Theta Burst Stimulation Plus Habit Override Training for Compulsive Behaviors

Study Overview
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Brief Summary
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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.

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

Conditions
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Compulsive Behavior, Obsessive-Compulsive Disorder

Intervention / Treatment
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* Behavioral: Habit Override Practice
* Device: Transcranial Magnetic Stimulation
* Behavioral: Sham Training
* Device: Sham Transcranial Magnetic Stimulation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Participants will: Be between the ages of 18 and 60 years Endorse problematic compulsive behaviors, per self-report and clinician-administered measures. Agree to video taping of structured clinical interview Report that they will reside in the Pittsburgh area for at least 5 weeks Exclusion Criteria: 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. Medical contraindications for Transcranial Magnetic Stimulation (TMS): 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) Recurrent seizures or epilepsy in participant or family history of hereditary epilepsy Pregnancy Metallic implants in body or other devices that may be affected by magnetic field Significant heart disease or cerebrovascular disease Medications with seizure threshold lowering potential, e.g., clomipramine, Monoamine Oxidase inhibitors (MAOi's), imipramine, clozapine Acute suicidality or other psychiatric crises requiring treatment escalation Changes made to treatment regimen within 4 weeks of baseline assessment Reading level <6th grade Presence of bipolar, psychotic, autism spectrum, or substance use disorder (i.e. current use of mood altering drugs such as cocaine, cannabis or marijuana, opiates, amphetamines, and barbiturates) Presence of movement disorder or tics affecting manual responses Inability to read text from 2 feet away (corrective lenses allowed)

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

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

What is the study measuring?
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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 |