Transcranial Magnetic Stimulation to Augment Behavior Therapy for Tics

项目总结/摘要 慢性抽搐影响美国1-3%的青少年，是一种致残性神经精神症状， 儿童期发作的多重精神障碍抽动抑制综合行为干预 抽动症（CBIT）是目前治疗抽动症的一线、金标准疗法。然而，许多患者并没有完全受益 从CBIT，可能是因为他们缺乏基本的抽搐抑制能力，CBIT渴望提高。我们 初步数据和文献表明，抑制性重复动作可以增强抽动抑制能力， 辅助运动区（SMA）的经颅磁刺激（rTMS）。SMA是一个关键节点， 皮质-纹状体回路，并且已知在抽动障碍中过度活跃和过度连接。因此我们 预期将CBIT与SMA的抑制性刺激组合可促进更高的CBIT响应率。 本研究将测试通过抑制性、非侵入性刺激SMA来增强CBIT是否正常化 活动SMA介导的电路和增强抽动障碍的年轻人的抽动抑制能力。的 R61阶段将比较两种rTMS方案，1 Hz rTMS和连续θ波群刺激（cTBS）， 对抗假刺激R61 aims将测试大脑（SMA介导的回路）和行为（tic 抑制能力）的目标，并确定最佳的rTMS方案。为此，60名12至21岁的青年， 慢性抽搐将完成10次每日CBIT加上随机分配的rTMS方案，使用fMRI， 治疗前后的行为和临床评估。R33阶段将研究以下因素的影响： 在一项新的双盲随机对照试验中使用最佳rTMS方案进行CBIT增强 60例慢性抽动症青年患者。R33旨在测试目标参与和功能之间的联系 结果，检查剂量-反应关系的临床轨迹，并评估干预的持久性 1个月随访时。两个阶段的TMS靶向将通过个性化电场建模进行通知。 该项目将建立CBIT+rTMS作为慢性抽动的治疗方法，并提供一个模型， 研究儿科干预结合行为疗法和神经刺激。这条线的结果 研究将为TMS治疗增强策略提供信息，并提高我们对神经系统疾病的理解。 CBIT、TMS和抽搐的潜在机制。

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.