Targeting Functional Improvement in rTMS Therapy

rTMS 治疗以功能改善为目标

• 批准号: 10411904
• 负责人: ALLYSON C ROSEN
• 金额: --
• 依托单位: VETERANS ADMIN PALO ALTO HEALTH CARE SYS
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-05-01 至 2024-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10411904
• 关键词: Address; Adopted; Area; Autopsy; Brain; Brain region; Clinic; Clinical; Clinical Trials; Collaborations; Cranial Nerves; Data; Depressed mood; Diagnosis; Disease remission; Effectiveness; Electrodes; Electroencephalography; Emotional; Equipment; FDA approved; Face; Facial Muscles; Facial nerve structure; Functional Magnetic Resonance Imaging; Functional disorder; Head; Health Surveys; Histology; Individual; Lead; Left; Location; Magnetic Resonance Imaging; Major Depressive Disorder; Measurement; Measures; Mental Depression; Methods; Outcome; Outcome Study; Pain; Patient-Focused Outcomes; Patients; Pharmaceutical Preparations; Physiologic pulse; Prefrontal Cortex; Process; Psychotherapy; Publishing; Quality of life; Recovery; Reporting; Research Personnel; Resistance; Resolution; Rest; Sampling; Scalp structure; Severities; System; Testing; Therapeutic; Training; Training Programs; Transcranial magnetic stimulation; Treatment Failure; Validation; Veterans; Vision; World Health Organization Disability Assessment Schedule; alternative treatment; base; clinical practice; clinically significant; cognitive control; cost; depressed patient; detection limit; distraction; experimental study; feasibility testing; functional improvement; functional outcomes; image guided; improved; innovation; model development; psychosocial; repetitive transcranial magnetic stimulation; response; standard of care; targeted imaging; tool; virtual

Depressed patients inadequately responsive to medication and psychotherapy often live with serious difficulties in psychosocial functioning; thus, repetitive transcranial magnetic stimulation (rTMS) is an important, alternative, FDA approved therapy. During typical rTMS therapy, clinicians place a stimulation coil on the patient's scalp that focally modulates the underlying cortical areas. The left dorsolateral prefrontal cortex region (DLPFC) is the most established target for treating depression; however, clinicians miss this target in a third of patients and treatment fails, likely contributing to the relatively low remission rate of 31%. The reason for errors in targeting the DLPFC is that clinicians typically do not have access to MR image-guidance to identify the underlying brain regions they target. Instead they use the current standard-of-care method to identify the stimulation location that uses scalp landmarks and moves a fixed distance over the scalp. A new, promising alternative scalp targeting approach based on EEG electrode placement, the Beam F3 accurately targeted the DLPFC in 92% of Veterans from our pilot data (n=12). Our collaborator has adopted the Beam F3 as his clinical standard and showed improved depression severity and changes in associated functional Magnetic Resonance Imaging (fMRI) data. Other labs also, have indirect evidence that the Beam F3 scalp targeting approach places the rTMS stimulation coil near an fMRI identified optimal subregion within the DLPFC that involves control over emotional distraction and reactivity. The overall aim of the current proposal is to test the feasibility of accurately reaching this fMRI based optimal subregion using the Beam F3 scalp-based targeting approach. We further hypothesize that, since psychosocial functioning is related to cognitive control that accurate stimulation of this fMRI region could also lead to improved psychosocial functioning (i.e. reduced functional limitations and improved quality of life). Our plan is to collect fMRI and MRI's with markers identifying where clinicians place the Beam F3 location in depressed Veterans. Our strategy is to test whether the Beam F3 rule places the coil close enough (i.e. within the spatial resolution of rTMS) to reach an optimal DLPFC subregion in 95% of Veterans. In Aim 1 we propose to use image-guidance to test with high precision how accurately the Beam F3 targets this optimal, fMRI defined, brain region. In Aim 2 we demonstrate the accuracy of the Beam F3 in rTMS clinic patients where treaters typically deviate from scalp rules to accommodate patient comfort since frontal stimulation causes facial twitches and painful cranial nerve stimulation in some scalp locations. To address clinical importance of our choice of brain targets, in our clinic-based sample we will evaluate whether spatial deviations from the optimal brain target correlate with improvements in psychosocial functioning on a composite score of the World Health Organization Disability Assessment Schedule 2.0 and the Veterans RAND 12-item health survey of quality of life. We will perform several additional analyses on the acquired data. We will use precise image-guidance and directly compare in the same patients the accuracy of the Beam F3 scalp targeting to that of the clinical standard to provide clinicians with compelling evidence of which approach is more accurate. If we discover a systematic deviation in the Beam F3 rule, we can identify how to adapt it to improve accuracy. Results from this proposal will improve the implementation of rTMS therapy for depressed Veterans. We will disseminate our findings through our clinical rTMS VA training to improve targeting accuracy at VA clinics nationwide. Our vision is that this image-guidance approach to validation of scalp-based targets will serve as a model for the development of new brain-informed scalp targets and will guide innovative large scale clinical trials to study the relationship between brain predictors, changes, and clinically meaningful outcomes. The tools developed in this proposal can thus enable large-scale collaborations between VA rTMS clinics that can identify brain and scalp targets treat dysfunction in Veterans they find clinically meaningful.

