这项研究得到瑞士国家科学基金会（316030_128826）的资助。

该协议经当地道德委员会批准，实验符合赫尔辛基宣言（1964年）。 主题准备 注意:主题说明 - 在开始实验之前，指导每个受试者了解研究的目的和潜在的危险因素。对于经颅磁刺激（TMS），医疗风险包括任何癫痫发作史 ，眼睛和/或头部精神植入物，心血管系统疾病和怀孕。排除所有确认其中一个风险因素的科目。此外，在测试健康个体的实验中，排除所有患有神经和/或骨科疾病的受试者。 <ol><li> 主题放置 <ol><li>将主体放在支撑腿，躯干和头部的椅子上。确保双腿伸展，使膝盖分开并且周围神经更接近皮肤，使得神经更容易并且更可靠地通过电刺激兴奋。 </li><li>确保受试者的头部弯曲，搁置在稳定的支撑表面（如桌子）上，并用垫子固定。确保颈部和寰枢椎弯曲，以刺激皮质脊髓通路。 </li><li>定位双锥形磁性线圈，使其中心部分放置在接近或接近的位置，感应电流的一阶导数被引导为19,26。在头部和躯干上使用弹性带，以确保在整个实验过程中保持这一位置。 </li></ol></li><li>使用表面电极测量外周神经刺激（PNS）和TMS的电生理反应。 <ol><li>通过剃须，用丙醇消毒和轻微磨损来准备皮肤在比目鱼肌肉的腹部ñ。 <ol><li>将自粘EMG电极放在肌肉腹部的肌肤上。比目鱼。将参考电极放在骨骼上的皮肤上， 例如在髌骨或内踝上。 </li><li>将所有电极连接到EMG放大器，最后连接模拟数字转换器。放大EMG信号（×1000），带通滤波器（10 - 1000 Hz）和4 kHz采样。 </li></ol></li><li> PNS <ol><li>对于H反射调理，通过刺激po窝中的胫后神经来记录比目鱼肌中的H反射。用持续1 ms的方波脉冲进行刺激。对于刺激，用胶带将5×5cm的阳极固定在膝盖正前方的髌骨下方。 注意:稳定的H反射幅度是成功的H反射调理的先决条件，并且从比目鱼肌记录时可以发现所有肌肉的最小变异性。 </li><li>移动阴极在popliteal窝，直到找到刺激的最佳位置。 注意:最佳位置是指在比目鱼肌中以最小的刺激强度记录H反射，在这些低刺激强度下在EMG记录中没有可见的M波，而在拮抗剂m中没有接收任何反应。胫骨。 </li><li>避免在m中的回应。胫骨肌，因为那些可能通过n的Ia传入的相互抑制影响结果。腓肠肌与比目鱼肌的脊柱运动神经元。找到最佳位置后，将自粘电极放在皮肤上，用胶带固定电极，以确保刺激条件一致。 </li></ol></li><li> TMS <ol><li>用图8线圈刺激对侧半球的运动皮质区域，以在比目鱼肌肌电图记录中引发运动诱发电位（MEPs）。 </li><li>为了找到最佳的刺激点，pla首先在顶点和1厘米正面线圈。线圈的手柄应向后指向，引起线圈中心的感应电流的后向通量。 </li><li>以最低刺激物输出的约20-30％的低强度开始刺激，使受试者习惯于磁刺激。选择连续刺激之间的暂停为4秒。 </li><li>经过几次试验，将刺激强度提高到最大刺激物输出的40-60％左右，并将线圈移动到前额叶和中外侧方向，以找到m的热点。比目鱼。热点被定义为m中的MEP的位置。可以以最小的刺激强度诱发比目鱼肌。 </li><li>在找到比目鱼的热点后，确定静息电动机阈值（1.0 MT）作为在十个连续试验中的六次中使EMG大于50μV的MEP峰 - 峰值振幅所需的最小强度30。在背景EMG已经在50μV附近的受试者中，使用100μV作为阈值。 </li></ol></li><li> 固定线圈 <ol><li>将受试者的头部放在桌子上（请参阅"主题放置"），并使用硬质泡沫来防止头部朝四面八方移动。将线圈固定在支架上，将受试者的头部固定在椅子上。 </li><li>使用魔术贴将线圈固定到头部，并使用图像引导的TMS导航系统来监控整个实验中的线圈和头部位置。避免线圈相对于受试者头部的小的运动，因为这改变了神经元由TMS的募集。 </li></ol></li><li> 颈动脉结的磁刺激 <ol><li>使用放置在颈髓髓结的双锥形磁性线圈激发皮质脊髓束的轴突。 </li><li>定位线圈，使感应电流的一阶导数i并且其中心部分位于或靠近入口处。以最大刺激物输出（100％）施加刺激。 注意:即使具有这种高刺激强度，刺激太弱，无法充分招募脊髓运动神经元，并激活大多数受试者的小腿肌肉（ 即比目鱼肌和胫前肌）。因此，在颈髓刺激下，小腿肌肉表面EMG无复合潜力。因此，将颈髓模拟与H反射相结合（参见"3.1"）来提高脊髓运动神经元的兴奋性。 </li></ol></li></ol></li></ol> 2.预测<ol><li>调整H反射的大小（周围神经刺激） <ol><li>对于H反射调理，通过改变电刺激器的刺激强度，将H反射的尺寸调整到最大M波（Mmax） 31的20％。要获得Mmax，请记录H反射招聘曲线。