我们感谢Shaili桑杰·贾和希瑟Decot与拍摄服务。

伦理声明：此程序是按照健康指引的动物研究（指南实验动物的护理和使用）的国家机构，并获北卡罗来纳机构动物护理和使用委员会的大学。 1。电极植入第一步是电极植入。在此步骤中，将电极单方面注入底丘脑核（STN），小核与使用以下方法帕金森氏病治疗的平移意义： <ol><li>这是一个短期的生存术，因而无菌技术是必不可少的：使用高压釜，或消毒液高压灭菌的地方是不可能的（ 如电极不育） 注意消毒所有的手术设备。手术后，动物可以经过一个短暂的复苏期（48小时）或最多几个星期成像后。 </li><li>麻醉大鼠（成年SD大鼠250-400克）用2.5％异氟醚通过气管插管和小动物呼吸机管理。修复大鼠的立体定向手术框，并使用无菌技术准备手术部位。 </li><li>准备并确保电极是无菌的。自制的双通道钨微丝电极用于此过程中，尽管许多MRI兼容电极类型将工作。所用的电极类型可能影响组织的由过程，组织的刺激区域，植入的准确度，机械的损伤的区域，从而影响了整体的实验结果。如果电极类型是不能够进行高压灭菌，用聚维酮碘的消毒灭菌的电极，只要是可能的。 </li><li>用剪刀取出头皮过植入部位的直径为大约1.5厘米，揭露前囟和lambda头骨上。去除肌肉和筋膜覆盖在颅骨并停止使用所有电灼止血。 </li><li>划伤颅骨表面在用手术刀沿多个方向，以提高牙科用粘固剂粘合性（步骤1.8）。级前囟门和Lambda在水平方向上。 </li><li>要针对STN，在3.6毫米后到前囟门和2.5mm的横向中线，用小尖电钻创建一个钻孔尺寸约为直径1.5毫米注：STN的参考中的确切位置，立体坐标可通过大鼠品系，体重和性别而变化。同性别的成年大鼠，应尽量减少使用中的位置的任何变化。如果可能的话，预操作解剖扫描术或电记录应被用来确定在一个单独被摄体基础的STN位置。此外，电极终端站点应组织学验证，以确保目标的准确性。 <ol><li>认真做一个切口在硬脑膜，并用小钝钳硬脑膜移动到第两侧Ë孔。用无菌棉浸泡在盐水停止任何出血。创建孔，用于一个或多个MR兼容的螺丝），轻轻地插入它们在颅骨直到它们是稳定的。螺钉可以被放置在它们不会破坏放置在外部连接器，用于对DBS电极的任何位置（ 例如 ，不直接背后的STN同侧的电极）。我们推荐的展示位置在头骨的侧边，非常直接后路给lambda缝合。在这一点上，头骨比较厚，减少了螺丝会损坏皮质的可能性“。 注意：切4-5毫米的长度黄铜螺丝是用来在这个协议中，虽然塑料螺丝也适用。 </li></ol></li><li>放置在立体定位臂的电极，以确保它是直的和竖直的。触摸电极前囟门，然后将电极正是3.6毫米后到前囟门和2.5mm的横向中线和触摸皮质表面用电极。从皮质表面，腹部插入电极7.8毫米。这些坐标是参考一个神经解剖学图谱1确定。 </li><li>将一层牙科水泥在颅骨包括颅骨螺钉和电极插入点。等到水泥是从立体定位框架取出电极之前完全硬化。弯曲电极向后和使用额外的水泥覆盖电极系和连接器的耐用性的其余部分。 </li></ol> 2。功能磁共振成像准备第二步是设置的功能磁共振成像，包括生理监测设备的线圈和设置的定位。 <ol><li>保护动物的头，以防止在扫描过程中移动注：自定义塑料耳内杆系统在这里用于头部固定。将棒插入耳道，并固定到头盔使头部转动顺畅在日Ë垂直方向，没有水平旋转。通过固定上齿向装置固定头位置。 </li><li>完全麻醉大鼠和监测呼气末二氧化碳 ，以确保在所有扫描的稳定性。维持麻醉，通风和控制呼气末二氧化碳在扫描期间2层 ，结合一个异氟烷蒸发器的MR兼容的小 ​​动物的通风系统是用在这里，虽然以类似的方式，可以使用多种麻醉剂和镇静药。呼吸用适当的音量，大约500毫升/分钟的空气作为起始体积设定为45次/ min。异氟醚设定为2％，而大鼠转移到扫描室。装上呼吸机的输出到老鼠的气管插管，并按下牢牢固定。 Capnometry应该使用作为紧密相连的气管导管连接器尽可能管被收购。调节通风量，以产生2.6％的呼气末二氧化碳至3.3％。 </LI&gt; <li>使用MR兼容的小动物保持器插入到大鼠用循环热水浴的温度控制在扫描仪。用胶带将浴垫到容器，并使用干净的吸水纸覆盖它。将鼠到热水床。 </li><li>温度和二氧化碳含量的监测是必不可少的BOLD功能磁共振成像，而动脉血氧饱和度和心脏率也是有用的生理参数。插入的MR兼容的直肠温度探头，并将其带至尾基部，然后调整水浴的温度，以维持正常的体温在37°C。监测使用小动物脉搏血氧饱和度的系统，保持它们在95〜98％和250-350 BPM，分别可以根据所使用的麻醉剂的类型而变化的动脉血氧饱和度和心脏速率。