The authors have no acknowledgements.

实验过程概述获得机构伦理委员会批准，并符合赫尔辛基宣言。数据来自一个代表性的参与者谁知道的程序，并给他的书面知情同意书收集。 1.仪器准备<ol><li>清洁皮肤在由剃须电极的位置，并用酒精，得到低阻抗（&lt;5千欧）的污垢。 </li><li>放置两个氯化银表面电极（10毫米直径的记录）在股骨内踝的比目鱼肌的内侧condylis之间的线路的2/3;对肌肉的内侧腓肠肌的最突出的隆起;在沿着腓骨和足跟的腓肠肌外侧的头部之间的线的距离的三分之一;并且在1/3沿着​​腓骨的前端与内踝对于胫骨前肌的尖端之间的线的距离，与interelectro德距离（中心到中心）的2厘米，按SENIAM建议30。 注意:比目鱼肌电极具有gastrocnemii肌肉的前端插入下被定位，以确保它们不会从gastrocnemii肌肉（串扰）的磁头记录活性。 </li><li>放置一个参考电极在上（刺激和记录点之间）相同的腿的中心位置。 </li><li>调整高度和椅子的深度，以获得90°（0°=满跖屈）脚踝角度，使比目鱼和gastrocnemii肌肉不拉伸，H反射不改变11,12。 <ol><li>设定为90°（0°=完全伸膝）的膝盖夹角由于gastrocnemii肌肉的biarticular性质。但是，最佳的踝关节角度进行跖屈肌群的最大自主扭矩为70-80°（0°=全跖屈）26。因此，踝关节角度将取决于对位计利息（电与机械录音）。 注意:无论选择的初始角度，它必须保持不变整个实验过程中，以规范神经肌肉兴奋性11,12,27,28。 </li><li>在测试过程中监测受试者的姿态，以保持对车辆调配场29的兴奋性不断皮质前庭的影响时，要特别注意。 </li></ol></li><li>牢牢表带脚踝到一个测力计，以与测力计25的旋转轴线对齐的接头（外踝）的解剖学轴线。 <ol><li>对附着在测力计脚板主体施加压力，记录跖屈扭矩。保持脚部动整个实验，以便可以检测到在扭矩小的变化。 </li></ol></li><li>注意:在某些情况下，脚跟可以略微抬离力板，如果足踝不固定，其可以乐广告到一个不完整的传输克服板的转矩。 图3给出了实验装置的说明。 </li></ol><img alt="图3" src="/files/ftp_upload/52974/52974fig3.jpg" /> 图3:实验装置经典实验装置来记录肌电（EMG）和扭矩信号。 <ol start="6"><li>电极连接的电缆放大器。 </li><li>采样率的扭矩和肌电图的测量设置为2-5千赫。记录使用模拟 - 数字（AD）转换系统的肌电信号。所述信号将显示用数据采集系统，其中瞬时给出几个参数值在监视器上（例如最大值，峰 - 峰幅度，持续时间）。肌电信号的频谱范围5 Hz和2 kHz的频率之间可以的，但主要是含10 Hz和1 kHz的31间。因此，采样频率必须足够高，以保持信号的形状，杜尔荷兰国际集团肌电图记录。放大和过滤使用的10赫兹和1千赫8,21,32带宽频率肌电信号（增益= 500-100）。 </li><li>放置阳极的电刺激在髌腱。 </li><li>确定胫后神经的最佳刺激位置，以获得最佳的比目​​鱼H反射一个给定的强度，在腘窝使用手持球阴极电极。测试多个刺激部位与阴极球电极，直到H反射的极大值为止。 <ol><li>记录胫骨前EMG活动，以确保腓总神经没有被激活，以避免影响来自拮抗剂IA传入12。在1毫秒设置脉冲宽度，以提供神经纤维，特别是传入纤维10的最佳活化。 </li></ol></li><li>放置一个自粘氯化银阴极的刺激位置的位置，以确保恒定的刺激条件（例如压力，东方通货膨胀）。 注:所有这些参数（主体地位，电极位置和刺激部位）不为不同的电生理测量的评估不变。刺激的唯一的强度和条件（其余与收缩）而有所不同。 </li></ol> 2.测试程序在休息<ol start="1"><li>指示主体保持放松，保持他/她的肌肉处于静止状态。 </li><li>调整刺激强度，以获得最大的比目鱼肌H反射幅度（H 最大 ;正常范围:20-50毫安）。的M波比目鱼肌的可为H 最大强度来观察。 注意:对于重复测量（ 如前和疲劳协议后），最佳的强度，以获得h最大响应在会议期间可能会有所不同。作为保持恒定强度可导致至H 的最大振幅的低估，则建议实验者定期重新评估h最大强度33。 </li><li>记录至少3比目鱼H反射响应在该强度与3秒的最小间隔，以避免二次活化抑郁34。 注意:虽然在记录多个反应是更适合，因为的H反射的特定灵敏度，单个刺激可能试图避 ​​免（一个疲劳协议期间例如 ）快速恢复的影响时会在某些情况下不够，例如。 </li><li>增加刺激强度，以获得最大的比目鱼M-波幅（M 最大 ;正常范围:40-100毫安）。一般，设置增量在刺激强度在2-4毫安，以8-10秒两个刺激器12,35之间的间隔。 m最大时获得所希望的强度达到，而没有H反射响应可以观察到。 </li><li>设置最终强度为M 的最大刺激强度的120-150％，以确保对M-波达到其最大值的一个平台期。这的IntensiTY被称为在下面的说明超最大强度。 </li><li>保持恒定的刺激强度的比目鱼肌M-波记录整个会话。 </li><li>记录3比目鱼肌M-浪和3个相关的抽搐扭矩在这个强度。 </li></ol> 3.