Mechanistic circuit markers of transcranial magnetic stimulation outcomes in pharmacoresistant depression

好了！ 项目摘要/摘要 尽管重复经颅磁刺激(rTMS，以下简称TMS)被广泛采用， 我们仍然缺乏机械驱动的生物标记物来确定谁最有可能做出反应，以及为什么。 RTMS适用于耐药抑郁症。我们必须为这些问题找到更准确的解决方案 被给予耐药抑郁症的患者可能会危及生命：自杀未遂的比率是 非抵抗型抑郁症。我们的目标是使用前瞻性设计来评估认知控制网络 连接性作为重复经颅磁刺激临床效果的预测生物标志物，以及AS TMS反应改变的生物标志物。我们有一个新的机会通过一个 100名参加退伍军人管理的患者对脑网络生物标记物的系统评估 现场临床TMS计划。通过利用临床RTMS计划，我们可以标准化交付 参数以确保一致性。我们的主要生物标记物是认知控制的功能连接 人脑的网络，对思想和情绪的调节起着中心作用。我们还将评估 相应的行为表现。临床结果是症状严重程度、自杀倾向和生活质量。 生物标志物将在5次rTMS(“低剂量”)治疗后的基线上进行评估，以探索早期高血压的机制。 在30次疗程后完成治疗(“高剂量”)。为这项研究提供动力 预期保守效应大小至少为0.25，我们将招募100名参与VA临床的患者 TMS计划。使用标准化的刺激参数和协调的神经成像程序，我们的目标是 1)探索rTMS在促进认知控制方面可能的机制效应，并评估 认知控制网络的连通性以剂量依赖的方式改变，2)评估程度 认知控制网络连通性的变化预测行为表现的相应变化 以及，3)确定基线功能连通性和行为，以及连通性和 行为，预测随后的症状严重程度、自杀意念和生活质量的结果。创新 我们的设计包括1)足够的功率来询问成像标记，2)标准化以最小化 可变性，3)实施纵向设计以量化与rTMS相关的成像标志物的变化，4) 任务诱发和静息状态成像标记的集成，以及5)为 将吸取的经验教训扩展到其他诊断和参数。 好了！

! PROJECT SUMMARY/ABSTRACT Despite the wide scale adoption of repetitive transcranial magnetic stimulation (rTMS, hereafter simply TMS), we still lack mechanistically-driven biomarkers designed to identify who is most likely to respond, and why. rTMS is indicated for pharmacoresistant depression. It is imperative that we find more precise solutions for these patients given that pharmacoresistant depression can be life threatening: suicide attempts are twice the rate of non-resistant depression. Our objective is to use a prospective design to evaluate cognitive control network connectivity as a predictive biomarker of the clinical effect of repetitive transcranial magnetic stimulation, and as a response biomarker of change with TMS. We have a novel opportunity to address this objective through a systematic evaluation of brain network biomarkers in 100 patients taking part in a Veterans Administration multi- site clinical TMS program. By utilizing the umbrella Clinical rTMS Program, we can standardize delivered parameters to ensure uniformity. Our primary biomarker is functional connectivity of the cognitive control network of the human brain that is central to the regulation of thought and emotion. We will also assess corresponding behavioral performance. Clinical outcomes are symptom severity, suicidality, and quality of life. Biomarkers will be assessed at baseline, after 5 sessions of rTMS (“low dose”) to explore mechanisms of early response, and upon completion of treatment after 30 sessions (“higher dose”). To power the study for an anticipated conservative effect size of at least .25, we will recruit 100 patients participating in the VA Clinical TMS Program. Using standardized stimulation parameters and harmonized neuroimaging procedures, our aims are to 1) probe the putative mechanistic effect of rTMS on promoting cognitive control and to assess whether connectivity of the cognitive control network changes in a dose-dependent manner, 2) to assess whether extent of change in cognitive control network connectivity predicts corresponding change in behavioral performance and, 3) to identify if baseline functional connectivity and behavior, along with early change in connectivity and behavior, predict subsequent outcomes in symptom severity, suicidal ideation, and quality of life. Innovations of our design include 1) adequate power to interrogate imaging markers, 2) standardization to minimize variability, 3) implementation of a longitudinal design to quantify rTMS-related changes in imaging markers, 4) integration of task-evoked and resting state imaging markers and, and 5) establishing the foundations for expanding lessons learned to additional diagnoses and parameters. !