Summary

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

Published: February 23, 2020
doi:

Summary

本文介绍了利用颅内磁刺激测量和加强功能特定的神经通路的新方法。这些先进的非侵入性脑刺激方法可以为理解大脑行为关系和开发治疗大脑疾病的新疗法提供新的机会。

Abstract

了解大脑区域之间的相互作用对于研究目标导向行为非常重要。大脑连通性功能神经成像为大脑的基本过程(如认知、学习和运动控制)提供了重要的见解。然而,这种方法不能为大脑感兴趣的区域的参与提供因果证据。颅内磁刺激(TMS)是一种强大的非侵入性工具,用于研究人脑,通过瞬时改变大脑活动来克服这种限制。在这里,我们重点介绍使用配对脉冲双位点 TMS 方法的最新进展,该方法具有两个线圈,它们在不同的任务上下文中对人体运动系统中的皮质-皮质相互作用进行因果探测。此外,我们描述了一种基于皮质成对关联刺激(cPAS)的双位点TMS协议,通过用两个线圈重复对皮质刺激,暂时地提高两个相互关联的大脑区域的突触效率。这些方法可以更好地了解认知运动功能背后的机制,以及以有针对性的方式操纵特定神经通路以调节大脑回路和改善行为的新视角。这种方法可能被证明是一个有效的工具,以开发更复杂的模型的大脑行为关系,并改善诊断和治疗许多神经和精神疾病。

Introduction

非侵入性脑刺激是一种有前途的评估工具和治疗许多神经系统疾病,如帕金森病,阿尔茨海默氏病,中风1,2,3,4。有越来越多的证据表明,神经系统疾病的行为表现与皮质兴奋性异常、神经可塑性、皮质皮质和皮质-皮下连通性5、6之间的关系。因此,关于大脑网络动力学和神经病中可塑性的基本知识可以为疾病诊断、进展和治疗反应提供宝贵的见解。功能磁共振成像(fMRI)是一个有用的工具,了解大脑和行为之间的复杂关系,在健康和患病的大脑网络,并有可能改善治疗基于网络视角7,8,9。然而,fMRI在本质上是相互关联的,不能提供大脑功能和行为之间的因果联系,也不能操纵功能连接来恢复与患者行为障碍相关的异常神经回路10,11,12。颅内磁刺激(TMS)可以因果地测量和调节人脑功能和行为在健康和疾病3,13,14,15。

TMS是一种安全、非侵入性的刺激人脑的方法16,17可用于诱导和测量可塑性18.这种方法可以促进我们对个体大脑区域和行为之间因果关系的理解10,11,12,19以及他们与大脑网络其他节点的特定功能交互20,21,22,23.迄今为止,大多数研究都集中在人体运动系统上,因为TMS到运动皮层(M1)的手部区域可以产生运动唤起电位(MEP),作为与运动行为相关的变化的生理读出24,允许在人脑系统水平上检查不同的抑制和兴奋回路25.使用两个线圈的调理测试TMS方法的最新进展表明,可以测量不同皮质区域之间的功能相互作用。在电机系统中,双位点 TMS 实验表明,与 M1 相连的皮质区域的输入会随任务需求、年龄或疾病而变化14,26.Ferbert 及其同事的开创性工作发现,在其他 M1 测试刺激之前对 M1 应用调理刺激可以抑制 MEP 振幅,这种现象称为短间隔半球间抑制 (SIHI)28.使用这种方法的一些TMS研究还表明,M1与反向M1、腹腔前运动皮层(PMv)、背前运动前皮层(PMd)、辅助运动区(SMA)、SMA前、初级感觉皮层(S1)密切相关,休息时背侧前额皮质 (DLPFC) 和后额皮质皮质 (PPC)27,28,29,30,31,32,33,34,35,36,37,38,39,40,41,42.有趣的是,这些皮质区域的刺激对运动皮质兴奋性的影响在解剖学、时间上和功能上都特定于运动准备过程中正在进行的大脑活动(状态和上下文相关)43,44,45,46,47,48,49,50,51,52,53,54,55,56,57,58,59,60,61,62,63,64,65,66,67,69).然而,使用双位点TMS的研究很少有特征模式的功能皮质-皮质连接与运动和认知障碍在脑疾患者70,71,72.这提供了开发评估和治疗运动和认知障碍的新方法的机会。