测试程序在随意收缩<ol start="1"><li>作为热身，让拍摄对象进行足底屈肌的10简短，不疲劳亚极量收缩，有几秒钟的休息每个宫缩之间。在热身结束后，至少要花1分钟休息，以避免疲劳影响11。 </li><li>连续记录小腿三头肌的活动。录音比目鱼肌和gastrocnemii肌肉使不同的肌肉类型学为一个单一的刺激部位24的行为进行分析。 </li><li>指示被摄体进行跖屈肌的等距最大自主收缩（MVC）。主题有硬推的possi通过收缩他的足底屈肌竹叶提取对测力计。提供视觉反馈在努力的主体，规范的口头鼓励19。当高原观察到的MVC为止。 </li><li>在MVC（叠加的双峰），而另一个配对刺激的高原期间提供一个配对的刺激（100赫兹频率）在超最大强度时，肌肉完全松弛收缩（增效双峰）后立即评估自愿激活水平。通过特定设备 （例如Digitimer D185多脉冲刺激）或通过与单个脉冲刺激器相关联的刺激程序提供这种成对刺激。 </li><li>指示受每次试验11之间至少有1分钟休息进行跖屈的第二个MVC。如果从第二个试验的峰值扭矩不是在第一的5％，额外的试验，必须执行36。所取得的最大扭矩受试者被取为MVC的转矩。 </li></ol> 4.数据分析<ol start="1"><li>数据分析在休息<ol><li>选择一个时间窗口，包括与抽搐在休息（H波或M波）相关的肌电图响应。 </li><li>测定峰-峰振幅，峰-峰持续时间和/或波浪的区域（图4A）。如果振幅不直接由软件提供，减去最小值到最大值。 <ol><li>对于持续时间，测定从最大峰的开始和结束的最小峰值的时间范围。对于面积，计算出肌电信号的由波的起点开始和结束的波结束的积分。 注意:峰-峰幅度可以反映:1）神经肌肉传递，2）电机单元动作电位幅度和/或运动单位动作电位37 3）颞分散体。 M-波时间反映神经肌肉的传播37。 </li></OL&gt; </li><li>对于多个试验，计算出波的平均水平。如果平均不能直接由软件，使用电子表格软件提供（例如，在电子表格程序通式函数）来计算从几个试验（至少3个）该值。 </li><li>选择休息抽搐。 </li><li>测量与所述静止抽搐（图4B）相关的峰值扭矩。 </li><li>对于多个试验，计算出休息抽搐的平均峰值扭矩。如果平均不能直接由软件，使用电子表格软件提供（例如，在电子表格程序通式函数）来计算从几个试验（至少3个）该值。 </li><li>重复点4.1.2其他所需的参数（收缩时间和半弛豫时间）描述了这些程序。的抽搐参数的分析提供了适应症的兴奋收缩耦联效率17。特别是，合同离子时提供收缩动力学8，其可取决于所选择的肌肉群38的索引。 </li><li>计算峰值转矩，并使用电子表格软件（ 例如Excel）M-1波的总和之间的比率，以量化所述机电效率（P 吨 / M）。如通过胫后神经刺激引起的力学响应对应于小腿三头作为一个整体，比目鱼肌和gastrocnemii M-波的幅度必须被求和39的活化。 </li></ol></li></ol><img alt="图4" src="/files/ftp_upload/52974/52974fig4.jpg" /> 图4:电和机械响应解释峰-峰幅度（毫伏）一个典型的M-波，延迟（ms）和区域（mV.ms）的（A）的测量。 （B）中测量的峰值抽搐矩（Nm）的，收缩时间（ms）和抽搐半松弛时间（毫秒）。 <aHREF ="htt​​ps://www.jove.com/files/ftp_upload/52974/52974fig4highres.jpg"目标="_空白"&gt;点击此处查看该图的放大版本。 <ol start="2"><li>在收缩数据分析<ol><li> MVC转矩的高原包括峰值转矩，但不包括刺激伪影和EMG的静音周期的结束之间的时间期间选择比目鱼EMG活动的一个500毫秒的时间窗口。沉默的周期对应于正在进行的自愿肌电活动的刺激后抑制。 </li><li>如果均方根（RMS）的不直接由软件提供，计算出的RMS使用下面的公式40来量化EMG活动:RMS 肌电 <img alt="式（1）" src="/files/ftp_upload/52974/52974eq1.jpg" /></li><li>测量或计算m最大的RMS在休息了波的持续时间。 </li><li>计算使用电子表格软件的RMS 肌电图 / RMS M最大比例。RMS 肌电值和RMS M最大值必须从同一肌肉选中。 </li><li>从扭矩中的其余的MVC的最大值基线不含诱导双峰刺激（ 图5）的叠加转矩测量了MVC的最大峰值扭矩。 </li><li>测量叠加转矩了MVC中诱导双峰刺激，从自愿转矩值在发作的刺激，以诱发响应的峰值（图5）。 </li><li>选择增效双峰。 </li><li>测量与增效双重关联的峰值扭矩。 </li><li>计算使用下面的公式40中的自愿激活电平（VAL）: <img alt="式（1）" src="/files/ftp_upload/52974/52974eq2.jpg" /></li></ol></li></ol><img alt="图5" src="/files/ftp_upload/52974/52974fig5.jpg" /> 图5:叠加测量和增效双重机械信号录制叠加的峰值扭矩（PTS），刺激双峰是等距最大随意收缩（MVC）的高原时诱发。要录制增效的峰值扭矩（PT P），刺激双峰是MVC的抵销后诱发休息。

