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

虽然广泛的研究已经探索了皮层下结构在唤醒中的参与， 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（即难以集中注意力）。因此， 对介导认知症状的中枢神经系统机制的机制研究是一个迫切的需要 焦虑症患者的经验。如果没有这样的研究，这些疾病的治疗开发将 继续取得缓慢进展。本申请的目的是确定关键的神经机制 调节焦虑的认知症状。我的主要假设是右背外侧前额叶 大脑皮层（dlPFC）通过对情绪相关区域的自上而下的抑制来调节情绪。我的方法是 目的：应用重复经颅磁刺激（rTMS）研究右侧背外侧前额叶皮层（dlPFC）活动对客观神经功能的影响。 和主观测量的诱导焦虑，焦虑相关的工作记忆缺陷（WM），和TMS诱发 在同时TMS/fMRI期间的血氧水平依赖性（BOLD）反应（即靶向 订婚）。我对这种方法的基本原理是，通过实验操纵右dlPFC活动， rTMS，我将能够因果地证明这个区域参与焦虑调节，这可能 转化为未来针对焦虑症的rTMS治疗。我的第一个目标是确定一周的效果 rTMS治疗过程（1 Hz vs. 10 Hz;右侧dlPFC目标）使用不可预测的威胁对焦虑进行治疗 休克范式我的第二个目标是确定1周rTMS治疗的效果（1 Hz vs. 10 Hz;右侧dlPFC目标）对焦虑相关WM缺陷的影响，使用斯滕贝格WM范式， 冲击.我的第三个目标是通过测量TMS引起的BOLD反应来证明目标参与 电击威胁时右前外侧前额叶皮层的脉冲这项工作是创新的，因为它将联合收割机先进的 神经调节技术（fMRI引导、电场建模、神经导航、主动-假对照） 一个转化的休克威胁范例。

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.