为此，应用不同刺激强度的刺激。连续试验之间的暂停是4秒。 </li><li>将H反射和M波作为记录软件在线的EMG（mV）峰 - 峰幅度计算。注意控制H反射的大小在整个实验期间保持恒定在Mmax的20％，并检查其在每次试验中的大小。当检测H反射大小的系统偏差（控制H反射总是小于或者更大的目标大小）时，在连续试验之前调整刺激强度。 </li></ol></li><li>在实验前调整TMS的刺激强度。 <ol><li>对于休息时的H反射调理，将运动皮质上的TMS的刺激强度设置为MT的90-100％。确保在没有PNS的试验中没有观察到MEP。 注意:模拟强度应接近MT的100％，以确保对r条件下的H反射具有很大的影响以便容易地检测到早期便利化。 </li><li>在实验前调整颈髓刺激强度。与皮层刺激不同，始终将刺激强度调整为颈部刺激的最大刺激输出的100％。 </li></ol></li><li>通过运动皮层的磁刺激来调节H反射。 <ol><li>通过改变两个刺激之间的时间（H反射调节）来应用TMS和PNS，以允许评估皮质类神经元传播的变化。为了检测早期便利化，以-5毫秒的间激间隔（ISI）启动调理协议，并以-5毫秒为单位改变ISI，从-5 - +1 ms（ 图1B ）。 注意:负ISI表示在TMS之前引发PNS，正ISI表示相反。 </li><li> TMS和PNS之间的ISI随机从刺激试验到刺激试验，使得由于一定的顺序没有偏差的刺激可能会出现。 注意:在运动皮层上应用TMS时，"早期促进"应发生在ISI周围-4毫秒至-2毫秒。这意味着最快的（单突触皮质脊髓通路）在此时由PNS在脊髓运动神经元的传入排阻中碰撞（见5.2检测早期促进）。 </li><li>将连续刺激试验之间的暂停设置为4秒。 </li></ol></li><li>通过磁刺激来调节颈部髓核结合处的H反射。 注意:使用颈髓刺激进行调理，皮质脊髓通路的激发在空间上更接近脊柱运动神经元，而不是刺激运动皮质。因此，对应于早期促进的ISI移位约3-4毫秒。作为一个例子，在-4毫秒的初级运动皮层上TMS的早期促进将对应于-7 - -8毫秒与宫颈髓核刺激之间的ISI。 <ol><li&gt;使用ISI -9 - -3 ms之间的ISI，以1 ms为间隔进行宫颈髓核调理。在一次试验中总是一起应用在运动皮层和TMS上的TMS施加ISI，并在本试验中记录控制H反射和对照MEP。使用控制H反射作为条件H反射和对照MEP的参考，以确保类似的刺激条件。在测量前记录（至少）十个试验。 </li></ol></li><li> 在运动皮质和颈椎结节交替刺激 <ol><li>在同一试验期间，通过磁刺激运动皮层（M1调理;参见2.1）和磁性颈髓刺激（CMS-调节;参见2.2）来调节SOL H反射。 注意:建议在同一个试验中交替应用M1-和CMS调理，以将调节的H反射参考到相同的对照H反射样品（see 图1 ）。 </li></ol></li></ol> 3.干预 - 慢速重复TMS <ol><li>将刺激强度设置为1.2 MT，其诱导长期持续的32,33抑制皮质脊髓兴奋性，因为H反射调节需要数分钟的时间才能完成。在rTMS干预过程中，应用TMS在主动脉皮质上以1Hz进行20分钟。 </li></ol> 4.测量<ol><li>干预后直接使用与测量中使用的ISI相同的H反射调理。 </li><li>使用相同的刺激强度用于M1和颈髓髓结的磁刺激比预测量。 </li><li>确保控制H反射具有与预测量相同的尺寸。如果检测到系统偏差，则调整刺激强度。 </li></ol>大卫ta处理<ol><li>计算所有生理反应，如H反射，MEPs和调节H反射作为未修正EMG的峰 - 峰幅度。 <ol><li>对于每个ISI，平均十个条件H反射a）皮质和b）子宫颈髓母细胞刺激。此外，平均十个控制（ 即无条件）H反射作为调节H反射的参考（ 即 100％）。 </li><li>因此，在测量之前和之后，将每个ISI的调节H反射的平均振幅表示为对照H反射的平均幅度的百分比。确定早期便利化时要小心，因为这是至关重要的: 注意:由于早期促进发生的发生之间存在个体间变异性，因此分别确定每个受试者的预测量的早期促进。 </li></ol></li><li>使用非参数Wilcoxon测试来确定e第一次上升的条件H反射。对于CMS调节，开始ISI -9 ms的测试，M1调节搜索从ISI -5 ms开始的早期促进。将预测中获得的早期促进的幅度与使用相同ISI的后测量中获得的早期促进的振幅进行比较。 </li><li>另外，通过目视检查来验证早期便利化。 注意:M1调理后，早期促进最有可能发生在ISI -3毫秒左右。在调节H反射的第一次上升之后不久， 即 1至2ms后，在再次升高之前，调节的H反射有下降。 CMS调理后，早期易于发生可能发生在ISI -7毫秒左右，因此比M1调理后早4毫秒。 </li></ol>

