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

经颅磁刺激可增加儿童强迫症的暴露和反应预防

• 批准号: 10722536
• 负责人: Kristen G Benito
• 金额: $ 122.47万
• 依托单位: EMMA PENDLETON BRADLEY HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-08-01 至 2025-07-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10722536
• 关键词: 2 arm randomized control trial; Adult; Adverse event; Aftercare; Age; Area; Award; Behavior; Behavior Therapy; Behavioral; Brain; Childhood; Clinical; Clinical Trials; Compulsive Behavior; Corpus striatum structure; Data; Distress; Dorsal; Equilibrium; Exposure to; Fright; Functional Magnetic Resonance Imaging; Goals; Habits; Lateral; Left; Link; Masks; Measures; Mediating; Motor; Neurocognitive; Outcome; Phase; Prefrontal Cortex; Prevention; Public Health; Randomized; Regimen; Research; Rest; Safety; Sampling; Severities; Study models; Subgroup; Symptoms; Task Performances; Testing; Transcranial magnetic stimulation; Treatment outcome; Work; Youth; aged; arm; compulsion; design; efficacious treatment; flexibility; functional outcomes; improved; learning extinction; neural; neuromechanism; novel; repetitive transcranial magnetic stimulation; response; success; symptomatic improvement; treatment arm; treatment effect; treatment response; virtual; young adult

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.

项目摘要 小儿强迫症是一个公共卫生问题，即使有效，许多人仍然有症状 治疗。暴露和反应预防（ERP）的成功，一种一线行为处理， 取决于在暴露任务期间避免强迫的能力。改善这种“关键疗法” 行为”是ERP增强的潜在重要策略。重复的经颅磁刺激 （RTMS）可以利用（RTMS）来刺激关键疗法的脑回路的健康功能 行为。此R61/R33的总体目标是测试是否通过皮质增强ERP 在强迫性中实现的精选皮层纹状体电路的节点可以使连通性正常化并增强 强迫症的青年和年轻人的反应预防。 该项目的R61阶段将使用蒙版的RCT设计来测试ERP+TMS是否参与1） 在ERP暴露期间，涉及强迫性的假设电路和2）观察到的预防反应预防 任务。 OCD 12-21岁的青年将完成ERP的完整课程以及随机分配的TMS 假手术的方案，ITB到DLPFC或CTBS到PSMA（每组n = 20）。 R61阶段的里程碑是 确定至少一个主动RTMS条件a）在假设的电路中更改RSFC。 主题间和b）是安全且可行的。 R33阶段将使用蒙版的RCT设计来确定电路的ERP+TMS参与度是否 行为目标介导强迫症症状严重程度的变化。一个新的12-21岁青年样本 使用在 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 绩效预测符号变化，通过治疗组的变化不同，并且与fmri-相对应 测量的皮质 - 纹状体电路指标。 在该奖项结束时，我们将确定RTM是否有效改善强迫行为 电路中的电路中的功能连通性，以及这些是否介导了临床的变化 结果。如果成功，我们将被毒死，以对ERP进行小儿OCD进行大规模试验， 包括对两种治疗的链接机制的确认测试。最终，这条线的结果 研究将为RTM和OCD中神经机制的理解提供信息，并将为 在增强试验中研究链接的机制。