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Neuroscienze

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

Published: April 21, 2023
doi:
10.3791/65212
, ,
1Department of Kinesiology and Health Sciences,University of Waterloo

Summary

短潜伏期传入抑制 （SAI） 是一种经颅磁刺激方案，用于探测感觉运动整合。本文介绍了如何使用SAI来研究感觉运动行为期间运动皮层中的收敛感觉运动环。

Abstract

熟练的运动能力取决于将感觉亲和力有效地整合到适当的运动指令中。传入抑制为探索熟练运动动作过程中对感觉运动整合的程序性和陈述性影响提供了一种有价值的工具。本手稿描述了短潜伏期传入抑制（SAI）对理解感觉运动整合的方法和贡献。SAI 量化了收敛传入凌空抽射对经颅磁刺激 （TMS） 诱发的皮质脊髓运动输出量的影响。传入凌空抽射由周围神经的电刺激触发。TMS刺激被传递到初级运动皮层上的某个位置，该位置在该传入神经服务的肌肉中引起可靠的运动诱发反应。运动诱发反应的抑制程度反映了传入凌空收敛在运动皮层上的大小，并涉及中枢GABA能和胆碱能的贡献。胆碱能参与SAI使SAI成为感觉运动表现和学习中陈述程序相互作用的可能标志物。最近，研究已经开始操纵SAI中的TMS当前方向，以梳理初级运动皮层中不同感觉运动回路的功能意义，以熟练的运动动作。使用最先进的可控脉冲参数TMS（cTMS）控制其他脉冲参数（例如脉冲宽度）的能力增强了TMS刺激探测的感觉运动回路的选择性，并为创建更精细的感觉运动控制和学习模型提供了机会。因此，目前的手稿侧重于使用cTMS进行SAI评估。然而，这里概述的原则也适用于使用传统的固定脉冲宽度TMS刺激器和其他形式的传入抑制（例如长潜伏期传入抑制（LAI））评估的SAI。

Introduction

多个感觉运动环在运动皮层中汇聚，形成锥体束投影到脊髓运动神经元和中间神经元1。然而，这些感觉运动环如何相互作用以塑造皮质脊髓投射和运动行为仍然是一个悬而未决的问题。短潜伏期传入抑制（SAI）提供了一种工具来探测运动皮层输出中收敛感觉运动环的功能特性。SAI 将运动皮质经颅磁刺激 （TMS） 与相应外周传入神经的电刺激相结合。

TMS是一种非侵入性方法，可安全地刺激人脑中经突触的锥体运动神经元2,3。TMS涉及通过放置在头皮上的盘绕线传递大的瞬态电流。电流的瞬态性质会产生快速变化的磁场，从而在大脑中感应出电流4。在单个TMS刺激的情况下，感应电流激活锥体运动神经元5-7的一系列兴奋性输入。如果产生的兴奋性输入的强度足够，则下降活动会引起对侧肌肉反应，称为运动诱发电位（MEP）。MEP 的潜伏期反映了皮质运动传导时间8。MEP 的振幅指数了皮质脊髓神经元的兴奋性9.引发MEP的单个TMS刺激也可以在条件刺激10,11,12之前进行。这些配对脉冲范式可用于索引各种中间神经元池对皮质脊髓输出的影响。在SAI的情况下，外周电调节刺激用于探测传入凌空对运动皮质兴奋性的影响11,13,14,15。TMS刺激和外周电刺激的相对时间使TMS刺激对运动皮层的作用与到达运动皮层的传入投影保持一致。对于上肢远端肌肉中的 SAI，正中神经刺激通常比 TMS 刺激早 18-24 ms11,13,15,16。同时，SAI随着外周刺激诱导的传入凌空抽射强度增加而增加13,17,18。

尽管SAI与运动皮层传入投射的外在特性密切相关，但它是一种可延展的现象，与许多运动控制过程有关。例如，在即将进行的运动19,20,21之前，SAI在与任务相关的肌肉中减少，但在相邻的任务无关运动表示19,20,22中保持不变。假设对任务相关性的敏感性反映了旨在减少不需要的效应物募集的环绕抑制机制23。最近，有人提出，任务相关效应器中SAI的减少可能反映了一种运动相关的门控现象，旨在抑制预期的感觉情感21并促进感觉运动计划和执行期间的纠正24。无论具体的功能作用如何，SAI都与手动灵活性和处理效率的降低相关25。SAI 改变还与老年人 26 跌倒的风险增加以及帕金森病 26、27、28 和局灶性手肌张力障碍29 中的感觉运动功能受损有关。