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</ol>

作者没有什么可以披露的。

这里描述的H反射调节程序已经专门用于评估在重复激活皮质脊髓通路28之后的皮质类神经元突触的传播的急性变化。在这方面，H反射调理已经突出表明，rTMS不仅影响皮质结构的兴奋性，而且还对皮质类膜转移突触的皮质转移传导有影响。然而，随着运动发育和衰老，运动学习，运动和训练，疲劳，不活动，从损伤恢复，神经生理学和治疗干预，病理学等方面发生皮质螺旋传播?...

在灵长类动物中，皮质脊髓束构成控制自愿行为的主要下降途径1 。皮质螺旋途径通过直接的单突触性皮质神经元连接和间接的寡聚和多突触连接2,3将运动皮质区域连接到脊髓α运动神经元。虽然运动皮质可以通过经颅磁刺激（TMS）非常侵入地很容易地被激发，但对这种刺激的诱发肌电图反应通常难以解释。其原因是复合运动诱发电位（MEP）可能受皮质和皮质脊髓神经元，脊髓中间神经元和脊髓α运动神经元4,5,6,7的兴奋性变化的影响。几种无创电生理学cal技术和刺激方案旨在确定皮质脊髓兴奋性和传播的变化是否由皮质或脊髓水平的变化引起。通常，电诱发H反射的振幅的变化被用作运动神经元池的兴奋性改变的"指示性"。然而，之前已经表明，H反射不仅依赖于运动神经元池的兴奋性，而且还受其他因素调节，例如突触前抑制8,9或同源突触后活化抑郁症5,10 。比较MEPs和H反射的另一个限制是检测11级12级神经元兴奋性变化的障碍。除了这些缺点，运动神经元可能不同于周围神经刺激而不是wi激活TMS使得运动神经元兴奋性的变化将以与通过皮质脊髓通路13,14,15介导的反应相比以不同的方式影响这些应答。 用于将脊柱与皮质作用分离的另一种方法代表运动皮质16的经颅电刺激（TES）。在低刺激强度下应用，TES被认为不受皮质兴奋性变化的影响。由于TES和TMS都通过皮质螺旋途径激活α运动神经元，所以磁诱发MEPs的比较提供了一种更有吸引力的方法来得出关于MEPs大小变化的皮层性质的结论，而不是H反射之间的比较和MEPs。然而，当刺激强度增加时，TES诱发的MEP也受皮层兴奋性变化的影响sup class ="xref"&gt; 17，18。当电刺激不施加到运动皮质但在颈髓髓结的时候，可以避免这个问题。然而，虽然电刺激可以引起上肢和下肢肌肉的颈动脉运动诱发电位（cMEP），但大多数受试者感觉到脑干（和皮层）的电刺激极其不愉快和痛苦。一个不那么痛苦的替代方案是通过使用磁刺激在宫颈髓核结合处激活皮质脊髓通路19 。通常接受的是，颈动脉磁刺激（CMS）激活许多与运动皮层TMS相同的下降纤维，并且通过将MEP与cMEP 19进行比较可以检测到皮质兴奋性的变化。皮层细胞和皮质神经元细胞的兴奋性增加被认为促进皮层诱发的MEP没有并发改变的宫颈诱发MEP。 然而，在大多数受试者中，不可能在休息20,21的下肢获得磁性诱发的cMEP。克服这个问题的一个方法是通过自愿预先收缩目标肌肉来提高脊柱运动神经元的兴奋性。然而，众所周知，收缩强度的轻微变化影响cMEP的尺寸。因此，难以比较不同的任务。此外，由于预收缩引起的运动神经元兴奋性的变化将影响MEPs和cMEP，但不一定在相同程度上。最后，通过比较化合物MEP和化合物cMEP，一些信息包含在下降的波浪中。通过研究包括通过磁力马达皮层刺激调节比目鱼肌，胫前肌和桡侧肌的H反射的研究揭示了这一点12日 ， 22日 。通过结合外周神经刺激和TMS在运动皮质上具有特异的刺激间期（ISI），可以研究不同下降球对H反射的促进和抑制作用。这种技术受到动物实验中用于确定神经通路传播的空间促进技术的极大启发，可被视为该技术的非侵入性间接版本23 。虽然H反射不仅对于区分皮质脊髓通路的不同部分（快速与较慢的皮质脊髓投射）是重要的，但是也必须以受控和可比较的方式提高脊柱兴奋性。因此，在休息和活动期间，这种刺激技术的组合允许以高时间分辨率评估皮质螺旋途径的不同部分的变化， 即在t他最快，可能是单突触性皮质神经元连接和慢性低聚和多突触通路12,22,24,25。最近，这种技术不仅通过运动皮质（M1调节）调节TMS的H反射，而且通过在宫颈髓核结合处（CMS-调节） 26进行额外的调理刺激来延长。通过比较M1-和CMS调节之间的效应，该技术允许具有高时间分辨率的途径特异性分化，并且允许对皮质与脊髓机制进行解释。此外，最重要的是，关于目前的研究，这种技术允许在考虑早期促进时评估皮质转移突触的传播。 H反射的早期促进很可能是由激活引起的对脊柱运动神经元12,26的直接，单突触性皮质转移瘤投射。为了测试最快的皮质脊髓途径，因此，早期促进，H反射必须在TMS之前2至4 ms引出。其原因是与H反射（约34ms;见25 ）相比，MEP的等待时间略短（约32ms;见27 ）。在应用TMS之前不久就引发H反射，导致脊柱运动神经元水平上升和最快下降兴奋的趋同。当TMS施加在颈髓髓结上时，下降排卵将在脊髓运动神经元游泳池的3〜4毫秒之前比在M1刺激之后达到。对于CMS调理，因此周围神经刺激应在磁脉冲前6 - 8 ms引起。 CMS调节后的早期促进变化表明差异tr在皮质脊髓束和α-运动神经元之间的突触28 。在目前的研究中，最近开发的技术用于区分脊髓与低频重复TMS（rTMS）后的皮层效应。更具体地说，我们假设，如果在rTMS干预之后，如果M1调节的早期促进减少，但CMS调节之后的早期促进不是，其效果应该是纯皮层的起源。相比之下，如果早期促进CMS调理也发生变化，这种改变应该与脊髓水平发生的机制有关。更具体地说，由于H反射的早期促进被认为是由对直接的脊髓运动神经元12,29的直接的皮质类神经元突起的激活引起的，所以在时间上改变了CMS-和M1-调节的H反射早期促进应该指示改变的皮质类神经元传播即突触功效28 。

