉的 3D 运动图,其结果包括地图区域、体积和重心。还包括测量这两种方法的安全性和耐受性的工具。其次,我们描述了tDCS和HD-tDCS在调节运动皮层和运动学习中的应用。介绍了实验训练模式和样本结果。这些方法将推动非侵入性脑刺激在儿童中的应用。
Introduction
非侵入性脑刺激可以测量和调节人脑功能1,2。最常见的目标是运动皮层,部分原因是直接和可测量的生物输出(运动诱发电位),但也由于神经系统疾病的高流行导致运动系统功能障碍和残疾。这种庞大的全球疾病负担包括影响儿童(如脑瘫)的高比例,脑瘫是影响全世界约1 700万人的终身残疾的主要原因。尽管这种临床相关性和神经刺激技术的多样化和不断增长的能力,在发展中的大脑中的应用才刚刚开始被定义4。需要改进儿童现有和新出现的非侵入性脑刺激方法的特征,以推动在发育中大脑的应用。
颅内磁刺激(TMS)是一种成熟的神经生理学工具,越来越多地用于成人的非侵入性、无痛、耐受性和安全性。TMS在儿童的经验相对有限,但稳步增加。TMS 提供磁场,以诱导大脑中皮质神经元群的区域激活,净输出反映在目标肌肉运动引发电位 (MEP) 中。系统应用单脉冲TMS可以定义体内运动皮层的图谱。开创性动物研究5和新兴的人类TMS研究6已经表明,运动图如何帮助为皮质神经可塑性机制提供信息。导航运动映射是一种TMS技术,用于绘制人体运动皮层以询问功能皮质区域。电机图的变化与人类马达系统的塑料变化有关7。机器人TMS技术的最新进展为提高电机映射效率和精度带来了新的机遇。我们小组最近证明,机器人TMS电机映射是可行的,高效,并且耐受性良好的儿童8。
颅内直接电流刺激(tDCS)是一种非侵入性脑刺激,可以改变皮质兴奋性和调节人类行为。已经有很多研究研究tDCS在成人的影响(>10,000受试者),但不到2%的研究集中在发育的大脑9。将成人证据翻译到儿科应用非常复杂,由于儿童差异复杂,需要修改协议。例如,我们和其他人已经表明,与10、11岁的成年人相比,儿童经历的电场更大、更强。在儿童中实现tDCS方法的标准化对于确保安全、一致的应用、改进复制和推进该领域具有重要意义。儿童运动学习调制tDCS的经验有限,但增加12。tDCS对特定脑瘫人群的转化应用正向晚期临床试验迈进13。通过高清晰度tDCS(HD-tDCS)进行更多焦刺激的努力,只是在14岁儿童中首次得到研究。我们证明HD-tDCS在运动学习方面与健康儿童14岁的传统tDCS相似。描述 HD-tDCS 方法将允许在子中复制和进一步应用此类协议。
Protocol
本协议中描述的所有方法均已获得卡尔加里大学联合健康研究伦理委员会(REB16-2474)的批准。该协议如图1所示。 1. 非侵入性脑刺激禁忌症 在招聘前,筛查所有参与者的 TMS15和 tDCS1的禁忌症。 2. 颅内磁刺激运动映射 为导航 TMS 准备 MRI 获取每个参与者的结构 MRI (T1)。如果 MRI 无法?…
Representative Results
使用这里介绍的方法,我们完成了一个随机的,假控制的介入试验8。右手儿童(n = 24,12-18岁),这两种非侵入性脑刺激均无禁忌症。在这项研究中,如果参与者使用神经性精神药物或对tDCS不天真,则被明确排除在外。没有辍学。 机器人TMS运动图获得基线运动图,并作为一种潜在的机制,监测神经塑性及皮质兴奋性变化后…
Discussion
TMS还在临床小儿科人群中进行了探索,包括围产期中风22和脑瘫,其中TMS运动图成功地在脑瘫儿童中创建,以探索介入可塑性机制。使用既定的协议8,TMS运动图成功地收集了在典型的发育的儿童,目前正在收集围产期中风和半脑瘫儿童的多中心临床试验(NCT03216837)。描述TMS运动映射方法将允许在健康儿童和运动障碍儿童中复制和进一步应用协议。
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Declarações
The authors have nothing to disclose.
Acknowledgements
这项研究得到了加拿大卫生研究院的支持。
Materials
| 1×1 SMARTscan Stimulator | Soterix Medical Inc. | https://soterixmedical.com/research/1×1/tdcs/device | |
| 4×1 HD-tDCS Adaptor | Soterix Medical Inc. | https://soterixmedical.com/research/hd-tdcs/4×1 | |
| Brainsight Neuronavigation | Roge Resolution | https://www.rogue-resolutions.com/catalogue/neuro-navigation/brainsight-tms-navigation/ | |
| Carbon Rubber Electrode | Soterix Medical Inc. | https://soterixmedical.com/research/1×1/accessories/carbon-ruber-electrode | |
| EASYpad Electrode | Soterix Medical Inc. | https://soterixmedical.com/research/1×1/accessories/1×1-easypad | |
| EASYstraps | Soterix Medical Inc. | https://soterixmedical.com/research/1×1/accessories/1×1-easystrap | |
| EMG Amplifier | Bortec Biomedical | http://www.bortec.ca/pages/amt_16.htm | |
| HD1 Electrode Holder | Soterix Medical Inc. | https://soterixmedical.com/research/hd-tdcs/accessories/hd1-holder | Standard Base HD-Electrode Holder for High Definition tES (HD-tES) |
| HD-Electrode | Soterix Medical Inc. | https://soterixmedical.com/research/hd-tdcs/accessories/hd-electrode | Sintered ring HD-Electrode. |
| HD-Gel | Soterix Medical Inc. | https://soterixmedical.com/research/hd-tdcs/accessories/hd-gel | HD-GEL for High Definition tES (HD-tES) |
| Micro 1401 Data Acquisition System | Cambridge Electronics http://ced.co.uk/products/mic3in | ||
| Purdue Pegboard | Lafayette Instrument Company | ||
| Saline solution | Baxter | http://www.baxter.ca/en/products-expertise/iv-solutions-premixed-drugs/products/iv-solutions.page | |
| Soterix Medical HD-Cap | Soterix Medical Inc. | https://soterixmedical.com/research/hd-tdcs/accessories/hd-cap | |
| TMS Robot | Axilium Robotics | http://www.axilumrobotics.com/en/ | |
| TMS Stimulator and Coil | Magstim Inc | https://www.magstim.com/neuromodulation/ |
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Citar este artigo
Giuffre, A., Cole, L., Kuo, H., Carlson, H. L., Grab, J., Kirton, A., Zewdie, E. Non-Invasive Modulation and Robotic Mapping of Motor Cortex in the Developing Brain. J. Vis. Exp. (149), e59594, doi:10.3791/59594 (2019).