Neural Mechanisms of Mindfulness-based Cognitive Therapy (MBCT) for Posttraumatic Stress Disorder (PTSD)

越来越多的证据表明，MBCT和MBSR对急性精神疾病有疗效，包括难治性精神疾病。 需要治疗的疾病，如创伤后应激障碍(PTSD)、难治性抑郁症和全身性 焦虑症(GAD)。然而，具体的机制不被理解，机制是否被理解也不是 与其他疗法(如暴露、行为激活)相同，或独特且可能 互补性。阐明MBCT机制可以促进正在进行的改进和最佳靶向。 MBCT的心理机制涉及“偏心”，注意训练增加元认知 意识，它可以减少过度个性化和消极反应，经验回避，沉思， 和精神症状。创伤后应激障碍和抑郁与异常的内在神经连接有关， 例如在默认模式网络(DMN)、显著网络(SN)和注意控制网络之间。 越来越多的证据表明，MBCT/MBSR可以改变这些连接性，以增强智力和 身体健康。例如，MBCT/MBSR增加了DMN与注意力网络节点(例如， DLPFC)，PTSD症状和血浆IL-6的相关减少。MBCT/MBSR也有所下降 DMN(vmPFC，膝下ACC)和SN(岛，杏仁核)之间的功能连接。这些发现 提示MCBT可能会将注意力资源重新定向，从而导致“去自动化”或部分 将厌恶的感知信号从快速/自动行为反应系统中分离出来，这可能是昂贵的 以及过度使用时的不适应性，并且可能代表潜在的核心跨诊断机制 情绪、焦虑和创伤障碍。我们假设MBCT/MBSR导致DMN注意力的增加 网络连接(例如PCC-DLPFC、vmPFC-DLPFC)和增强的元认知注意能力， 情景设置和注意力转移(H1)，以及DMN-SN连接性降低(例如vmPFC-Island)，领先 提高去个人化潜在厌恶线索和相互感知信号的能力，减少负面影响 反应性(H2)。我们将在创伤后应激障碍的治疗中检验这些假设，这提供了一个有用的模型系统， 由于已知受到MBCT影响的网络也已知涉及创伤后应激障碍，且MBCT 已知可以减少创伤后应激障碍症状。我们的R61将通过MBCT(H1或H2)在创伤后应激障碍中测试网络目标参与度 42例患者(n=42)，在MBCT前使用基于种子和全脑的连接术(A)在静息状态下的功能 连接性和(B)在自我参照处理期间。《GO-Criteria》将增加DMN-注意网络或 MBCT后DMN-SN连通性降低。我们的R33将使用MBCT(N=53)的RCT与Extended 活体暴露治疗暴露组(N=53)，通过MBCT验证靶点接触和中介 症状的改善，以及与PE体内暴露的机制是否不同。 我们将测试治疗组在网络目标参与及其对变化的调节方面的差异 偏心、创伤后应激障碍症状、接受度、应激反应、功能和生活质量。

There is growing evidence that MBCT and MBSR have efficacy for acute psychiatric conditions, including hard- to-treat ones like posttraumatic stress disorder (PTSD), treatment-resistant depression, and generalized anxiety disorder (GAD). However, specific mechanisms are not understood, nor is whether mechanisms are shared with other therapies (e.g. exposure, behavioral activation), or are distinct and potentially complementary. Elucidating MBCT mechanisms can enhance ongoing refinement and optimal targeting. Psychological mechanisms of MBCT involve “decentering”, attentional training increases metacognitive awareness, which can reduce over-personalization and negative reactivity, experiential avoidance, rumination, and psychiatric symptoms. PTSD and depression are associated with aberrant intrinsic neural connectivity, e.g. between default mode network (DMN), salience network (SN) and attentional control networks. Converging evidence suggests that MBCT/MBSR can alter these connectivities to enhance mental and physical health. For example, MBCT/MBSR increases connectivity of DMN with attention networks nodes (e.g. DLPFC), with associated reductions in PTSD symptoms and plasma IL-6. MBCT/MBSR also decreases functional connectivity between DMN (vmPFC, subgenual ACC) and SN (insula, amygdala). These findings suggest MCBT may redirect attentional resources in ways that lead to a “de-automatization” or partial uncoupling of aversive perceptual signals from rapid/automatic behavioral response systems that can be costly and maladaptive when overused, and which may represent core transdiagnostic mechanisms underlying mood, anxiety, and trauma disorders. We hypothesize that MBCT/MBSR leads to increased DMN-attention network connectivity (e.g. PCC-DLPFC, vmPFC-DLPFC) and increased meta-cognitive attentional capacity, contextualizing, and attention shifting (H1), and decreased DMN-SN connectivity (e.g. vmPFC-insula), leading to increased ability to depersonalize potentially aversive cues and interoceptive signals, reducing negative reactivity (H2). We will test these hypotheses in treatment of PTSD, which provides an useful model system, since the networks known to be impacted by MBCT are also known to be involved in PTSD, and MBCT is known to reduce PTSD symptoms. Our R61 will test network target engagement by MBCT (H1 or H2) in PTSD patients (N=42), using pre-post MBCT seed-based and whole brain connectomics (a) in resting state functional connectivity and (b) during self-referential processing. “Go-criteria” will be increased DMN-attention network or decreased DMN-SN connectivity post MBCT. Our R33 will use an RCT of MBCT (N=53) vs a Prolonged Exposure therapy in vivo exposure group (N=53) to validate target engagement by MBCT and mediation of symptom improvement, and whether mechanisms are different from those engaged by PE in vivo exposure. We will test for treatment group differences in network target engagement and its mediation of changes in decentering, PTSD symptoms, acceptance, stress reactivity, functionality, and quality of life.