<table><tbody><tr><td>Self-adhesive EMG electrodes</td><td>Blue sensor N, Ambu, Ballerup, Denmark</td><td></td><td>Used to record EMG signals</td></tr><tr><td>Electrical stimulator</td><td>Digitimer DS7A, Hertfordshire, UK</td><td></td><td>Used to elicit the soleus H-reflex</td></tr><tr><td>Stimulating electrode</td><td>Blue sensor N, Ambu, Ballerup, Denmark</td><td></td><td>Used to elicit the soleus H-reflex</td></tr><tr><td>Magnetic stimulator #1</td><td>Magstim Rapid&lt;sup&gt;2&lt;/sup&gt; TMS stimulator, Magstim Company Ltd., Whitland, UK</td><td></td><td>Used to elicit contralateral motor evoked potentials in the soleus muscle</td></tr><tr><td>Coil #1: 90 mm figure-of-eight coil&amp;nbsp;</td><td>Magstim Company Ltd., Whitland, UK</td><td></td><td>Used to elicit contralateral motor evoked potentials in the soleus muscle</td></tr><tr><td>&amp;nbsp; &amp;nbsp;</td><td>&amp;nbsp; &amp;nbsp;</td><td>&amp;nbsp; &amp;nbsp;</td><td>Stimulator #1 and coil #1 were used in the original publication (Taube et al. 2014; Cerebral Cortex)</td></tr><tr><td>Magnetic stimulator #2</td><td>MagPro X100 with MagOption, MagVenture A/S, Farum, Denmark</td><td></td><td>Used to elicit contralateral motor evoked potentials in the soleus muscle</td></tr><tr><td>Co#2: 95 mm focal &amp;ldquo;butterfly-shaped&amp;rdquo; coil (D-B80)&amp;nbsp;</td><td>MagVenture A/S, Farum, Denmark</td><td></td><td></td></tr><tr><td colspan="4">Stimulator no2 and coil no2 were used in the video session</td></tr><tr><td>Magnetic stimulator #3</td><td>Magstim Company Ltd., Whitland, UK</td><td></td><td>Used to stimulate at the cervicomedullary junction</td></tr><tr><td>Coil #3: double-cone magnetic coil</td><td>Magstim Company Ltd., Whitland, UK</td><td></td><td>Used to stimulate at the cervicomedullary junction</td></tr><tr><td>Image-guided TMS navigational system #1</td><td>Brainsight 2, Rouge Research, Montreal, Canada</td><td></td><td>Used in the original publication (Taube et al. 2014; Cerebral Cortex) to monitor coil position throughout the experiment</td></tr><tr><td>Image-guided TMS navigational system #2</td><td>TMS Navigator SW-Version 2.0, LOCALITE GmbH, Sankt Augustin, Germany</td><td>Used for the video session</td><td></td></tr><tr><td>Literature:&amp;nbsp;</td><td>&lt;a name=&quot;RANGE!B15&quot;&gt;&lt;/a&gt;</td><td></td><td></td></tr><tr><td>Taube et al. 2014</td><td>Taube, W., Leukel, C., Nielsen, J. B. &amp;amp; Lundbye-Jensen, J. Repetitive Activation of the Corticospinal Pathway by Means of rTMS may Reduce the Efficiency of Corticomotoneuronal Synapses. Cerebral cortex, doi:10.1093/cercor/bht359 (2014).</td><td></td><td></td></tr></tbody></table>

