Examining the mechanisms of anxiety regulation using a novel, sham-controlled, fMRI-guided rTMS protocol and a translational laboratory model of anxiety.

尽管广泛的研究已经探索了皮层下结构在唤醒中的参与，但唤醒 症状只是焦虑症共有症状的一个方面。知之甚少 关于焦虑症患者所经历的认知症状（即注意力不集中）。据此，有 迫切需要对介导认知症状的中枢神经系统机制进行机制研究 焦虑症患者所经历的。如果没有这样的研究，这些疾病的治疗方法的开发将会 继续取得缓慢的进展。该应用程序的目的是确定关键的神经机制 介导焦虑的认知症状。我的中心假设是右背外侧前额叶 皮质（dlPFC）通过自上而下抑制情绪相关区域来调节情绪。我的方法是 使用重复经颅磁刺激（rTMS）研究右侧 dlPFC 活动对客观的影响 诱发焦虑、焦虑相关工作记忆缺陷 (WM) 和 TMS 诱发的主观测量 同时 TMS/fMRI 期间的血氧水平依赖性 (BOLD) 反应（即目标 参与）。我采用这种方法的理由是，通过使用 dlPFC 实验操纵右 dlPFC 活动 rTMS，我将能够因果地证明该区域参与焦虑调节，这可能 转化为未来针对焦虑症的针对性 rTMS 治疗。我的首要目标是确定 1 周的效果 使用不可预测的威胁对焦虑进行 rTMS 治疗过程（1 Hz 与 10 Hz；右 dlPFC 目标） 震惊范式。我的第二个目标是确定 1 周 rTMS 治疗疗程的效果（1 Hz 与 1 Hz）。 10赫兹；正确的 dlPFC 目标）在威胁期间使用 Sternberg WM 范式处理与焦虑相关的 WM 缺陷 震惊。我的第三个目标是通过测量 TMS 引起的大胆反应来证明目标参与度 在受到电击威胁时向右侧 dlPFC 发出脉冲。这项工作具有创新性，因为它将结合先进的 神经调节技术（功能磁共振成像引导、电场建模、神经导航、主动假控制） 具有休克范式的转化威胁。

Although extensive research has explored the involvement of subcortical structures in arousal, arousal symptoms are only one facet of the symptom profile shared across anxiety disorders. Much less is known about the cognitive symptoms (i.e. difficulty concentrating) experienced by anxiety patients. Accordingly, there is a critical need for mechanistic research into the CNS mechanisms that mediate the cognitive symptoms experienced by anxiety patients. Without such research, treatment development for these disorders will continue to make slow progress. The objective of this application is to determine the key neural mechanisms that mediate the cognitive symptoms of anxiety. My central hypothesis is that the right dorsolateral prefrontal cortex (dlPFC) regulates emotion through top-down inhibition of emotion-related regions. My approach will be to use repetitive transcranial magnetic stimulation (rTMS) to study the effect of right dlPFC activity on objective and subjective measures of induced anxiety, anxiety-related working memory deficits (WM), and TMS-evoked blood oxygenation-level dependent (BOLD) responses during simultaneous TMS/fMRI (i.e. target engagement). My rationale for this approach is that by experimentally manipulating right dlPFC activity using rTMS, I will be able to causally demonstrate involvement of this region in anxiety regulation, which could translate to future targeted rTMS treatments for anxiety. My first aim will be to determine the effect of a 1-week course of rTMS treatment (1 Hz vs. 10 Hz; right dlPFC target) on anxiety using the threat of unpredictable shock paradigm. My second aim will be to determine the effect of a 1-week course of rTMS treatment (1 Hz vs. 10 Hz; right dlPFC target) on anxiety-related WM-deficits using the Sternberg WM paradigm during threat of shock. My third aim will be to demonstrate target engagement by measuring BOLD responses evoked by TMS pulses to the right dlPFC during threat of shock. The work is innovative because it will combine advanced neuromodulatory techniques (fMRI guidance, electric-field modelling, neuronavigation, active-sham control) with a translational threat of shock paradigm.