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

项目总结 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，这是一种一线行为治疗， 取决于在暴露任务中抑制强迫症的能力。改善这一“关键疗法” 行为“是ERP增强的一个潜在的重要战略。重复经颅磁刺激 (RTMS)可以被用来刺激作为关键治疗基础的大脑回路更健康的功能 行为。此R61/R33的总体目标是测试使用rTMS增强ERP是否优于皮质 与强迫症有关的选定皮质-纹状体回路的节点可以使连接正常化并增强 青少年和青壮年强迫症的反应预防。 该项目的R61阶段将使用掩蔽RCT设计来测试ERP+TMS是否参与1) 与强迫症有关的假想回路和2)在事件相关电位暴露中观察到的反应预防 任务。12-21岁患有强迫症的青少年将完成完整的ERP课程和随机分配的TMS Sham方案、ITBS至dlPFC方案或CTBS至PSMA方案(n=20)。R61阶段的里程碑是 确定至少一个激活的RTMS条件a)改变了假设电路中的RSFC-AND 受试者之间和b)是安全和可行的。 R33阶段将使用屏蔽RCT设计来确定电路和 行为目标调节强迫症症状严重程度的变化。12-21岁强迫症患者的新样本 将接受ERP加上假的或主动的TMS刺激，使用在 R61组(n=30)。这两个阶段的探索性分析都将检验神经认知任务 性能预测症状变化，根据治疗臂的不同而变化，并与fMRI- 皮质-纹状体回路的测量指标。 在本奖项结束时，我们将确定rTMS在改善强迫行为方面是否有效 以及强迫症背后的回路中的功能连接，以及这些是否在临床上调节变化 结果。如果成功，我们将准备进行一项大规模的rTMS和ERP治疗儿童强迫症的试验， 包括对两种治疗方法的相关机制进行验证性测试。最终，这条线路的结果是 研究将有助于理解rTMS和强迫症的神经机制，并将为 研究增强试验中的关联机制。

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.