Evaluating a Novel Method to Determine the rTMS Dose Needed for Treating Depression After Spinal Cord Injury

抑郁症是世界范围内导致残疾的主要原因，也是最常见的神经精神疾病之一 脊髓损伤(SCI)后。脊髓损伤后抑郁的负担是显著的，因为它与更高的 成本较低，生活质量较低，生存时间较短。治疗抑郁症可能很复杂，但它是至关重要的。 重复经颅磁刺激(RTMS)是FDA批准的一种非侵入性脑刺激 在整个退伍军人事务部(VA)健康系统中使用的抑郁症治疗选项。然而，没有 已发表的研究已经检验了rTMS治疗脊髓损伤后抑郁的有效性。最新的临床资料 脊髓医学精神卫生疾病管理实践指南(2020) 美国瘫痪退伍军人会明确建议，未来的研究应检查脊髓损伤人群中的rTMS。 应用rTMS治疗脊髓损伤后抑郁的关键挑战是剂量。目前，休眠马达 阈值是右侧拇短展肌的运动反应，用于给rTMS剂量。超过一半的SCI 人群有不完全或完全四肢瘫痪，表明上肢[(UE)]有一定程度的损害。 因此，如果使用目前的rTMS剂量参数，似乎可以得出结论，超过一半的脊髓损伤人群可以 被排除在接受rTMS治疗抑郁症的范围之外，或可能接受不适当的剂量，影响干预的 安全性和有效性。[这项研究专门针对目前治疗抑郁症后抑郁的局限性 使用rTMS的SCI将：(1)识别rTMS的目标电场(e-field)；(2)评价一部小说 反向计算电磁场模型确定rTMS治疗抑郁症剂量的方法 脊髓损伤患者；(3)使用反向计算电磁场模型进行试点临床试验，以剂量 治疗脊髓损伤后抑郁的rTMS；(4)为申请者提供适当的培训环境 发展成为独立的退伍军人研究人员；以及(5)生成必要的试点数据，以支持未来 退伍军人荣誉奖申请。]电场建模是考虑TMS线圈类型的计算模型， 电路和位置，通过T1和T2加权磁共振图像获得的个体解剖， 组织类型之间的电导率差异。[首先，使用现有的试验数据，将使用e-field建模来 确定rTMS治疗抑郁症的目标电场剂量。]接下来，24名患有脊髓损伤和 抑郁症将随机接受为期6周的rTMS治疗，剂量使用反向计算e- 现场造模(n=18)或假处理(n=6)。我们将检查治疗的组间效应 用汉密尔顿抑郁量表评定抑郁症状。反算确定的剂量 电场模拟将与FDA批准的参数结合使用：3,000个脉冲/疗程，10赫兹，5 每周6天，共6周。研究结果将包括抑郁症状、生活质量[(QOL)]、 和参与度。在奖励期间，申请者将利用拉尔夫基金会提供的资源。 约翰逊退伍军人医学中心及其附属学术机构，南卡罗来纳医科大学。一 主要的例子是国家神经调节康复中心(NIH P2 CHD086844)。通过利用 这些资源和来自当地知名专家的实践培训，申请者的目标是开发必要的 具备数据采集、分析和解释神经生物学变量、成像、 和电磁场建模。这个CDA-2应用程序的总体目标是将候选人暴露给一个富有的本地 为脊髓损伤恢复研究提供环境，为发展成为独立的退伍军人管理局提供基础 研究人员研究脊髓损伤后抑郁的疗效和可行的治疗方案以改善 退伍军人的生活和康复结果。拟议的培训计划将提高候选人的 了解神经调节、神经精神障碍以及神经康复的设计和实施 审判。所产生的数据将为开发专注于神经调节的其他干预措施提供信息 改善脊髓损伤患者和其他UE运动障碍患者的功能和生活质量。

Depression is a leading cause of disability worldwide and is one of the most prevalent neuropsychiatric disorders following spinal cord injury (SCI). The burden of depression post-SCI is significant, as it is associated with higher cost, lower quality of life, and shorter survival time. Treating depression can be complicated, but it is vital. Repetitive transcranial magnetic stimulation (rTMS), a type of non-invasive brain stimulation, is an FDA-approved treatment option for depression that is utilized throughout the Veterans Affairs (VA) health system. However, no published studies have examined the effectiveness of rTMS for depression post-SCI. The updated Clinical Practice Guidelines for Spinal Cord Medicine for the Management of Mental Health Disorders (2020) by the Paralyzed Veterans of America recommends explicitly that future research examines rTMS in the SCI population. The critical challenge of administering rTMS for depression post-SCI is dosing. Currently, the resting motor threshold, a motor response of the right abductor pollicis brevis, is used to dose rTMS. Over half of the SCI population has incomplete or complete tetraplegia, indicating some degree of upper extremity [(UE)] impairment. Thus, if using current rTMS dosing parameters, it is plausible to conclude that over half the SCI population could be excluded from receiving rTMS for depression or may receive an improper dose, impacting the intervention's safety and effectiveness. [This study specifically addresses current limitations in treating depression post- SCI using rTMS and will: (1) identify the target electric-field (e-field) for rTMS; (2) evaluate a novel method, reverse-calculation e-field modeling, to determine the rTMS dose to treat depression in individuals with SCI; (3) conduct a pilot clinical trial using reverse-calculation e-field modeling to dose rTMS for depression post-SCI; (4) provide the appropriate training environment for the applicant to develop into an independent VA researcher; and (5) generate the necessary pilot data to support a future VA Merit Award application.] E-field modeling is a computational model that accounts for the TMS coil type, circuitry and placement, individual anatomy obtained through T1 and T2- weighted magnetic resonance images, and conductivity variance between tissue types. [First, using existing trial data, e-field modeling will be used to determine the target e-field dose for treating depression with rTMS.] Next, twenty-four individuals with SCI and depression will be randomized to receive either 6-weeks of rTMS treatment dosed using reverse-calculation e- field modeling (n=18) or sham treatment (n=6). We will examine the between-group effects of treatment on depressive symptoms using the Hamilton Rating Scale for Depression. The dose identified by reverse-calculation e-field modeling will be used in combination with FDA-approved parameters: 3,000 pulses/session at 10 Hz, 5 days/week for 6 weeks. Study outcomes will include changes in depressive symptoms, quality of life [(QOL)], and participation. During the award period, the applicant will capitalize on resources available through the Ralph H. Johnson VA Medical Center and its affiliated academic institution, Medical University of South Carolina. One primary example is the National Center for Neuromodulation for Rehabilitation (NIH P2 CHD086844). By utilizing these resources and hands-on training from renowned local experts, the applicant aims to develop the requisite skills and understanding of data acquisition, analysis, and interpretation of neurobiological variables, imaging, and e-field modeling. The overall goal of this CDA-2 application is to expose the candidate to a rich local environment for SCI recovery research, providing the foundation for developing into an independent VA researcher studying the effects of and viable treatment options for depression post-SCI to improve the lives and rehabilitation outcomes of Veterans. The proposed training plan will enhance the candidate's understanding of neuromodulation, neuropsychiatric disorders, and the design and delivery of neurorehabilitation trials. The data generated will inform the development of additional interventions focused on neuromodulation to improve function and QOL for individuals following SCI and other patient populations with UE motor impairment.