Transcranial Magnetic Stimulation to Augment Exposure and Response Prevention for Pediatric OCD

项目摘要 儿童强迫症是一个公共卫生问题，许多人即使在接受有效的治疗后仍有症状。 治疗。暴露和反应预防（ERP）的成功，一线行为治疗， 取决于在暴露任务中抑制强迫的能力。改善这种“治疗至关重要 行为”是ERP增强的一个潜在的重要策略。重复经颅磁刺激 （rTMS）可以用来刺激大脑回路的健康功能， 行为。R61/R33的总体目标是测试rTMS增强ERP是否超过皮层 参与强迫行为的皮质-纹状体回路的节点可以使连接正常化， 在青年和年轻的成年人与强迫症的反应预防。 本项目的R61阶段将使用设盲RCT设计来测试ERP+TMS是否参与1） 参与强迫性的假设回路和2）在ERP暴露期间观察到的反应预防 任务12-21岁的强迫症青少年将完成ERP的完整课程加上随机分配的TMS 假手术、iTBS至dlPFC或cTBS至pSMA方案（每组n=20）。R61阶段的主要任务是 a）改变所述假设回路中的RSFC， 受试者之间和B）是安全可行的。 R33阶段将使用设盲RCT设计，以确定ERP+TMS是否参与回路， 行为目标介导强迫症症状严重程度的变化。一个新的12-21岁强迫症青年样本 将接受ERP加假刺激或主动TMS刺激，使用 R61（每组n=30）。两个阶段的探索性分析将检查神经认知任务是否 表现预测症状变化，治疗组的变化差异，并与fMRI相对应- 皮质-纹状体回路的测量指标。 在这个奖项结束时，我们将确定rTMS是否对改善强迫行为有效 以及这些是否介导了强迫症的临床变化。 结果。如果成功，我们将准备对儿童强迫症进行大规模的rTMS与ERP试验， 包括对两种治疗的相关机制的验证性测试。最终，这条线的结果 研究将为rTMS和OCD的神经机制的理解提供信息，并将提供一个模型， 研究隆乳试验中的相关机制。

PROJECT SUMMARY Pediatric OCD is a public health problem and many remain symptomatic even after receiving efficacious treatments. The success of exposure and response prevention (ERP), a first-line behavioral treatment, depends on the ability to refrain from compulsions during exposure tasks. Improving this “therapy critical behavior” is a potentially important strategy for ERP augmentation. Repetitive transcranial magnetic stimulation (rTMS) can be leveraged to stimulate healthier functioning of brain circuits underlying therapy critical behaviors. The overall objective of this R61/R33 is to test whether augmenting ERP with rTMS over cortical nodes of select cortico-striatal circuits implicated in compulsivity can normalize connectivity and enhance response prevention in youth and young adults with OCD. The R61 phase of this project will use a masked RCT design to test whether ERP+TMS engages 1) hypothesized circuits involved in compulsivity and 2) observed response prevention during ERP exposure tasks. Youth ages 12-21 years with OCD will complete a full course of ERP plus randomly assigned TMS regimens of sham, iTBS to dlPFC, or cTBS to pSMA (n=20 per group). Milestones for the R61 phase are determination that at least one active rTMS condition a) changes RSFC in the hypothesized circuit within- and between-subjects and b) is safe and feasible. The R33 phase will use a masked RCT design to establish whether ERP+TMS engagement of the circuit and behavioral targets mediates changes in OCD symptom severity. A new sample of youth ages 12-21 with OCD will receive ERP plus either sham or active TMS stimulation, using the optimal TMS regimen identified in the R61 (n=30 per group). Exploratory analyses in both phases will examine whether neurocognitive task performance predicts symptom change, changes differentially by treatment arm, and corresponds with fMRI- measured metrics of cortico-striatal circuitry. At the end of this award, we will have determined whether rTMS is effective for improving compulsive behavior and functional connectivity in circuits underlying compulsivity, and whether these mediate change in clinical outcomes. If successful, we will be poised to conduct a large-scale trial of rTMS with ERP for pediatric OCD, including a confirmatory test of the linked mechanisms of both treatments. Ultimately, results from this line of research will inform understanding of neural mechanisms in rTMS and OCD and will provide a model for studying linked mechanisms in augmentation trials.