侧前额叶皮质联合经颅磁刺激与脑电图的研究
Summary
这里提出的协议是利用 intracortical 兴奋性测试-重新测试设计范式的 TMS-脑电图研究。该议定书的目的是制定可靠和可重复的皮质兴奋性措施, 以评估与治疗干预措施有关的神经功能, 如严重抑郁症等精神疾病。
Abstract
经颅磁刺激 (TMS) 是一种非侵入性的方法, 通过短暂的、时变的磁场脉冲, 在皮层产生神经激发。皮质激活或其调制的启动取决于皮质区神经元的背景活化、线圈的特征、其位置和朝向。TMS 结合同时 electrocephalography (eeg) 和神经导航 (nTMS 脑电图), 可以对皮质皮质兴奋性和连通性的几乎所有皮层区域的可重现的方式进行评估。这一进步使 nTMS 脑电图成为一种强有力的工具, 能够准确地评估临床试验所需的测试复测范式中的大脑动力学和神经生理学。这种方法的局限性包括包含初始脑反应刺激的工件。因此, 删除工件的过程也可以提取有价值的信息。此外, 侧前额 (DLPFC) 刺激的最佳参数还不完全知道, 目前的协议利用运动皮层 (M1) 刺激范式的变化。然而, 进化的 nTMS-EEG 设计希望能够解决这些问题。这里提出的议定书介绍了一些标准的做法, 以评估神经功能从刺激到 DLPFC, 可适用于治疗精神障碍患者接受治疗, 如经颅直接电流刺激 (tDCS), 反复经颅磁刺激 (rTMS), 磁性癫痫治疗 (MST) 或抽搐治疗 (ECT)。
Introduction
经颅磁刺激 (TMS) 是一种神经工具, 它允许非侵入性评估皮质神经元活动通过使用快速, 时变磁场脉冲1。这些磁场脉冲在线圈下方的表面皮层产生弱电流, 导致膜退极化。随后的皮质激活或调制直接关系到线圈的特点, 其角度和方向的头骨2。从线圈中排出的脉冲波形和神经元的底层状态也影响皮层激活3。
TMS 通过唤起行为或运动反应或通过中断与任务相关的处理来评估皮质功能。皮质-脊柱过程的兴奋性可以通过记录肌 (肌电图) 的反应, 从单一的 TMS 脉冲的运动皮层, 而 intracortical 兴奋 (intracortical 促进;ICF) 和抑制机制 (短和长的 intracortical 抑制;SICI 和 LICI) 可以用配对脉冲 TMS 进行探测。重复的 TMS 可以扰乱各种认知过程, 但主要是作为治疗工具的各种精神疾病。此外, tms 与同时脑电图 (tms 脑电图) 的结合可用于评估皮质皮质兴奋性和连接度4。最后, 如果对 TMS 的管理是用神经导航 (nTMS) 提供的, 它将允许精确的测试复测范式, 因为可以记录刺激的确切地点。大多数皮质地幔可以被靶向和刺激 (包括那些不产生可测量的物理或行为反应的区域), 从而可以在功能上映射皮层。
从单或配对脉冲 TMS 诱发的脑电图信号可以促进评估皮质皮质连接5和目前的大脑状态。TMS 引起的电流导致动作电位, 可以激活突触。突触后电流的分布可以通过脑电图6记录。eeg 信号可以用来量化和定位突触电流分布通过偶极模型7或最小范数估计8, 当多通道脑电图被使用, 并与电导率结构的头部占。结合 TMS-脑电图可用于研究皮质抑制过程9, 振荡10, 皮质皮质11和大脑纵裂相互作用12, 皮质可塑性13。最重要的是, TMS-脑电图可以探测在认知或运动任务中的兴奋性变化, 具有良好的测试复验可靠性14,15。重要的是, TMS-EEG 有可能确定神经信号, 可能作为反应的预测因素的治疗干预 (rTMS 或药理作用) 在测试复验设计16,17。
基于无框立体定向的原理, 对 TMS 的神经导航原理进行了研究。系统使用一个光学跟踪系统18 , 它采用了一个发光摄像头, 与连接到头部的光反射光学元件 (通过参考跟踪器) 和 TMS 线圈进行通信。在数字化参考工具或钢笔的帮助下, 神经导航允许在3维 MRI 模型上进行线圈定位。使用神经导航方便捕获的线圈方向, 位置和对准对象的头部, 以及数字化的脑电图电极位置。这些功能是测试重新检测设计实验和准确刺激侧前额叶皮质内特定位置的关键。
为了在测试复验实验中使用 TMS-EEG 协议, 需要对皮层区域进行准确的靶向和一致的刺激, 以获得可靠的信号。脑电记录可能容易受到不同的工件的影响。在脑电图电极上的 TMS 诱发的伪影可以用放大器过滤, 在延迟19、20或与不能饱和21的放大器后恢复。然而, 其他类型的伪影产生的眼球运动或眨眼, 颅内肌肉激活接近脑电图电极, 随机电极运动和他们的极化, 并通过线圈点击或躯体感觉必须考虑。仔细的主题准备, 确保电极阻抗低于 5 kΩ, 固定线圈在电极和泡沫之间的线圈和电极, 以减少振动 (或间隔消除低频工件22), 耳塞, 甚至听觉掩蔽应用于最小化这些文物23。这里提出的协议介绍了一个标准的过程, 以评估神经功能时, 刺激是应用在侧前额 (DLPFC)。重点是在 M19,15,16的研究中证实的共同配对脉冲范式。
