Theta Burst Stimulation Plus Habit Override Training for Compulsive Behaviors

Experimental Manipulation of OFC Function and Behavioral Context: Towards an Integrative Translational Model of Compulsive Behaviors

This project seeks to identify causal neural mechanisms underlying unwanted, repetitive behaviors (compulsions). Using non-invasive brain stimulation coupled with practice in a computer task, we will modulate activity in a target brain region and measure effects on compulsive behaviors and related measures. This work could ultimately lead to the ability to treat compulsions more effectively by targeting the regions of the brain that can help or hinder attempts to overcome compulsions.

Study Overview

• Status: Completed
• Conditions: Obsessive-Compulsive Disorder; Compulsive Behavior
• Intervention / Treatment: Behavioral: Habit Override Practice; Device: Transcranial Magnetic Stimulation; Device: Sham Transcranial Magnetic Stimulation; Behavioral: Sham Training

• Study Type: Interventional
• Enrollment (Actual): 203
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15213
      • Western Psychiatric Institute And Clinic

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 60 years (Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

Participants will:

1. Be between the ages of 18 and 60 years
2. Endorse problematic compulsive behaviors, per self-report and clinician-administered measures.
3. Agree to video taping of structured clinical interview
4. Report that they will reside in the Pittsburgh area for at least 5 weeks

Exclusion Criteria:

1. Failure to meet standard MRI inclusion criteria: those who endorse claustrophobia, those who have cardiac pacemakers, neural pacemakers, surgical clips in the brain or blood vessels, surgically implanted metal plates, screws or pins, cochlear implants, implanted uterine devices, metal braces, or other metal objects in their body, especially in the eye. Dental fillings do not present a problem. Plastic or removable dental appliances do not require exclusion. History of significant injury or surgery to the brain or spinal cord that would impair interpretation of results. Pregnancy, determined by pregnancy tests on females.

2. Medical contraindications for Transcranial Magnetic Stimulation (TMS):

   1. Presence of a neurologic disorder or medication therapy known to alter seizure threshold (e.g., stroke, aneurysm, brain surgery, structural brain lesion, brain injury, frequent/severe headaches)
   2. Recurrent seizures or epilepsy in participant or family history of hereditary epilepsy
   3. Pregnancy
   4. Metallic implants in body or other devices that may be affected by magnetic field
   5. Significant heart disease or cerebrovascular disease
   6. Medications with strong seizure threshold lowering potential or which may interfere with the efficacy of TMS (e.g., clozapine, stimulants)
3. Acute suicidality or other psychiatric crises requiring treatment escalation
4. Changes made to treatment regimen within 4 weeks of baseline assessment
5. Reading level <6th grade as per participant self-report
6. Presence of bipolar, psychotic, autism spectrum, or substance use disorder (i.e. current problematic use of mood altering drugs such as cocaine, opiates, amphetamines, and barbiturates)
7. Presence of movement disorder or tics affecting manual responses
8. Inability to read text from 2 feet away (corrective lenses allowed)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: cTBS + Habit Override Training; Transcranial Magnetic Stimulation delivered in a continuous Theta Burst Stimulation (cTBS) pattern, paired with Habit Override Training.	Behavioral: Habit Override Practice; Computerized "brain training" to provide practice in overriding avoidance habits.; Device: Transcranial Magnetic Stimulation; Non-invasive method for temporary, focal stimulation of brain areas. Delivered in a continuous Theta Burst Stimulation (TBS) pattern.; Other Names: cTBS
Active Comparator: Sham TBS + Habit Override Training; Sham Transcranial Magnetic Stimulation, paired with Habit Override Training.	Behavioral: Habit Override Practice; Computerized "brain training" to provide practice in overriding avoidance habits.; Device: Sham Transcranial Magnetic Stimulation; Sham stimulation of non-brain areas. Delivered in a continuous Theta Burst Stimulation (TBS) pattern.; Other Names: Sham cTBS
Active Comparator: cTBS + Sham Training; Transcranial Magnetic Stimulation delivered in a continuous Theta Burst Stimulation (cTBS) pattern, paired with Sham Training.	Device: Transcranial Magnetic Stimulation; Non-invasive method for temporary, focal stimulation of brain areas. Delivered in a continuous Theta Burst Stimulation (TBS) pattern.; Other Names: cTBS; Behavioral: Sham Training; Computer-based task practice in a non-active/inert task.
Sham Comparator: Sham TBS + Sham Training; Sham Transcranial Magnetic Stimulation, paired with Sham Training.	Device: Sham Transcranial Magnetic Stimulation; Sham stimulation of non-brain areas. Delivered in a continuous Theta Burst Stimulation (TBS) pattern.; Other Names: Sham cTBS; Behavioral: Sham Training; Computer-based task practice in a non-active/inert task.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Brain activation in target region	Mean Cerebral Blood Flow (CBF) in orbitofrontal cortex collected via functional Magnetic Resonance Imaging (fMRI)	10-60min post-intervention
Effort to resist compulsive behaviors in response to laboratory triggers	Custom-made laboratory assessment of ability to override compulsive behaviors in response to idiographic triggers: self-reported effort needed to resist (0-100 scale)	60min post-intervention
Duration of compulsive behaviors in response to laboratory triggers	Custom-made laboratory assessment of ability to override compulsive behaviors in response to idiographic triggers: duration of compulsive behavior performance (% of total time allotted)	60min post-intervention
Intensity of urges to perform compulsive behaviors in response to laboratory triggers	Custom-made laboratory assessment of ability to override compulsive behaviors in response to idiographic triggers: self-reported urge intensity (0-100 scale)	60min post-intervention

