The authors wish to thank Aisha Dar, Vanathy Niranjan, and Dr. Umar Dar for technical assistance with rTMS delivery and data collection. The authors also wish to acknowledge the generous support of the Toronto General and Western Hospital Foundation, the Buchan Family Foundation, and the Ontario Brain Institute in funding this work.

这项研究是在大学健康网络经研究伦理委员会。 1.选题<ol><li>在一个准病人进行初步评估。纳入标准包括一个当前抑郁发作是抗至少1适当药物的试验的情况下，和一个精神障碍诊断和统计手册，第五版，（DSM-5）诊断的MDD作为由评估精神科医生建立。明确诊断与标准化简易精神状态检查（MINI）。 </li><li>确保患者在一个稳定的药物或之前将其第一磁刺激治疗会话洗出他们的药物治疗例程的至少4周。不要改变整个治疗的rTMS这种药物团，以帮助消除歧义的任何临床上观察到的改善或恶化的原因。 </li><li>谁排除可能有一个潜在的禁忌rTMS治疗或MRI检查的患者，我ncluding发作史，心律失常，植入或外来设备/金属的颗粒，不稳定的医疗条件，或妊娠。患者合并症创伤后应激障碍，强迫症，其它焦虑障碍，注意缺陷多动障碍，神经性贪食症或暴食症，或中度集B个性特征也适用于这种处理，不需要被排除在外。双相障碍患者，而不是MDD也可以是适于这种待遇。患者的精神障碍，活性物质的使用，边缘型或反社会型人格障碍，性或持续性抑郁障碍（精神抑郁症）的主要诊断可能不太适合于治疗和可能需要排除。 </li></ol> 2.采集磁共振图像<ol><li>获得患者的核磁共振成像，在治疗前的任何时间。在这里，使用3特斯拉的扫描仪具有8通道相控阵头线圈（见表垫的erials），或能够产生一个病人的大脑的3D表示任何扫描仪。 </li><li>秉承本地站点协议，收购T1加权快速梯度回波扫描解剖。使用下面的参数:TE = 12毫秒，TI = 300毫秒，翻转角= 20°，116矢状切片，厚度= 1.5毫米，没有间隙，256×256矩阵，FOV 240毫米以下在电机阈值和疗程这种扫描将用于实时的rTMS神经导航。 </li></ol> 3.预处理解剖扫描的实时神经导航<ol><li>准备利用神经导航系统指导MRI。 注意:下面的步骤使用遮阳2.0神经导航系统（参考表材料），但是其它的导航系统，如Brainsight TMS导航，StealthStation，Aimnav，和NBS系统4使用类似的程序。 </li><li>段解剖核磁共振到其头皮和大脑的组件。注册两段成标准stereotactic空隙，如塔莱拉什和Tournoux空间19。 </li><li>地方目标标记通过选择MRI以下几点:鼻根;左耳和右耳，针对耳屏;前连合;后连合;纵裂点（两半球之间的点）;前最点的大脑;后最点的大脑;上级最点的大脑;和左，右最点的大脑。 </li><li>重建患者的头皮和大脑中的标准空间创建一个三维表面的基于头部模型的表面 - 该图像将被用于识别立体头皮坐标覆dmPFC（塔莱拉什和Tournoux坐标X0，Y + 60，Z + 60），用于在治疗过程中的最佳线圈顶点放置。 注意:此方法使用人口坐标来确定目标的刺激。其他的方法来确定一个目标的刺激，在讨论中概述，包括单科解剖或FMR我激活的地图。 </li><li>注册的大脑和立体空间坐标头皮为个性化的线圈放置病人的空间。 </li></ol> 4.运动阈值评估<ol><li>座椅病人在治疗椅，调节摄像机为病人一览无遗。 </li><li>放置与连接到它绕患者的头部的标记片段的​​头带。标记的剪辑应该坐下上面鼻梁。 </li><li>预处理对于在步骤3中描述上面的病人的解剖扫描。 </li><li>加载预处理解剖扫描到神经导航程序并打开相机。 </li><li>使用神经导航笔，突出对患者头皮各目标点。与神经导航笔所完成的动作将被投影的红色线条的形式在电视屏幕上。 </li><li>评估患者的运动阈值，需要在全球范围内的最小强度激发运动通路，之前的rTMS treatm耳鼻喉科。对于此步骤，通过使患者的下肢延伸并从下方支撑，使用粪便或装有一个可扩展的腿支承椅子开始。 </li><li>对于运动阈值测定，神经导航下，目标内侧初级运动皮层。将线圈顶点在矢状裂，0.5-1.0厘米前方中央沟。使用有角度或锥双线圈脉冲更深渗透到内侧区域。使用刺激搭载了流体冷却盘管，其绕组角度为120°，以允许脉冲更深地穿透（参见表材料）。 </li><li>分别执行电动机阈值用于左和右半球。定向线圈横向引导磁刺激诱 ​​发的电流流动到所需的半球20。例如，刺激左半球，定位线圈与把手指向向右和电流流向左半球的方向。观察对侧（右）下肢对于此过程中的运动。 </li><li>视觉的大脚趾的halluces长肌确定的阈值和诱发的电机运动。 注:不同于传统的运动阈值检测为目标的手部肌肉，刺激管壁内侧运动皮层的将目标锁定在脚趾的肌肉。