The authors have nothing to disclose.

经皮神经刺激使的神经肌肉系统不仅要了解神经运动功能的健康人的基本控制，而且还能够通过疲劳或训练17来分析急性或慢性改编许多特征的量化。这是非常有益的特别是对疲劳的协议，其中，测量必须尽快进行锻炼结束后，以避免快速恢复42的影响。 虽然许多研究都集中在小腿三头肌24，经皮神经刺激可以在其它下肢施加（例如胫前43,44?...

经皮神经电刺激被广泛用于评估神经肌肉功能1。其基本原理是感应电刺激到周围运动神经唤起肌肉收缩。机械（扭矩测量）和电生理（肌电活动）响应，同时记录。扭矩，记录在考虑联合，用测力计进行评估。采用表面电极记录的肌电（EMG）信号已被证明代表肌肉2的活性。这种非侵入性方法是不痛，更容易比肌内录音实现。两个单极和双极电极都可以使用。单极电极结构已被证明是变化的肌肉活动3，其可以为小肌肉是有用的更敏感。然而，双极性电极已被证明是更有效地改善了信号 - 噪音r加信息4和是最常用的作为记录和量化运动单位活性的方法。下面描述的方法将集中于双极记录。 EMG活动是神经肌肉系统的有效性和完整性的指标。使用经皮神经电刺激的提供进一步深入了解神经肌肉功能，在肌肉，脊柱，或超脊髓水平（图1），即改变。 <img alt="图1" src="/files/ftp_upload/52974/52974fig1.jpg" /> 图1:神经肌肉测量概述 STIM:神经刺激。肌电图检查:肌电图。 VAL:自愿激活水平。 RMS:均方根。 m最大:最大M-波幅。 静止时，复合肌肉动作电位，也称为M-波，是刺激假象后观察到的短潜伏期反应，并表示可激发的肌肉质量的直接ACTIV<html>通货膨胀运动轴突导致肌肉（图2，3号）的。 M-波振幅增大与强度，直到达到其最大价值的平台。这种反应，称为M max时，表示表面肌电电极 5下记录，所有马达单元和/或肌纤维动作电位的同步求和。的峰-峰幅值或波区域的进化用于识别神经肌肉传导6的改动。变化中，与M-波， 即峰值抽搐转矩/力，相关联的机械响应可能是由于肌肉兴奋和/或内的肌纤维7的改变。 m最大振幅和峰抽搐扭矩幅值（铂/ M比）的协会提供的肌肉8机电效率， 即对于给定的电动机命令机械响应的索引。 52974 / 52974fig2.jpg"/&gt; 图2:电机和神经刺激激活反身途径的混合（电机/感觉）神经（STIM）的电刺激诱 ​​导两个运动轴突和Ia传入射击的去极化。 1a的去极化传入朝脊髓激活的α-运动神经元，这反过来又唤起一个H-反射反应（途径1 + 2 + 3）。根据不同的刺激强度，运动轴突去极化唤起了直接的肌肉反应:M波（途径3）。以最大的M-波强度，一个逆向电流也产生（3&#39;）和碰撞与反射凌空（2）。这个碰撞部分或完全取消H反射响应。 该H-反射是用来评估变化IA-α运动神经元突触9的电生理学反应。此参数可以在休息或在自主收缩进行评估。 H反射表示牵张反射的变体（ 图2，γMBER 1-3）。该H-反射激活马达单元由IA传入神经 ​​通路10,11 monosynaptically招募，并且可以进行外周和中枢的影响12。唤起H反射的方法是已知的具有高的被检体内的可靠性在休息13,14和期间等长收缩15，以评估脊髓兴奋性。 在一个自主收缩，自愿神经驱动器的大小可以用肌电信号的幅度进行评估，使用均方根通常量化（RMS）。 RMS 肌电图是常用期间自主收缩力（图1）量化电机系统的激励的水平的手段。由于区域内和跨学科的变异16，RMS 肌电必须使用过程中肌肉特异性最大自主收缩（RMS EMGmax）录制的肌电图进行归一化。此外，由于改变肌电信号可能bë由于使用外围参数在周边电，正常化的改变如M波是必需的，以评估肌电信号的只有中央部分。这可以通过将RMS 肌电由最大振幅或M波的RMS M最大来完成。使用RMS M最大正常化（ 即 RMS 肌电图 / RMS M最大 ）是首选的方法，因为它考虑到了M-波持续时间17的可能变化。 马达命令也可以通过计算自愿激活电平（VAL）来评价。该方法通过在一个最大随意收缩叠加在m最大强度的电刺激使用抽搐插值技术18。额外的扭矩诱发刺激神经 ​​相比，由相同的神经刺激，在轻松增效肌肉19产生的控制抽搐。为了评估最大VAL，原来抽搐interpo由默顿18描述LATION技术涉及到一个单一的刺激插在一个自主收缩。