血氧饱和度和心脏速率均由麻醉，通风量和通风量的深度影响。通风量和速度可能需要仔细平衡，以维持足够的潮气末二氧化碳水平和充足的血氧饱和度。 </li><li>表面线圈所需要的功能磁共振成像BOLD收购。将表面线圈尽可能靠近头的表面成为可能。一旦固定，将牙膏头部上的水泥盖的表面上，以减少邻近脑表面敏感伪影注意 ：我们使用自制的收发表面线圈具有约1.6厘米的内部直径，虽然较大的表面线圈可以是用于优化在更深的皮层下区域中的BOLD响应。 </li><li>刺激电极连接到一个可编程的电刺激系统注 ：我们使用一个定制的可编程的TTL触发系统连接到一个双极刺激，提供从MR扫描同步到射频激发电脉冲。 </li><li>对于fMRI数据采集过程中镇静和麻痹，使用右美托咪的鸡尾酒（0.1毫克/公斤/小时，IP）和泮库溴铵（1毫克/千克/小时，IP），联合小剂量异氟醚0.5％，以防止癫痫活动2。用于药物输注，一个MR兼容的注射器泵必须如果泵被放置在磁场环境中使用。可替换地，非相容泵可放置提供了延长的导管管被使用的磁性环境之外。 </li></ol> 3。功能磁共振成像数据采集第三步是磁共振成像采集，包括定位，匀场，解剖扫描和功能性扫描。阿9.4特斯拉系统用自制的表面线圈是用在这里，虽然该技术可以适用于其它高场系统和商业上取得的MRI线圈。 <ol><li>将大鼠放入扫描仪和位置在磁铁的中心。使用三平面跟踪图像来精确居中大鼠磁铁内相对于感兴趣的大脑区域，并FASTMAP垫补到均质nize磁场在感兴趣的区域。 </li><li>使用矢状T2加权RARE序列（FOV，2.56 x2.56厘米2;矩阵尺寸，256×256，层厚1.5毫米，TR / TE，1500至1511年质谱; RARE因子，8;翻转角，180°）找到前连合的位置，并对准后续图像到这个位置。对齐八片单杆GE-EPI扫描（FOV，2.56 x2.56厘米2，矩阵的大小，96×96，重建到128×128，层厚，1毫米; TR / TE，1000年至1014年MS）这一点与冠状方向。 </li><li>对于功能的扫描，可使用70个连续EPI扫描与同步的刺激输出1第二时间分辨率，设置为20秒的休息，10秒的刺激，其次是40秒休息。允许的最小扫描间90秒，以允许对神经血管的恢复。掌握在每个刺激参数的多个重复扫描通过平均来提高信号的信噪比。使用一系列假的扫描（通常4-8）来扫描降噪前夕。确认BOLD响应在图像采集的时间，以确保实验的成功使用在第4节中描述的方法，虽然平均，配准和头骨剥离可在此设置可以跳过。 </li><li>经过功能扫描完成后，使用T2加权稀土自旋回波序列（FOV，2.56 x2.56厘米2，矩阵的大小，256×256，层厚1毫米; TR / TE，三十三分之二千五百毫秒，平均，8 ）来测量体内的电极的解剖位置。获取多个冠状和矢状切片来测量沿前/后，内侧/外侧和背/腹轴的工件电极的尖端，并确认电极放置。高分辨率磁共振显微镜（FOV，1.8×1.28厘米;矩阵尺寸，360×256，层厚为0.5毫米; TR / TE，2500/12.6质谱; RARE因子，8;平均值，280）可以被用来检查电极道的去除对于后精确位置到附近的神经解剖结构，并确认电极放置3的精度。 </li></ol> 4。功能磁共振成像数据处理与分析第四步是处理和fMRI数据，包括产生的响应图和百分比BOLD信号变化的计算分析。在计算环境运行（ 如 MATLAB）或商业功能磁共振成像软件工具（ 例如 ，SPM，FSL，或AFNI）自定义程序可以使用。 <ol><li>与图像配准和数据的平均个体内通过频率初开始，其次是跨学科注 ：我们做到这一点使用SPM的代码。 </li><li>剥离用权益手动定义区域（ROI）与信号阈值以消除非脑组织进行颅骨。自动颅骨剥离算法都可以使用。 </li><li>通过计算血氧清晰度之间的关系的相关系数编译响应图ponse随着时间的推移和刺激范式为每个体素。延迟范式几秒钟来考虑延迟血流动力学反应可能是必要的。以P设定显著水准&lt;0.05 Bonferroni校正后。其他的统计方法可以采用。修正使用随机场论或群集级别的修正基于高斯随机场多重比较来代替Bonferroni校正更敏感的分析4来执行注 ：根据目标脑区的血流动力学延迟可能会有所不同，药物制剂使用，和生理参数。至关重要的是，为了防止受试者内与受试者间变异性控制这些参数。 </li><li>通过定义的ROI提取时间进程的数据量化BOLD响应。在相同的解剖结构平均在所有体素的百分比信号变化。采用一般线性模型体素明智的分析也可以用于5。 </li></ol>