Protocol
在《赫尔辛基宣言》的指导方针下, 我们当地道德委员会批准了这里提出的所有实验程序。 1. Neuronavigated 脑电图的头部注册 为每个参与者获得高分辨率的全头 T1-weighted 结构 MRI。根据神经导航制造商指南进行扫描。 在导航系统上上传图像。检查是否正确扫描了核磁共振。选择基点 (耳前点, nasion 和鼻尖)。插入刺激目标 (基于解剖学或基于头部坐标、MNI 或 Talairac…
Representative Results
图 1一个健康志愿者在平均100个世纪以后 DLPFC 刺激在 F3 电极以后的 TMSevoked 潜力说明。在本例中, 我们在单独应用 ts 时, 突出显示 CS 对 ts 的影响。即使在一个主题中, CS 也会以清晰的方式调节 N100 偏转。在 SICI 和 LICI 会话中, 与 SP 条件16相比, N100 通常会增加, 并且在 ICF 中的绝对值会降低。在图 1<s…
Discussion
TMS-脑电图使大多数皮质区域的直接和无创刺激和获得的结果神经元活动具有很好的时空分辨率30, 特别是当神经导航被利用。这一方法的进步的好处是基于事实, TMS 诱发脑电图信号来源于电神经活动, 它是一个指标的皮质皮质兴奋性。这在神经精神病人的人群中具有巨大的潜力, 在那里, TMS 脑电图可以作为当前和未来治疗干预的标志物。
该协议最关键的步骤?…
Divulgaciones
The authors have nothing to disclose.
Acknowledgements
这项工作由镍氢 R01 MH112815 部分提供资金。这项工作还得到了 Temerty 家庭基金会、赠款家庭基金会和坎贝尔家庭心理健康研究所在成瘾和精神健康中心的支持。
Materials
| CED Micro1401-3 | Cambridge Electronic Design Limited | CED Micro1401-3 | Digital Data Recocrder |
| BISTIM'2 Package Option 1 | Magstim | 3234-00 | TMS paired pulse stimulator |
| Magstim 200'2 Unit (2 items) | Magstim | 3010-00 | TMS stimulators |
| UI controller | Magstim | 3020-00 | TMS controller |
| BISTIM'2 UI controller | Magstim | 3021-00 | TMS controller |
| BISTIM connecting module | Magstim | 3330-00 | TMS connecting module |
| D70 Alpha Coil – P/N 4150-00 (Alpha 70mm double coil) | Magstim | 4150-00 | TMS coil |
| Brainsight | Rogue-Resolutions | Brainsight 2 | Neuronavigator |
| Model 2024F | Intronix | 2024F | Electromyograph |
| Neuroscan SynAmps RT 64 channel System | Compumedics Neuroscan | 9032-0010-01 | Electroencephalograph |
| Quick-Cap electrode system 64 | Compumedics Neuroscan | 96050255 | EEG Cap |
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Citar este artículo
Lioumis, P., Zomorrodi, R., Hadas, I., Daskalakis, Z. J., Blumberger, D. M. Combined Transcranial Magnetic Stimulation and Electroencephalography of the Dorsolateral Prefrontal Cortex. J. Vis. Exp. (138), e57983, doi:10.3791/57983 (2018).