近来，采用成对的刺激已经变得越来越流行，因为相比于单一刺激反应20诱发扭矩增量更大，更容易检测出来，变化较少。 VAL子提供对中枢神经系统，以最大程度地激活工作肌肉21的容量的指标。目前，VAL评价使用抽搐插技术是评估肌肉激活22的水平的最有价值的方法。此外，使用一个测力计评估峰值扭矩是适用于研究和临床设置23使用的最适当的研究强度测试参数。 神经电刺激可以以各种肌肉群（如肘屈肌，腕屈肌，膝伸肌，跖屈肌）的使用。然而，神经访问使技术很难在某些肌肉群。跖屈肌肉，尤其小腿三头（比目鱼肌和gastrocnemii）肌肉，经常研究在文献24。的确，这些肌肉都参与运动，证明他们的特别的兴趣。刺激位置和记录电极间的距离允许小腿三头肌的不同引起波的识别。胫后神经的腘窝浅部和大量纱锭使得相对于其他的肌肉24更容易来记录反射响应。由于这些原因，在目前提出的反射方法侧重于小腿三头肌肉群（比目鱼肌和腓肠肌）。因此，该协议的目的是描述的经皮神经刺激技术研究的小腿三头肌神经肌肉功能。

<table border="0" cellpadding="0" cellspacing="0">
	<tbody>
		<tr>
			<td>Biodex dynamometer</td>
			<td>Biodex Medical System Inc., New York, USA</td>
			<td></td>
			<td><a href="http://www.biodex.com/">www.biodex.com</a></td>
		</tr>
		<tr>
			<td>MP150 Data Acquisition System</td>
			<td>Biopac Systems Inc., Goleta, USA</td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td>Acknowledge 4.1.0 software</td>
			<td>Biopac Systems Inc., Goleta, USA</td>
			<td></td>
			<td><a href="http://www.biopac.com/">www.biopac.com</a></td>
		</tr>
		<tr>
			<td>DS7A constant current high voltage stimulator</td>
			<td>Digitimer, Hertfordshire, UK</td>
			<td></td>
			<td><a href="http://www.digitimer.com/">www.digitimer.com</a></td>
		</tr>
		<tr>
			<td>Silver chloride surface electrodes</td>
			<td>Control Graphique Medical, Brie-Comte-Robert, France</td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td>Computer</td>
			<td></td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td>1 Cable for connecting the Biodex to the MP150</td>
			<td></td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td>1 Cable for connecting the Digitimer to the MP150</td>
			<td></td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td>1 Cable for connecting the MP150 to the computer</td>
			<td></td>
			<td></td>
			<td></td>
		</tr>
	</tbody>
</table>

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.

