Elucidating Neural Mechanisms and Sex Differences in Response to Mindfulness Based Stress Reduction in Generalized Anxiety Disorder

项目摘要/摘要 基于正念的减压疗法(MBSR)对广泛性焦虑症有效 (GAD)，然而关于它的神经机制仍然存在重大的知识差距。到目前为止的神经成像研究 主要集中在MBSR对结构和静息状态大脑变化的影响，这些研究 主要是在健康参与者中进行的。GAD的核心特征，如沉思的担忧， 代表着功能失调的情绪调节策略，这些策略增加了对未来威胁的偏见。MBSR成功是 与改善情绪调节、加强对当下时刻的关注、以及不加评判有关 接受内部和外部暗示。我们的主要目标是阐明驱动反应的神经机制 对广泛性焦虑症(GAD)患者的MBSR，并检查性别差异的程度 在MBSR中的反应可以用这些机制中的性别差异来解释。我们最重要的假设是 MBSR增强了广泛的自上而下的学习和记忆能力，影响了自上而下以及 “本能”调节恐惧和情绪的能力(自下而上)。我们将首先研究大脑的功能激活 与恐惧消退网络相关的区域(腹内侧前额叶皮质(VmPFC)、海马体和 杏仁核)作为情绪调节的“本能”类型的特定探测器。其次，我们将使用一种新的分析方法 检查大规模功能连通性作为神经可塑性变化标志的方法(前后 MBSR)在整个大脑的恐惧消退学习过程中逐一试验，重点分析默认模式 额顶神经网络(DMN)和腹侧注意网络(VAN)。接下来，我们将检讨性 临床GAD反应中MBSR诱导的神经改变的差异及其与性别差异的关系。 最后，我们将使用一种新的统计方法来探索基线神经测量是否可以预测MBSR- 诱导神经改变和临床症状减轻，以确定可能的MBSR应答者。参与者将 在fMRI扫描仪中进行标准化的为期2天的恐惧条件反射和消退实验 MBSR或压力教育(SE)，在终点和3个月的随访中有主要临床结果。这项研究是 目标与NCCIH的PA-18-323一致：关于心理和身体方法的基础科学研究 广泛性焦虑症患者MBSR神经作用机制及性别差异的研究 (GAD)，这是一种在初级保健中常见的流行疾病，MBSR对其建立了疗效。这项研究将 部署严格的科学方法和时间和注意力控制干预，以实现MBSR的隔离 对涉及情绪调节和临床反应的大脑区域的机械性影响。独一无二的 将注意力集中在典型的焦虑症和既定的情绪调节困难相结合，这涉及到 靶神经回路，先前证明了MBSR的有效性和性别差异，与严格的fMRI行为 具有新的分析方法的探针应该提供关于MBSR机制和性别的主要新见解 考虑，转向可以指导未来治疗开发研究的精准医学。

PROJECT SUMMARY/ABSTRACT Mindfulness-Based Stress Reduction (MBSR) has demonstrated efficacy for Generalized Anxiety Disorder (GAD), yet there remains a major knowledge gap about its neural mechanisms. Neuroimaging studies thus far have mostly focused on the impact of MBSR on structural and resting-state brain changes, and these studies have been predominantly conducted in healthy participants. Core features of GAD, such as ruminative worry, represent dysfunctional emotion regulation strategies that increase bias towards future threat. MBSR success is associated with improved emotion regulation, enhanced attention to the present moment, and non-judgmental acceptance of internal and external cues. Our primary aim is to elucidate neural mechanisms that drive response to MBSR in patients with generalized anxiety disorder (GAD), and to examine the degree to which sex differences in MBSR response are explained by sex differences in these mechanisms. Our overarching hypothesis is that MBSR enhances ‘top-down’ learning and memory capacities that are broad and impact ‘top-down’ as well as ‘instinctual’ abilities (bottom-up) to regulate fear and emotions. We will first study the functional activation of brain regions associated with the fear extinction network (ventromedial prefrontal cortex (vmPFC), hippocampus, and amygdala) as a specific probe of the ‘instinctual’ type of emotion regulation. Second, we will use a novel analytic approach to examine large-scale functional connectivity as a marker of neural plasticity changes (pre- and post- MBSR) trial-by-trial during fear extinction learning across the entire brain, focusing analyses on the default mode network (DMN), frontoparietal network (FPN), and ventral attention network (VAN). Next, we will examine sex differences in MBSR-induced neural changes and their relationship to sex differences in clinical GAD response. Finally, we will use a novel statistical approach to explore whether baseline neural measures can predict MBSR- induced neural changes and clinical symptom reduction to identify likely MBSR responders. Participants will undergo a standardized 2-day fear conditioning and extinction paradigm in the fMRI scanner before and after MBSR or stress education (SE) with primary clinical outcomes at endpoint and 3 month follow-up. This study’s objectives are aligned with NCCIH’s PA-18-323: Fundamental Science Research on Mind and Body Approaches by studying MBSR’s neural mechanism of action and sex differences in patients with generalized anxiety disorder (GAD), a prevalent condition often seen in primary care for whom MBSR efficacy is established. This study will deploy rigorous scientific methods with a time and attention control intervention to enable isolation of MBSR’s mechanistic impact on brain regions involved in emotion regulation and clinical response. The unique combination of a focus on a classic anxiety condition with established emotion regulation difficulties implicating target neural circuits, previously demonstrated MBSR efficacy, and sex differences with rigorous fMRI behavioral probes with novel analytic approaches ought to provide major new insights about MBSR mechanisms and sex considerations, moving towards precision medicine that could guide future treatment development research.