对药物和心理治疗反应不足的抑郁症患者往往患有严重的抑郁症 心理社会功能困难；因此，重复经颅磁刺激（rTMS）是一种重要的、 FDA 批准的替代疗法。在典型的 rTMS 治疗过程中，临床医生将刺激线圈放置在 患者的头皮集中调节下面的皮质区域。左背外侧前额叶皮层区域 (DLPFC) 是治疗抑郁症最确定的目标；然而，临床医生有三分之一的时间未能实现这一目标 患者和治疗失败，可能导致缓解率相对较低（31%）。错误原因 针对 DLPFC 的一个缺点是临床医生通常无法使用 MR 图像指导来识别 DLPFC 他们瞄准的底层大脑区域。相反，他们使用当前的护理标准方法来识别 使用头皮标志并在头皮上移动固定距离的刺激位置。一个新的、有前途的 基于 EEG 电极放置的替代头皮定位方法，Beam F3 准确定位 根据我们的试点数据 (n=12)，92% 的退伍军人存在 DLPFC。我们的合作者已采用 Beam F3 作为他的 临床标准，并显示出抑郁症严重程度的改善和相关功能性磁力的变化 共振成像 (fMRI) 数据。其他实验室也有间接证据表明 Beam F3 头皮靶向 方法将 rTMS 刺激线圈放置在 DLPFC 内功能磁共振成像 (fMRI) 确定的最佳子区域附近，该子区域 涉及控制情绪分心和反应。当前提案的总体目标是测试 使用 Beam F3 基于头皮的定位准确到达基于功能磁共振成像的最佳子区域的可行性 方法。我们进一步假设，由于心理社会功能与认知控制有关， 对该功能磁共振成像区域的准确刺激也可能导致心理社会功能的改善（即减少 功能限制和生活质量提高）。我们的计划是收集带有识别标记的功能磁共振成像和磁共振成像 临床医生将 Beam F3 的位置放置在抑郁的退伍军人身上。我们的策略是测试 Beam 是否 F3 规则将线圈放置得足够近（即在 rTMS 的空间分辨率内）以达到最佳 DLPFC 95% 的退伍军人属于次区域。在目标 1 中，我们建议使用图像引导来高精度测试如何 Beam F3 准确地瞄准了 fMRI 定义的最佳大脑区域。在目标 2 中，我们展示了准确性 Beam F3 在 rTMS 诊所患者中的应用，治疗师通常会偏离头皮规则以适应 患者的舒适度，因为额部刺激会导致面部抽搐，并在某些情况下会导致痛苦的脑神经刺激 头皮位置。为了解决我们选择的大脑目标的临床重要性，在我们的临床样本中，我们将 评估最佳大脑目标的空间偏差是否与社会心理的改善相关 根据世界卫生组织残疾评估表 2.0 的综合评分进行运作，并且 退伍军人兰德 12 项生活质量健康调查。我们将进行一些额外的分析 获取的数据。我们将使用精确的图像引导并直接比较同一患者的准确性 Beam F3 头皮针对临床标准，为临床医生提供令人信服的证据 哪种方法更准确。如果我们发现 Beam F3 规则存在系统偏差，我们可以识别 如何调整它以提高准确性。该提案的结果将改善 rTMS 的实施 抑郁退伍军人的治疗。我们将通过临床 rTMS VA 培训传播我们的发现 提高全国 VA 诊所的定位准确性。我们的愿景是这种图像引导方法 基于头皮的目标的验证将作为开发新的大脑知情头皮目标的模型 并将指导创新的大规模临床试验，以研究大脑预测因子、变化、 和有临床意义的结果。因此，本提案中开发的工具可以实现大规模 VA rTMS 诊所之间的合作可以识别大脑和头皮目标，治疗退伍军人的功能障碍 他们发现具有临床意义。