增加刺激强度导致H和M-波之间的反应振幅不同的进化。休息时，H反射达到最大值是由肌电信号完全不存在之前，而X波逐渐增加，直到达到高原最大强度（参见图4为 M-波的图示，图6的演变的M-波和H反射与强度）。为比目鱼肌，刺激发病和M-波之间的延迟为大约10毫秒（图4A）和一般在25和40毫秒为H-波。然而，将延迟的肌肉群和被检者的肢体长度或?...

Watch this Scientific Journal Video about Assessment of Neuromuscular Function Using Percutaneous Electrical Nerve Stimulation at JoVE.com

Assessment of Neuromuscular Function Using Percutaneous Electrical Nerve Stimulation

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, ...

assessment-neuromuscular-function-using-percutaneous-electrical-nerve

Research

JoVE Journal

Neuroscience

21.7K 次观看.  Univ. Bourgogne Franche–Comté. 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). 

视频: Assessment of Neuromuscular Function Using Percutaneous Electrical Nerve Stimulation

Studying Synaptic Vesicle Pools using Photoconversion of Styryl Dyes

The fusion of synaptic vesicles with the plasma membrane (exocytosis) is a required step in neurotransmitter release and neuronal communication. The vesicles are then retrieved from the plasma membrane (endocytosis) and grouped together with the general pool of vesicles within the nerve terminal, until they undergo a new exo- and endocytosis cycle (vesicle recycling). These processes have been studied using a variety of techniques such as electron microscopy, electrophysiology recordings, amperometry and capacitance measurements. Importantly, during the last two decades a number of fluorescently labeled markers emerged, allowing optical techniques to track vesicles in their recycling dynamics. One of the most commonly used markers is the styryl or FM dye 1; structurally, all FM dyes contain a hydrophilic head and a lipophilic tail connected through an aromatic ring and one or more double bonds (Fig. 1B). A classical FM dye experiment to label a pool of vesicles consists in bathing the preparation (Fig. 1Ai) with the dye during the stimulation of the nerve (electrically or with high K+). This induces vesicle recycling and the subsequent loading of the dye into recently endocytosed vesicles (Fig. 1Ai-iii). After loading the vesicles with dye, a second round of stimulation in a dye-free bath would trigger the FM release through exocytosis (Fig. 1Aiv-v), process that can be followed by monitoring the fluorescence intensity decrease (destaining).

Although FM dyes have contributed greatly to the field of vesicle recycling, it is not possible to determine the exact localization or morphology of individual vesicles by using conventional fluorescence microscopy. For that reason, we explain here how FM dyes can also be used as endocytic markers using electron microscopy, through photoconversion. The photoconversion technique exploits the property of fluorescent dyes to generate reactive oxygen species under intense illumination. Fluorescently labeled preparations are submerged in a solution containing diaminobenzidine (DAB) and illuminated. Reactive species generated by the dye molecules oxidize the DAB, which forms a stable, insoluble precipitate that has a dark appearance and can be easily distinguished in electron microscopy 2,3. As DAB is only oxidized in the immediate vicinity of fluorescent molecules (as the reactive oxygen species are short-lived), the technique ensures that only fluorescently labeled structures are going to contain the electron-dense precipitate. The technique thus allows the study of the exact location and morphology of actively recycling organelles.

FM dyes have been of invaluable help in the understanding of synaptic dynamics. FMs are normally followed under the fluorescent microscope during different stimulation conditions. However, photoconversion of FM dyes combined with electron microscopy allows the visualization of distinct synaptic vesicle pools, among other ultrastructure components, in synaptic boutons.

突触小泡池，利用苯乙烯染料的光转化的研究

The fusion of synaptic vesicles with the plasma membrane (exocytosis) is a required step in neurotransmitter release and neuronal communication. The ...

科研

神经科学

TMS: Using the Theta-Burst Protocol to Explore Mechanism of Plasticity in Individuals with Fragile X Syndrome and Autism

Fragile X Syndrome (FXS), also known as Martin-Bell Syndrome, is a genetic abnormality found on the X chromosome.1,2 Individuals suffering from FXS display abnormalities in the expression of FMR1 - a protein required for typical, healthy neural development.3 Recent data has suggested that the loss of this protein can cause the cortex to be hyperexcitable thereby affecting overall patterns of neural plasticity.4,5
In addition, Fragile X shows a strong comorbidity with autism: in fact, 30% of children with FXS are diagnosed with autism, and 2 - 5% of autistic children suffer from FXS.6
Transcranial Magnetic Stimulation (a non-invasive neurostimulatory and neuromodulatory technique that can transiently or lastingly modulate cortical excitability via the application of localized magnetic field pulses 7,8) represents a unique method of exploring plasticity and the manifestations of FXS within affected individuals. More specifically, Theta-Burst Stimulation (TBS), a specific stimulatory protocol shown to modulate cortical plasticity for a duration up to 30 minutes after stimulation cessation in healthy populations, has already proven an efficacious tool in the exploration of abnormal plasticity.9,10 
Recent studies have shown the effects of TBS last considerably longer in individuals on the autistic spectrum - up to 90 minutes.11 This extended effect-duration suggests an underlying abnormality in the brain's natural plasticity state in autistic individuals - similar to the hyperexcitability induced by Fragile X Syndrome.
In this experiment, utilizing single-pulse motor-evoked potentials (MEPs) as our benchmark, we will explore the effects of both intermittent and continuous TBS on cortical plasticity in individuals suffering from FXS and individuals on the Autistic Spectrum.

