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

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.

Grant Number: 5R61MH133666-02
NIH Institute/Center: NIH
Principal Investigator: Kristen Benito