Transcranial Magnetic Stimulation to Augment Behavior Therapy for Tics

项目摘要/摘要 慢性抽搐影响美国1-3%的年轻人，是一种与以下疾病相关的致残神经精神症状 儿童时期出现的多发性精神障碍。综合行为干预对抽动的抑制作用 抽搐(CBIT)是目前治疗抽搐的一线黄金标准疗法。然而，许多患者并没有完全受益。 来自CBIT，可能是因为他们缺乏CBIT渴望增强的基本抽动抑制能力。我们的 初步数据和文献表明，通过抑制重复可以增强对TIC的抑制能力 辅助运动区的经颅磁刺激(RTMS)。SMA是以下领域的关键节点 皮质-纹状体回路，在抽动障碍中被认为是过度活跃和过度连接。因此，我们 预计CBIT结合抑制刺激SMA可能有助于更高的CBIT反应率。 这项研究将测试用抑制性、非侵入性刺激SMA来增强CBIT是否正常 SMA介导的回路中的活动，并增强抽动障碍青少年的抽动抑制能力。这个 R61阶段将比较两种rTMS方案，1 HzrTMS和持续theta Burst刺激(CTBS)， 反对虚假的刺激。R61 AIMS将测试大脑的参与(SMA介导的回路)和行为(抽搐 抑制能力)，并确定最佳rTMS方案。为此，60名年龄在12-21岁之间的青年 慢性抽搐将完成10个疗程的CBIT加随机分配的rTMS方案，使用功能磁共振成像， 治疗前后的行为和临床评估。R33阶段将调查以下方面的影响 一项新的双盲随机对照试验中最佳rTMS方案对CBIT的强化作用 对60例慢性抽搐青年进行抽样调查。R33旨在测试目标参与度和功能之间的联系 结果，检查剂量-反应关系的临床轨迹，并评估干预的持久性 术后1个月随访。这两个阶段的TMS目标将通过个性化的电场建模进行通知。 该项目将建立CBIT+rTMS作为慢性抽搐的治疗方法，并提供一个机械治疗的模型 研究结合行为疗法和神经刺激的儿科干预措施。这条线的结果是 研究将为TMS治疗强化策略提供信息，并提高我们对神经的理解 CBIT、TMS和TICS背后的机制。

PROJECT SUMMARY/ABSTRACT Chronic tics affect 1-3% of youth in the US and are a disabling neuropsychiatric symptom associated with multiple childhood-onset mental disorders. Tic suppression using Comprehensive Behavioral Intervention for Tics (CBIT) is the current first-line, gold-standard therapy for tics. However, many patients do not fully benefit from CBIT, likely because they lack the fundamental tic suppression ability that CBIT aspires to enhance. Our preliminary data and the literature show that tic suppression ability can be enhanced with inhibitory repetitive transcranial magnetic stimulation (rTMS) of the supplementary motor area (SMA). SMA is a key node of cortico-striatal circuits and is known to be hyperactive and hyperconnected in tic disorders. We therefore anticipate that combining CBIT with inhibitory stimulation of SMA may facilitate higher CBIT response rates. This study will test whether augmenting CBIT with inhibitory, noninvasive stimulation of SMA normalizes activity in SMA-mediated circuits and enhances tic suppression ability in young people with tic disorder. The R61 phase will compare two rTMS regimens, 1 Hz rTMS and continuous theta burst stimulation (cTBS), against sham stimulation. R61 aims will test engagement of brain (SMA-mediated circuits) and behavior (tic suppression ability) targets and identify the optimal rTMS regimen. To this end, 60 youth ages 12-21 years with chronic tics will complete 10 daily sessions of CBIT plus randomly assigned rTMS regimen, with fMRI, behavioral, and clinical assessments before and after treatment. The R33 phase will investigate the effects of CBIT augmentation with the optimal rTMS regimen in a double blinded randomized control trial in a new sample of 60 youth with chronic tics. R33 aims test the link between target engagement and functional outcomes, examine the clinical trajectory of the dose-response relationship, and assess intervention durability at 1 month follow-up. TMS targeting in both phases will be informed by individualized electric field modeling. This project will establish CBIT+rTMS as a treatment for chronic tics and provide a model for mechanistically studying pediatric interventions combining behavior therapy with neurostimulation. Results from this line of research will inform TMS therapy augmentation strategies and improve our understanding of neural mechanisms underlying CBIT, TMS, and tics.