In this article, we examine the effects of Theta-Burst TMS stimulation on cortical plasticity in individuals suffering from Fragile X syndrome and individuals on the autistic spectrum.

TMS:使用的Theta突发协议，以探索个人与脆性X综合征与孤独症的可塑性Mechasnism

Fragile X Syndrome (FXS), also known as Martin-Bell Syndrome, is a genetic abnormality found on the X chromosome.1,2 Individuals suffering from FXS ...

Nerve Excitability Assessment in Chemotherapy-induced Neurotoxicity

Chemotherapy-induced neurotoxicity is a serious consequence of cancer treatment, which occurs with some of the most commonly used chemotherapies1,2. Chemotherapy-induced peripheral neuropathy produces symptoms of numbness and paraesthesia in the limbs and may progress to difficulties with fine motor skills and walking, leading to functional impairment. In addition to producing troubling symptoms, chemotherapy-induced neuropathy may limit treatment success leading to dose reduction or early cessation of treatment. Neuropathic symptoms may persist long-term, leaving permanent nerve damage in patients with an otherwise good prognosis3. As chemotherapy is utilised more often as a preventative measure, and survival rates increase, the importance of long-lasting and significant neurotoxicity will increase.
There are no established neuroprotective or treatment options and a lack of sensitive assessment methods. Appropriate assessment of neurotoxicity will be critical as a prognostic factor and as suitable endpoints for future trials of neuroprotective agents. Current methods to assess the severity of chemotherapy-induced neuropathy utilise clinician-based grading scales which have been demonstrated to lack sensitivity to change and inter-observer objectivity4. Conventional nerve conduction studies provide information about compound action potential amplitude and conduction velocity, which are relatively non-specific measures and do not provide insight into ion channel function or resting membrane potential. Accordingly, prior studies have demonstrated that conventional nerve conduction studies are not sensitive to early change in chemotherapy-induced neurotoxicity4-6. In comparison, nerve excitability studies utilize threshold tracking techniques which have been developed to enable assessment of ion channels, pumps and exchangers in vivo in large myelinated human axons7-9.
Nerve excitability techniques have been established as a tool to examine the development and severity of chemotherapy-induced neurotoxicity10-13. Comprising a number of excitability parameters, nerve excitability studies can be used to assess acute neurotoxicity arising immediately following infusion and the development of chronic, cumulative neurotoxicity. Nerve excitability techniques are feasible in the clinical setting, with each test requiring only 5 -10 minutes to complete. Nerve excitability equipment is readily commercially available, and a portable system has been devised so that patients can be tested in situ in the infusion centre setting. In addition, these techniques can be adapted for use in multiple chemotherapies.
In patients treated with the chemotherapy oxaliplatin, primarily utilised for colorectal cancer, nerve excitability techniques provide a method to identify patients at-risk for neurotoxicity prior to the onset of chronic neuropathy. Nerve excitability studies have revealed the development of an acute Na+ channelopathy in motor and sensory axons10-13. Importantly, patients who demonstrated changes in excitability in early treatment were subsequently more likely to develop moderate to severe neurotoxicity11. However, across treatment, striking longitudinal changes were identified only in sensory axons which were able to predict clinical neurological outcome in 80% of patients10. These changes demonstrated a different pattern to those seen acutely following oxaliplatin infusion, and most likely reflect the development of significant axonal damage and membrane potential change in sensory nerves which develops longitudinally during oxaliplatin treatment10. Significant abnormalities developed during early treatment, prior to any reduction in conventional measures of nerve function, suggesting that excitability parameters may provide a sensitive biomarker.

This abstract describes a novel method to assess the development of neurotoxicity in patients receiving chemotherapy treatment. While conventional assessment methods are limited in their ability to detect early changes in nerve function, nerve excitability techniques provide early identification of patients at risk of severe neurotoxicity and insight into pathophysiology.

化疗引起的毒性神经的兴奋性评估

Chemotherapy-induced neurotoxicity is a serious consequence of cancer treatment, which occurs with some of the most commonly used chemotherapies1,2. ...