运动诱发电位（MEPS）也可以用作更精确地确定的运动阈值，但它是一个更冗长的方法。 <ol><li>通过刺激在最大强度的机器55％开始，然后向上或向下调整的〜5％的增量取决于是否反应观察​​。稳步减小增量大小至〜1％作为电动机阈逼近，如前所述21。刺激不超过0.2赫兹（每秒5秒）更频繁，以免随着时间的推移抑制或兴奋作用。 </li><li>一旦运动阈值被确定，移动顶点1-2厘米向前向后，并在2-3毫米探索增量，以阻止矿井是否有替代的网站提供了一个较低的运动阈值。使用沿此弧形每侧达到的最低阈值。 </li></ol></li></ol> 5.治疗颅磁刺激适应性和滴定<ol><li>执行neuronavigated dmPFC-rTMS治疗一个疗程，共使用20-30日常会话超过4-6周。对于治疗，使用120°角度的，流体冷却盘管和下面dmPFC刺激在每一次治疗（参考表材料 ）中列出的参数。 </li><li>座椅病人在治疗椅，调节摄像机为病人一览无遗。 </li><li>放置与连接到它围绕病人的头部的标记剪辑头带（置于横向以免挡住磁刺激线圈放置在内侧目标部位），如上所述。使用照相机中，神经导航系统，将检测标记片段和将允许预处理和神经导航。 </li><li>加载预处理ANAtomical扫描到神经导航程序，并打开相机。 </li><li>使用神经导航笔，突出对患者头皮各目标点。与神经导航笔所完成的动作将被投影的红色线条的形式在电视屏幕上。 </li><li>放置在线圈采用神经导航系统MRI指导下dmPFC目标。为了进行校验，这点应位于接近距离的25％，从鼻根到INION。横向。定向线圈横向，与把手指向远离半球被刺激。刺激左半球，然后重新定向线圈180°，以刺激右半球，保持在同一位置过dmPFC头皮位点的顶点。 </li><li>确保头皮的网站dmFPC保持与线圈本身在整个治疗紧密接触。确保患者和操作人员在治疗期间佩戴耳塞或其它听力保护。 </li><li>对于10 Hz的刺激，使用5秒的上10秒关，总共每会话半球60列车（3000脉冲）的占空比。通过横向定向线圈执行左然后右半球的这个协议，如前所述20。 注:所描述的协议，用于10赫兹rTMS治疗是以外的国际安全准则（Rossi 等 ，2009）。有证据表明它的安全性18,22。 </li><li>为TBS刺激，使用2秒时，8秒关的占空比为总共600个脉冲每半球每个会话。通过横向定向线圈执行左然后右半球的这个协议，如前所述20。 </li><li>自适应从20％最大刺激强度的初始值滴定颅磁刺激刺激强度向上，以允许患者使其习惯到在初始会话期间23与磁刺激相关的疼痛和头皮不适。由2-5％增加刺激强度的刺激每列车，作为容忍。 <ol><li>为了评估耐受性，对从0口头模拟评分（VAS）病人率痛到10（0 =无疼痛，10 =极限耐受性无情绪困扰）刺激每列车交付后。 </li></ol></li><li>首先每个会话更高的刺激强度，使用与前一交易日中度耐受性（VAS 5-6）相关联的水平，直到患者开始在休息运动阈值的每个半球120％的目标强度。在此滴定过程保持低于9整个处理口头模拟量表。滴定通常在完成2-5天。 </li><li>监测患者在治疗期间的其他不利影响。 注意:最常见的治疗中断的不利影响是一个晕厥发作，治疗的患者〜1％的第一或第二会话期间所产生的。患者可追述感到头晕，淡淡的，或迷失方向，并可能短暂（约10秒）LOSE意识。经常，反复抽搐或运动后发作混淆超过几秒钟持久的更多的应该是不存在的，但是。在晕厥发作的情况下，降低在椅子上，如果可能的头枕和鼓励病人保持静止不动，直到痊愈。如果患者被回收并愿意几分钟后，以继续该会话可以继续。 </li><li>监测患者的治疗过程中全身强直 - 阵挛性发作。 注意:这些事件是罕见的，我们还没有观察到扣押dmPFC-rTMS治疗的〜8000届跨&gt; 200个别病人的日期。正规，有节奏的，充满活力的运动抽搐持续10-40秒，最初约3赫兹和逐渐变得不那么快，并伴有反应迟钝，均提示癫痫发作，而不是晕厥。然而，这两种可能难以区分对于未经训练的观察者。 <ol><li>在所有的治疗使用视频监控，这样的情节可以由neurologis进行审查T对于以后的评估，如果有必要的。在这样的情节的情况下，应用标准的发作急救措施，包括清除对象的面积与可能造成的伤害，将病人在地面上，如果可能的或降低治疗椅到水平位置，如果不是，铺设患者在左侧如果可能的话，确保清理呼吸道，并确保人仍然与病人直至发作终止和该人恢复全部的警觉。 </li><li>呼叫紧急服务，如果扣押不〜60秒后自行终止。 </li></ol></li></ol> 6.临床数据采集<ol><li>收集标准化自我报告问卷在基线，每周在整个治疗和随访（ 例如 ，2，4，6，12，和26周治疗后）。收集以下自我报告的数据:贝克抑郁量表（BDI-II）24，和贝克焦虑量 ​​表25在整个TR每天eatment。 </li><li>通过临床医生额定17项汉密尔顿量表收集抑郁严重程度评分为抑郁评分26（HAMD 17）在基线，每周治疗期间，并在2，4，6，12和26周治疗后的随访。 </li></ol>

Authors Ms. Dunlop and Ms. Gapriellian have no disclosures to report.