临床和药理学证据表明，介导SAI的抑制途径对中枢胆碱能调节敏感30。例如，施用毒蕈碱乙酰胆碱受体拮抗剂东莨菪碱可降低SAI31。相反，通过乙酰胆碱酯酶抑制剂增加乙酰胆碱的半衰期可增强SAI32,33。与药理学证据一致，SAI对中枢胆碱能参与的几种认知过程敏感，包括唤醒34，奖励35，注意力分配21,36,37和记忆38,39,40。在与胆碱能神经元缺失相关的认知缺陷的临床人群中，SAI 也会发生改变，例如阿尔茨海默病 41,42,43,44,45,46,47、帕金森病（伴轻度认知障碍）48,49,50 和轻度认知障碍 47，51,52.对各种γ-氨基丁酸A型（GABAA）受体亚基类型具有差异亲和力的各种苯二氮卓类药物对SAI的差异调节表明，SAI抑制途径不同于介导其他形式的配对脉冲抑制的途径30。例如，劳拉西泮降低SAI，但增强短间隔皮质抑制（SICI）53。唑吡坦可降低SAI，但对SICI53影响不大。地西泮增加SICI，但对SAI53影响不大。GABAA受体功能的这些正变构调节剂降低SAI，再加上观察到GABA控制脑干和皮层中乙酰胆碱的释放54，导致了GABA调节胆碱能途径的假设，该途径投射到感觉运动皮层以影响SAI55。

最近，SAI已被用于研究设置程序运动控制过程的感觉运动环与将程序过程与明确的自上而下目标和认知控制过程对齐的感觉运动回路之间的相互作用21,36,37,38。SAI31 中枢胆碱能受累表明 SAI 可能指对程序性感觉运动控制和学习的执行影响。重要的是，这些研究已经开始通过使用不同的TMS电流方向评估SAI来确定认知对特定感觉运动回路的独特影响。SAI研究通常使用后-前（PA）感应电流，而只有少数SAI研究使用前后（AP）感应电流55。然而，在SAI评估期间，使用TMS诱导AP与PA电流相比，招募了不同的感觉运动回路16,56。例如，对 AP 敏感但不对 PA 敏感的感觉运动回路被小脑调节改变37,56。此外，对AP敏感但不对PA敏感的感觉运动电路由注意力负荷36调制。最后，注意力和小脑影响可能汇聚在相同的AP敏感感觉运动回路上，导致这些回路的适应不良改变37。

TMS技术的进步为操纵单脉冲，配对脉冲和重复应用期间使用的TMS刺激的配置提供了额外的灵活性57,58。可控脉冲参数TMS（cTMS）刺激器现已在全球范围内商业化用于研究用途，这些刺激器提供了对脉冲宽度和形状的灵活控制57。灵活性的提高源于控制两个独立电容器的放电持续时间，每个电容器负责TMS激励的独立相位。激励的双相或单相性质由每个电容器的相对放电幅度（称为M比）控制。cTMS研究将脉冲宽度操作与不同的电流方向相结合，以证明传统TMS刺激器使用的固定脉冲宽度（70-82μs）59,60可能在SAI56期间招募功能不同的感觉运动回路的混合。因此，cTMS是一个令人兴奋的工具，可以进一步解开各种收敛的感觉运动环在感觉运动表现和学习中的功能意义。

这份手稿详细介绍了一种独特的SAI方法来研究感觉运动整合，该方法在感觉运动行为期间将外周电刺激与cTMS相结合。这种方法通过评估传入投影对运动皮层中控制皮质脊髓输出的运动皮层中特定中间神经元群体的影响，改进了典型的SAI方法。虽然相对较新，但cTMS在研究典型和临床人群的感觉运动整合方面具有明显的优势。此外，目前的方法可以很容易地适应于与传统的TMS刺激器一起使用，并量化其他形式的传入抑制和促进，例如长潜伏期传入抑制（LAI）13 或短潜期传入促进（SAF）15。

