Targeting the Default Mode Network: A TMS-fMRI Study

针对默认模式网络：TMS-fMRI 研究

• 批准号: 10590968
• 负责人: ALLYSON C ROSEN
• 金额: $ 20.36万
• 依托单位: PALO ALTO VETERANS INSTIT FOR RESEARCH
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-01-16 至 2024-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10590968
• 关键词: Affect; Amygdaloid structure; Anatomy; Anterior; Anxiety; Area; Atlases; Autobiography; Brain; Brain region; Clinical; Clinical Trials; Cognition; Complement; Data; Detection; Disease; Emotional; Evaluation; Fright; Functional Magnetic Resonance Imaging; Goals; Human; Inferior; Insula of Reil; Laboratories; Lead; Learning; Left; Measures; Mediating; Memory; Mental Depression; Moods; Parietal Lobe; Patients; Persons; Physiologic pulse; Post-Traumatic Stress Disorders; Prefrontal Cortex; Process; Protocols documentation; Reporting; Resistance; Rest; Scalp structure; Symptoms; System; Techniques; Testing; Transcranial magnetic stimulation; Veterans; Work; anxiety symptoms; anxiety treatment; blood oxygenation level dependent response; connectome; cranium; emotion regulation; executive function; follow-up; frontal lobe; improved; interest; neuroregulation; novel; response; secondary analysis; support network; symptomatic improvement; treatment response; virtual

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.

项目概要/摘要 创伤后应激障碍（PTSD）是一种毁灭性的疾病，其中创伤性自传体记忆 具有侵入性并导致焦虑症状。这些症状与默认模式的功能一致 事实上，PTSD 患者在 DMN 内及其与其他网络的相互作用中存在异常。 网络，特别是显着网络和额顶或中央执行网络。焦点重复 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症状，但支持这种 PTSD 疗法的大脑目标尚不清楚 发现。最近的一项分析发现了与焦虑和躯体症状改善相关的大脑回路 rTMS 治疗抑郁症后出现的症状。左半球功能磁共振成像最强的区域 与该回路的功能连接位于解剖区域 8Av 和 DMN 内。该协会建议 通过刺激左侧 8Av 来调节 DMN 可能是一种新的 rTMS 治疗方法 焦虑，可能有助于改善 PTSD 的焦虑症状。这个目标是新颖的，因为绝大多数 rTMS 治疗 PTSD 的临床试验针对的是显着性的右额叶区域和额顶叶 网络而不是 DMN。一个潜在的原因是 DMN 最成熟的节点不会说谎 位于头皮/头骨正下方，因此 rTMS 无法到达。在这个提案中，我们测试总体假设 左侧 8Av 区域可以作为 DMN 的强大、直接的大脑靶标，从而促进 PTSD 和 许多其他涉及 DMN 的疾病。我们建议对 30 名患有 PTSD 的退伍军人使用 TMS-fMRI 进行测试 左 8Av 和其他可以调节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，下顶叶 (IPL) 是 DMN 中涉及上下文的区域 处理和 DMN 的其他节点（例如后扣带回、腹内侧前额叶皮层）。我们有 试验数据中，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 可以减轻焦虑。我们还将探讨是否 8Av 的刺激可调节前岛叶，这是突出网络的一个节点，其功能连接 预测长期暴露疗法对 PTSD 的益处。我们将测量 TMS 引起的 BOLD 反应 这些区域对 8Av 的刺激，并将这种反应与传统的基于种子的静息态功能磁共振成像进行比较 功能连接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 刺激并研究连通性如何变化 基线。我们的总体目标是表征 PTSD 中的左 8Av 功能连接，并探索 rTMS 刺激参数的影响。因此，该项目将提供对 rTMS 治疗的强度为 8Av，并将揭示基于连接的新型图谱目标的效果。