Developing a Novel rTMS Intervention for Transdiagnostic Psychosocial Rehabilitation: ADose-finding Study

开发一种用于跨诊断心理社会康复的新型 rTMS 干预措施：AD 剂量探索研究

• 批准号: 10336336
• 负责人: Lisa M McTeague
• 金额: --
• 依托单位: RALPH H JOHNSON VA MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-01-01 至 2023-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10336336
• 关键词: Adherence; Affect; Affective; Anxiety; Anxiety Disorders; Area; Borderline Personality Disorder; Brain; Caring; Clinical Research; Cognition; Cognitive; Cognitive Therapy; Decision Trees; Depressed mood; Depressive disorder; Disease; Doctor of Medicine; Dose; Emotional; Ensure; Equipment and supply inventories; FDA approved; Follow-Up Studies; Foundations; Frequencies; Functional disorder; Goals; Healthcare; Healthcare Systems; Impaired cognition; Impairment; Individual; Intervention; Investigation; Left; Life; Light; Magnetic Resonance Imaging; Major Depressive Disorder; Measures; Mental Depression; Mental disorders; Modality; Neurocognitive; Neuronal Plasticity; Neuronavigation; Occupational Therapy; Outcome; Pain; Participant; Patients; Pharmacotherapy; Physical therapy; Physiologic pulse; Pilot Projects; Post-Traumatic Stress Disorders; Prefrontal Cortex; Problem Solving; Process; Protocols documentation; Quality of life; Randomized; Regulation; Rehabilitation therapy; Reporting; Research Personnel; Sampling; Schedule; Secondary to; Site; Structure; Suggestion; Therapeutic; Time; Veterans; Work; antidepressant effect; anxious; base; brain circuitry; cognitive control; cognitive enhancement; cognitive function; cognitive task; craving; executive function; experience; flexibility; food restriction; functional disability; improved; innovation; meetings; neural circuit; neuropsychiatric disorder; neuropsychiatry; noninvasive brain stimulation; novel; psychosocial; psychosocial rehabilitation; reduce symptoms; repetitive transcranial magnetic stimulation; response; safety and feasibility; treatment optimization; treatment planning

High frequency repetitive transcranial magnetic stimulation (rTMS) to left dorsolateral prefrontal cortex (dlPFC) is FDA-approved for the treatment of major depression. The left dlPFC site typically targeted with rTMS is seated in an area of cortex integral to intact higher order cognition (i.e., executive function). The PI has demonstrated that this left dlPFC region is commonly hypoactivated during cognitive tasks across neuropsychiatric disorders. Accordingly, cognitive improvements have been reported as ancillary benefits to rTMS treatment and that rTMS improves cognition in mild to moderate cognitive impairment. We propose that because rTMS to dlPFC is targeting cognitive neurocircuitry integral to adaptive cognitive functioning, promoting neuroplasticity in this network with rTMS could be more precisely optimized to improve quality of life across psychosocial domains and across neuropsychiatric presentations. We postulate that through up-regulating cognitive control circuitry with rTMS that an individual would have 1) enhanced capacity for successfully contending with the shifting contingencies of daily life and 2) improved ability to regulate intrusive affect and impulses. As a function of these processes an individual is expected to experience reduced psychosocial impairment. Thus, we propose that rather than targeting specific symptom reductions in specific disorders, rTMS could be dosed for efficacy in enhancing psychosocial functioning. Such an approach has the potential to enhance rehabilitation for far more veterans suffering a range of neuropsychiatric conditions. A therapeutic course of rTMS typically consists of approximately 30-40 minutes of high-frequency (i.e., 10 Hz) treatment on each weekday, for 4 to 6 weeks. This schedule can be burdensome and reduce adherence. Recently, Co-investigator Mark George, M.D. and colleagues demonstrated that delivering multiple high-dose sessions to veterans on each of three consecutive days was safe, feasible, and suggestive of rapid antidepressant effects. These patients received in three days, the equivalent dose (i.e., total number of pulses) of a conventional 4- to 6-week course. We propose that establishing an efficacious accelerated protocol delivered within 1 week would greatly increase the likelihood of implementation in the VA healthcare system. Furthermore, an accelerated course of rTMS that enhances psychosocial functioning across disorders, would be a ready adjunct for other modalities of rehabilitation already utilized in the VA healthcare system including pharmacotherapy and cognitive-behavioral therapy as well as occupational and physical therapy. In light of the goal to utilize accelerated rTMS to reduce psychosocial functional impairment, it is essential to establish the associated dose-response curve as a first step in laying the foundation for this line of work. Prior rTMS investigations have relied upon rational decision trees in determining TMS dose, typically founded upon the rTMS outcomes for depression in non-veteran samples. For example, accelerated protocols have typically endeavored to fit the conventional rTMS dose for depression (i.e., 54,000 total pulses) into a truncated time period. We propose that the SPiRE mechanism is ideal for empirically determining the dose-response curve specific to accelerated rTMS to left dlPFC for improving psychosocial functional impairment. In the current study we propose to randomize a transdiagnostic sample of veterans [ (n=40) ] with moderate to severe psychosocial impairment. Participants would be randomized to 10 different doses of accelerated rTMS. For appropriate randomization across different doses in this pilot study, participants would be restricted to meeting criteria for an anxiety and/or depressive disorder. Cutting-edge neuronavigation-based targeting with structural MRI would be performed to ensure individualized placement at left dlPFC. In summary, we propose to innovate veteran care with this SPiRE proposal by 1) implementing a 1-week accelerated rTMS protocol, 2) establishing the dose-response curve, and 3) optimizing the treatment to enhance transdiagnostic psychosocial functioning.

