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.

抽象的 当前针对严重抑郁症的治疗策略是全球残疾的主要原因，留下超过 一半没有有意义治疗的患者。此R61/R33提案是根据 NIMH战略目标3.1“基于基因组学，神经科学的发现，制定新的干预措施 和行为科学。 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 基于此状态的动态调节任务刺激（在“闭环”中），而不是标准方法 通过单独的量规传达反馈，该规格跟踪在感兴趣的局部区域中的激活。 此R61/R33的总体目标是测试闭环实时fMRI Neurofeackback是否 特别针对我们假设的抑郁症注意机制（即神经持久性负面 状态）减轻了抑郁症的严重程度。这项研究将是实时fMRI效应的首次剂量调查测试 负关注偏见。 在R61阶段60期参与者中，年龄18-65岁的参与者将随机分配给 主动神经反馈（n = 30）vs假反馈（n = 30）。我们有三个目标：1）建立神经靶标 在活动与假手术中的神经验证前使用验证前变化的参与度变化 神经反馈； 2）确定减少阴性神经侵犯所需的最低训练的“剂量” 国家3）（探索性）在负面图像上建立行为目标参与 眼目视觉任务比较主动与假神经反馈。 R61的GO/NO-GO标准：神经持久性至少有中等效应大小（Cohen'sD≥0.4） 比较真实NF的还原。我们的试点研究（Mennen等人20）发现效应大小为0.83。所以 该标准在临床上有意义且现实，并且将展示目标参与。 在R33阶段80期参与者中，年龄在18-65岁的参与者将随机分配给主动治疗 神经反馈（n = 40）vs假反馈（n = 40）。我们有三个目标：1）进行随机控制 试验（RCT）比较实时神经反馈与假对抑郁症结果的影响； 2）确定 在R61阶段建立的神经植物标记与降低 抑郁症状； 3）通过比较MADRS得分来确定治疗效果的耐用性 与假NF相比，在收到真实的人之间进行了3个月的随访。 影响。该项目将建立实时fMRI神经反馈，以减少神经服务的手段 负状态作为MDD的治疗。这一研究的结果将为反馈策略提供信息，并 提高对负面关注和MDD的神经机制的理解。我们的基于云的平台 将很容易扩展，并允许将数千家医院和研究设施传播。