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.

项目摘要 /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保持一致 网络（DMN），实际上，PTSD患者在DMN内有异常，并且与其他相互作用 网络，尤其是显着网络和额叶或中央执行网络。局灶性重复 脉冲经颅磁刺激（RTMS）可实现选定的大脑区域的神经调节和 连接的网络以治疗特定症状，但是在PTSD中支持这种疗法的大脑目标是 发现。最近的分析发现了与焦虑和躯体改善相关的脑电路 RTMS治疗抑郁症后的症状。 FMRI最强的左半球区域 与该电路的功能连通性位于解剖区域8AV和DMN中。该协会建议 通过左8AV刺激调节DMN可能是一种新颖的RTMS方法 焦虑并可能有助于减轻PTSD的焦虑症状。这个目标将是新颖的，因为绝大多数 PTSD中RTMS的临床试验针对显着性和额叶的右额叶区域 网络而不是DMN。一个潜在的原因是，DMN最成熟的节点不撒谎 直接在头皮/头骨下方，因此RTM无法实现。在此提案中，我们检验总体假设 左侧8AV可以作为DMN的强大，直接的大脑目标，从而促进PTSD和PTSD的治疗 涉及DMN的许多其他疾病。我们建议在30位具有PTSD的退伍军人中使用TMS-FMRI进行测试 左8AV与其他可以调节反应的其他区域之间的因果关系。我们将测试 8av和下顶叶（IPL）之间的连通性，DMN中涉及的区域 DMN的加工和其他节点（例如，后扣带回，腹侧前额叶皮层）。我们有 我们发现8AV和IPL之间的功能连接相对于相对于8AV和IPL之间的功能连接，相对于 控制，以及向这些地区提供RTM的控制可以缓解焦虑。我们还将探讨是否 8av处的刺激调节了前岛，这是显着网络的节点，其功能连接性 预测PTSD中长期暴露疗法受益。我们将测量TMS引起的粗体响应 在这些领域，刺激8AV并将这种反应与常规种子基于种子的静止状态fMRI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，我们还将提供thetaburst rtms刺激，并研究连通性如何相对于 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，该项目将提供对机械的理解 RTMS治疗在8AV，并将揭示基于连通性的Atlas靶标的效果。