Reducing neural perseveration through closed loop real time fMRI neurofeedback to alleviate depressive symptoms

通过闭环实时功能磁共振成像神经反馈减少神经持久性，以缓解抑郁症状

• 批准号: 10539326
• 负责人: YVETTE I SHELINE
• 金额: $ 77.79万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-12-15 至 2024-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10539326
• 关键词: Age; Attention; Behavioral; Behavioral Sciences; Brain; Classification; Clinical; Depressed mood; Dose; Eye; Eye Movements; Face; Feedback; Functional Magnetic Resonance Imaging; Genomics; Hospitals; Image; Individual; Intervention; Major Depressive Disorder; Measures; Memory; Mental Depression; National Institute of Mental Health; Neurosciences; Outcome; Participant; Patients; Pattern; Persons; Phase; Pilot Projects; Probability; Procedures; Randomized; Randomized, Controlled Trials; Research; Severities; Source; Stimulus; Testing; Time; Training; attentional bias; cloud based; cognitive control; depressive symptoms; design; disability; efficacy testing; experience; follow-up; gaze; improved; interest; neural; neurofeedback; neuromechanism; research facility; response; rumination; selective attention; success; time use; treatment effect; treatment strategy

ABSTRACT Current treatment strategies for major depression, the leading cause of disability worldwide, leave more than half of patients with no meaningful treatment benefit. This R61/R33 proposal was developed in keeping with NIMH Strategic Objective 3.1 to “Develop new interventions based on discoveries in genomics, neuroscience and behavioral science.” We will test the efficacy of a new psychotherapeutic strategy, the first real-time fMRI neurofeedback therapy to use cloud-based pattern classification to decode the patient’s attentional state and dynamically modulate task stimuli (in a “closed loop”) based on this state, rather than the standard approach of conveying feedback through a separate gauge that tracks activation in a localized region of interest. The overall objective of this R61/R33 is to test whether closed-loop real-time fMRI neurofeedback that specifically targets our hypothesized attentional mechanism of depression (i.e., neural perseveration of negative states) reduces depression severity. This study will be the first dose-finding test of real-time fMRI effect on negative attention bias. During the R61 Phase 60 participants with MDD ages 18-65 years will be randomly assigned to treatment with active neurofeedback (n=30) vs sham feedback (n=30). We have three aims: 1) Establish neural target engagement using pre-post change in neural perseveration of negative attentional states in active vs sham neurofeedback; 2) Determine the lowest “dose” of training necessary to reduce neural perseveration of negative states; 3) (Exploratory) Establish behavioral target engagement using perseveration on negative images in an eye gaze task comparing active vs sham neurofeedback. Go/No-Go Criteria for R61: There will be at least a medium effect size (Cohen’s d ≥ 0.4) in neural perseveration reduction comparing real to sham NF. Our pilot study (Mennen et al 20) found an effect size of 0.83. Therefore this criterion is both clinically meaningful and realistic and will demonstrate target engagement. During the R33 Phase 80 participants with MDD ages 18-65 will be randomly assigned to treatment with active neurofeedback (n=40) vs sham feedback (n=40). We have three aims: 1) To conduct a randomized controlled trial (RCT) to compare the effect of real-time neurofeedback vs. sham on depression outcome; 2) To determine the relationship between the markers of neural perseveration established in the R61 phase and the reduction in depressive symptoms; and 3) To determine the durability of the treatment effect by comparing MADRS scores at 3 months followup between those who received real as compared to sham NF. Impact. This project will establish real-time fMRI neurofeedback as a means of reducing neural perseveration of negative states as a treatment for MDD. Results from this line of research will inform feedback strategies and improve understanding of neural mechanisms underlying negative attention and MDD. Our cloud based platform would be readily scalable and allow dissemination to thousands of hospital and research facilities.

摘要 重度抑郁症是全球残疾的主要原因，目前的治疗策略留下了超过 没有有效治疗的患者中有一半受益。本R61/R33提案是根据 NIMH战略目标3.1：根据基因组学、神经科学的发现，开发新的干预措施 和行为科学。“我们将测试一种新的心理治疗策略的有效性，第一种实时功能磁共振成像 神经反馈疗法使用基于云的模式分类来解码患者的注意状态和 基于此状态动态调整任务刺激(在“闭环”中)，而不是 通过单独的量规传递反馈，该量规跟踪感兴趣区域的激活情况。 此R61/R33的总体目标是测试闭环实时fMRI神经反馈是否 特别针对我们假设的抑郁症的注意机制(即，负性的神经坚持 减少抑郁症的严重程度。这项研究将是第一次实时功能磁共振成像效应的剂量发现测试 消极的注意偏向。 在R61阶段，年龄在18-65岁的60名患有MDD的参与者将被随机分配到 主动神经反馈(n=30)与假反馈(n=30)。我们的目标有三个：1)建立神经靶点 主动与假注意状态负性注意状态持续状态的投入度研究 神经反馈；2)确定减少负性神经坚持所需的最低训练剂量 状态；3)(探索性)通过对负面形象的坚持不懈来建立行为目标参与 眼神凝视任务：比较主动神经反馈和假神经反馈。 通过/不通过R61的标准：在神经持续性方面将至少有一个中等效应大小(科恩的d≥0.4) 减少真实与虚假的净额。我们的初步研究(Mennen等人20)发现效应大小为0.83。因此 这一标准既具有临床意义，又具有现实意义，并将证明目标参与。 在R33阶段80，年龄在18-65岁的MDD患者将被随机分配到Active 神经反馈(n=40)与假反馈(n=40)。我们有三个目标：1)进行随机对照 试验(RCT)比较实时神经反馈与假神经反馈对抑郁结局的影响；2)确定 R61期建立的神经持续性标记物与神经功能减退的关系 3)通过比较MADRS评分确定治疗效果的持久性 在接受REAL的患者和接受假的NF患者之间进行3个月的随访。 冲击力。该项目将建立实时功能磁共振神经反馈，作为减少神经持续性的一种手段。 阴性状态作为MDD的一种治疗方法。这一系列研究的结果将为反馈策略和 提高对负面注意力和多动症的神经机制的理解。我们基于云的平台 将很容易扩展，并允许传播到数千家医院和研究设施。