Transcranial Magnetic Stimulation to Augment Behavior Therapy for Tics

经颅磁刺激增强抽动行为疗法

• 批准号: 10041139
• 负责人: Christine A Conelea
• 金额: $ 124.89万
• 依托单位: UNIVERSITY OF MINNESOTA
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-08-10 至 2023-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10041139
• 关键词: Acute; Adolescent; Adverse event; Affect; Aftercare; Age; Analysis of Variance; Area; Behavior; Behavior Therapy; Behavior assessment; Behavioral; Brain; Child; Childhood; Chronic; Clinical; Clinical assessments; Corpus striatum structure; Data; Development; Dose; Double-Blind Method; Functional Magnetic Resonance Imaging; Gilles de la Tourette syndrome; Gold; Hyperactive behavior; Intervention; Link; Literature; Measures; Mediating; Mental disorders; Modeling; Motor; Motor Cortex; Movement; Outcome; Pathway interactions; Patients; Phase; Pilot Projects; Randomized; Regimen; Research; Rest; Safety; Sampling; Severities; Symptoms; Testing; Tic disorder; Time; Transcranial magnetic stimulation; Youth; associated symptom; base; control trial; design; electric field; follow-up; functional outcomes; improved; neuromechanism; neuropsychiatric symptom; putamen; repetitive transcranial magnetic stimulation; response; tic suppression; vocalization

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.

项目概要/摘要 慢性抽动症影响美国 1-3% 的青少年，是一种与以下疾病相关的致残性神经精神症状： 多种儿童期发病的精神障碍。使用综合行为干预抑制抽动 抽动症 (CBIT) 是目前抽动症的一线金标准治疗方法。然而，许多患者并没有完全受益 来自 CBIT，可能是因为它们缺乏 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，抑制性重复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 已知皮质纹状体回路在抽动障碍中过度活跃和过度连接。我们因此 预计将 CBIT 与 SMA 抑制性刺激相结合可能会促进更高的 CBIT 反应率。 这项研究将测试通过抑制性、无创性刺激 SMA 来增强 CBIT 是否可以使 SMA 正常化 SMA 介导的回路中的活性并增强患有抽动障碍的年轻人的抽动抑制能力。这 R61 阶段将比较两种 rTMS 方案，1 Hz rTMS 和连续 theta 突发刺激 (cTBS)， 对抗假刺激。 R61 的目标将测试大脑（SMA 介导的回路）和行为（tic 抑制能力）目标并确定最佳 rTMS 方案。为此，60名12-21岁的青少年 慢性抽动症将完成 10 次每日 CBIT 疗程，加上随机分配的 rTMS 方案，并使用功能磁共振成像 (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 方案增强 CBIT 60 名患有慢性抽动症的青少年样本。 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，并评估干预持久性 1个月随访时。两个阶段的 TMS 目标都将通过个性化电场建模来确定。 该项目将建立 CBIT+rTMS 作为慢性抽动症的治疗方法，并提供一个机制模型 研究将行为疗法与神经刺激相结合的儿科干预措施。这行的结果 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的理解 CBIT、TMS 和抽动症的潜在机制。

项目成果

Considerations for Pairing Cognitive Behavioral Therapies and Non-invasive Brain Stimulation: Ignore at Your Own Risk.

• DOI: 10.3389/fpsyt.2021.660180
• 发表时间: 2021
• 期刊: Frontiers in psychiatry
• 影响因子: 4.7
• 作者: Conelea CA;Jacob S;Redish AD;Ramsay IS
• 通讯作者: Ramsay IS

The CBIT+TMS Trial: study protocol for a two-phase randomized controlled trial testing neuromodulation to augment behavior therapy for youth with chronic tics.

CBIT TMS 试验：两阶段随机对照试验的研究方案，测试神经调节以增强患有慢性抽动症的青少年的行为治疗。

• DOI: 10.21203/rs.3.rs-2949388/v1
• 发表时间: 2023
• 期刊: Research square
• 作者: Conelea,Christine;Greene,Deanna;Alexander,Jennifer;Houlihan,Kerry;Hodapp,Sarah;Wellen,Brianna;Francis,Sunday;Mueller,Bryon;Hendrickson,Timothy;Tseng,Angela;Chen,Mo;Fiecas,Mark;Lim,Kelvin;Opitz,Alexander;Jacob,Suma
• 通讯作者: Jacob,Suma

The CBIT + TMS trial: study protocol for a two-phase randomized controlled trial testing neuromodulation to augment behavior therapy for youth with chronic tics.

• DOI: 10.1186/s13063-023-07455-1
• 发表时间: 2023-07-03
• 期刊: Trials
• 影响因子: 2.5