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: 10356604
• 负责人: YVETTE I SHELINE
• 金额: $ 82.2万
• 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 2023-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10356604
• 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; base; cloud based; cognitive control; depressive symptoms; design; disability; efficacy testing; experience; follow-up; gaze; improved; interest; neurofeedback; neuromechanism; relating to nervous system; 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 重度抑郁症是全球残疾的主要原因，目前的治疗策略还剩下超过 一半的患者没有任何有意义的治疗益处。该 R61/R33 提案是根据以下内容制定的。 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，即第一个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力状态和 基于此状态动态调节任务刺激（在“闭环”中），而不是标准方法 通过一个单独的仪表传达反馈，该仪表跟踪局部感兴趣区域的激活。 R61/R33 的总体目标是测试闭环实时 fMRI 神经反馈是否 专门针对我们的抑郁症注意力机制（即神经持续消极的 状态）降低抑郁症的严重程度这项研究将是第一个实时功能磁共振成像效果的剂量探索测试。 负面注意偏差。 在 R61 第 60 阶段期间，年龄为 18-65 岁的 MDD 参与者将被随机分配接受以下治疗： 主动神经反馈（n=30）与假反馈（n=30）我们有三个目标：1）建立神经目标。 使用主动与假动作中消极注意力状态的神经持久性的前后变化进行参与 神经反馈；2）确定减少神经持续负面情绪所需的最低训练“剂量” 3)（探索性）通过对负面形象的坚持来建立行为目标参与度 比较主动与假神经反馈的眼睛凝视任务。 R61 的通过/不通过标准：神经坚持至少有中等效应大小（Cohen d ≥ 0.4） 我们的初步研究（Mennen 等人 20）发现效果大小为 0.83。 该标准既具有临床意义又现实，并将证明目标参与度。 在 R33 第 80 阶段期间，年龄为 18-65 岁的 MDD 参与者将被随机分配接受积极治疗 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。 比较实时神经反馈与假手术对抑郁结果的影响的试验 (RCT) 2) 确定 R61 期建立的神经持久性标记物与神经持续性减少之间的关系 抑郁症状；以及 3) 通过比较 MADRS 评分来确定治疗效果的持久性 在 3 个月的随访中，将接受真实 NF 治疗的患者与接受假 NF 治疗的患者进行比较。 影响 该项目将建立实时功能磁共振成像神经反馈作为减少神经持久性的一种手段。 消极状态作为 MDD 的治疗方法，这方面的研究结果将为反馈策略和治疗提供信息。 提高对负面注意力和 MDD 背后神经机制的理解。 将易于扩展并允许传播到数千家医院和研究机构。