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 抗治疗抑制（TRD）大约有2.5％的人口，并且与与之相关。 大量的个人痛苦和社会成本。 以及在世界各地的临床医院中越来越多地用于TRD的有效治疗。 尽管有说服力证明RTMS治疗的有效性，但总体改建率却很疼痛 在患者中，通常少于50％。 该有限的疗效对管理（最多6周）的时间影响了临床公用事业 刺激（ITB）是TMS的一种新形式，它涉及两个故事中刺激脉冲的光顾。 theta和伽马频率最近是不属于标准RTM的 在急剧短的时间内使用，通常每天三分钟，而20-40分钟。 与RTM相比，ITB的使用尚未显示出增强总体治疗效率 正在研究以试图提高ITBS治疗的疗效，部分原因是个性化 治疗参数。 频率个性化涉及刺激每个患者的内源性脑部节律，这些节奏源自theta- 在工作记忆任务中伽马耦合。 ITB对健康受试者的神经塑料，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 解剖学变异性和最大化的剂量。 特定的皮质区域与Talairach坐标相关（–45，45，35） Cortex（DLPFC）。 与传统的目标相比 基于自由质量和E-Field模型的个性化ITB在IN IN中具有增强性 该应用程序的R61阶段，我们将测试本新颖的批准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， 或标准的ITB刺激。 theta连接的更大变化是一种capace的证明，以改变相关额叶的活动的活动 电路。 R33年阶段。 144例TRD患者的标准ITB的个性化免费物 两者都靶向英语（额叶theta的连接）和临床成果（抑郁严重程度） 该研究的总体目标是开发一种更有效的ITB处理形式，以使用TRD使用特定性。