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Goal-directed cognition	Neuropsychological test of flexible goal-directed cognition (two-step task): switch score (higher score=better performance)	90min-1 week
Yale-Brown Obsessive Compulsive Scale (Y-BOCS)	Clinician-administered measurement of obsessions and compulsions (range: 0-40; higher score=worse outcome)	1 week
WHO Disability Assessment Scale 2.0	Self-report measure of general functioning and disability (0-100; higher score=worse outcome)	1 week
Obsessive Compulsive Inventory-Revised (OCI-R)	Self-report measure of obsessions and compulsions (0-72; higher score=worse outcome)	1 week
Effort to resist compulsive behaviors in response to laboratory triggers	Custom-made laboratory assessment of ability to override compulsive behaviors in response to idiographic triggers: self-reported effort needed to resist (0-100 scale)	1 week
Duration of compulsive behaviors in response to laboratory triggers	Custom-made laboratory assessment of ability to override compulsive behaviors in response to idiographic triggers: duration of compulsive behavior performance (% of total time allotted)	1 week
Intensity of urges to perform compulsive behaviors in response to laboratory triggers	Custom-made laboratory assessment of ability to override compulsive behaviors in response to idiographic triggers: self-reported urge intensity (0-100 scale)	1 week
Brain activation in target region	Mean Cerebral Blood Flow (CBF) in orbitofrontal cortex collected via functional Magnetic Resonance Imaging (fMRI)	1 week

Collaborators and Investigators

• Sponsor: Rebecca Price
• Collaborators: National Institute of Mental Health (NIMH)
• Investigators: Principal Investigator: Rebecca B Price, PhD, University of Pittsburgh

Study record dates

Study Major Dates

• Study Start (Actual): December 28, 2020
• Primary Completion (Actual): December 15, 2025
• Study Completion (Actual): December 15, 2025

Study Registration Dates

• First Submitted: October 1, 2020
• First Submitted That Met QC Criteria: October 1, 2020
• First Posted (Actual): October 8, 2020

Study Record Updates

• Last Update Posted (Actual): February 10, 2026
• Last Update Submitted That Met QC Criteria: February 6, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Impulsive Behavior; Anxiety Disorders; Behavior; Obsessive-Compulsive Disorder; Compulsive Behavior; Therapeutics; Magnetic Field Therapy; Transcranial Magnetic Stimulation
• Other Study ID Numbers: STUDY19090219 (Part 2); R01MH124707 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes