Frequency and E-field Enhancement of iTBS for Depression (FREED)

iTBS 的频率和电场增强治疗抑郁症（免费）

• 批准号: 10645423
• 负责人: Zafiris J. Daskalakis
• 金额: $ 80.42万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN DIEGO
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-07-01 至 2025-04-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10645423
• 关键词: Anatomy; Biological; Brain; Clinical; Clinical Trials; Clinical assessments; Coupled; Coupling; Data; Diagnosis; Disease; Disease remission; Dose; Double-Blind Method; Effectiveness; Electroencephalography; Ensure; Frequencies; Goals; Individual; Investigation; Left; Link; Location; Major Depressive Disorder; Measures; Mental Depression; Methods; Modeling; Moods; Neuronal Plasticity; Outcome; Parietal; Patients; Pattern; Performance; Phase; Physiologic pulse; Population; Prefrontal Cortex; Randomized; Randomized, Controlled Trials; Reporting; Research; Resistance; Rest; Safety; Severities; Short-Term Memory; Site; Testing; Time; Treatment Cost; Treatment Efficacy; arm; clinical efficacy; clinical practice; cognitive function; comparative efficacy; cost effectiveness; depressive symptoms; effective therapy; electric field; improved; individual patient; individualized medicine; interest; neuroimaging; novel; novel strategies; programs; repetitive transcranial magnetic stimulation; response; societal costs; symptomatic improvement; treatment response; treatment-resistant depression; trial comparing

Abstract Treatment resistant depression (TRD) is present in about 2.5 percent of the population and is associated with considerable personal suffering and societal costs. Repetitive transcranial magnetic stimulation (rTMS) is a safe and effective treatment for TRD that is increasingly being used in clinical practice across the world. However, while there is convincing evidence for the effectiveness of rTMS treatment, the overall remission rate achieved in patients is typically considerably less than 50%. Coupled with the fact that a course of rTMS takes considerable time to administer (up to 6 weeks), this limited efficacy substantially impacts clinical utility. Intermittent theta burst stimulation (iTBS) is a new form of TMS that involves the patterned application of stimulation pulses in both the theta and gamma frequencies. iTBS has recently been shown to be non-inferior to standard rTMS but can be applied in a dramatically shorter time, typically three minutes per day compared to 20-40 minutes. However, the use of iTBS has not been shown to enhance overall treatment efficacy compared to rTMS. Several methods are under investigation to try to improve the efficacy of iTBS treatment, in part through the individualization of treatment parameters. In this study, individualization of iTBS will include frequency and location optimization. Frequency individualization involves stimulating at each patient’s endogenous brain rhythms derived from theta- gamma coupling during a working memory task. Our findings suggest that such frequency individualization of iTBS produces greater effects on neuroplasticity, cognitive function, and mood enhancement in healthy subjects. Next, we have developed methods to individualize coil placement using electric field (E-field) modelling to limit anatomic variability and maximize dosing for each patient. We will aim to individually target the TMS e-field to a specific cortical region corresponding to Talairach coordinate (–45, 45, 35) in the left dorsolateral prefrontal cortex (DLPFC). We also previously reported that targeting this region with rTMS produces superior efficacy compared to conventional targeting. We now propose to undertake a 2-phase program to determine if individualized iTBS based on frequency and E-field modelling will enhance its efficacy in patients with TRD. In the R61 phase of this application, we will test if this novel approach produces target engagement by randomizing 75 patients with TRD to a course of frequency and location individualized iTBS, location individualized iTBS only, or standard iTBS stimulation. We aim to establish whether individualized frequency/location iTBS produces a greater change in theta connectivity as a demonstration of its capacity to alter activity in relevant frontal–parietal circuitry. If this is established, we will have achieved our go-criterion and will request to proceed with the three- year R33 phase. During this phase, we will conduct a larger scale randomized controlled trial comparing individualized frequency/location iTBS to standard iTBS in 144 patients with TRD and compare the effects on both target engagement (fronto-parietal theta connectivity) and clinical outcomes (depression severity). The overall goal of this research is to develop a more effective form of iTBS treatment for patients with TRD.

抽象的 抗治疗抑郁症（TRD）大约2.5％的人口呈现 巨大的个人痛苦和社会成本。重复的经颅磁刺激（RTMS）是安全的 以及越来越多地用于全球临床实践中的TRD治疗。然而， 尽管有令人信服的证据证明RTMS治疗的有效性，但总体缓解率达到了 通常认为患者小于50％。再加上RTM的课程需要相当多的事实 该有限的有限有效地影响了临床公用事业，该有限的有限有限。间歇性theta爆发 刺激（ITB）是一种新的TMS theta和伽马频率。最近已显示ITB不属于标准RTM，但可以是 在动态较短的时间内应用，通常每天三分钟，而20-40分钟。但是， 与RTMS相比，ITB的使用尚未显示可提高总体治疗效率。几种方法是 投资不足以试图提高ITBS治疗的效率，部分通过 治疗参数。在这项研究中，ITB的个性化将包括频率和位置优化。 频率个性化涉及刺激每个患者的内源性脑节律，这些脑部节律源自theta- 在工作记忆任务中伽马耦合。我们的发现表明，这种频率个性化的 ITB对健康受试者的神经可塑性，认知功能和情绪增强产生更大的影响。 接下来，我们开发了使用电场（E-Field）建模来限制线圈放置的方法 解剖学变异性并最大化每个患者的给药。我们将旨在将TMS单独定位为 对应于左下角前额叶的特定下士区域（–45，45，35） 皮质（DLPFC）。我们先前还报道说，用RTMS靶向该区域会产生较高的效率 与常规靶向相比。我们现在建议进行2阶段计划，以确定是否是否 基于频率和电子场建模的个性化ITB将提高其在TRD患者中的效率。在 该应用程序的R61阶段，我们将测试这种新颖的方法是否通过随机化产生目标参与 有75例TRD的患者到频率和位置个性化的ITB，仅位置个性化ITB， 或标准ITB刺激。我们旨在确定个性化的频率/位置ITB是否会产生 theta连接性的更大变化，以证明其改变相关额叶活动活动的能力 电路。如果建立了这一点，我们将实现我们的措施，并要求进行三个 R33年期。在此阶段，我们将进行大规模的随机对照试验，以比较 144例TRD患者的个性化频率/位置ITB与标准ITB的标准ITB，并比较对 目标参与（额叶 - 顶theta连接性）和临床结果（抑郁严重程度）。这 这项研究的总体目标是为TRD患者开发一种更有效的ITB治疗形式。