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

基本信息

批准号：
10525806
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
项目类别：
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/10525806
关键词：
Action Potentials Adult Affect Aftercare Anatomy Area Behavior Behavioral Biological Markers Brain Chemosensitization Chronic Clinical Clinical Trials Cognition 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 Testing Therapeutic Time Transcranial magnetic stimulation Treatment outcome United States Work approach avoidance behavior base 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 circuit neuroregulation novel personalized approach personalized medicine placebo controlled study precision medicine programs prototype reduce symptoms relating to nervous system repetitive transcranial magnetic stimulation skills spatiotemporal success

项目摘要

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.

项目概要抑郁症在现代社会中越来越普遍。临床抑郁症是导致抑郁症的主要原因全球范围内的残疾，也是美国三分之二的自杀企图的潜在病症。精确神经调节，特别是经颅磁刺激（TMS）有望成为一种独特的技术抑郁症的治疗方法。 TMS 可产生良好控制的磁场，从而感应出焦点电场大脑中的场，可以引起神经元的动作电位。 Rhythmic TMS 已获得 FDA 批准用于主要治疗领域抑郁症、强迫症和尼古丁成瘾。新颖的 TMS 协议，例如间歇性θ突发刺激（TBS）可以快速诱导神经回路的持久增强。 2019年，TBS 在证明三分钟的 TBS 课程同样有效后，FDA 批准其治疗抑郁症相当于 40 分钟的传统节律性 TMS。尽管取得了初步成功，TMS 和 TBS 仍面临重大挑战个体间和个体内的结果仍然存在持续的变异性。这可能是由于目前有限时空精度和缺乏个性化。在这里，我建议开发和验证时空精确的个性化 TBS，专为治疗沮丧。为此，我将创建一个闭环 TBS-EEG 系统，通过利用个体结构磁共振成像，用于神经导航和实时时间精度脑电图（EEG）。使用神经导航，我将补偿已知的个体间差异前额叶解剖结构并聚焦于先前发现的最佳 TMS 目标的 DLPFC 个体中心处于抑郁状态。持续的脑电图将告知系统有关前额皮质的兴奋/抑制状态，正如大脑振荡所反映的那样，在最兴奋的时间触发刺激脉冲。进一步我会改进通过标记与抑郁行为有关的个体前额叶脑振荡来提高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 gamma 振荡是已知的生物标志物前额叶活动和抑郁症。从单独的 theta 和 gamma 频率，我将得出 TBS的个性化参数。最后，我将在健康人群中进行一项双盲、安慰剂对照研究人类和临床人群的可行性研究，以评估个性化 TBS 的长期效果脑电图对前额电生理学和抑郁行为的影响。所有这些共同努力将增强我们对前额叶回路机制的基本理解潜在的抑郁症并在精准医学中实现抑郁症的新型个性化治疗框架。