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.

项目总结