这里，MRI引导dmPFC-磁刺激涂敷了用于治​​疗难治性抑郁症。在一般情况下，的rTMS在这个网站的耐受性良好，轻度头皮不适和疼痛刺激时的网站使用自适应滴定充分的管理。在开放性试验和图审查，既10赫兹和theta爆裂刺激导致抑郁症的严重程度显著的改善为由HAMD 17和BDI-II测量。 有两个值得注意的rTMS治疗过程中进行优化dmPFC刺激的关键步骤。首先，有角度的，双锥形线圈允许进行更深入的结构内的前额叶皮层28的内侧面最佳刺激。第二，120％静息运动阈值，在此中间部位的治疗刺激强度是良好耐受的，没有严重的不良事件，尽管在绝对值计算所施加的刺激的强度比较高时相比较低的绝对需要常规DLPFC-磁刺激强度。此相同的强度也似乎是安全和可耐受的对TBS协议与dmPFC-磁刺激，尽管80％的活性马达阈用TBS 18更常用的显著较低的值。如前所述，显著的疼痛和不适的前壁内侧前额叶刺激在较高强度29相关联。自适应滴定快速，成功地用于在助手rTMS治疗相关的不适适应。总之，使用有角度的磁刺激线圈和相对高的刺激强度（具有自适应滴定）可以允许刺激内侧前额叶和底层扣带皮层28的更深的渗透，而不引起癫痫发作的不可容忍的头皮疼痛的风险较高。 神经导航通常用于精确个体解剖学界标为线圈顶点放置。然而，一个问题MRI引导是神经导航它可能忽略了所需的刺激目标到其他脑区的功能关系有利于跨学科的解剖的特殊性。事实上，有显著功能连接变异关联皮层中找到，包括前额叶皮层的区域，这可能妨碍治疗功效30。例如，最近的一项研究中使用静息态功能连接，表明在MDD左DLPFC-磁刺激治疗的疗效是依赖于左DLPFC连接到膝下扣带皮层31。患者与左DLPFC，磁刺激改善人往往反相关的DLPFC和膝下扣带皮质在基线之间的功能连接。因此，静息态功能连接，可以开发利用，进一步优化目标定位和识别潜在的生物标志物一旦响应的功能特性识别32。 rT的的一个主要限制MS作为治疗是，目前还不清楚的刺激参数如何某些影响其治疗功效。有一个在不同研究传统的左DLPFC刺激MDD的参数很大的变异，并有大量的个体间变异也越来越多的证据在某些颅磁刺激参数如何影响大脑皮层的兴奋和抑制或治疗效果33,34。例如，10赫兹刺激对电机的影响诱发电位（MEP）最近显示变化很大受试者，具有一定的表现下降而不是增加的MEP强度刺激35之后。其它磁刺激治疗参数可能需要进一步优化（或个性化），以最大限度地提高治疗功效包括每个会话的脉冲数，每天，刺激强度和占空比会话的数目（多少秒刺激是开和关每循环） 。 有ALSo一般限制的rTMS作为一种治疗。这些措施包括对患者的后勤需求，使医院多次访问进行治疗，难以获得治疗的患者在偏远地区，治疗（&gt; 250美元会话）与常规参数的高成本，低体积的病人谁可每使用常规参数（每1-2小时最多）装置处理。参数优化可以帮助解决一些在未来的这些问题。其他形式的非侵入性的刺激，如经颅直流电刺激（TDCS），也可能会充当一个较为便宜的替代颅磁刺激，适合在家中使用，而不是在诊所36。 尽管它的技术限制，dmPFC，磁刺激是有前途的临床治疗性抑郁症。磁刺激，和dmPFC-磁刺激，特别是也可以探测，可以在其他药物治疗耐药的精神疾病，包括饮食失调10一种很有前途的选择</suP&gt;，强迫症37，和创伤后应激障碍38。确定好治疗的候选人为这些疾病可能需要额外的工具比传统的基于症状的诊断分类模式等 - 尤其是，神经影像学。治疗前后采集患者神经影像数据允许潜在生物预处理预测和治疗反应的机制的鉴定。背内侧与膝下扣带回静息态功能连接已被确定为潜在的预测治疗反应27。此外，图论的措施，例如中间中心已显示出区分dmPFC-磁刺激应答者和非应答者的基线基于分量表为享乐响应23。神经影像学还指出，前路中间扣带皮层和丘脑背内侧休息状态功能连通性变化的相关治疗RESponse 27。总之，脑功能成像可能成为一个有用的临床工具，潜在的预测和治疗反应机制确定。 由于目前dmPFC-的rTMS研究使用开放式标签设计，未来的发展方向应该包括建立一个假对照试验，以评估其疗效在MDD与假和常规的刺激。但是，创建了令人信服的假控制臂在技术上是挑战性的，特别是对于模拟体感或疼痛的感觉，以及令人信服致盲的rTMS技师39。在最近的一项荟萃分析，超过一半的患者能够正确地猜出他们的治疗臂39。在另一个荟萃分析，安慰剂效应是很大，但相媲美依他普仑试验40。未来的研究涉及的rTMS假臂应该考虑，解决的rTMS的所有感官方面为病人和技术人员设计的。 Nonethe少，通过TBS 41充实磁刺激技术，吸刺激42或辅助认知行为治疗43或44的药物治疗也可能有助于优化rTMS治疗的治疗效果。 TBS尤其具有实现在治疗时间在患者卷，访问时间，以及治疗成本显著改善，因此电势，同时实现等效的结果，以更长的常规协议18,45。 综上所述，dmPFC的颅磁刺激是一种很有前途的新的方法来治疗脑刺激用于治疗性MDD。通过将使用一个MRI引导神经导航系统中，流体冷却，120°角度的刺激线圈，一个高刺激强度和自适应滴定日程，dmPFC-磁刺激可以安全，准确地输送到深层目标在内侧前额叶皮质。由于这些地区是中央的​​许多neurops的​​病理生理ychiatric病症，这种方法可能有前景的应用不仅对MDD，而且适用于各种有抗药性的标准治疗其他精神疾病。

