Targeting the Default Mode Network: A TMS-fMRI Study

项目总结/摘要 创伤后应激障碍（PTSD）是一种毁灭性的疾病， 是侵入性的，并导致焦虑症状。这些症状与默认模式的功能一致 事实上，PTSD患者在DMN及其与其他神经元的相互作用中存在异常。 网络，特别是显着性网络和额顶或中央执行网络。局灶性重复 脉冲经颅磁刺激（rTMS）能够对选定的大脑区域进行神经调节， 连接网络来治疗特定的症状，但是支持这种治疗PTSD的大脑靶点在 的发现最近的一项分析揭示了一种与焦虑和躯体疾病改善相关的大脑回路。 rTMS治疗抑郁症后的症状。功能磁共振成像最强的左半球区域 与该回路的功能连接位于解剖区域8Av和DMN内。这种关联表明 通过刺激左侧8Av来调节DMN可能是治疗 可能有助于改善PTSD的焦虑症状。这一目标将是新颖的，因为绝大多数 rTMS治疗创伤后应激障碍的临床试验针对的是右额叶的突出区域和额顶叶 网络而不是DMN。一个潜在的原因是DMN中最成熟的节点不说谎 直接位于头皮/颅骨下方，因此无法通过rTMS到达。在这个建议中，我们测试了整体假设 左侧区域8Av可以作为DMN的强大的直接脑靶点，从而促进PTSD的治疗， 与DMN有关的其他疾病我们建议使用TMS功能磁共振成像在30名退伍军人与创伤后应激障碍，以测试 左8Av和其他可能介导反应的区域之间的因果关系。我们将测试 8Av和下顶叶（IPL）之间的连接，这是DMN中涉及背景的区域 处理，以及DMN的其它节点（例如，后扣带回、腹内侧前额叶皮质）。我们有 我们发现8Av和IPL之间的功能连接相对于 控制，并且向这些区域提供rTMS可以改善焦虑。我们还将探讨 在8Av处的刺激调节前额叶，前额叶是显著性网络的一个节点，其功能连接 预测PTSD患者长期暴露治疗的益处。我们将测量TMS诱导的BOLD反应 并将这种反应与传统的基于种子的静息态fMRI进行比较 功能连接性分析，可以作为调制能力的替代标记。在 此外，我们将提供thetaburst rTMS刺激，并研究连接如何改变， 基线。我们的总体目标是描述PTSD中左8Av功能连接的特征，并探索PTSD中左8Av功能连接的变化。 rTMS刺激参数的影响。因此，该项目将提供一个机械的理解， rTMS治疗在8Av，并将揭示一种新的连接性为基础的地图集目标的影响。

PROJECT SUMMARY / ABSTRACT Post-traumatic stress disorder (PTSD) is a devastating illness in which traumatic autobiographical memories are intrusive and lead to anxiety symptoms. These symptoms align with the functions of the default mode network (DMN) and, in fact, PTSD patients have abnormalities within the DMN and in its interactions with other networks, notably the salience network and the frontoparietal or central executive network. Focal repetitive pulse transcranial magnetic stimulation (rTMS) enables neuromodulation of selected brain regions and connected networks to treat specific symptoms, but the brain targets to support this therapy in PTSD are under discovery. A recent analysis uncovered a brain circuit associated with improvement in anxiety and somatic symptoms following the rTMS treatment of depression. The left hemisphere region with the strongest fMRI functional connectivity with this circuit lies within anatomical area 8Av and the DMN. This association suggests that modulating the DMN through stimulation at left 8Av could be a novel rTMS approach for the treatment of anxiety and may help ameliorate anxiety symptoms in PTSD. This target would be novel since the vast majority of clinical trials of rTMS in PTSD have targeted the right frontal regions of the salience and frontoparietal networks instead of the DMN. One potential reason is that the most established nodes of the DMN do not lie directly below the scalp/skull and are thus unreachable by rTMS. In this proposal we test the overall hypothesis that left area 8Av can serve as a robust, direct brain target for the DMN thus facilitating therapy for PTSD and the many other disorders involving the DMN. We propose to use TMS-fMRI in 30 Veterans with PTSD to test the causal connections between left 8Av and other regions that could mediate a response. We will test the connectivity between 8Av and the inferior parietal lobe (IPL), a region in the DMN involved in context processing, and other nodes of the DMN (e.g., posterior cingulate, ventromedial prefrontal cortex). We have pilot data in which we found the functional connection between 8Av and the IPL to be abnormal relative to controls, and also that delivering rTMS to these regions ameliorates anxiety. We will also explore whether stimulation at 8Av modulates the anterior insula, a node of the salience network whose functional connectivity predicts benefit from prolonged exposure therapy in PTSD. We will measure the TMS induced BOLD response in these areas to stimulation of 8Av and compare this response to conventional seed-based resting-state fMRI functional connectivity analyses that could serve as an alternative marker for capacity for modulation. In addition we will deliver thetaburst rTMS stimulation and study how connectivity changes with respect to baseline. Our overall goal is to characterize left 8Av functional connectivity in PTSD, and explore the effects of rTMS stimulation parameters. This project will thus provide a mechanistic understanding of rTMS therapy at 8Av, and will reveal the effects of a novel connectivity-based atlas target.