non-invasive assessment of changes in corticomotoneuronal transmission in humans

皮质脊髓通路是连接大脑与肌肉的主要途径，因此对运动控制和运动学习非常重要。存在一些研究该途径的兴奋性和可塑性的无创电生理方法。然而，大多数方法是基于化合物电位的定量，并忽略皮质螺旋途径由许多或多或少直接的不同连接组成。在这里，我们提出一种允许测试皮质脊髓传播的不同部分的兴奋性的方法。这种所谓的H反射调节技术允许评估最快（单突触）和多突触皮质螺旋途径的兴奋性。此外，通过使用两个不同的刺激部位，运动皮层和颈椎管连接处，它不仅允许皮层和脊柱效应之间的分化，还允许评估皮质的传播耳聋突触在这份手稿中，我们描述了这种方法如何用于评估低频重复经颅磁刺激后的皮质类固醇传播，这是先前显示的减少皮层细胞兴奋性的方法。在这里我们证明，不仅皮质细胞受到这种重复刺激的影响，而且在脊髓水平的皮质类神经元突触期间的传播。这一发现对于了解神经可塑性的基本机制和部位很重要。除了基本机制的调查之外，H反射调理技术可以用于测试行为（ 例如 ，训练）或治疗干预，病理学或老化后皮质脊髓传播的变化，因此可以更好地理解运动控制和运动的基础的神经过程学习。

<html> 在M1-和CMS调理之后发生早期促进 在TMS上的H反射调理导致早期促进发生在ISI -3和-4毫秒周围。 CMS调理后的早期促进发生在3毫秒前（分别为ISI -6和-7毫秒）。 图1中显示了一个对象的示例性ISI曲线。在本研究中，早期的促进是在其发生的第一个毫秒内进行评估，同时使用M1-和CMS-调理（参见<strong c...

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Non-invasive Assessment of Changes in Corticomotoneuronal Transmission in Humans

本研究的目的是评估重复经颅磁刺激后人类皮质类神经元突触的变化。为此目的，引入电生理方法，其允许评估途径特异性皮质脊髓传播， 即快速，直接皮质螺旋途径从多突触连接的分化。

非侵入性评估人类皮质神经元传播的变化

The corticospinal pathway is the major pathway connecting the brain with the muscles and is therefore highly relevant for movement control and motor ...

non-invasive-assessment-changes-corticomotoneuronal-transmission

Research

JoVE Journal

Neuroscience

7.8K 次观看.  University of Fribourg (Switzerland). 本研究的目的是评估重复经颅磁刺激后人类皮质类神经元突触的变化。为此目的，引入电生理方法，其允许评估途径特异性皮质脊髓传播， 即快速，直接皮质螺旋途径从多突触连接的分化。 

视频: Non-invasive Assessment of Changes in Corticomotoneuronal Transmission in Humans

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

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 ...

医学

In Vivo Electrophysiological Measurements on Mouse Sciatic Nerves

Electrophysiological studies allow a rational classification of various neuromuscular diseases and are of help, together with neuropathological techniques, in the understanding of the underlying pathophysiology1. Here we describe a method to perform electrophysiological studies on mouse sciatic nerves in vivo.
The animals are anesthetized with isoflurane in order to ensure analgesia for the tested mice and undisturbed working environment during the measurements that take about 30 min/animal. A constant body temperature of 37 &#176;C is maintained by a heating plate and continuously measured by a rectal thermo probe2. Additionally, an electrocardiogram (ECG) is routinely recorded during the measurements in order to continuously monitor the physiological state of the investigated animals.
Electrophysiological recordings are performed on the sciatic nerve, the largest nerve of the peripheral nervous system (PNS), supplying the mouse hind limb with both motoric and sensory fiber tracts. In our protocol, sciatic nerves remain in situ and therefore do not have to be extracted or exposed, allowing measurements without any adverse nerve irritations along with actual recordings. Using appropriate needle electrodes3 we perform both proximal and distal nerve stimulations, registering the transmitted potentials with sensing electrodes at gastrocnemius muscles. After data processing, reliable and highly consistent values for the nerve conduction velocity (NCV) and the compound motor action potential (CMAP), the key parameters for quantification of gross peripheral nerve functioning, can be achieved.

