The Neurocircuitry of Relief During Avoidance Learning in Patients With Obsessive-compulsive Disorder

Study Overview
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Brief Summary
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To investigate the neuro-mechanisms underpinning persistent avoidance in OCD patients

Detailed Description
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Many compulsions displayed by obsessive-compulsive disorder (OCD) patients serve to protect against perceived threat and can, therefore, be conceptualized as 'avoidance responses'. Exposure treatment with response prevention (ET+RP) is aimed at exposing patients to their obsessive thoughts and perceived threats while preventing engagement in compulsive avoidant responses. This induces extinction of threat perception and fearful arousal and hence reduces the motivation to avoid. While successful in many patients, however, as much as 40% dropout during treatment or display persistent avoidance after ET+RP. There is a clear need for treatment improvement for these often highly disabled patients. Improving ET+RP outcomes requires a deeper understanding of the mechanisms that drive excessive and persistent avoidance in OCD patients. Psychological theories ascribe an important role to the relief that follows avoidance when the anticipated threat is successfully averted. This positive feeling arguably functions as a reward to reinforce the foregoing avoidance actions. Indeed, fMRI studies have found that the neurocircuitry of relief overlaps with that of reward, including the ventral tegmental area, ventral striatum and orbitofrontal cortex. Here, the authors will test the hypothesis that excessive-persistent avoidance is linked to exaggerated activation of the relief circuitry in OCD patients. For that purpose, we will acquire functional brain images of OCD patients in an MRI scanner and compare to healthy participants, while they participate in a computer task that is designed to model avoidance learning and relief.

Official Title
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The Neurocircuitry of Relief During Avoidance Learning in Patients With Obsessive-compulsive Disorder

Conditions
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Obsessive-Compulsive Disorder

Intervention / Treatment
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* Device: fMRI acquisition


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy volunteers 18-60 years old; Participants are motivated and give written informed consent; Adequate demand of Dutch language; Subjects have never participated in a fear conditioning task; Diagnosis of OCD (for OCD group only); Contraindications for the MRI exam. Exclusion Criteria: Current neurological (e.g. Epilepsia), respiratory, cardiovascular, metabolic, gastrointestinal, endocrine (especially diabetes), renal or urinary diseases, psychiatric disorder or other relevant medical histories (except for OCD in the OCD group); Being pregnant or lactating; Alcohol intake greater than 14 alcoholic units per week (one alcoholic unit = 10 gr ethanol); History of cannabis use or any other drug of abuse during the 3 months prior to the study; The medical doctor has asked to the participant to stay away from stressful situations; Electronic implants (e.g., pacemaker); Pain or other condition of the hand or the wrist.

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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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| HC<br>Mentally and medically healthy adults between 18 and 60 years, free from any current or previous medical or psychiatric condition. | Device: fMRI acquisition<br>* Participants from the two groups will perform an avoidance-relief task inside an MRI scanner<br>* Other names: Behavioral task;|
| OCD<br>Adults between 18 and 60 years, with a diagnosis of Obsessive-Compulsive Disorder and medication-free or with stable medication regimen for at least 3 weeks prior to the study. | Device: fMRI acquisition<br>* Participants from the two groups will perform an avoidance-relief task inside an MRI scanner<br>* Other names: Behavioral task;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Avoidance responses during the avoidance-relief task | Avoidance responses during avoidance learning and test will be recorded in terms of button press and Reaction times | 1 hour for avoidance task | 
| Relief during the omissions of the US | Relief will be measured as: Brain data during fMRI: whole-brain activations, as well as activations in specific regions of interest (ROI: VTA, NAcc, OFC) at the moment of the omissions of the electrical stimulation (US) during both the avoidance learning and the extinction learning phase of the avoidance-relief task; Individual ratings: relief pleasantness ratings measured on a Likert scale from 0 (neutral) to 3 (very pleasant) after each omission of the electrical stimulation (US) during both the avoidance learning and the extinction learning phase of the avoidance-relief task; Physiological data: skin conductance responses (SCR) at the moment of the omissions of the electrical stimulation (US) during both the avoidance learning and the extinction learning phase of the avoidance-relief task. | 1 hour to perform the avoidance task | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Tolerance to stress | The individual level of tolerance to distress will be measured via the self-administration of the Distress Tolerance Scale | 1 hour to perform the avoidance task | 
| Therapeutic outcome in OCD | The therapeutic outcome in OCD individuals will be evaluated by using the Y-BOCS (self-administered) questionnaire | 1 hour to perform the avoidance task | 
| Resting-state connectivity | The strength of connectivity between NAcc, VTA, and OFC, will be measured during the resting state MRI acquisition | 1 hour to perform the avoidance task | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Avoidance behavior, Reward, Conditioning, Extinction, Anxiety Disorders, OCD, fMRI