重复经颅磁刺激（rTMS治疗）是间接的局灶性皮质刺激的一种形式。颅磁刺激员工短暂，焦电磁场脉冲穿透颅骨刺激目标的大脑区域。磁刺激被认为是啮合的突触长期增强，长期抑郁的机制，从而增加或减少区域的皮层的兴奋性刺激的1。一般地，磁刺激脉冲的频率决定其效应:较高频率刺激趋向于兴奋性，而较低的频率是抑制性的。非侵入性的刺激程序也被广泛使用作为因果探针以诱导临时"皮质性病变"，并且通过暂时禁用期望皮层区2的功能建立神经行为关系或功能区域- 4。 颅磁刺激治疗涉及多个刺激会话，通常施一次ðaily在几个星期，治疗各种疾病，包括重度抑郁症（MDD）5，进食障碍6，和强迫症7。磁刺激MDD的是难治的患者潜在的选择，并且允许临床医生能够无创靶向并改变直接参与与抑郁病因或病理生理学皮质区的兴奋性。对于MDD-rTMS治疗常规皮质目标是背外侧前额叶皮层（DLPFC）8。然而，从神经影像学，病变组织，刺激研究的证据，确定背内侧前额皮层（dmPFC）作为MDD 9潜在的重要治疗靶标和各种在自我调节的思想，行为特征在于赤字其它精神障碍和情感规定10。该dmPFC是一致的活化在情绪调节11，行为监管12,13的区域。该dmPFC也与神经化学相关的14，15的结构和功能异常16在MDD 此处所描述的程序是用于磁共振成像（MRI）引导的磁刺激的dmPFC双边的20届（4周），作为用于抑郁症的治疗。除了 ​​施加在30分钟的常规10赫兹协议，间歇THETA突发刺激方案（TBS）进行了讨论，其在6分钟会话17施加50赫兹三峰脉冲串在5赫兹。这两个协议都被认为是兴奋性的，与具有实现使用短得多的会话18可比效 ​​应的可能性的TBS协议。在这两个协议，解剖核磁共振成像以及临床评估之前将磁刺激获得的。神经导航使用解剖扫描占dmPFC的解剖变化和优化磁刺激的位置。一个相对较新的120°-angled流体冷却磁刺激线圈也是我们ED为了刺激更深中线皮质结构。最后，磁刺激强度滴定，使用过的rTMS会话的第一个星期，以确保病人能，观察者与dmPFC刺激相关的更高的疼痛水平相对于传统DLPFC刺激。

<table><tbody><tr><td>3T GE Signa HDx Scanner</td><td>GE</td><td>n/a</td><td></td></tr><tr><td>Visor 2.0 Neuronavigation System</td><td>ANT Neuro</td><td>n/a</td><td></td></tr><tr><td>MagPro R30 Stimulator</td><td>MagVenture</td><td>n/a</td><td></td></tr><tr><td>Cool-DB80 Coil</td><td>MagVenture</td><td>n/a</td><td></td></tr></tbody></table>

mri-guided dmpfc-rtms as a treatment for treatment-resistant major depressive disorder

Here we outline the protocol for magnetic resonance imaging (MRI) guided repetitive transcranial magnetic stimulation (rTMS) to the dorsal medial prefrontal cortex (dmPFC) in patients with major depressive disorder (MDD). Technicians used a neuronavigation system to process patient MRIs to generate a 3-dimensional head model. The head model was subsequently used to identify patient-specific stimulatory targets. The dmPFC was stimulated daily for 20 sessions. Stimulation intensity was titrated to address scalp pain associated with rTMS. Weekly assessments were conducted on the patients using the Hamilton Rating Scale for Depression (HamD17) and Beck Depression Index II (BDI-II). Treatment-resistant MDD patients achieved significant improvements on both HAMD and BDI-II. Of note, angled, double-cone coil rTMS at 120% resting motor threshold allows for optimal stimulation of deeper midline prefrontal regions, which results in a possible therapeutic application for MDD. One major limitation of the rTMS field is the heterogeneity of treatment parameters across studies, including duty cycle, number of pulses per session and intensity. Further work should be done to clarify the effect of stimulation parameters on outcome. Future dmPFC-rTMS work should include sham-controlled studies to confirm its clinical efficacy in MDD.