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同时DBS和功能磁共振成像是一个有希望的实验工具包的全球下游反应，神经回路刺激的识别和表征， 在体内 。这种技术比其它可用的工具，如电生理记录的主要优点在于，功能磁共振成像，由此大量不同区域的脑组织可在任何靶检查其响应于DBS的相对中立性质。虽然所描述的协议是专用于DBS-fMRI的大鼠，DBS响应的神经影像也已成功地在其他模式生物，包括猪6进行。 <p class="jove_c...

确定神经回路活动的全球下游效应代表了系统神经科学许多领域的一个重大挑战和目标。工具贫乏当前可用以满足这种需要，并因此存在于相应的实验设置的提高可访问性的要求。一种这样的方法，用于评估神经电路激活的全局结果依赖于同时应用脑深部电刺激（DBS）和功能性磁共振成像（fMRI）。 DBS-fMRI的允许的下游响应于一个空间尺度大电路激活的检测，并且可以在几乎任何刺激靶被应用。这个工具是非常适合平移临床前研究，包括反应治疗高频率的刺激表征。 除了获得合适的MRI扫描仪，成功DBS-fMRI的实验需要考虑许多variabl的ES，包括电极类型，镇静方法和维护生理参数。例如，电极的选择应基于与刺激功效（ 例如 ，引线尺寸和电导，单-与双极性），以及MR兼容性和电极的工件尺寸的因素。电极工件根据电极的材料和尺寸，以及所使用的扫描序列有所不同;彻底预实验测试应采用确定每个研究合适的电极类型。一般情况下，钨电极微丝推荐此协议。麻痹和镇静药的选择应以有效地固定在动物和减少某些镇静剂对血氧水平依赖（BOLD）信号的抑制效果。最后，重要的是维持动物在最佳的生理参数，包括体温和血氧饱和度。 我们已经开发了星展银行的协议- 功能磁共振成像克服了这些潜在的障碍，并在我们的手中，可以提供强大且一致的结果。此外，这些实验程序可以很容易地采用功能磁共振成像与另类的刺激方法，包括光遗传学刺激的组合。

