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

基本信息

批准号：
10450118
负责人：
Mohammed R Milad
金额：
$ 71.31万
依托单位：
NEW YORK UNIVERSITY SCHOOL OF MEDICINE
依托单位国家：
美国
项目类别：
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/10450118
关键词：
Adherence Affect Amygdaloid structure Animals Anxiety Attention Awareness Behavioral Brain Brain region Clinical Clinical effectiveness Conditioned Stimulus Coupling Cues Data Deductibles Diagnosis Education Emotional Emotions Exhibits Expectancy Extinction (Psychology)Fright Functional Magnetic Resonance Imaging Future Generalized Anxiety Disorder Hippocampus (Brain)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 Health 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 mindfulness-based stress reduction neural circuit neural network neurobiological mechanism neuroimaging neuromechanism novel precision medicine predictive modeling reduce symptoms relating to nervous system research and development response restoration rumination sex stress reduction success symptomatic improvement therapy development treatment response

项目摘要

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.

项目概要/摘要基于正念的减压（MBSR）已被证明对广泛性焦虑症有效（GAD），但迄今为止，关于其神经影像学研究仍然存在重大知识空白。主要关注MBSR对大脑结构和静息状态变化的影响，这些研究主要针对广泛性焦虑症的核心特征进行，例如沉思性忧虑、 MBSR 的成功是功能失调的情绪调节策略，增加了对未来威胁的偏见。与改善情绪调节、增强对当下时刻的注意力以及不评判性相关我们的主要目标是阐明驱动反应的神经机制。广泛性焦虑症 (GAD) 患者的 MBSR，并检查性别差异的程度 MBSR 反应中的性别差异可以解释这些机制的性别差异。 MBSR 增强了“自上而下”的学习和记忆能力，这些能力广泛并影响“自上而下”以及调节恐惧和情绪的“本能”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（腹内侧前额叶皮层 (vmPFC)、海马体和杏仁核）作为“本能”类型情绪调节的具体探针其次，我们将使用一种新颖的分析方法。检查大规模功能连接作为神经可塑性变化标记的方法（前和后） MBSR）在整个大脑的恐惧消退学习过程中进行逐次试验，重点分析默认模式接下来，我们将检查性别。 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，我们将使用一种新颖的统计方法来探索基线神经测量是否可以预测 MBSR- 神经诱发的变化和临床症状减轻，以确定可能的 MBSR 反应者。前后在功能磁共振成像扫描仪中进行标准化的 2 天恐惧调节和消退范例 MBSR 或压力教育 (SE) 以及本研究的终点和 3 个月随访的主要临床结果。目标与 NCCIH 的 PA-18-323 一致：身心方法的基础科学研究通过研究MBSR的神经作用机制以及广泛性焦虑症患者的性别差异 (GAD)，这是初级保健中常见的一种常见疾病，本研究将针对其确定 MBSR 的疗效。部署严格的科学方法，并进行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影响。对典型焦虑状况的关注与既定的情绪调节困难相结合目标神经回路、先前证明的 MBSR 功效以及严格的功能磁共振成像行为的性别差异采用新颖分析方法的探索应该提供关于 MBSR 机制和性别的重要新见解考虑因素，转向可以指导未来治疗开发研究的精准医学。