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

尽管广泛的研究探索了皮质下结构参与觉醒、觉醒 症状只是焦虑症共有的症状特征的一个方面。我们知道的要少得多 关于焦虑症患者的认知症状(即注意力难以集中)。因此，在那里 迫切需要对中枢神经系统调节认知症状的机制进行机械性研究 焦虑症患者所经历的。如果没有这样的研究，这些疾病的治疗开发将 继续取得缓慢进展。这个应用程序的目标是确定关键的神经机制 这调节了焦虑的认知症状。我的中心假设是右侧背外侧前额叶 大脑皮层(DlPFC)通过自上而下抑制情绪相关区域来调节情绪。我的方法将是 应用重复经颅磁刺激(RTMS)研究右侧dlPFC活动对目标的影响 以及诱发焦虑、与焦虑相关的工作记忆缺陷(WM)和TMS诱发的主观测量 同时TMS/fMRI(即靶点)期间的血氧水平依赖(BOLD)反应 接洽)。我使用这种方法的基本原理是，通过使用 RTMS，我将能够因果地证明这一区域参与焦虑调节，这可能 转化为未来针对焦虑的rTMS治疗。我的第一个目标将是确定一周的影响 使用不可预测的威胁进行rTMS治疗(1赫兹与10赫兹；正确的dlPFC目标)治疗焦虑症 震撼范式。我的第二个目标是确定为期一周的rTMS治疗的效果(1赫兹与 10赫兹；正确的dlPFC目标)在威胁期间使用Sternberg WM范式对焦虑相关的WM缺陷进行研究 令人震惊。我的第三个目标将是通过测量TMS引起的大胆反应来展示目标参与度 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(fMRI引导、电场建模、神经导航、主动-假控制) 带有惊吓范式的翻译威胁。

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.