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

项目概要/摘要 正念减压（MBSR）已被证明对广泛性焦虑症有效 (GAD)然而，关于其神经机制仍然存在重大知识空白。神经影像学研究迄今 大多集中在正念减压疗法对大脑结构和休息状态变化的影响上，这些研究 主要在健康参与者中进行。广泛性焦虑症的核心特征，如沉思性焦虑， 代表了失调的情绪调节策略，增加了对未来威胁的偏见。MBSR的成功在于 与改善情绪调节，增强对当前时刻的注意力和非判断性相关 接受内部和外部线索。我们的主要目的是阐明驱动反应的神经机制 对广泛性焦虑症（GAD）患者进行MBSR，并检查性别差异的程度 在正念减压反应中的性别差异可以用这些机制来解释。我们的首要假设是 正念减压疗法增强了“自上而下”的学习和记忆能力，这种能力是广泛的， “本能”的能力（自下而上），以调节恐惧和情绪。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（腹内侧前额叶皮层（vmPFC），海马体， 杏仁核）作为“本能”型情绪调节的特定探针。其次，我们将使用一种新的分析方法， 方法来检查大规模的功能连接作为神经可塑性变化的标志（前和后）， 正念减压疗法（MBSR）在整个大脑的恐惧消退学习过程中进行一次又一次的试验，重点分析默认模式 网络（DMN），额顶叶网络（FPN）和腹侧注意网络（货车）。接下来，我们将考察性 MBSR诱导的神经变化的差异及其与临床GAD反应性别差异的关系。 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。 诱导的神经变化和临床症状减轻，以确定可能的MBSR反应者。参与者将 在fMRI扫描仪中进行标准化的2天恐惧条件反射和消退范例， MBSR或压力教育（SE），终点和3个月随访时的主要临床结局。这项研究的 目标与NCCIH的PA-18-323：关于身心方法的基础科学研究相一致 通过研究广泛性焦虑症患者正念减压疗法的神经作用机制及性别差异， (GAD)这是一种在初级保健中常见的普遍疾病，对这种疾病已经确立了正念减压疗法的疗效。本研究将 采用严格的科学方法，并进行时间和注意力控制干预，以隔离MBSR 对涉及情绪调节和临床反应的大脑区域的机械影响。独特的 对典型焦虑状态的关注与既定的情绪调节困难相结合， 目标神经回路，以前证明的正念减压疗效，以及严格的功能磁共振成像行为的性别差异， 新的分析方法的探索应该提供关于正念减压机制和性别的重要新见解 考虑，走向精确医学，可以指导未来的治疗开发研究。

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.