在先前的工作中，HAMD 17被用来作为10赫兹dmPFC-磁刺激。 表1显示了前和后处理HAMD 17的分数，在预先公布的情况下，一系列的27治疗反应的量度。在所有科目，治疗前HAMD 17得分21.66.9由4331％的显著下降到12.58.2后颅磁刺激（T 22 = 6.54，P &lt;0.0001），27。使用HAMD 17≤7，一个缓解准则23例8汇至如下处理。 表2显示，在相同的情况下，27系列的前和后处理BDI-II分数。前处理BDI-II是32.59.9和34.231.7％显著下降至22.012.8后颅磁刺激（T 22 = 5.11，P &lt;0.001）。 HAMD 17和BDI-II的改善百分比呈正相关，以确定是否相同的受试者的反应在两个措施相关（r = 0.72，p值= 0.0001）。 自适应titrat离子报道，在47 MDD患者进行10赫兹dmPFC-的rTMS 23更大的子集。在一个病例，其中包括对这类病人，科目0.91.8会议达到了目标刺激强度，并能在4.53.7会议23完成在预期强度整个会议的rTMS。自适应滴定没有相关的治疗改善。 最近在最近185主题图审查执行18 TBS至10赫兹dmPFC刺激比较。结果没有显著不同群体之间。在HAMD 17，10赫兹患者有50.6％的回应和38.5％的缓解率，而TBS患者取得了48.5％的回应和27.9％，缓解率。在BDI-II，10赫兹患者有40.6％的应答29.2％的缓解率，而TBS患者取得了43.0％的响应和31.0％，缓解率18。 <table border="0" cellpadding="0" cellspacing="0"><tbody><tr><td>学科 ＃ </td><td> 治疗前HAMD </td><td> 治疗后HAMD </td><td> 改进％ </td></tr><tr><td> 11 </td><td> 21 </td><td> 1 </td><td> 95.24 </td></tr><tr><td> 6 </td><td> 18 </td><td> 2 </td><td> 88.89 </td></tr><tr><td> 4 </td><td> 28 </td><td> 4 </td><td> 85.71 </td></tr><tr><td> 2 </td><td> 12 </td><td> 2 </td><td> 83.33 </td></tr><tr><td> 9 </td><td> 22 </td><td> 4 </td><td> 81.82 </td></tr><tr><td> 25 </td><td> 19 </td><td> 4 </td><td> 78.95 </td></tr><tr><td> 12 </td><td> 20 </td><td>五</td><td> 75.00 </td></tr><tr><td> 10 </td><td> 20 </td><td>五</td><td> 75.00 </td></tr><tr><td> 14 </td><td> 14 </td><td> 4 </td><td> 71.43 </td></tr><tr><td> 16 </td><td> 26 </td><td> 10 </td><td> 61.54 </td></tr><tr><td> 7 </td><td> 19 </td><td> 8 </td><td> 57.89 </td></tr><tr><td> 24 </td><td> 17 </td><td> 9 </td><td> 47.06 </td></tr><tr><td> 3 </td><td> 19 </td><td> 11 </td><td> 42.11 </td></tr><tr><td> 8 </td><td> 21 </td><td> 14 </td><td> 33.33 </td></tr><tr><td>五</td><td> 36 </td><td> 24 </td><td> 33.33 </td></tr><tr><td> 17 </td><td> 23 </td><td> 16 </td><td> 30.43 </td></tr><tr><td> 15 </td><td> 37 </td><td> 27 </td><td> 27.03 </td></tr><tr><td> 23 </td><td> 12 </td><td> 9 </td><td> 25.00 </td></tr><tr><td> 19 </td><td> 28 </td><td> 21 </td><td> 25.00 </td></tr><tr><td> 13 </td><td> 29 </td><td> 22 </td><td> 24.14 </td></tr><tr><td> 1 </td><td> 12 </td><td> 10 </td><td> 16.67 </td></tr><tr><td> 21 </td><td> 13 </td><td> 12 </td><td> 7.69 </td></tr><tr><td> 18 </td><td> 23 </td><td> 22 </td><td> 4.35 </td></tr><tr><td> 22 </td><td> 21 </td><td> 22 </td><tD&gt; -4.76 </td></tr><tr><td> 20 </td><td> 22 </td><td> 24 </td><td> -9.09 </td></tr><tr><td></td><td></td><td></td><td></td></tr><tr><td>意味着</td><td> 21.28 </td><td> 11.68 </td><td> 46.​​28 </td></tr><tr><td>标准的开发。 </td><td> 6.68 </td><td> 8.24 </td><td> 31.81 </td></tr></tbody></table> 表1:个别受试者HAMD 17的改进，用基线和治疗后HAMD 17分数。 <table border="0" cellpadding="0" cellspacing="0"><tbody><tr><td> 学科 ＃ </td><td> 预磁刺激BDI </td><td> 后磁刺激BDI </td><td> 改进％ </td></tr><tr><td> 11 </td><td> 26 </td><td> 3 </td><td> 88.46 </td></tr><tr><td> 6 </td><td> 21 </td><td> 4 </td><td> 80.95 </td></tr><tr><td> 4 </td><td> 45 </td><td> 9 </td><td> 80.00 </td></tr><tr><td> 2 </td><td> 17 </td><td> 4 </td><td> 76.47 </td></tr><tr><td> 16 </td><td> 36 </td><td> 13 </td><td> 63.89 </td></tr><tr><td>五</td><td> 35 </td><td> 17 </td><td> 51.43 </td></tr><tr><td> 3 </td><td>三十</td><td> 15 </td><td> 50.00 </td></tr><tr><td> 12 </td><td> 26 </td><td> 14 </td><td> 46.​​15 </td></tr><tr><td> 14 </td><td> 22 </td><td> 12 </td><td> 45.45 </td></tr><tr><td> 1 </td><td> 33 </td><td> 19 </td><td> 42.42 </td></tr><tr><td> 10 </td><td> 34 </td><td> 20 </td><td> 41.18 </td></tr><tr><td> 23 </td><td> 32 </td><td> 19 </td><td> 40.63 </td></tr><tr><td> 9 </td><td> 22 </td><td> 15 </td><td> 31.82 </td></tr><tr><td> 15 </td><td> 57 </td><td> 40 </td><td> 29.82 </td></tr><tr><td> 19 </td><td> 38 </td><td> 28 </td><td> 26.32 </td></tr><tr><td> 7 </td><td> 25 </td><td> 22 </td><td> 12.00 </td></tr><tr><td> 18 </td><td> 45 </td><td> 41 </td><td> 8.89 </td></tr><tr><td> 20 </td><td> 45 </td><td> 43 </td><td> 4.44 </td></tr><tr><td> 17 </td><td> 25 </td><td> 24 </td><td> 4.00 </td></tr><tr><td> 13 </td><td> 44 </td><td> 44 </td><td> 0.00 </td></tr><tr><td> 22 </td><td> 36 </td><td> 37 </td><td> -2.78 </td></tr><tr><td> 21 </td><td>三十</td><td> 32 </td><td> -6.67 </td></tr><tr><td> 8 </td><td> 24 </td><td> 31 </td><td> -29.17 </td></tr><tr><td></td><td></td><td></td><td></td></tr><tr><td>意味着</td><td> 32.52 </td><td> 22.00 </td><td> 34.16 </td></tr><tr><td>标准的开发。 </td><td> 9.86 </td><td> 12.83 </td><td> 31.70 </td></tr><tr><td></td><td></td><td></td><td></td></tr><tr><td></td><td></td><td></td><td></td></tr><tr><td></td><td> TTEST </td><td align="right"> 3.99713E-05 &lt;/ TD&gt; <td align="right"> 5.114221135 </td></tr></tbody></table> 表2:个别受试者BDI-II的改进，用基线和治疗后的BDI-II的分数。