<table border="0" cellpadding="0" cellspacing="0" width="573">
	<colgroup>
		<col />
		<col />
		<col />
		<col />
	</colgroup>
	<tbody>
		<tr height="22">
			<td height="22" style="height:22px;width:216px;">Isoflurane (Forane)</td>
			<td style="width:71px;">Baxter</td>
			<td style="width:119px;">1001936060</td>
			<td style="width:167px;"></td>
		</tr>
		<tr height="43">
			<td height="43" style="height:43px;width:216px;">Dexmedetomidine (Dexdomitor)</td>
			<td style="width:71px;">Pfizer</td>
			<td style="width:119px;">145108-58-3</td>
			<td style="width:167px;"></td>
		</tr>
		<tr height="43">
			<td height="43" style="height:43px;width:216px;">Pancuronium Bromide</td>
			<td style="width:71px;">Selleckchem</td>
			<td style="width:119px;">S2497</td>
			<td style="width:167px;"></td>
		</tr>
		<tr height="43">
			<td height="43" style="height:43px;width:216px;">9.4T Small Animal MRI</td>
			<td style="width:71px;">Bruker</td>
			<td style="width:119px;"></td>
			<td style="width:167px;">BioSpec System with BGA-9S gradient</td>
		</tr>
		<tr height="22">
			<td height="22" style="height:22px;width:216px;">Sterotactic Frame</td>
			<td style="width:71px;">Kopf</td>
			<td style="width:119px;"></td>
			<td style="width:167px;">Model 962</td>
		</tr>
		<tr height="22">
			<td height="22" style="height:22px;width:216px;">Small Animal Ventilator</td>
			<td style="width:71px;">CWE, Inc.&#160;</td>
			<td style="width:119px;">12-02100</td>
			<td style="width:167px;">Model SAR-830</td>
		</tr>
		<tr height="43">
			<td height="43" style="height:43px;width:216px;">Dental Cement</td>
			<td style="width:71px;">A-M Systems</td>
			<td style="width:119px;">525000</td>
			<td style="width:167px;">Teets Cold Curing</td>
		</tr>
		<tr height="85">
			<td height="85" style="height:85px;width:216px;">MouseOx Plus System</td>
			<td style="width:71px;">STARR Life Science Corp.</td>
			<td style="width:119px;"></td>
			<td style="width:167px;"></td>
		</tr>
		<tr height="64">
			<td height="64" style="height:64px;width:216px;">Capnometer</td>
			<td style="width:71px;">Surgivet, Smith Medical</td>
			<td style="width:119px;"></td>
			<td style="width:167px;">V9004 Series</td>
		</tr>
		<tr height="85">
			<td height="85" style="height:85px;width:216px;">Stimulus Isolator</td>
			<td style="width:71px;">World Precision Instruments</td>
			<td style="width:119px;"></td>
			<td style="width:167px;">Model A365</td>
		</tr>
		<tr height="64">
			<td height="64" style="height:64px;width:216px;">MR-compatible Brass Screws</td>
			<td style="width:71px;">McMaster Carr</td>
			<td>94070A031</td>
			<td style="width:167px;">0-80 thread size, 1/4 inch. Can be cut to desired length.</td>
		</tr>
		<tr height="64">
			<td height="64" style="height:64px;width:216px;">Tungsten Wire</td>
			<td style="width:71px;">California Fine Wire Company</td>
			<td>100211</td>
			<td style="width:167px;">Used to construct MR-compatible stimulating microelectrode</td>
		</tr>
		<tr height="43">
			<td height="43" style="height:43px;width:216px;">Syringe Pump</td>
			<td style="width:71px;">Harvard Appartus</td>
			<td style="width:119px;"></td>
			<td style="width:167px;">Model PHD 2000 (not MRI-compatible)</td>
		</tr>
	</tbody>
</table>