Optogenetic Stimulation of the Auditory Nerve

Direct electrical stimulation of spiral ganglion neurons (SGNs) by cochlear implants (CIs) enables open speech comprehension in the majority of implanted deaf subjects1-6. Nonetheless, sound coding with current CIs has poor frequency and intensity resolution due to broad current spread from each electrode contact activating a large number of SGNs along the tonotopic axis of the cochlea7-9. Optical stimulation is proposed as an alternative to electrical stimulation that promises spatially more confined activation of SGNs and, hence, higher frequency resolution of coding. In recent years, direct infrared illumination of&#160;the cochlea has been used to evoke responses in the auditory nerve10. Nevertheless it requires higher energies than electrical stimulation10,11 and uncertainty remains as to the underlying mechanism12. Here we describe a method based on optogenetics to stimulate SGNs with low intensity blue light, using transgenic mice with neuronal expression of channelrhodopsin 2 (ChR2)13 or virus-mediated expression of the ChR2-variant CatCh14. We used micro-light emitting diodes (&#181;LEDs) and fiber-coupled lasers to stimulate ChR2-expressing SGNs through a small artificial opening (cochleostomy) or the round window. We assayed the responses by scalp recordings of light-evoked potentials (optogenetic auditory brainstem response: oABR) or by microelectrode recordings from the auditory pathway and compared them with acoustic and electrical stimulation.

Cochlear implants (CIs) enable hearing by direct electrical stimulation of the auditory nerve. However, poor frequency and intensity resolution limits the quality of hearing with CIs. Here we describe optogenetic stimulation of the auditory nerve in mice as an alternative strategy for auditory research and developing future CIs.

听觉神经的光遗传学刺激

Direct electrical stimulation of spiral ganglion neurons (SGNs) by cochlear implants (CIs) enables open speech comprehension in the majority of implanted ...

A Human-machine-interface Integrating Low-cost Sensors with a Neuromuscular Electrical Stimulation System for Post-stroke Balance Rehabilitation

A stroke is caused when an artery carrying blood from heart to an area in the brain bursts or a clot obstructs the blood flow to brain thereby preventing delivery of oxygen and nutrients. About half of the stroke survivors are left with some degree of disability. Innovative methodologies for restorative neurorehabilitation are urgently required to reduce long-term disability. The ability of the nervous system to reorganize its structure, function and connections as a response to intrinsic or extrinsic stimuli is called neuroplasticity. Neuroplasticity is involved in post-stroke functional disturbances, but also in rehabilitation. Beneficial neuroplastic changes may be facilitated with non-invasive electrotherapy, such as neuromuscular electrical stimulation (NMES) and sensory electrical stimulation (SES). NMES involves coordinated electrical stimulation of motor nerves and muscles to activate them with continuous short pulses of electrical current while SES involves stimulation of sensory nerves with electrical current resulting in sensations that vary from barely perceivable to highly unpleasant. Here, active cortical participation in rehabilitation procedures may be facilitated by driving the non-invasive electrotherapy with biosignals (electromyogram (EMG), electroencephalogram (EEG), electrooculogram (EOG)) that represent simultaneous active perception and volitional effort. To achieve this in a resource-poor setting, e.g., in low- and middle-income countries, we present a low-cost human-machine-interface (HMI) by leveraging recent advances in off-the-shelf video game sensor technology. In this paper, we discuss the open-source software interface that integrates low-cost off-the-shelf sensors for visual-auditory biofeedback with non-invasive electrotherapy to assist postural control during balance rehabilitation. We demonstrate the proof-of-concept on healthy volunteers.

A novel low-cost human-machine interface for interactive post-stroke balance rehabilitation system is presented in this article. The system integrates off-the-shelf low-cost sensors towards volitionally driven electrotherapy paradigm. The proof-of-concept software interface is demonstrated on healthy volunteers.

人机界面集成的低成本传感器，具有神经肌肉电刺激系统中风后康复平衡

A stroke is caused when an artery carrying blood from heart to an area in the brain bursts or a clot obstructs the blood flow to brain thereby preventing ...

Transcranial Electrical Brain Stimulation in Alert Rodents

Transcranial electrical brain stimulation can modulate cortical excitability and plasticity in humans and rodents. The most common form of stimulation in humans is transcranial direct current stimulation (tDCS). Less frequently, transcranial alternating current stimulation (tACS) or transcranial random noise stimulation (tRNS), a specific form of tACS using an electrical current applied randomly within a pre-defined frequency range, is used. The increase of noninvasive electrical brain stimulation research in humans, both for experimental and clinical purposes, has yielded an increased need for basic, mechanistic, safety studies in animals. This article describes a model for transcranial electrical brain stimulation (tES) through the intact skull targeting the motor system in alert rodents. The protocol provides step-by-step instructions for the surgical set-up of a permanent epicranial electrode socket combined with an implanted counter electrode on the chest. By placing a stimulation electrode into the epicranial socket, different electrical stimulation types, comparable to tDCS, tACS, and tRNS in humans, can be delivered. Moreover, the practical steps for tES in alert rodents are introduced. The applied current density, stimulation duration, and stimulation type may be chosen depending on the experimental needs. The caveats, advantages, and disadvantages of this set-up are discussed, as well as safety and tolerability aspects.