利用这种技术,还发现,与M1相连的皮质TMS的重复对,如逆向M1 68、69、70、PMv76、77、78、SMA71和PPC 80、81、82,可以诱导基于关联可塑性83的赫比安原理,在特定神经通路的突触效率发生变化。,84,85,86和增强行为表现72,73,74。然而,很少有研究用这种方法来研究神经系统疾病2,75,76,77,78,79,80,81,82,83,84,90,91,92,92, 93,949596.使用TMS加强功能特定的神经通路能否恢复功能特定的神经通路,或者未来加强完整电路是否能增强大脑网络中支持整个寿命和疾病中的运动和认知功能的复原力97,仍有待证明。缺乏对神经紊乱背后的神经机制和刺激对相互连接的功能失调的大脑网络的影响的基本理解限制了目前的治疗。

尽管TMS具有这种能力,但它尚未成为神经科学和临床工具的标准部分,用于理解大脑行为关系、脑疾患的病理生理学和治疗的有效性。因此,要发挥其潜力并支持其大规模应用,标准化 TMS 方法非常重要,因为它更有可能提高未来 TMS 实验的严格性,并增强独立实验室的可重复性。本文概述了如何使用 TMS 测量和操作功能交互。在这里,我们通过测量基于 TMS 的输出度量(例如 MEP)来描述电机系统中的此技术(例如,prieto-电机通路44),其中最了解该方法。然而,重要的是要注意到,该协议也可以适应其他皮下85,小脑86,87和皮质区域的目标功能耦合73、74、88 此外,神经成像技术,如脑电图89、90、91和fMRI92、93可用于评估TMS引起的活动和连接性变化26、94。最后,我们提出,研究电路级皮质连接与这些TMS方法在健康和疾病中的功能参与,使得基于更复杂的大脑行为关系网络模型开发有针对性的诊断和创新疗法成为可能。

Protocol

下面介绍了以下三种 TMS 方法。首先,描述了两种方法,使用双位点颅磁刺激(dsTMS)测量皮质皮质-皮质连接,而参与者为1)处于静止状态(静止状态)或2)执行物体定向的到达抓合运动(与任务相关)。其次,描述皮质成对关联刺激 (cPAS) 方法,通过配对皮质刺激(例如,后皮和原运动皮质),以受控方式调节两个大脑区域之间的相互作用,以增强功能与TMS的特定神经通路,并诱导皮质兴奋…

Representative Results

图 5显示了在参与者处于静止(顶部面板)或计划对对象(底部面板)进行目标导向的抓握操作时,TMS 在 FDI 肌肉中针对非空调测试刺激(仅 TS 到 M1,蓝色轨迹)或来自 PPC(CS-TS,红色轨迹)的有条件刺激而引出的 EP 响应的大小。在静止时,PPC 对 ipsi侧 M1 施加抑制性影响,如在超阈值 TS 超过 M1(顶部面板)之前通过 PPC 5 ms 交付的子阈值 CS 的 MEP 振幅减小就可以看出。在准…

Discussion

此处描述的双站点 TMS 方法可用于研究参与者处于静止或计划目标导向操作时与主运动皮层连接的不同皮质区域之间的功能交互。虽然大脑成像是相关的,但双位点TMS方法的基本知识可以揭示与皮质-皮质回路变化相关的因果脑行为关系。此外,在与 M1 相连的区域应用的两个 TMS 线圈的皮质成对关联刺激可用于增强运动控制的功能特定连接,并提高诱导可塑性的效率。总之,这些方法表明,这些TMS?…

Disclosures

The authors have nothing to disclose.

Acknowledgements

这项工作得到了密歇根大学:MCubed学者项目和运动学学院的支持。

Materials

Alpha B.I. D50 coil (coated) Magstim 50mm coil
BrainSight 2.0 Software Rogue Research Neuronavigation software
BrainSight frameless Stereotactic System Rogue Research Neuronavigation equiptment
D702 Coil Magstim 70mm coil
Discovery MR750 General Electric 3.0T MRI machine
Disposable Earplugs 3M Foam earplugs
ECG Electrodes 30mm x 24mm Coviden-Kendall H124SG Disposable electrodes
Four Channel Isolated Amplifier Intronix Technologies Corporation 2024F EMG amplifier
gGAMMAcap g.tec Medical Engineering EEG head cap
Micro1401-3 Cambridge Electronic Design Scientific data recorder and processing machine
Nuprep Skin Prep Gel Weaver and Company Skin prep abrasive gel
Signal v.7 Cambridge Electronic Design Data acquisition and analysis software
The Magstim BiStim2 Magstim Transcranial magnetic stimulator (two 2002 units)

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Goldenkoff, E. R., Mashni, A., Michon, K. J., Lavis, H., Vesia, M. Measuring and Manipulating Functionally Specific Neural Pathways in the Human Motor System with Transcranial Magnetic Stimulation. J. Vis. Exp. (156), e60706, doi:10.3791/60706 (2020).

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