Watch this Scientific Journal Video about MRI-guided dmPFC-rTMS as a Treatment for Treatment-resistant Major Depressive Disorder at JoVE.com

MRI-guided dmPFC-rTMS as a Treatment for Treatment-resistant Major Depressive Disorder

Here we outline the procedure for MRI-guided repetitive transcranial magnetic stimulation to the dorsomedial prefrontal cortex as an experimental treatment for major depressive disorder.

MRI引导dmPFC-rTMS治疗作为治疗难治性抑郁症

Here we outline the protocol for magnetic resonance imaging (MRI) guided repetitive transcranial magnetic stimulation (rTMS) to the dorsal medial ...

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13.8K 次观看.  University of Toronto. Here we outline the procedure for MRI-guided repetitive transcranial magnetic stimulation to the dorsomedial prefrontal cortex as an experimental treatment for major depressive disorder.

视频: MRI-guided dmPFC-rTMS as a Treatment for Treatment-resistant Major Depressive Disorder

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 ...

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神经科学

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

Treating Clinical Depression with Repetitive Deep Transcranial Magnetic Stimulation Using the Brainsway H1-coil

Repetitive transcranial magnetic stimulation (rTMS) is an emerging non-pharmacological approach to treating many brain-based disorders. rTMS uses electromagnetic coils to stimulate areas of the brain non-invasively. Deep transcranial magnetic stimulation (dTMS) with the Brainsway H1-coil system specifically is a type of rTMS indicated for treating patients with major depressive disorder (MDD) who are resistant to medication. The unique H1-coil design of this device is able to stimulate neuronal pathways that lie deeper in the targeted brain areas than those reached by conventional rTMS coils. dTMS is considered to be low-risk and well tolerated, making it a viable treatment option for people who have not responded to medication or psychotherapy trials for their depression.
Randomized, sham-control studies have demonstrated that dTMS produces significantly greater improvement in depressive symptoms than sham dTMS treatment in patients with major depression that has not responded to antidepressant medication. In this paper, we will review the methodology for treating major depression with dTMS using an H1-coil.

Here we present a protocol outlining the methodology for treatment of Major Depressive Disorder using the deep Transcranial Magnetic Stimulation (dTMS) system.

临床治疗抑郁症的深层重复经颅磁刺激使用Brainsway H1线圈

Repetitive transcranial magnetic stimulation (rTMS) is an emerging non-pharmacological approach to treating many brain-based disorders. rTMS uses ...

行为学

Repetitive Transcranial Magnetic Stimulation to the Unilateral Hemisphere of Rat Brain

Previous rodent models of repetitive transcranial magnetic stimulation (rTMS) adopted whole-brain stimulation instead of unilateral hemispheric rTMS, which is unlike the protocols used for human subjects. We report a successful application of rTMS to the unilateral hemisphere of rat brain. The rTMS was delivered with a low-frequency (1 Hz), high-frequency (20 Hz), or sham stimulation protocol to one side of the brain by using a small 25-mm figure-8 coil. We placed the center of the coil 1 cm lateral to the vertex on the biauricular line and angulated the coil 45&#176; to the ground to minimize a potential direct effect of rTMS on the contralateral cortex. We also used an in-house water cooling system to enable repetitive magnetic stimulation for more than 20 min, even at a 20-Hz stimulation frequency. Increases in the transcriptions of immediate early genes (Arc, Junb, and Egr2) were greater after rTMS than after sham stimulation. After 5 consecutive days of 20-min 1-Hz rTMS, bdnf mRNA expression was significantly higher in stimulated cortex than in contralateral side. The model presented herein will elucidate the molecular mechanisms of rTMS by allowing analysis of the inter-hemispheric difference in its effect.

