Whole Brain Connectivity and Connectomics of Mindfulness-based Cognitive Therapy for PTSD

项目摘要 该候选人是一位临床心理学家和神经科学家，对现象学有浓厚的兴趣， 情感神经回路和有效治疗创伤后应激障碍（PTSD）。PTSD是一种高度 流行（男性7%，女性12%），慢性和高度衰弱。每五个退伍军人中就有一个 在阿富汗和伊拉克都有明显的创伤后应激障碍症状经验支持治疗（EST） 在随机对照试验中，使用创伤暴露的PTSD具有非常大的效应量;然而，最近的研究发现， 退伍军人中的拒绝和早期辍学（30-50%）。我们以前报告过大规模分布的赤字， PTSD中的神经网络，包括默认模式网络（DMN）和 显著性网络（SN），我们目前的试点数据表明，PTSD回避症状与DMN减少有关 中央执行网络（CEN）。我们还报告了一种基于正念的干预， PTSD减少了回避，增加了DMN和CEN之间的连接。K23培训计划 将允许候选人学习和应用强大的全脑连接和动态连接 研究大规模分布式神经网络的改变所需的方法， 治疗机制我们的假设是H1：DMN-CEN减少和DMN-SN增加是 情绪/行为回避与PTSD患者临床可接受性和结局差相关， H2：基于正念的认知疗法（MBCT）针对与PTSD相关的相同DMN-CEN连接 H3：MBCT诱导的DMN-CEN连接增加介导PTSD的改善 回避，情绪/行为回避和改善的结果。目的是：1.）测试是否行为 PTSD中的情绪回避与DMN-CEN连接性降低有关，2.）识别 使用强大的连接组学分析MBCT对DMN-CEN的影响，以及3.）探索调解 DMN-CEN连接与行为和情感参与之间的关系 后续治疗和临床结果。fMRI与N=60战斗PTSD患者与rsFC使用 动态因果模型和上下文处理范式将测试与回避的关联 情绪回避的症状和实验室测量。一项随机对照试验（N=30 MBCT，N=30对照）， 后fMRI和组x时间相互作用分析将确定MBCT之间的连接， DMN、CEN和SN之间的关系。中介分析将测试神经目标和纵向措施， 情感投入这项研究将是第一个针对功能性神经网络潜在的回避 行为，并可能导致额外的策略，以帮助约50%的创伤后应激障碍患者， 没有完全参与现有的EST，并阐明与新的潜在的神经机制， PTSD治疗（正念训练）。它还将为候选人提供高级培训， R级资金的试点数据，以确定治疗变化的机制和创伤后应激障碍的新疗法。

Project Summary The candidate is a clinical psychologist and neuroscientist with a strong interest in the phenomenology, affective neurocircuitry, and effective treatment of posttraumatic stress disorder (PTSD). PTSD is highly prevalent (7% in males, 12% in females), chronic and highly debilitating. One in every five veterans deployed to Afghanistan and Iraq have clinically significant PTSD symptoms. Empirically supported treatment (ESTs) for PTSD using trauma exposure have very large effect sizes in RCTs; however, recent work finds high rates of refusal and early drop-out among veterans (30-50%). We previously reported deficits in large scale distributed neural networks in PTSD, including increased connectivity between Default Mode Network (DMN) and Salience Network (SN), and we present pilot data that PTSD avoidant symptoms are linked to decreased DMN connectivity with Central Executive Network (CEN). We also reported a mindfulness-based intervention for PTSD decreased avoidance and increased connectivity between DMN and CEN. This K23 training program will allow the candidate to learn and apply the powerful whole-brain connectomic and dynamic connectivity methodologies needed to study the alterations in large scale distributed neural networks underlying PTSD and therapeutic mechanisms. Our hypotheses are H1: Decreased DMN-CEN and increased DMN-SN underlie emotional / behavioral avoidance associated with poor clinical acceptability and outcomes in PTSD patients, H2: Mindfulness-based Cognitive Therapy (MBCT) targets the same DMN-CEN connectivity linked with PTSD avoidance, and H3: MBCT-induced increased DMN-CEN connectivity mediates improvement in PTSD avoidance, emotional / behavioral avoidance, and improved outcomes. The aims are to: 1.) test if behavioral and emotional avoidance in PTSD are associated with decreased DMN-CEN connectivity, 2.) identify effects of MBCT on DMN-CEN using powerful connectomics analyses, and 3.) explore mediation relationships between DMN-CEN connectivity and behavioral and emotional engagement in subsequent therapy and clinical outcomes. fMRI with N=60 combat PTSD patients with rsFC using dynamic causal modeling, and contextual processing paradigms, will test association with avoidance symptoms and laboratory measures of emotional avoidance. An RCT (N=30 MBCT, N=30 control) with pre- post fMRI and group x time interaction analyses will identify effects of MBCT on connectivity among and between DMN, CEN, and SN. Mediation analyses will test neural targets and longitudinal measures of emotional engagement. This study will be the first targeting functional neural networks underlying avoidance behaviors in PTSD treatment, and may lead to additional strategies to help the ~50% PTSD patients who do not fully engage with existing ESTs, and elucidate neural mechanisms associated with a novel potential component of PTSD treatment (mindfulness training). It will also provide the candidate advanced training and pilot data for R-level funding to identify mechanisms of therapeutic change and novel treatments for PTSD.