Closing the loop: development of real-time, personalized brain stimulation

闭环：开发实时、个性化的大脑刺激

• 批准号: 10556323
• 负责人: Corey J Keller
• 金额: $ 39.13万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-09-18 至 2024-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10556323
• 关键词: Affect; Algorithms; American; Antidepressive Agents; Award; Bayesian learning; Biological Markers; Book Chapters; Brain; Brain Mapping; Clinical; Clinical Trials; Collaborations; Computer Models; Controlled Clinical Trials; Dedications; Department chair; Development; Discipline; Dose; Double-Blind Method; Electroencephalography; Engineering; Enrollment; Event; FDA approved; Frequencies; Goals; Grant; Health Services Accessibility; Human; Human Resources; Incubators; Individual; Institution; International; Intervention; Laboratories; Legal patent; Length; Maps; Measures; Mental Depression; Mental disorders; Mentors; Modality; Modeling; Monitor; Morphologic artifacts; Neurologist; Neurosurgeon; Obsessive-Compulsive Disorder; Outcome; Patients; Pattern; Physiologic pulse; Placebo Control; Placebos; Population; Positioning Attribute; Post-Traumatic Stress Disorders; Publications; Publishing; Reporting; Research; Residencies; Risk; Secure; Severities; Signal Transduction; Students; Supervision; System; Techniques; Testing; Time; Update; Work; Writing; biomarker development; brain based; brain circuitry; brain dysfunction; clinical predictors; depressed patient; design; diagnostic platform; effective therapy; improved; individualized medicine; innovation; instructor; journal article; lectures; neural network; neuroimaging marker; neuropsychiatric disorder; placebo controlled study; primary outcome; professor; randomized, clinical trials; real time monitoring; repetitive transcranial magnetic stimulation; response; side effect; substance use; tenure track; time use; tool; translational neuroscience; treatment optimization; treatment responders; treatment stratification

Project Summary We are in critical need of targeted and individualized treatments for mental health disorders, which affect nearly 50% of Americans during our lifetimes. Brain stimulation treatments, including repetitive transcranial magnetic stimulation (rTMS), represent the front-line of innovative approaches to correct dysfunctional brain networks for patients suffering from mental illness. rTMS is FDA-approved for depression and obsessive- compulsive disorder (OCD) with clinical trials underway for post-traumatic stress disorder (PTSD) and substance use, among others. However, as currently administered, rTMS lacks a biomarker to individually optimize treatment and thus suffers from a poor clinical response rate (<50%). Without personalization of rTMS, we risk a one-size-fits-all treatment for all psychiatric disorders, not dissimilar to how antidepressants are administered. Using simultaneous TMS and electroencephalography (TMS-EEG), I identified a depression severity biomarker from a double-blind randomized clinical trial treating depressed patients with one month of active or placebo rTMS. The degree of this biomarker change significantly predicted clinical improvement after rTMS treatment. Direct brain recordings further suggest that a single stimulation session is sufficient to modulate this biomarker, indicating that this brain-based biomarker can be monitored daily to support empiric treatment optimization. With this in mind, I propose to develop the first broadly generalizable platform for real-time biomarker monitoring (Aim #1) and personalized rTMS treatment (Aims #2 & 3). I will enroll 54 depressed patients to participate in a cross-over, placebo-controlled study directly comparing personalized, adaptive rTMS to standard rTMS. Primary outcome will be target engagement and dose-response of the depression severity biomarker. Successful implementation of this work includes the early stratification of treatment responders and personalized and more effective treatments for non-responders. This approach is broadly applicable to other depression biomarkers, all psychiatric populations treated with rTMS, and other brain stimulation modalities. More generally, my goals are to establish the fundamental principles of human brain plasticity and to construct platforms for rapid biomarker development, engagement, and integration into personalized brain stimulation treatments.

项目摘要 我们迫切需要对精神健康障碍进行有针对性和个性化的治疗，这些疾病会影响到 在我们有生之年，近50%的美国人。脑刺激治疗，包括重复经颅 磁刺激(RTMS)，代表了纠正大脑功能障碍的创新方法的前线 为精神疾病患者建立的网络。RTMS是FDA批准的治疗抑郁症和强迫症的药物 强迫症(OCD)创伤后应激障碍(PTSD)和物质的临床试验正在进行中 在其他方面，使用。然而，由于目前的管理，rTMS缺乏一个单独优化的生物标志物 治疗，因此临床应答率很低(50%)。如果不对RTMS进行个性化，我们将面临风险 一种适用于所有精神疾病的一刀切的治疗方法，与抗抑郁药的使用方式没有什么不同。 使用TMS和同步脑电(TMS-EEG)，我确定了抑郁症的严重程度 一项治疗抑郁症患者的双盲随机临床试验中的生物标记物 安慰剂rTMS。这一生物标志物的变化程度显著预示着rtms术后的临床改善。 治疗。直接的大脑记录进一步表明，一个单独的刺激阶段就足以调节这一点 生物标志物，表明这种基于大脑的生物标志物可以每天进行监测，以支持经验性治疗 优化。 考虑到这一点，我建议开发第一个可广泛推广的实时生物标记物平台 监测(目标1)和个性化rTMS治疗(目标2和3)。我将招募54名抑郁症患者参加 参与直接比较个性化、适应性rTMS与标准rTMS的交叉、安慰剂对照研究 RTMS。主要结果将是抑郁症严重程度生物标记物的靶点参与和剂量反应。 这项工作的成功实施包括对治疗应答者的早期分层和个性化 对无反应者进行更有效的治疗。这种方法广泛适用于其他抑郁症。 生物标志物，所有接受rTMS治疗的精神疾病人群，以及其他脑刺激方式。更广泛地说， 我的目标是建立人脑可塑性的基本原理，并为快速 生物标记物的开发、参与和整合到个性化脑刺激治疗中。