Protocol

以下协议可应用于各种实验。所提供的信息详细介绍了一个实验，其中SAI用于量化手指对有效或无效提示探针的反应期间的感觉运动整合。在该协议中，SAI在没有任务的情况下进行评估，然后在提示的感觉运动任务期间同时评估，然后在没有任务的情况下再次评估。cTMS刺激器可以被任何市售的常规TMS刺激器取代。然而，传统TMS刺激器的脉冲宽度将固定在70-82μs之间，具体取决于特定的硬件<sup class…

Representative Results

图3 显示了使用PA120-和AP30-（下标表示脉冲宽度）感应电流在感觉运动任务期间在FDI肌肉中引发的单个参与者的无条件和条件MEP的示例。中间列中的条形图说明了无条件试验和有条件试验的原始平均峰峰值MEP振幅。右侧的条形图显示了同一参与者的 PA120 和 AP30 感应电流的 SAI 和 MEP 起始延迟。 外周电调节刺激的平均效果是…

Discussion

这里描述的SAI方法探测了在感觉运动表现和学习中发挥作用的神经通路子集。在参与者执行受控感觉运动任务时评估 SAI 对于解开众多感觉运动环的复杂贡献至关重要，这些感觉运动环会聚在运动皮质脊髓神经元上，以塑造健康和临床人群的运动输出。例如，类似的方法已被用于确定小脑对程序性运动控制过程的影响37,56以及声明性记忆系统可能影响健康人群21,36,37,38和先前脑震?…

Divulgazioni

The authors have nothing to disclose.

Acknowledgements

作者感谢自然科学和工程研究委员会（NSERC），加拿大创新基金会（CFI）和安大略省研究基金（ORF）授予S.K.M.的资助。

Materials

Acquisition software (for EMG) AD Instruments, Colorado Springs, CO, USA PL3504/P LabChart Pro version 8
Alcohol prep pads Medline Canada Corporation, Mississauga, ON, Canada 211-MM-05507 Alliance Sterile Medium, Antiseptic Isopropyl Alcohol Pad (200 per box)
Amplifier (for EMG) AD Instruments, Colorado Springs, CO, USA FE234 Quad Bio Amp
Cotton round Cliganic, San Francisco, CA, USA ‎CL-BE-019-6PK Premium Cotton Rounds (6-pack, 90 per package)
cTMS coils Rogue Research, Montréal, QC, Canada COIL70F80301 70 mm Medium Inductance Figure-8 coil
cTMS coils Rogue Research, Montréal, QC, Canada COIL70F80301-IC 70 mm Medium Inductance Figure-8 coil (Inverted Current)
cTMS stimulator Rogue Research, Montréal, QC, Canada CTMSMU0101 Elevate cTMS stimulator
Data acquisition board (for EMG) AD Instruments, Colorado Springs, CO, USA PL3504 PowerLab 4/35
Digital to analog board National Instruments, Austin, TX, USA 782251-01 NI USB-6341, X Series DAQ Device with BNC Termination
Dispoable adhesive electrodes (for EMG) Covidien, Dublin, Ireland 31112496 Kendal 130 Foam Electrodes
Electrogel Electrodestore.com E9 Electro-Gel for Electro-Cap (16 oz jar)
Nuprep Weaver and Company, Aurora, CO, USA 10-30 Nuprep skin prep gel (3-pack of 4 oz tubes) 
Peripheral electrical stimulator Digitimer, Hertfordshire, UK DS7R  DS7R High Voltage Constant Current Stimulator
Reusable bar electrode Electrodestore.com DDA-30 Black Bar Electrode, Flat, Cathode Distal
Software (for behaviour and stimulator triggering) National Instruments, Austin, TX, USA 784503-35 Labview 2020
TMS stereotactic coil guidance system Rogue Research, Montréal, QC, Canada KITBSF0404 BrainSight Neuronavigation System
Transpore tape 3M, Saint Paul, MN, USA 50707387794571 Transpore Medical Tape (1 in x 10 yds)
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Sensorimotor ControlMotor LearningSensory-motor IntegrationAfferent InhibitionTranscranial Magnetic StimulationControllable Pulse Parameter TMSMotor CortexMotor PerformanceSkill AcquisitionRehabilitationNeurological Disorders

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Graham, K. R., Hayes, K. D., Meehan, S. K. Combined Peripheral Nerve Stimulation and Controllable Pulse Parameter Transcranial Magnetic Stimulation to Probe Sensorimotor Control and Learning. J. Vis. Exp. (194), e65212, doi:10.3791/65212 (2023).
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