Personalized Closed-loop Theta Burst Stimulation for Treatment of Depression

个性化闭环 Theta 突发刺激治疗抑郁症

• 批准号: 10701017
• 负责人: Ivan Alekseichuk
• 金额: $ 10.61万
• 依托单位: UNIVERSITY OF MINNESOTA
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-09-08 至 2024-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10701017
• 关键词: Action Potentials; Adult; Affect; Aftercare; Anatomy; Area; Behavior; Behavioral; Biological Markers; Brain; Chemosensitization; Chronic; Clinical; Clinical Trials; Cognition; Compensation; Coupled; Coupling; Cross-Over Studies; Depressive disorder; Development; Double-Blind Method; Drug resistance; Electroencephalography; Electrophysiology (science); Equilibrium; FDA approved; Feasibility Studies; Frequencies; Functional disorder; Future; Goals; Hamilton Rating Scale for Depression; Human; Image; Individual; Intervention; Left; Life; Link; Magnetic Resonance Imaging; Major Depressive Disorder; Mental Depression; Mental disorders; Methods; Modernization; Motor; Neuronal Plasticity; Neuronavigation; Neurons; Nicotine Dependence; Obsessive-Compulsive Disorder; Outcome; Patients; Performance; Periodicity; Personal Satisfaction; Phase; Physiologic pulse; Population; Prefrontal Cortex; Protocols documentation; Randomized; Research; Research Personnel; Role; Societies; Specificity; Suicide attempt; Symptoms; System; Technology; Testing; Therapeutic; Time; Transcranial magnetic stimulation; Treatment outcome; United States; Work; avoidance behavior; career; cognitive testing; depressive behavior; depressive symptoms; disability; electric field; experimental study; feasibility trial; improved; improved outcome; individual variation; individualized medicine; insight; inter-individual variation; magnetic field; neural; neural circuit; neuroregulation; novel; personalized approach; personalized medicine; placebo controlled study; precision medicine; programs; prototype; reduce symptoms; repetitive transcranial magnetic stimulation; skills; spatial integration; spatiotemporal; success

PROJECT SUMMARY Depressive disorders are increasingly prevalent in modern societies. Clinical depression is the leading cause of disability worldwide and an underlying condition for two-thirds of suicidal attempts in the United States. Precision neuromodulation and particularly transcranial magnetic stimulation (TMS) promise a unique technological approach to the therapy of depression. TMS creates a well-controlled magnetic field that induces a focal electric field in the brain and can elicit action potentials in neurons. Rhythmic TMS is already FDA-approved for major depressive disorder, obsessive-compulsive disorder, and nicotine addiction. Novel TMS protocols such as intermittent theta-burst stimulation (TBS) can rapidly induce lasting potentiation of neural circuits. In 2019, TBS was FDA-approved for depression after it was demonstrated that a three-minute TBS session was as effective as 40 minutes of conventional rhythmic TMS. Despite their initial success, a major challenge for TMS and TBS remains a persistent inter- and intra-individual variability of outcomes. This is likely due to currently limited spatiotemporal precision and lack of personalization. Here, I propose to develop and validate spatiotemporally precise personalized TBS tailored for the therapy of depression. For that, I will create a closed-loop TBS-EEG system that integrates spatial precision by leveraging individual structural magnetic resonance imaging for neuronavigation and temporal precision due to real-time electroencephalography (EEG). Using neuronavigation, I will compensate for known inter-individual variability in the prefrontal anatomy and focus the individual center of DLPFC previously found to be an optimal TMS target in depression. Ongoing EEG will inform the system about the excitatory/inhibitory states of the prefrontal cortex, as reflected in the brain oscillations, to trigger stimulation pulses at the most excitable time. Further, I will improve the functional precision by tagging the individual prefrontal brain oscillations implicated in depressive behavior using EEG during a validated cognitive test. In particular, theta and gamma oscillations are known biomarkers of prefrontal activity and depressive disorders. From the individual theta and gamma frequencies, I will derive the personalized parameters of TBS. Finally, I will conduct a double-blinded, placebo-controlled study in healthy humans and a feasibility study in a clinical population to assess the long-lasting effects of the personalized TBS- EEG on prefrontal electrophysiology and depressive behavior. All these combined efforts will enhance our fundamental understanding of the prefrontal circuitry mechanisms underlying depression and enable novel personalized therapy of depression within the precision-medicine framework.

项目摘要 在现代社会中，抑郁症越来越普遍。临床抑郁是主要原因 在全球范围内的残疾和三分之二的自杀企图的潜在状况。精确 神经调节，特别是经颅磁刺激（TMS）有望独特的技术 抑郁症治疗的方法。 TMS创建一个控制良好的磁场，可引起局灶性电气 大脑中的田地，可以在神经元中发挥作用潜力。有节奏的TMS已被FDA批准为主要 抑郁症，强迫症和尼古丁成瘾。新颖的TMS协议，例如 间歇性theta-burst刺激（TBS）可以迅速诱导神经回路的持久增强。 2019年，TBS 在证明三分钟的TBS疗程中，FDA批准为抑郁症 作为常规节奏的TMS 40分钟。尽管他们最初的成功，但对TMS和TBS来说是一个重大挑战 仍然是结果的持续性和个体内部变异性。这可能是由于目前有限的 时空精度和缺乏个性化。 在这里，我建议开发和验证针对治疗的时空精确的个性化TBS 沮丧。为此，我将创建一个闭环TBS-EEG系统，该系统通过利用来集成空间精度 由于实时而引起的，用于神经量和时间精度的个体结构磁共振成像 脑电图（EEG）。使用神经元活动，我将弥补已知的个体间变异性 前额叶解剖结构和集中于先前发现的DLPFC的单个中心是最佳的TMS目标 在抑郁症中。正在进行的脑电图将告知系统有关前额叶皮层的兴奋性/抑制状态， 如大脑振荡中所反映的，以在最兴奋的时期触发刺激脉冲。此外，我将改进 通过标记单个前额叶脑振荡与抑郁行为有关的功能精度 在经过验证的认知测试中使用脑电图。特别是，theta和γ振荡是已知的生物标志物 前额叶活动和抑郁症。从单个theta和伽马频率中，我将得出 TBS的个性化参数。最后，我将在健康中进行双盲，安慰剂对照研究 人类和对临床人群的可行性研究，以评估个性化TBS-的长期影响 脑电图前额叶电生理学和抑郁行为。 所有这些综合努力将增强我们对前额叶电路机制的基本理解 抑郁症的基本抑郁症并启用精密中等抑郁症的新型个性化治疗 框架。