对左背外侧前额皮质 (dlPFC) 进行高频重复经颅磁刺激 (rTMS) 经 FDA 批准用于治疗重度抑郁症。 rTMS 通常针对的左侧 dlPFC 位点是 位于大脑皮层的一个区域，该区域是完整的高阶认知（即执行功能）不可或缺的一部分。该PI有 研究表明，在认知任务期间，左侧 dlPFC 区域通常处于低激活状态。 神经精神疾病。因此，认知改善已被报道为辅助益处 rTMS 治疗以及 rTMS 可以改善轻度至中度认知障碍的认知。 我们认为，因为 rTMS 到 dlPFC 的目标是认知神经回路，是适应性认知的组成部分 功能，通过 rTMS 促进该网络的神经可塑性可以更精确地优化以改善 跨心理社会领域和跨神经精神病学表现的生活质量。我们假设 通过使用 rTMS 上调认知控制电路，个人将具有 1) 增强的能力 成功应对日常生活中不断变化的突发事件；2）提高调节能力 侵入性影响和冲动。作为这些过程的功能，个人预计会经历减少 心理社会障碍。因此，我们建议不要针对特定​​的特定症状减轻 对于疾病，rTMS 可以有效增强心理社会功能。这种方法具有 有潜力加强更多患有一系列神经精神疾病的退伍军人的康复。 rTMS 的治疗过程通常包括大约 30-40 分钟的高频（即 10 Hz） 每个工作日进行治疗，持续 4 至 6 周。这个时间表可能会很繁重并且会降低依从性。 最近，联合研究员马克·乔治医学博士及其同事证明，提供多次高剂量 连续三天的每一天为退伍军人提供的课程是安全、可行的，并且表明可以快速 抗抑郁作用。这些患者在三天内接受了等效剂量（即脉冲总数） 传统的 4 至 6 周课程。我们建议建立一个有效的加速方案 在 1 周内交付将大大增加在 VA 医疗保健系统中实施的可能性。 此外，rTMS 的加速过程可以增强跨疾病的心理社会功能， 成为 VA 医疗保健系统中已使用的其他康复方式的现成辅助手段，包括 药物治疗和认知行为治疗以及职业和物理治疗。 鉴于利用加速 rTMS 来减少社会心理功能障碍的目标，有必要 建立相关的剂量反应曲线，作为为这一工作奠定基础的第一步。事先的 rTMS 研究依赖于理性决策树来确定 TMS 剂量，通常基于 非退伍军人样本中抑郁症的 rTMS 结果。例如，加速协议通常具有 努力将治疗抑郁症的传统 rTMS 剂量（即 54,000 次总脉冲）纳入缩短的时间 时期。我们认为 SPiRE 机制非常适合凭经验确定剂量反应曲线 专门针对左 dlPFC 的加速 rTMS，以改善社会心理功能障碍。 在当前的研究中，我们建议对退伍军人 [ (n=40) ] 的跨诊断样本进行随机化，其中中等到 严重的社会心理障碍。参与者将被随机分配接受 10 种不同剂量的加速 rTMS。 为了在这项试点研究中对不同剂量进行适当的随机化，参与者将被限制 符合焦虑和/或抑郁症的标准。基于尖端神经导航的靶向 将进行结构 MRI 以确保左侧 dlPFC 的个性化放置。综上所述，我们建议 通过此 SPiRE 提案，通过 1) 实施为期 1 周的加速 rTMS 方案，2) 创新退伍军人护理 建立剂量反应曲线，3) 优化治疗以增强跨诊断 心理社会功能。