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

阐明广泛性焦虑症正念减压的神经机制和性别差异

• 批准号: 10599978
• 负责人: Candace M Raio
• 金额: $ 71.31万
• 依托单位: NEW YORK UNIVERSITY SCHOOL OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-07-15 至 2026-04-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10599978
• 关键词: Adherence; Affect; Amygdaloid structure; Animals; Anxiety; Attention; Awareness; Behavioral; Brain; Brain region; Clinical; Clinical effectiveness; Conditioned Stimulus; Coupling; Cues; Data; Diagnosis; Education; Emotional; Emotions; Exhibits; Expectancy; Extinction; Fright; Functional Magnetic Resonance Imaging; Future; Generalized Anxiety Disorder; Hippocampus; Human; Intervention; Knowledge; Learning; Literature; Measures; Memory; Methodology; Methods; Mind-Body Intervention; National Center for Complementary and Integrative Health; Neuronal Plasticity; Outcome; Participant; Patients; Phase; Prediction of Response to Therapy; Prefrontal Cortex; Premenopause; Primary Care; Process; Randomized; Research; Rest; Science; Sex Differences; Standardization; Stress; Synapses; Testing; Time; Woman; Work; anxiety reduction; attentional control; conditioned fear; emotion regulation; evidence base; follow-up; improved; insight; learning extinction; men; mind/body; mindfulness-based stress reduction; neural; neural circuit; neural network; neurobiological mechanism; neuroimaging; neuromechanism; novel; precision medicine; predictive modeling; reduce symptoms; research and development; response; restoration; rumination; sex; stress reduction; success; symptomatic improvement; therapy development; treatment response

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.

项目摘要/摘要 基于正念的压力减轻（MBSR）证明了普遍焦虑症的效率 （GAD），但仍然存在有关其神经机制的主要知识差距。迄今为止的神经影像学研究 主要集中于MBSR对结构和静止状态大脑变化的影响，这些研究 在健康的参与者中主要进行。 GAD的核心特征，例如反刍的担忧， 代表功能失调的情绪调节策略，增加对未来威胁的偏见。 MBSR成功是 与改善情绪调节，对当前时刻的关注以及非判断力有关 接受内部和外部提示。我们的主要目的是阐明推动反应的神经机制 在患有广义动画障碍（GAD）患者的MBSR中，并检查性别差异的程度 在MBSR中，这些机制的性别差异可以解释。我们的总体假设是 MBSR增强了“自上而下”的学习和记忆能力，这些学习能力宽广，影响着“自上而下” “本能”能力（自下而上）来调节恐惧和情感。我们将首先研究大脑的功能激活 与恐惧扩展网络相关的区域（腹前额叶皮层（VMPFC），海马和 杏仁核）是对情绪调节的“本能”类型的特定探针。其次，我们将使用一种新颖的分析 检验大规模功能连通性作为神经塑性变化的标志的方法（前后 MBSR）在整个大脑的恐惧扩展学习期间进行试验，将分析集中在默认模式上 网络（DMN），额叶网络（FPN）和腹侧注意网络（VAN）。接下来，我们将检查性 MBSR引起的神经变化及其与临床GAD反应中性别差异的关系差异。 最后，我们将使用一种新颖的统计方法来探讨基线神经测量是否可以预测MBSR- 诱导的神经变化和减少临床症状，以识别可能的MBSR反应者。参与者会 在fMRI扫描仪中进行标准化的2天恐惧条件和扩展范式 MBSR或压力教育（SE）在端点和3个月随访中具有主要的临床结果。这项研究是 目标与NCCIH的PA-18-323保持一致：思想和身体方法的基础科学研究 通过研究MBSR的神经动作和性别差异的神经机制 （GAD），这是一种在基层保健中经常看到的普遍状况，以建立MBSR效率。这项研究会 通过时间和注意力控制干预部署严格的科学方法，以隔离MBSR 机械影响对情绪调节和临床反应涉及的大脑区域的影响。独特 对经典焦虑条件的关注与既定情绪的困难的结合隐含 靶神经元电路，以前证明了MBSR效率，并且具有严格的fMRI行为的性别差异 新型分析方法的问题应该提供有关MBSR机制和性别的主要新见解 考虑因素，朝着可以指导未来治疗发展研究的精确医学迈进。