Mechanistic circuit markers of transcranial magnetic stimulation outcomes in pharmacoresistant depression

耐药性抑郁症经颅磁刺激结果的机械回路标记

• 批准号: 10441148
• 负责人: Leanne Williams
• 金额: $ 65.77万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-09-10 至 2024-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10441148
• 关键词: Address; Adoption; Aftercare; Anterior; Antidepressive Agents; Attention; Back; Behavior; Behavioral; Biological Markers; Brain; Clinical; Clinical assessments; Cognitive; Diagnosis; Distal; Dose; Emotional; Emotions; Ensure; Evaluation; Feeling suicidal; Foundations; Functional disorder; Gold; Human; Impairment; Life; Measures; Mental Depression; Outcome; Patients; Performance; Pharmacotherapy; Prefrontal Cortex; Procedures; Process; Quality of life; Regulation; Resistance; Rest; Role; Sampling; Severities; Short-Term Memory; Standardization; Suicide; Suicide attempt; Symptoms; System; Transcranial magnetic stimulation; United States Department of Veterans Affairs; behavior measurement; biomarker-driven; cingulate cortex; clinical effect; clinical research site; cognitive control; depressed patient; depressive symptoms; design; disability; imaging biomarker; innovation; interest; longitudinal design; neuroimaging; neuroimaging marker; novel; predictive marker; programs; prospective; recruit; repetitive transcranial magnetic stimulation; response; response biomarker; standard care; standard of care; suicidal risk

! 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. !

！ 项目概要/摘要 尽管经颅磁刺激（rTMS，以下简称 TMS）已被广泛采用， 我们仍然缺乏机械驱动的生物标志物，旨在确定谁最有可能做出反应以及原因。 rTMS 适用于治疗耐药性抑郁症，我们迫切需要找到更精确的解决方案。 药物耐药性抑郁症患者可能会危及生命：自杀企图是自杀率的两倍 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 我们有一个新的机会通过 TMS 来实现这一目标。 对参加退伍军人管理局多项研究的 100 名患者的大脑网络生物标志物进行系统评估 现场临床 TMS 计划 通过利用伞形临床 rTMS 计划，我们可以标准化交付的内容。 确保一致性的参数。我们的主要生物标志物是认知控制的功能连接。 我们还将评估对思想和情绪调节至关重要的人脑网络。 相应的临床结果是症状严重程度、自杀倾向和生活质量。 经过 5 次 rTMS（“低剂量”）治疗后，将在基线时评估生物标志物，以探索早期的机制。 反应，并在 30 次治疗后完成（“更高剂量”）为研究提供动力。 预计保守效应大小至少为 0.25，我们将招募 100 名患者参与 VA 临床 TMS 计划。我们的目标是使用标准化刺激参数和统一的神经影像程序。 1) 探讨 rTMS 对促进认知控制的假定机制效应，并评估是否 认知控制网络的连接性以剂量依赖性方式变化，2）评估程度是否 认知控制网络连接性的变化预示着行为表现的相应变化 3) 确定基线功能连接和行为，以及连接和行为的早期变化 行为，预测症状严重程度、自杀意念和生活质量的后续结果。 我们的设计包括 1) 足够的能力来询问成像标记，2) 标准化以最大限度地减少 变异性，3) 实施纵向设计来量化成像标记物中与 rTMS 相关的变化，4) 任务诱发和静​​息状态成像标记的整合，以及 5) 奠定基础 吸取的经验教训可用于额外的诊断和扩展参数。 ！