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.

抑郁症患者对药物和心理治疗的反应不足通常很严重 社会心理功能的困难；因此，重复的经颅磁刺激（RTMS）是重要的 替代方案，FDA批准的疗法。在典型的RTMS治疗期间，临床医生将刺激线圈放在 患者的头皮局部调节基础皮质区域。左侧外侧前额叶皮层区域 （DLPFC）是治疗抑郁症的最成熟的靶标；但是，临床医生错过了三分之一的目标 患者和治疗失败，可能导致相对较低的缓解率31％。错误的原因 在针对DLPFC时，临床医生通常无法访问MR图像识别来识别 他们针对的基础大脑区域。相反，他们使用当前的护理标准方法来识别 刺激位置使用头皮地标，并在头皮上移动固定距离。一个新的，有前途的 替代性头皮靶向方法基于EEG电极的放置，光束F3准确地针对 来自我们的试点数据中92％的退伍军人的DLPFC（n = 12）。我们的合作者采用了光束F3作为他的 临床标准，显示出改善的抑郁严重程度和相关功能磁的变化 共振成像（fMRI）数据。其他实验室也有间接证据表明梁F3头皮靶向 接近将RTMS刺激线圈放在fMRI附近，识别出DLPFC内的最佳子区域 涉及控制情绪干扰和反应性。当前建议的总体目的是测试 使用基于光束F3头皮的靶向准确达到此基于fMRI的最佳子区域的可行性 方法。我们进一步假设，由于社会心理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改善的社会心理功能（即减少 功能限制和改善的生活质量）。我们的计划是收集fMRI和MRI的标记，以识别 临床医生将光束F3位置放在压抑的退伍军人中。我们的策略是测试光束是否 F3规则将线圈放置足够近（即在RTM的空间分辨率内）以达到最佳DLPFC 95％的退伍军人中区域。在AIM 1中，我们建议使用图像指导以高精度测试 精确的梁F3靶向了这个最佳的fMRI定义的大脑区域。在AIM 2中，我们证明了准确性 RTMS诊所患者的束F3的横梁F3通常偏离头皮规则以适应 患者舒适，因为额叶刺激会导致面部抽搐和某些疼痛的颅神经刺激 头皮位置。为了解决我们选择大脑靶标的临床重要性，在我们的基于诊所的样本中，我们将 评估与最佳大脑目标的空间偏差是否与社会心理的改善相关 在世界卫生组织残疾评估附表2.0和 退伍军人兰德（Rand Rand）对生活质量的12项健康调查。我们将对 获得的数据。我们将使用精确的图像指导，并直接在同一患者中进行比较 梁F3头皮针对临床标准的靶向 哪种方法更准确。如果我们发现光束F3规则中的系统偏差，我们可以识别 如何调整它以提高准确性。该建议的结果将改善RTM的实施 沮丧的退伍军人治疗。我们将通过临床RTMS VA培训传播我们的发现 提高全国VA诊所的目标准确性。我们的愿景是这种图像指导方法 基于头皮的目标的验证将成为开发新脑膜化头皮目标的模型 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， 和临床上有意义的结果。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 他们发现临床上有意义。