deep brain stimulation with simultaneous fmri in rodents

为了形象化全球和下游神经元对脑深部电刺激（DBS）在不同的目标，我们已经开发了一个协议，用于使用血氧水平依赖（BOLD）的功能磁共振成像（fMRI）与星展同时啮齿动物形象。星展功能磁共振成像提出了一些技术挑战，包括电极植入的准确性，由电极，选择麻醉和麻痹的创建，以尽量减少任何神经元的影响，同时消除了动物的运动，并维持生理参数的MR文物，偏离它可以混淆BOLD信号。我们实验室已经开发出一套能够克服大多数这些可能出现的问题的程序。对于电刺激，一个自制的双极钨微电极时，在刺激部位在麻醉学科插入立体定位。在准备成像，老鼠被固定在一个塑料头盔和转移到磁铁孔。扫描时镇静和麻痹，右美托咪和泮库溴铵的鸡尾酒不断注入，随着异氟醚的最小剂量，这最大限度地减少准备挥发性麻醉药的BOLD天花板效应。在这个例子中实验，丘脑底核（STN）的刺激产生这是在同侧皮层区域主要是观察集中在运动皮层BOLD信号。同时DBS和功能磁共振成像允许的神经回路的调制明确依赖于刺激位置和刺激参数，并允许自由观察区域偏见的神经调制的。这种技术可以用来探索在几乎任何脑区的神经调制电路的下游效应，对实验和临床DBS影响。

根据在与植入到右侧的底丘脑核刺激电极的单个大鼠上述协议购入代表的功能数据。基本设置为星展银行的fMRI图像采集的示意图在图1中提供。刺激施加与上述协议相一致，以0.3毫安，130赫兹，0.09毫秒的脉冲宽度的频率的振幅。同侧运动皮层的鲁棒激活已使用该协议与丘脑底核的刺激目标一致可视化。用方波刺激模式，BOLD信号将预计相对于基线（未刺激状态）与一个时间过程相关的?...

Watch this Scientific Journal Video about Deep Brain Stimulation with Simultaneous fMRI in Rodents at JoVE.com

Deep Brain Stimulation with Simultaneous fMRI in Rodents

本协议描述为同步功能磁共振成像和深部脑刺激在啮齿动物的标准方法。这些实验工具的结合使用使得全球下游业务的探索响应电刺激在几乎所有的大脑目标。

深部脑刺激与同步功能磁共振成像在鼠害

In order to visualize the global and downstream neuronal responses to deep brain stimulation (DBS) at various targets, we have developed a protocol for ...

deep-brain-stimulation-with-simultaneous-fmri-in-rodents

Research

JoVE Journal

Neuroscience

14.0K 次观看.  University of North Carolina. 本协议描述为同步功能磁共振成像和深部脑刺激在啮齿动物的标准方法。这些实验工具的结合使用使得全球下游业务的探索响应电刺激在几乎所有的大脑目标。 

视频: Deep Brain Stimulation with Simultaneous fMRI in Rodents

Simultaneous fMRI and Electrophysiology in the Rodent Brain

To examine the neural basis of the blood oxygenation level dependent (BOLD) magnetic resonance imaging (MRI) signal, we have developed a rodent model in which functional MRI data and in vivo intracortical recording can be performed simultaneously. The combination of MRI and electrical recording is technically challenging because the electrodes used for recording distort the MRI images and the MRI acquisition induces noise in the electrical recording. To minimize the mutual interference of the two modalities, glass microelectrodes were used rather than metal and a noise removal algorithm was implemented for the electrophysiology data. In our studies, two microelectrodes were separately implanted in bilateral primary somatosensory cortices (SI) of the rat and fixed in place. One coronal slice covering the electrode tips was selected for functional MRI. Electrode shafts and fixation positions were not included in the image slice to avoid imaging artifacts. The removed scalp was replaced with toothpaste to reduce susceptibility mismatch and prevent Gibbs ringing artifacts in the images. The artifact structure induced in the electrical recordings by the rapidly-switching magnetic fields during image acquisition was characterized by averaging all cycles of scans for each run. The noise structure during imaging was then subtracted from original recordings. The denoised time courses were then used for further analysis in combination with the fMRI data. As an example, the simultaneous acquisition was used to determine the relationship between spontaneous fMRI BOLD signals and band-limited intracortical electrical activity. Simultaneous fMRI and electrophysiological recording in the rodent will provide a platform for many exciting applications in neuroscience in addition to elucidating the relationship between the fMRI BOLD signal and neuronal activity.

