An Attempt at Translating Novelty-enhanced Extinction of Context Conditioning From Rodents to Humans

Study Overview
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Brief Summary
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In rodents, novel exploration has been used to strengthen the consolidation of a variety of hippocampal-dependent learning tasks. To our knowledge, no attempt have been made to translate the effect of strengthening the memory of an extinction of a context conditioning memory. This study uses virtual reality for both context conditioning and novel exploration in an attempt at translating these findings from rodents to humans, thus, using novel exploration to strengthen an extinction memory. Threat responses are measured with skin conductance and startle responses. If this effect could be shown experimentally in humans, that experimental setup could become an important tool in understanding important memory processes of fear, such as reconsolidation and behavioral tagging.

Detailed Description
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The study employs healthy participants and includes three experimental sessions, roughly 24 h apart. During the first session, participants undergo context conditioning in virtual reality where the CS+ and CS- are two different rooms. During the second session, half of the participants perform an exploration of a novel virtual environment, and the other half performs a visual attention task. About 60 min later, participants undergo extinction to the context conditioning performed in session 1, again in virtual reality. In session 3, remaining threat responses are measured through a reinstatement procedure, again in virtual reality.

Official Title
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An Attempt at Translating Novelty-enhanced Extinction of Context Conditioning From Rodents to Humans

Conditions
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Healthy

Intervention / Treatment
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* Behavioral: Novel Exploration
* Behavioral: Threat conditioning
* Behavioral: Extinction
* Behavioral: Reinstatement
* Behavioral: Visual attention control task


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Willing and able to provide informed consent and complete study procedures Exclusion Criteria: Current psychiatric disorder. Current use of psychotropic medication Current use of neurological conditions

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 50 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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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Experimental group<br>Novel exploration is used before extinction in an attempt to strengthen the extinction consolidation. | Behavioral: Novel Exploration<br>* Exploration of a novel 3D-environment in virtual reality.<br>Behavioral: Threat conditioning<br>* Session 1. Threat conditioning to two different (CS+, CS-) virtual reality contexts (i.e rooms). One of these is paired with a mild electric shock. The context paired with the electric shock (CS+) is counterbalanced across participants. Participants are instructed that they may receive electrical shocks during the procedure.<br>Behavioral: Extinction<br>* Session 2. Participants are repeatedly exposed to the both contexts from session 1 (CS+, CS-), but no shocks are delivered.<br>Behavioral: Reinstatement<br>* Session 3. Participants are again repeatedly exposed to both contexts from session 1 (CS+, CS-), after a few shocks delivered in a neutral context.<br>|
| Experimental: Control group<br>Participants perform a control task (visual attention) instead of the novel exploration. | Behavioral: Threat conditioning<br>* Session 1. Threat conditioning to two different (CS+, CS-) virtual reality contexts (i.e rooms). One of these is paired with a mild electric shock. The context paired with the electric shock (CS+) is counterbalanced across participants. Participants are instructed that they may receive electrical shocks during the procedure.<br>Behavioral: Extinction<br>* Session 2. Participants are repeatedly exposed to the both contexts from session 1 (CS+, CS-), but no shocks are delivered.<br>Behavioral: Reinstatement<br>* Session 3. Participants are again repeatedly exposed to both contexts from session 1 (CS+, CS-), after a few shocks delivered in a neutral context.<br>Behavioral: Visual attention control task<br>* Session 2. A visual attention task used as a control task instead of novel exploration.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Physiological arousal response during reinstatement. | Startle responses and skin conductance responses are used as measures of physiological arousal response. | Day 3 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Physiological arousal response during extinction | Startle responses and skin conductance responses are used as measures of physiological arousal response | Day 2 | 
| Physiological arousal response during threat conditioning | Startle responses and skin conductance responses are used as measures of physiological arousal response | Day 1 | 
| Subjective fear ratings | Subjective ratings of fear (0-100) where 0 is no fear and 100 is worst imaginable fear. | Day 1, 2 & 3. | 
| Subjective discomfort ratings | Subjective ratings of discomfort where 0 is no discomfort and 100 is worst imaginable discomfort. | Day 1, 2 & 3 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Threat conditioning, Virtual reality, Extinction, Behavioral tagging