This protocol describes a surgical set-up for a permanent epicranial electrode socket and an implanted chest electrode in rodents. By placing a second electrode into the socket, different types of transcranial electrical brain stimulation can be delivered to the motor system in alert animals through the intact skull.

警惕啮齿动物的经颅电脑刺激

Transcranial electrical brain stimulation can modulate cortical excitability and plasticity in humans and rodents. The most common form of stimulation in ...

Chronic Transcranial Electrical Stimulation and Intracortical Recording in Rats

Transcranial electrical stimulation (TES) is a powerful and relatively simple approach to diffusely influence brain activity either randomly or in a closed-loop event-triggered manner. Although many studies are focusing on the possible benefits and side-effects of TES in healthy and pathologic brains, there are still many fundamental open questions regarding the mechanism of action of the stimulation. Therefore, there is a clear need for a robust and reproducible method to test the acute and the chronic effects of TES in rodents. TES can be combined with regular behavioral, electrophysiological, and imaging techniques to investigate neuronal networks in vivo. The implantation of transcranial stimulation electrodes does not impose extra constraints on the experimental design while it offers a versatile, flexible tool to manipulate brain activity. Here we provide a detailed, step-by-step protocol to fabricate and implant transcranial stimulation electrodes to influence brain activity in a temporally constrained manner for months.

This detailed protocol describes transcranial stimulation electrode placement on the temporal bone in order to investigate the short- and long-term effects of transcranial electrical stimulation in freely moving rats.

大鼠慢性经颅电刺激及 Intracortical 记录

Transcranial electrical stimulation (TES) is a powerful and relatively simple approach to diffusely influence brain activity either randomly or in a ...

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 ...

Laboratory Administration of Transcutaneous Auricular Vagus Nerve Stimulation (taVNS): Technique, Targeting, and Considerations

Non-invasive vagus nerve stimulation (VNS) may be administered via a novel, emerging neuromodulatory technique known as transcutaneous auricular vagus nerve stimulation (taVNS). Unlike cervically-implanted VNS, taVNS is an inexpensive and non-surgical method used to modulate the vagus system. taVNS is appealing as it allows for rapid translation of basic VNS research and serves as a safe, inexpensive, and portable neurostimulation system for the future treatment of central and peripheral disease. The background and rationale for taVNS is described, along with electrical and parametric considerations, proper ear targeting and attachment of stimulation electrodes, individual dosing via determination of perception threshold (PT), and safe administration of taVNS.

Laboratory Administration of Transcutaneous Auricular Vagus Nerve Stimulation taVNS: Technique, Targeting, and Considerations

A methodological description of the technique, potential targets, and proper administration of transcutaneous auricular vagus nerve stimulation (taVNS) on the human ear is described.

经皮耳穴神经刺激实验室管理 (tavns): 技术、定位和考虑

Non-invasive vagus nerve stimulation (VNS) may be administered via a novel, emerging neuromodulatory technique known as transcutaneous auricular vagus ...

Stimulation Location Determination using a 3D Digitizer with High-Definition Transcranial Direct Current Stimulation

The abundance of neuroimaging data and rapid development of machine learning has made it possible to investigate brain activation patterns. However, causal evidence of brain area activation leading to a behavior is often left missing. Transcranial direct current stimulation (tDCS), which can temporarily alter brain cortical excitability and activity, is a noninvasive neurophysiological tool used to study causal relationships in the human brain. High-definition transcranial direct current stimulation (HD-tDCS) is a noninvasive brain stimulation (NIBS) technique that produces a more focal current compared to conventional tDCS. Traditionally, the stimulation location has been roughly determined through the 10-20 EEG system, because determining precise stimulation points can be difficult. This protocol uses a 3D digitizer with HD-tDCS to increase accuracy in determination of stimulation points. The method is demonstrated using a 3D digitizer for more accurate localization of stimulation points in the right temporo-parietal junction (rTPJ).

Presented here is a protocol to achieve higher accuracy in determination of stimulation location combining a 3D digitizer with high-definition transcranial direct current stimulation.

使用具有高清晰度颅内直接电流刺激的 3D 数字化仪确定刺激位置

The abundance of neuroimaging data and rapid development of machine learning has made it possible to investigate brain activation patterns. However, ...