We have developed a method for simultaneous functional magnetic resonance imaging and electrophysiological recording in the rodent brain, providing a platform for the investigation of the relationship between neural activity and the blood oxygenation level dependent (BOLD) MRI signal.

同时在啮齿动物脑功能磁共振成像和电

To examine the neural basis of the blood oxygenation level dependent (BOLD) magnetic resonance imaging (MRI) signal, we have developed a rodent model in ...

科研

神经科学

Design and Construction of a Cost Effective Headstage for Simultaneous Neural Stimulation and Recording in the Water Maze

Headstage preamplifiers and source followers are commonly used to study neural activity in behavioral neurophysiology experiments. Available commercial products are often expensive, not easily customized, and not submersible. Here we describe a method to design and build a customized, integrated circuit headstage for simultaneous 4-channel neural recording and 2-channel simulation in awake, behaving animals. The headstage is designed using a free, commercially available CAD-type design package, and can be modified easily to accommodate different scales (e.g. to add channels). A customized printed circuit board is built using surface mount resistors, capacitors and operational amplifiers to construct the unity gain source follower circuit. The headstage is made water-proof with a combination of epoxy, parafilm and a synthetic rubber putty. We have successfully used this device to record local field potentials and stimulate different brain regions simultaneously via independent channels in rats swimming in a water maze. The total cost is &lt; $30/unit and can be manufactured readily.

We present a low-cost method to design and construct a light headstage pre-amplifier system with simultaneous neural recording and stimulation capability. This device can be waterproofed for use in swimming animals.

同时神经刺激，并记录在水迷宫的设计和构建一个具有成本效益探头

Headstage preamplifiers and source followers are commonly used to study neural activity in behavioral neurophysiology experiments. Available commercial ...

Combining Transcranial Magnetic Stimulation and fMRI to Examine the Default Mode Network

The default mode network is a group of brain regions that are active when an individual is not focused on the outside world and the brain is at "wakeful rest."1,2,3 It is thought the default mode network corresponds to self-referential or "internal mentation".2,3
It has been hypothesized that, in humans, activity within the default mode network is correlated with certain pathologies (for instance, hyper-activation has been linked to schizophrenia 4,5,6 and autism spectrum disorders 7 whilst hypo-activation of the network has been linked to Alzheimer's and other neurodegenerative diseases 8). As such, noninvasive modulation of this network may represent a potential therapeutic intervention for a number of neurological and psychiatric pathologies linked to abnormal network activation. One possible tool to effect this modulation is Transcranial Magnetic Stimulation: a non-invasive neurostimulatory and neuromodulatory technique that can transiently or lastingly modulate cortical excitability (either increasing or decreasing it) via the application of localized magnetic field pulses.9
In order to explore the default mode network's propensity towards and tolerance of modulation, we will be combining TMS (to the left inferior parietal lobe) with functional magnetic resonance imaging (fMRI). Through this article, we will examine the protocol and considerations necessary to successfully combine these two neuroscientific tools.

In this article, we examine the methodology and considerations relevant to the combination of TMS and fMRI to examine the effects of brain stimulation on the default network.

结合经颅磁刺激和功能磁共振成像检查默认模式网络

The default mode network is a group of brain regions that are active when an individual is not focused on the outside world and the brain is at "wakeful ...

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 ...