In Vivo Electrophysiological Measurements on Mouse Sciatic Nerves

Measurements of nerve conduction properties in vivo exemplify a powerful tool to characterize various animal models of neuromuscular diseases. Here, we present an easy and reliable protocol by which electrophysiological analysis on sciatic nerves of anesthetized mice can be performed.

在对小鼠坐骨神经体内的电测量

Electrophysiological studies allow a rational classification of various neuromuscular diseases and are of help, together with neuropathological ...

神经科学

Assessment of Neuromuscular Function Using Percutaneous Electrical Nerve Stimulation

Percutaneous electrical nerve stimulation is a non-invasive method commonly used to evaluate neuromuscular function from brain to muscle (supra-spinal, spinal and peripheral levels). The present protocol describes how this method can be used to stimulate the posterior tibial nerve that activates plantar flexor muscles. Percutaneous electrical nerve stimulation consists of inducing an electrical stimulus to a motor nerve to evoke a muscular response. Direct (M-wave) and/or indirect (H-reflex) electrophysiological responses can be recorded at rest using surface electromyography. Mechanical (twitch torque) responses can be quantified with a force/torque ergometer. M-wave and twitch torque reflect neuromuscular transmission and excitation-contraction coupling, whereas H-reflex provides an index of spinal excitability. EMG activity and mechanical (superimposed twitch) responses can also be recorded during maximal voluntary contractions to evaluate voluntary activation level. Percutaneous nerve stimulation provides an assessment of neuromuscular function in humans, and is highly beneficial especially for studies evaluating neuromuscular plasticity following acute (fatigue) or chronic (training/detraining) exercise.

We present a protocol to assess changes in neuromuscular function. Percutaneous electrical nerve stimulation is a non-invasive method that evokes muscular responses. Electrophysiological and mechanical properties of these responses permit the evaluation of neuromuscular function from brain to muscle (supra-spinal, spinal and peripheral levels).

神经肌肉功能的应用经皮神经电刺激评估

Percutaneous electrical nerve stimulation is a non-invasive method commonly used to evaluate neuromuscular function from brain to muscle (supra-spinal, ...

In Vivo Electrophysiological Measurement of the Rat Ulnar Nerve with Axonal Excitability Testing

Electrophysiology enables the objective assessment of peripheral nerve function in vivo. Traditional nerve conduction measures such as amplitude and latency detect chronic axon loss and demyelination, respectively. Axonal excitability techniques &#34;by threshold tracking&#34; expand upon these measures by providing information regarding the activity of ion channels, pumps and exchangers that relate to acute function and may precede degenerative events. As such, the use of axonal excitability in animal models of neurological disorders may provide a useful in vivo measure to assess novel therapeutic interventions. Here we describe an experimental setup for multiple measures of motor axonal excitability techniques in the rat ulnar nerve.
The animals are anesthetized with isoflurane and carefully monitored to ensure constant and adequate depth of anesthesia. Body temperature, respiration rate, heart rate and saturation of oxygen in the blood are continuously monitored. Axonal excitability studies are performed using percutaneous stimulation of the ulnar nerve and recording from the hypothenar muscles of the forelimb paw. With correct electrode placement, a clear compound muscle action potential that increases in amplitude with increasing stimulus intensity is recorded. An automated program is then utilized to deliver a series of electrical pulses which generate 5 specific excitability measures in the following sequence: stimulus response behavior, strength duration time constant, threshold electrotonus, current-threshold relationship and the recovery cycle.
Data presented here indicate that these measures are repeatable and show similarity between left and right ulnar nerves when assessed on the same day. A limitation of these techniques in this setting is the effect of dose and time under anesthesia. Careful monitoring and recording of these variables should be undertaken for consideration at the time of analysis.

In Vivo Electrophysiological Measurement of the Rat Ulnar Nerve with Axonal Excitability Testing

Axonal excitability techniques provide a powerful tool to examine pathophysiology and biophysical changes that precede irreversible degenerative events. This manuscript demonstrates the use of these techniques on the ulnar nerve of anesthetized rats.

在体内轴突兴奋性试验对大鼠尺神经的电生理测量

Electrophysiology enables the objective assessment of peripheral nerve function in vivo. Traditional nerve conduction measures such as amplitude and ...

