Precision Brain Mapping to Predict and Track Response to Exposure and Response Prevention Therapy in Youth With Obsessive-Compulsive Disorder

Precision Functional Mapping to Predict and Track ERP Response in Pediatric Obsessive-Compulsive Disorder: A Longitudinal fMRI Study

The goal of this clinical trial is to learn whether brain scan results can help predict and track changes in obsessive-compulsive disorder, or OCD, symptoms in children and teens ages 10 to 17 who receive Exposure and Response Prevention therapy, also called ERP. ERP is a type of therapy in which participants practice facing OCD-related fears while resisting rituals or compulsions.

The main question this study aims to answer is:

Can each participant's pattern of brain connections, measured with functional MRI brain scans, help predict and track weekly changes in OCD symptoms during and after a 14-week course of ERP, including during planned monthly booster sessions and additional booster sessions offered if symptoms worsen?

All participants will receive ERP. There is no placebo and no comparison group.

Participants will:

• Complete screening, consent or assent, interviews, questionnaires, and MRI safety checks
• Receive 14 weekly ERP sessions
• Complete OCD symptom assessments and functional MRI brain scans before, during, and after ERP
• Receive planned monthly ERP booster sessions after the 14 weekly sessions
• Receive additional brief ERP booster sessions if OCD symptoms worsen during follow-up
• Take part for up to about 62 weeks

This study examines whether individualized brain-connectivity measures obtained with repeated functional magnetic resonance imaging can help predict and track symptom change during exposure and response prevention, an evidence-based cognitive-behavioral therapy for pediatric obsessive-compulsive disorder.

OCD is characterized by obsessions, compulsions, or both, and in youth it can substantially interfere with school, family life, social development, and daily functioning. Although ERP and serotonin reuptake inhibitor medications are standard treatments for pediatric OCD, clinical outcomes vary. Some youth respond robustly, while others have partial improvement, persistent residual symptoms, or symptom recurrence after initial gains. Current clinical practice lacks individualized biological markers that can track treatment response over time or help identify which patients may require more intensive or alternative intervention strategies.

The scientific rationale for this study is that OCD symptoms have been linked to dysfunction in cortico-striato-thalamo-cortical brain circuits, including orbitofrontal cortex and striatal regions. However, these circuits vary across individuals, and group-average neuroimaging findings have not yet yielded clinically useful biomarkers for individual patients. Precision functional mapping uses repeated fMRI scans from the same person to generate individualized estimates of functional brain networks. By pairing ERP with longitudinal clinical assessment and repeated neuroimaging, this study will evaluate whether participant-specific functional connectivity features, particularly resting-state functional connectivity between orbitofrontal cortex and ventral striatum, are associated with changes in OCD symptom severity over time.

The broader anticipated benefit is scientific: the study may help clarify how individualized brain-connectivity patterns change during ERP and how those changes relate to symptom trajectory, treatment response, and maintenance or recurrence of symptoms. Findings may inform future approaches to personalized pediatric OCD care, including earlier identification of youth who may benefit from treatment augmentation or alternative strategies.

Inclusion Criteria:

• Age 10 to 17 years at the time of initial consent. Participants who reach age 18 while enrolled may remain in the study after completing the adult re-consent process; no new participants age 18 years or older will be recruited.
• DSM-5 diagnosis of obsessive-compulsive disorder, established through a clinical interview by a clinician.
• Parent or guardian able to provide informed consent and participant able to provide assent.
• Participant has sufficient English fluency to complete cognitive tasks and assessments. Parent or guardian English fluency is not required; interpreter support is available.

Exclusion Criteria:

• History or current evidence of a significant neurological disorder, including but not limited to seizure disorder, stroke, or traumatic brain injury with loss of consciousness.
• Any standard MRI contraindication identified during initial screening or on the MRI safety checklist, including but not limited to ferromagnetic implants, certain medical devices or metal fragments, severe claustrophobia, or pregnancy.
• Pregnancy at screening or pregnancy identified during study participation.
• Active suicidal ideation.
• Any psychiatric condition that, in the investigator's judgment, would interfere with study participation or data interpretation, including but not limited to psychotic disorders, bipolar disorders, severe neurodevelopmental disorders, intellectual disability, severe eating disorders, or recent significant substance use disorders within the past 6 months. Stable psychiatric comorbidities, including anxiety disorders, depressive disorders, ADHD, or tic disorders, are permitted if OCD remains the primary diagnosis.
• Any medical, psychiatric, or situational factor judged by the investigator as likely to compromise participant safety, adherence, or data integrity.