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

高频重复经颅磁刺激左侧背外侧前额叶皮质(DlPFC) 是FDA批准用于治疗严重抑郁症的药物。左侧通常以rTMS为目标的dlPFC站点是 坐在一个完整的高级认知(即执行功能)完整的皮质区域。少年派有 证明在认知任务中，左侧dlpfc区域通常处于低激活状态。 神经精神障碍。因此，认知能力的改善已被报告为对 RTMS治疗，rTMS改善轻至中度认知障碍的认知。 我们提出，因为rTMS to dlPFC针对的是适应性认知所必需的认知神经回路。 使用rTMS可以更精确地优化该网络中的功能，促进神经可塑性，以改进 跨心理社会领域和跨神经精神病学表现的生活质量。我们假定 通过使用rTMS上调认知控制回路，个体将拥有增强的能力 为了成功应对日常生活中不断变化的突发事件，2)提高了调控能力 侵扰性的情感和冲动。作为这些过程的函数，预计个人经历的减少 心理社会障碍。因此，我们建议，与其以特定的症状减少为目标，不如 在精神障碍的情况下，rTMS可用于增强心理社会功能的疗效。这种方法具有 有可能加强更多患有一系列神经精神疾病的退伍军人的康复。 RTMS的一个疗程通常包括大约30-40分钟的高频(即10赫兹)。 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，并会减少遵从性。 最近，联合调查员马克·乔治、医学博士和他的同事们证明，提供多次高剂量 在连续三天中的每一天与退伍军人进行会谈是安全、可行的，并提示快速 抗抑郁作用。这些患者在三天内接受的等量剂量(即脉冲总数) 传统的4到6周的课程。我们建议建立一个有效的加速协议 在1周内交付将大大增加在退伍军人管理局医疗保健系统中实施的可能性。 此外，加快rtms的疗程，提高各种障碍的心理社会功能，将 成为退伍军人管理局医疗保健系统中已经采用的其他康复模式的现成附属工具，包括 药物疗法和认知行为疗法以及职业和物理疗法。 鉴于利用加速rtms减少心理社会功能损害的目标，至关重要的是 建立相关的剂量-反应曲线，作为为这项工作奠定基础的第一步。之前 RTMS研究依赖于合理的决策树来确定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 努力将用于抑郁症的常规rTMS剂量(即，总共54,000次脉冲)适合于截断时间 句号。我们认为，螺旋机制是经验性地确定剂量-效应曲线的理想方法。 具体为加速rTMS至左侧dlPFC，以改善心理社会功能障碍。 在目前的研究中，我们建议将退伍军人[(n=40)]的跨诊断样本随机分为中度到 严重的社会心理障碍。参与者将随机接受10种不同剂量的加速rTMS。 在这项先导研究中，对于不同剂量的适当随机化，参与者将被限制为 符合焦虑和/或抑郁障碍的标准。尖端的基于神经导航的目标定位 行结构磁共振检查，确保左侧dlPFC的个体化放置。总而言之，我们建议 通过以下方式创新退伍军人护理：1)实施为期1周的加速rTMS方案；2) 建立剂量-反应曲线；3)优化治疗，提高诊断率 心理社会功能。

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.