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

To investigate the neuro-mechanisms underpinning persistent avoidance in OCD patients

Study Overview

• Status: Unknown
• Conditions: Obsessive-Compulsive Disorder
• Intervention / Treatment: Device: fMRI acquisition

Detailed Description

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.

• Study Type: Observational
• Enrollment (Anticipated): 40

Contacts and Locations

Study Locations

• Belgium
  • Leuven, Belgium, 3000
    • Recruiting
    • Psychiatry | UZ Leuven campus Gasthuisberg
    • Contact: Bram Vervliet, Prof. Dr.; Phone Number: +32 16 3 26145; Email: bram.vervliet@kuleuven.be
    • Contact: Chris Bervoets, Prof. Dr.; Email: chris.bervoets@upckuleuven.be
    • Principal Investigator: Bram Vervliet
    • Sub-Investigator: Chris Bervoets

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 60 years (ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Healthy group: Mentally and medically healthy adults between 18 and 60 years, free from any current or previous medical or psychiatric condition.

OCD group: Same as the healthy group, except for the diagnosis of OCD and medication-free or with a stable medication regimen for at least 3 weeks prior to the study.

Description

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.

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
HC; Mentally and medically healthy adults between 18 and 60 years, free from any current or previous medical or psychiatric condition.	Device: fMRI acquisition; Participants from the two groups will perform an avoidance-relief task inside an MRI scanner; Other Names: Behavioral task
OCD; 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; Participants from the two groups will perform an avoidance-relief task inside an MRI scanner; Other Names: Behavioral task

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: KU Leuven

Publications and helpful links

General Publications

• Vervliet B, Lange I, Milad MR. Temporal dynamics of relief in avoidance conditioning and fear extinction: Experimental validation and clinical relevance. Behav Res Ther. 2017 Sep;96:66-78. doi: 10.1016/j.brat.2017.04.011. Epub 2017 Apr 23.
• Milad MR, Furtak SC, Greenberg JL, Keshaviah A, Im JJ, Falkenstein MJ, Jenike M, Rauch SL, Wilhelm S. Deficits in conditioned fear extinction in obsessive-compulsive disorder and neurobiological changes in the fear circuit. JAMA Psychiatry. 2013 Jun;70(6):608-18; quiz 554. doi: 10.1001/jamapsychiatry.2013.914.
• Leknes S, Lee M, Berna C, Andersson J, Tracey I. Relief as a reward: hedonic and neural responses to safety from pain. PLoS One. 2011 Apr 7;6(4):e17870. doi: 10.1371/journal.pone.0017870.
• Gillan CM, Morein-Zamir S, Urcelay GP, Sule A, Voon V, Apergis-Schoute AM, Fineberg NA, Sahakian BJ, Robbins TW. Enhanced avoidance habits in obsessive-compulsive disorder. Biol Psychiatry. 2014 Apr 15;75(8):631-8. doi: 10.1016/j.biopsych.2013.02.002. Epub 2013 Mar 16.

Study record dates

Study Major Dates

• Study Start (ACTUAL): January 10, 2020
• Primary Completion (ANTICIPATED): January 10, 2022
• Study Completion (ANTICIPATED): May 1, 2022

Study Registration Dates

• First Submitted: December 14, 2020
• First Submitted That Met QC Criteria: December 21, 2020
• First Posted (ACTUAL): December 28, 2020

Study Record Updates

• Last Update Posted (ACTUAL): December 28, 2020
• Last Update Submitted That Met QC Criteria: December 21, 2020
• Last Verified: December 1, 2020

More Information

Terms related to this study

• Keywords: OCD; fMRI; Reward; Extinction; Anxiety Disorders; Conditioning; Avoidance behavior
• Additional Relevant MeSH Terms: Mental Disorders; Pathologic Processes; Personality Disorders; Anxiety Disorders; Disease; Compulsive Personality Disorder; Obsessive-Compulsive Disorder
• Other Study ID Numbers: bram vervliet

Drug and device information, study documents

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