In Vivo Electrophysiological Measurement of Compound Muscle Action Potential from the Forelimbs in Mouse Models of Motor Neuron Degeneration

Assessing the functionality of the nerve axon provides detailed information on the progression of neuromuscular disorders. Electrophysiological recordings provide a sensitive approach to measure nerve conduction in humans and rodent models. To broaden the technical possibilities for electromyography in mice, the measurement of compound muscle action potentials (CMAPs) from the brachial plexus nerve in the forelimb using needle electrodes is described here. CMAP recordings after stimulating the sciatic nerve in hindlimbs have been previously described. The newly introduced method here allows for the evaluation of the nerve conductivity at an additional site, and thus provides a more profound overview of the neuromuscular functionality. The technique provides information on both the relative number of functional axons and the myelination level. Thereby, this method can be applied to assess both axonal diseases as well as demyelinating conditions. This minimally invasive method does not require extraction of the nerve and therefore it is suitable for repeated measurements for longitudinal follow-up in the same animal. Similar recordings are performed in clinical setups to emphasize the translational relevance of the method.

In Vivo Electrophysiological Measurement of Compound Muscle Action Potential from the Forelimbs in Mouse Models of Motor Neuron Degeneration

The measurement of nerve conduction is a useful tool to assess mouse models of neurodegeneration but it is frequently only applied to stimulate the sciatic nerve in hindlimbs. Here, we describe a technique to measure compound muscle action potential (CMAP) in vivo in the mouse forelimb muscles innervated by the brachial plexus.

体内运动神经元变性小鼠前肢肌作用电位的电生理测量

Assessing the functionality of the nerve axon provides detailed information on the progression of neuromuscular disorders. Electrophysiological recordings ...

Bilateral Assessment of the Corticospinal Pathways of the Ankle Muscles Using Navigated Transcranial Magnetic Stimulation

Distal leg muscles receive neural input from motor cortical areas via the corticospinal tract, which is one of the main motor descending pathway in humans and can be assessed using transcranial magnetic stimulation (TMS). Given the role of distal leg muscles in upright postural and dynamic tasks, such as walking, a growing research interest in the assessment and modulation of the corticospinal tracts relative to the function of these muscles has emerged in the last decade. However, methodological parameters used in previous work have varied across studies making the interpretation of results from cross-sectional and longitudinal studies less robust. Therefore, use of a standardized TMS protocol specific to the assessment of leg muscles&#39; corticomotor response (CMR) will allow for direct comparison of results across studies and cohorts. The objective of this paper is to present a protocol that provides the flexibility to simultaneously assess the bilateral CMR of two main ankle antagonistic muscles, the tibialis anterior and soleus, using single pulse TMS with a neuronavigation system. The present protocol is applicable while the examined muscle is either fully relaxed or isometrically contracted at a defined percentage of maximum isometric voluntary contraction. Using each subject&#39;s structural MRI with the neuronavigation system ensures accurate and precise positioning of the coil over the leg cortical representations during assessment. Given the inconsistency in CMR derived measures, this protocol also describes a standardized calculation of these measures using automated algorithms. Though this protocol is not conducted during upright postural or dynamic tasks, it&#160;can be used to assess bilaterally any pair of leg muscles, either antagonistic or synergistic, in both neurologically intact and impaired subjects.

The present protocol describes the simultaneous, bilateral assessment of the corticomotor response of the tibialis anterior and soleus during rest and tonic voluntary activation using a single pulse transcranial magnetic stimulation and neuronavigation system.

导航经颅磁刺激踝关节脊椎通路的双边评价

Distal leg muscles receive neural input from motor cortical areas via the corticospinal tract, which is one of the main motor descending pathway in humans ...

In Vivo Intracellular Recording of Type-Identified Rat Spinal Motoneurons During Trans-Spinal Direct Current Stimulation

Intracellular recording of spinal motoneurons in vivo provides a &#8220;gold standard&#8221; for determining the cells&#8217; electrophysiological characteristics in the intact spinal network and holds significant advantages relative to classical in vitro or extracellular recording techniques. An advantage of in vivo intracellular recordings is that this method can be performed on adult animals with a fully mature nervous system, and therefore many observed physiological mechanisms can be translated to practical applications. In this methodological paper, we describe this procedure combined with externally applied constant current stimulation, which mimics polarization processes occurring within spinal neuronal networks. Trans-spinal direct current stimulation (tsDCS) is an innovative method increasingly used as a neuromodulatory intervention in rehabilitation after various neurological injuries as well as in sports. The influence of tsDCS on the nervous system remains poorly understood and the physiological mechanisms behind its actions are largely unknown. The application of the tsDCS simultaneously with intracellular recordings enables us to directly observe changes of motoneuron membrane properties and characteristics of rhythmic firing in response to the polarization of the spinal neuronal network, which is crucial for the understanding of tsDCS actions. Moreover, when the presented protocol includes the identification of the motoneuron with respect to an innervated muscle and its function (flexor versus extensor) as well as the physiological type (fast versus slow) it provides an opportunity to selectively investigate the influence of tsDCS on identified components of spinal circuitry, which seem to be differently affected by polarization. The presented procedure focuses on surgical preparation for intracellular recordings and stimulation with an emphasis on the steps which are necessary to achieve preparation stability and reproducibility of results. The details of the methodology of the anodal or cathodal tsDCS application are discussed while paying attention to practical and safety issues.