We applied repetitive transcranial magnetic stimulation (rTMS) to the unilateral hemisphere of rat brain, by placing a 25-mm figure-8 coil 1 cm lateral to the vertex on the biauricular line and angulating the coil by 45&#176;. An in-house water cooling system was used for rTMS for more than 20 min.

重复经颅磁刺激对大鼠大脑的单边半球

Previous rodent models of repetitive transcranial magnetic stimulation (rTMS) adopted whole-brain stimulation instead of unilateral hemispheric rTMS, ...

How to Use the H1 Deep Transcranial Magnetic Stimulation Coil for Conditions Other than Depression

Deep transcranial magnetic stimulation (dTMS) is a relatively new technique that uses different coils for the treatment of different neuropathologies. The coils are made of soft copper windings in multiple planes that lie adjacent to the skull. They are located within a special helmet so that their magnetic fields combine and improve depth penetration. The H1 dTMS coil is designed to stimulate bilateral prefrontal cortices with greater effective stimulation over the left than the right. By positioning the left side of the coil close to the left dorsolateral prefrontal cortex (DLPFC), the H1 coil was used in a multisite study, leading to FDA approval for treatment-resistant depression. In this same position, the H1 coil was also explored as a possible treatment for negative symptoms of schizophrenia, bipolar depression, and migraine. When moved to different positions over the subject's skull, the H1 coil was also explored as a possible treatment for other conditions. Such manipulation of the H1 coil was demonstrated for PTSD and alcohol dependence by positioning it over the medial prefrontal cortex (mPFC), for anxiety by positioning it over the right prefrontal cortex (rPFC), for auditory hallucinations and tinnitus by positioning it over the temporoparietal junction (TPJ), and for Parkinson's and fatigue from multiple sclerosis (MS) by positioning it over the motor cortex (MC) and PFC. Corresponding electrical field diagrams measured with an oscilloscope through a saline-filled head are included.

The H1 deep transcranial magnetic stimulation coil is FDA-cleared for the treatment of depression. We demonstrate how to utilize the H1 for other conditions, such as auditory hallucinations and PTSD, by moving the helmet to different locations over the subject's skull.

如何使用H1深经颅磁刺激线圈条件除抑郁症

Deep transcranial magnetic stimulation (dTMS) is a relatively new technique that uses different coils for the treatment of different neuropathologies. The ...

Utilizing Repetitive Transcranial Magnetic Stimulation to Improve Language Function in Stroke Patients with Chronic Non-fluent Aphasia

Transcranial magnetic stimulation (TMS) has been shown to significantly improve language function in patients with non-fluent aphasia1. In this experiment, we demonstrate the administration of low-frequency repetitive TMS (rTMS) to an optimal stimulation site in the right hemisphere in patients with chronic non-fluent aphasia. A battery of standardized language measures is administered in order to assess baseline performance. Patients are subsequently randomized to either receive real rTMS or initial sham stimulation. Patients in the real stimulation undergo a site-finding phase, comprised of a series of six rTMS sessions administered over five days; stimulation is delivered to a different site in the right frontal lobe during each of these sessions. Each site-finding session consists of 600 pulses of 1 Hz rTMS, preceded and followed by a picture-naming task. By comparing the degree of transient change in naming ability elicited by stimulation of candidate sites, we are able to locate the area of optimal response for each individual patient. We then administer rTMS to this site during the treatment phase. During treatment, patients undergo a total of ten days of stimulation over the span of two weeks; each session is comprised of 20 min of 1 Hz rTMS delivered at 90% resting motor threshold. Stimulation is paired with an fMRI-naming task on the first and last days of treatment. After the treatment phase is complete, the language battery obtained at baseline is repeated two and six months following stimulation in order to identify rTMS-induced changes in performance. The fMRI-naming task is also repeated two and six months following treatment. Patients who are randomized to the sham arm of the study undergo sham site-finding, sham treatment, fMRI-naming studies, and repeat language testing two months after completing sham treatment. Sham patients then cross over into the real stimulation arm, completing real site-finding, real treatment, fMRI, and two- and six-month post-stimulation language testing.

We explore the use of repetitive transcranial magnetic stimulation (rTMS) to improve language abilities in patients with chronic stroke and non-fluent aphasia. After identifying a site in the right frontal gyrus for each patient that responds optimally to stimulation, we target this site during ten days of rTMS treatment.

利用重复经颅磁刺激改善脑卒中患者的语言功能与慢性非流利性失语

Transcranial magnetic stimulation (TMS) has been shown to significantly improve language function in patients with non-fluent aphasia1. In this ...

Individualized rTMS Treatment for Depression using an fMRI-Based Targeting Method

To achieve greater clinical efficacy, a revolution in treatment for major depressive disorder (MDD) is highly anticipated. Repetitive transcranial magnetic stimulation (rTMS) is a non-invasive and safe neuromodulation technique that immediately changes brain activity. Despite its wide application in the treatment for MDD, the treatment response remains different among individuals, which may be attributable to the inaccurate positioning of the stimulation target. Our study aims to examine whether the functional magnetic resonance imaging (fMRI)-assisted positioning improves the efficacy of rTMS in treating depression. We intend to identify and stimulate the subregion of dorsolateral prefrontal cortex (DLPFC) in MDD with strongest anti-correlation with the subgenual anterior cingulate cortex (sgACC), and to conduct a comparative investigation of this novel method and the traditional 5-cm rule. To achieve more precise stimulation, both methods were applied under the guidance of neuronavigation system. We expected that the TMS treatment with individualized positioning based on resting state functional connectivity may show better clinical efficacy than the 5-cm method.