The NeuroStar TMS Device: Conducting the FDA Approved Protocol for Treatment of Depression

The Neuronetics NeuroStar Transcranial Magnetic Stimulation (TMS) System is a class II medical device that produces brief duration, pulsed magnetic fields. These rapidly alternating fields induce electrical currents within localized, targeted regions of the cortex which are associated with various physiological and functional brain changes.1,2,3
In 2007, O'Reardon et al., utilizing the NeuroStar device, published the results of an industry-sponsored, multisite, randomized, sham-stimulation controlled clinical trial in which 301 patients with major depression, who had previously failed to respond to at least one adequate antidepressant treatment trial, underwent either active or sham TMS over the left dorsolateral prefrontal cortex (DLPFC). The patients, who were medication-free at the time of the study, received TMS five times per week over 4-6 weeks.4
The results demonstrated that a sub-population of patients (those who were relatively less resistant to medication, having failed not more than two good pharmacologic trials) showed a statistically significant improvement on the Montgomery-Asberg Depression Scale (MADRS), the Hamilton Depression Rating Scale (HAMD), and various other outcome measures. In October 2008, supported by these and other similar results5,6,7, Neuronetics obtained the first and only Food and Drug Administration (FDA) approval for the clinical treatment of a specific form of medication-refractory depression using a TMS Therapy device (FDA approval K061053).
In this paper, we will explore the specified FDA approved NeuroStar depression treatment protocol (to be administered only under prescription and by a licensed medical profession in either an in- or outpatient setting).

In this article, we examine the methodology and considerations relevant to the FDA approved depression treatment protocol using the Neuronetics NeuroStar TMS device.

NeuroStar TMS的设备进行美国FDA批准用于治疗抑郁症的议定书“

The Neuronetics NeuroStar Transcranial Magnetic Stimulation (TMS) System is a class II medical device that produces brief duration, pulsed magnetic ...

Analysis of Gene Expression Changes in the Rat Hippocampus After Deep Brain Stimulation of the Anterior Thalamic Nucleus

Deep brain stimulation (DBS) surgery, targeting various regions of the brain such as the basal ganglia, thalamus, and subthalamic regions, is an effective treatment for several movement disorders that have failed to respond to medication. Recent progress in the field of DBS surgery has begun to extend the application of this surgical technique to other conditions as diverse as morbid obesity, depression and obsessive compulsive disorder. Despite these expanding indications, little is known about the underlying physiological mechanisms that facilitate the beneficial effects of DBS surgery. One approach to this question is to perform gene expression analysis in neurons that receive the electrical stimulation. Previous studies have shown that neurogenesis in the rat dentate gyrus is elicited in DBS targeting of the anterior nucleus of the thalamus1. DBS surgery targeting the ATN is used widely for treatment refractory epilepsy. It is thus of much interest for us to explore the transcriptional changes induced by electrically stimulating the ATN. In this manuscript, we describe our methodologies for stereotactically-guided DBS surgery targeting the ATN in adult male Wistar rats. We also discuss the subsequent steps for tissue dissection, RNA isolation, cDNA preparation and quantitative RT-PCR for measuring gene expression changes. This method could be applied and modified for stimulating the basal ganglia and other regions of the brain commonly clinically targeted. The gene expression study described here assumes a candidate target gene approach for discovering molecular players that could be directing the mechanism for DBS.

The mechanism underlying the therapeutic effects of Deep Brain Stimulation (DBS) surgery needs investigation. The methods presented in this manuscript describe an experimental approach to examine the cellular events triggered by DBS by analyzing the gene expression profile of candidate genes that can facilitate neurogenesis post DBS surgery.

基因表达的变化大鼠海马后，前丘脑核脑深部刺激分析

Deep brain stimulation (DBS) surgery, targeting various regions of the brain such as the basal ganglia, thalamus, and subthalamic regions, is an effective ...

Acrylic Resin Molding Based Head Fixation Technique in Rodents

Head fixation is a technique of immobilizing animal's head by attaching a head-post on the skull for rigid clamping. Traditional head fixation requires surgical attachment of metallic frames on the skull. The attached frames are then clamped to a stationary platform resulting in immobilization of the head. However, metallic frames for head fixation have been technically difficult to design and implement in general laboratory environment. In this study, we provide a novel head fixation method. Using a custom-made head fixation bar, head mounter is constructed during implantation surgery. After the application of acrylic resin for affixing implants such as electrodes and cannula on the skull, additional resins applied on top of that to build a mold matching to the port of the fixation bar. The molded head mounter serves as a guide rails, investigators conveniently fixate the animal&#8217;s head by inserting the head mounter into the port of the fixation bar. This method could be easily applicable if implantation surgery using dental acrylics is necessary and might be useful for laboratories that cannot easily fabricate CNC machined metal head-posts.