This protocol describes in vivo intracellular recording of rat lumbar motoneurons with simultaneous trans-spinal direct current stimulation. The method enables us to measure membrane properties and to record rhythmic firing of motoneurons before, during and after anodal or cathodal polarization of the spinal cord.

在跨脊柱直流刺激期间类型识别大鼠脊柱腺瘤的 Vivo 细胞内记录

Intracellular recording of spinal motoneurons in vivo provides a &#8220;gold standard&#8221; for determining the cells&#8217; electrophysiological ...

Assessing Corticospinal Excitability During Goal-Directed Reaching Behavior

Reaching is a widely studied behavior in motor physiology and neuroscience research. While reaching has been examined using a variety of behavioral manipulations, there remain significant gaps in the understanding of the neural processes involved in reach planning, execution, and control. The novel approach described here combines a two-dimensional reaching task with transcranial magnetic stimulation (TMS) and concurrent electromyography (EMG) recording from multiple muscles. This method allows for the noninvasive detection of corticospinal activity at precise time points during the unfolding of reaching movements. The example task code includes a delayed response reaching task with two possible targets displayed &#177; 45&#176; off the midline. Single pulse TMS is delivered on the majority of task trials, either at the onset of the preparatory cue (baseline) or 100 ms prior to the imperative cue (delay). This sample design is suitable for investigating changes in corticospinal excitability during reach preparation. The sample code also includes a visuomotor perturbation (i.e., cursor rotation of &#177; 20&#176;) to investigate the effects of adaptation on corticospinal excitability during reach preparation. The task parameters and TMS delivery can be adjusted to address specific hypotheses about the state of the motor system during reaching behavior. In the initial implementation, motor evoked potentials (MEPs) were successfully elicited on 83% of TMS trials, and reach trajectories were recorded on all trials.

Reaching is a fundamental skill that allows humans to interact with the environment. Several studies have aimed to characterize reaching behavior using a variety of methodologies. This paper offers an open-source application of transcranial magnetic stimulation to assess the state of corticospinal excitability in humans during reaching task performance.

评估目标导向到达行为期间的皮质脊髓兴奋性

Reaching is a widely studied behavior in motor physiology and neuroscience research. While reaching has been examined using a variety of behavioral ...

Open-Source Real-Time Closed-Loop Electrical Threshold Tracking for Translational Pain Research

Nociceptors are a class of primary afferent neurons that signal potentially harmful noxious stimuli. An increase in nociceptor excitability occurs in acute and chronic pain conditions. This produces abnormal ongoing activity or reduced activation thresholds to noxious stimuli. Identifying the cause of this increased excitability is required for the development and validation of mechanism-based treatments. Single-neuron electrical threshold tracking can quantify nociceptor excitability. Therefore, we have developed an application to allow such measurements and demonstrate its use in humans and rodents. APTrack provides real-time data visualization and action potential identification using a temporal raster plot. Algorithms detect action potentials by threshold crossing and monitor their latency after electrical stimulation. The plugin then modulates the electrical stimulation amplitude using an up-down method to estimate the electrical threshold of the nociceptors. The software was built upon the Open Ephys system (V0.54) and coded in C++ using the JUCE framework. It runs on Windows, Linux, and Mac operating systems. The open-source code is available (<a data-saferedirecturl="https://www.google.com/url?q=https://github.com/Microneurography/APTrack&amp;source=gmail&amp;ust=1680789829274000&amp;usg=AOvVaw0nMk9J_EI2jUn8SlmC5JJm" href="https://github.com/Microneurography/APTrack" target="_blank">https://github.com/Microneurography/APTrack</a>). The electrophysiological recordings were taken from nociceptors in both a mouse skin-nerve preparation using the teased fiber method in the saphenous nerve and in healthy human volunteers using microneurography in the superficial peroneal nerve. Nociceptors were classified by their response to thermal and mechanical stimuli, as well as by monitoring the activity-dependent slowing of the conduction velocity. The software facilitated the experiment by simplifying the action potential identification through the temporal raster plot. We demonstrate real-time closed-loop electrical threshold tracking of single-neuron action potentials during&#160;in vivo&#160;human microneurography, for the first time, and during&#160;ex vivo&#160;mouse electrophysiological recordings of C-fibers and A&#948;-fibers. We establish proof of principle by showing that the electrical threshold of a human heat-sensitive C-fiber nociceptor is reduced by heating the receptive field. This plugin enables the electrical threshold tracking of single-neuron action potentials and allows the quantification of changes in nociceptor excitability.

APTrack is a software plugin developed for the Open Ephys platform that enables real-time data visualization and the closed-loop electrical threshold tracking of neuronal action potentials. We have successfully used this in microneurography for human C-fiber nociceptors and mouse C-fiber and A&#948;-fiber nociceptors.

用于转化疼痛研究的开源实时闭环电阈值跟踪

Nociceptors are a class of primary afferent neurons that signal potentially harmful noxious stimuli. An increase in nociceptor excitability occurs in ...