The present protocol describes the application of repetitive transcranial magnetic stimulation (rTMS), where a subregion of the dorsolateral prefrontal cortex (DLPFC) with the strongest functional anticorrelation with the subgenual anterior cingulate cortex (sgACC) was located as the stimulation target under the assistance of a fMRI-based neuronavigation system.

使用基于fMRI的靶向方法对抑郁症进行个体化的rTMS治疗

To achieve greater clinical efficacy, a revolution in treatment for major depressive disorder (MDD) is highly anticipated. Repetitive transcranial ...

Combined Transcranial Magnetic Stimulation and Electroencephalography of the Dorsolateral Prefrontal Cortex

Transcranial magnetic stimulation (TMS) is a non-invasive method that produces neural excitation in the cortex by means of brief, time-varying magnetic field pulses. The initiation of cortical activation or its modulation depends on the background activation of the neurons of the cortical region activated, the characteristics of the coil, its position and its orientation with respect to the head. TMS combined with simultaneous electrocephalography (EEG) and neuronavigation (nTMS-EEG) allows for the assessment of cortico-cortical excitability and connectivity in almost all cortical areas in a reproducible manner. This advance makes nTMS-EEG a powerful tool that can accurately assess brain dynamics and neurophysiology in test-retest paradigms that are required for clinical trials. Limitations of this method include artifacts that cover the initial brain reactivity to stimulation. Thus, the process of removing artifacts may also extract valuable information. Moreover, the optimal parameters for dorsolateral prefrontal (DLPFC) stimulation are not fully known and current protocols utilize variations from the motor cortex (M1) stimulation paradigms. However, evolving nTMS-EEG designs hope to address these issues. The protocol presented here introduces some standard practices for assessing neurophysiological functioning from stimulation to the DLPFC that can be applied in patients with treatment resistant psychiatric disorders that receive treatment such as transcranial direct current stimulation (tDCS), repetitive transcranial magnetic stimulation (rTMS), magnetic seizure therapy (MST) or electroconvulsive therapy (ECT).

The protocol presented here is for TMS-EEG studies utilizing intracortical excitability test-retest design paradigms. The intent of the protocol is to produce reliable and reproducible cortical excitability measures for assessing neurophysiological functioning related to therapeutic interventions in the treatment of neuropsychiatric diseases such as major depression.

侧前额叶皮质联合经颅磁刺激与脑电图的研究

Transcranial magnetic stimulation (TMS) is a non-invasive method that produces neural excitation in the cortex by means of brief, time-varying magnetic ...

Vagus Nerve Stimulation As an Adjunctive Neurostimulation Tool in Treatment-resistant Depression

Vagus nerve stimulation (VNS) is an approved neurostimulation therapy. The purpose of the method is to treat patients with therapy-resistant depression (TRD). VNS exhibits antidepressive and stabilizing effects. This method is particularly useful as a long-term treatment, in which up to two-thirds of patients respond. The vagus nerve stimulator is positioned on the left vagus nerve during a surgical procedure and is activated telemetrically by a wand connected to a handheld computerized device. The treating physician can perform various adjustments of the vagus nerve stimulator during in-office visits (e.g., by modifying stimulation intensity or stimulation frequency) to achieve maximum therapeutic effects with low side effects. Set-up of the device usually takes several months. Typical side effects include wound infection, temporary salivation, coughing, paralysis of the vocal cords, bradycardia, or even asystole. The patient can stop the VNS by placing a magnet over the generator. The current protocol describes delivery of the specific stimulation tool and methods for adjusting the tuning parameters to achieve the best remission rates in patients with TRD.

Vagus nerve stimulation (VNS) has been shown to be effective as an adjunct treatment for treatment-resistant depression (TRD). VNS leads to antidepressive and antisuicidal effects and quality of life improvements. This protocol offers a step-by-step guide to managing and adjusting a vagus nerve stimulator for efficient treatment of TRD.

迷走神经刺激作为抗抑郁抑郁症的辅助神经刺激工具

Vagus nerve stimulation (VNS) is an approved neurostimulation therapy. The purpose of the method is to treat patients with therapy-resistant depression ...

Employing Transcranial Magnetic Stimulation in a Resource Limited Environment to Establish Brain-Behavior Relationships

Neuroimaging is typically perceived as a resource demanding discipline. While this is the case in certain circumstances, institutions with limited resources have historically contributed significantly to the field of neuroscience, including neuroimaging. In the study of self-deception, we have successfully employed single-pulse TMS to determine the brain correlates of abilities including overclaiming and self-enhancement. Even without the use of neuro-navigation, methods provided here lead to successful outcomes. For example, it was discovered that decreases in self-deceptive responding lead to a decrease in affect. These methods provide data that are reliable and valid, and such methods provide research opportunities otherwise unavailable.&#160;Through the use of these methods, the overall knowledge base in the field of neuroscience is expanded, providing research opportunities to students such as those at our institution&#160;(Montclair State University is a Hispanic-Serving Institute) who are often denied such research experiences.

Transcranial Magnetic Stimulation (TMS) and low-frequency TMS (lfTMS) have&#160;been demonstrated to be major contributors to brain literature. Here we highlight the methods for investigating the cortical correlates of self-deception using TMS.