Traditional head fixation techniques have used metallic frames attached on the skull as an interface for head fixation apparatus. This protocol demonstrates a frameless, acrylic resin molding based head fixation technique for behavioral tasks in rodents.

在鼠害丙烯酸树脂模塑基头固定技术

Head fixation is a technique of immobilizing animal's head by attaching a head-post on the skull for rigid clamping. Traditional head fixation requires ...

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 ...

Real-Time fMRI Brain Mapping in Animals

Dynamic fMRI responses vary largely according to the physiological conditions of animals either under anesthesia or in awake states. We developed a real-time fMRI platform to guide experimenters to monitor fMRI responses instantaneously during acquisition, which can be used to modify the physiology of animals to achieve desired hemodynamic responses in animal brains. The real-time fMRI set-up is based on a 14.1T preclinical MRI system, enabling the real-time mapping of dynamic fMRI responses in the primary forepaw somatosensory cortex (FP-S1) of anesthetized rats. Instead of a retrospective analysis to investigate confounding sources leading to the variability of fMRI signals, the real-time fMRI platform provides a more effective scheme to identify dynamic fMRI responses using customized macro-functions and a common neuroimage analysis software in the MRI system. Also, it provides immediate troubleshooting feasibility and a real-time biofeedback stimulation paradigm for brain functional studies in animals.

Animal brain functional mapping can benefit from the real-time functional magnetic resonance imaging (fMRI) experimental set-up. Using the latest software implemented in the animal MRI system, we established a real-time monitoring platform for small animal fMRI.

动物实时功能磁共振成像大脑映射

Dynamic fMRI responses vary largely according to the physiological conditions of animals either under anesthesia or in awake states. We developed a ...

In vivo Positron Emission Tomography to Reveal Activity Patterns Induced by Deep Brain Stimulation in Rats

Deep brain stimulation (DBS) is an invasive neurosurgical technique based on the application of electrical pulses to brain structures involved in the patient&#39;s pathophysiology. Despite the long history of DBS, its mechanism of action and appropriate protocols remain unclear, highlighting the need for research aiming to solve these enigmas. In this sense, evaluating the in vivo effects of DBS using functional imaging techniques represents a powerful strategy to determine the impact of stimulation on brain dynamics. Here, an experimental protocol for preclinical models (Wistar rats), combined with a longitudinal study [18F]-fluorodeoxyclucose positron emission tomography (FDG-PET), to assess the acute consequences of DBS on brain metabolism is described. First, animals underwent stereotactic surgery for bilateral implantation of electrodes into the prefrontal cortex. A post-surgical computerized tomography (CT) scan of each animal was acquired to verify electrode placement. After one week of recovery, a first static FDG-PET of each operated animal without stimulation (D1) was acquired, and two days later (D2), a second FDG-PET was acquired while animals were stimulated. For that, the electrodes were connected to an isolated stimulator after administering FDG to the animals. Thus, animals were stimulated during the FDG uptake period (45 min), recording the acute effects of DBS on brain metabolism. Given the exploratory nature of this study, FDG-PET images were analyzed by a voxel-wise approach based on a paired T-test between D1 and D2 studies. Overall, the combination of DBS and imaging studies allows describing the neuromodulation consequences on neural networks, ultimately helping to unravel the conundrums surrounding DBS.

In vivo Positron Emission Tomography to Reveal Activity Patterns Induced by Deep Brain Stimulation in Rats

We describe a preclinical experimental method to evaluate metabolic neuromodulation induced by acute deep brain stimulation with in vivo FDG-PET. This manuscript includes all experimental steps, from stereotaxic surgery to the application of the stimulation treatment and the acquisition, processing, and analysis of PET images.

体内 正电子发射断层扫描揭示大鼠深部脑刺激诱导的活动模式

Deep brain stimulation (DBS) is an invasive neurosurgical technique based on the application of electrical pulses to brain structures involved in the ...