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

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.

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Behavioral: Novel Exploration; Behavioral: Threat conditioning; Behavioral: Extinction; Behavioral: Reinstatement; Behavioral: Visual attention control task

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 60
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Sweden
  • Uppsala, Sweden, 75142
    • Uppsala University, deparmtent of Psychology

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 50 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Experimental group; Novel exploration is used before extinction in an attempt to strengthen the extinction consolidation.	Behavioral: Novel Exploration; Exploration of a novel 3D-environment in virtual reality.; Behavioral: Threat conditioning; 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.; Behavioral: Extinction; Session 2. Participants are repeatedly exposed to the both contexts from session 1 (CS+, CS-), but no shocks are delivered.; Behavioral: Reinstatement; Session 3. Participants are again repeatedly exposed to both contexts from session 1 (CS+, CS-), after a few shocks delivered in a neutral context.
Experimental: Control group; Participants perform a control task (visual attention) instead of the novel exploration.	Behavioral: Threat conditioning; 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.; Behavioral: Extinction; Session 2. Participants are repeatedly exposed to the both contexts from session 1 (CS+, CS-), but no shocks are delivered.; Behavioral: Reinstatement; Session 3. Participants are again repeatedly exposed to both contexts from session 1 (CS+, CS-), after a few shocks delivered in a neutral context.; Behavioral: Visual attention control task; Session 2. A visual attention task used as a control task instead of novel exploration.

What is the study measuring?

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Navigation success	Questions designed to probe the amount of navigation performed by participants doing the novel exploration task. Three yes/no question of "Did you find object X?" and then participants are asked to point at their position in a stylized map overviewing the novel exploration context.	Day 2
State-Trait Anxiety Inventory (STAI-T)	This is a self-rated questionnaire measuring trait anxiety. Higher scores indicate higher level of trait-anxiety (range 20-80).	Day 2
Generalized anxiety disorder 7 (GAD-7)	This is a self-rated questionnaire for screening and severity measuring of generalized anxiety disorder (range 0-21). Higher scores indicate more symptoms of generalized anxiety.	Day 2
Patient Health Questionnaire 9 (PHQ-9)	This is a self-rated questionnaire for screening for the presence and severity of depression (0-27). Higher scores indicate a more symptoms, and severity of symptoms, of depression	Day 2

Collaborators and Investigators

• Sponsor: Uppsala University
• Investigators: Principal Investigator: Thomas Ågren, PhD, Uppsala University

Publications and helpful links

General Publications

• Moncada D, Ballarini F, Viola H. Behavioral Tagging: A Translation of the Synaptic Tagging and Capture Hypothesis. Neural Plast. 2015;2015:650780. doi: 10.1155/2015/650780. Epub 2015 Aug 25.

Study record dates

Study Major Dates

• Study Start (Actual): November 15, 2021
• Primary Completion (Actual): May 1, 2022
• Study Completion (Actual): May 1, 2022

Study Registration Dates

• First Submitted: November 6, 2021
• First Submitted That Met QC Criteria: November 26, 2021
• First Posted (Actual): December 9, 2021

Study Record Updates

• Last Update Posted (Actual): June 10, 2022
• Last Update Submitted That Met QC Criteria: June 9, 2022
• Last Verified: June 1, 2022

More Information

Terms related to this study

• Keywords: Virtual reality; Extinction; Threat conditioning; Behavioral tagging
• Other Study ID Numbers: 2021-03596

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: We plan to share anonymous behavioural data, training material, Statistical Analysis plan, and informed consent form on the project site on Open Science Framework (https://osf.io/4yjev/). Statistical Analysis Plan will be pre-registered on the same site (Open Science Framework).
• IPD Sharing Time Frame: Data will be available from completion of analysis and publication, and onwards.
• IPD Sharing Access Criteria: Anonymous behavioural data, training material, Statistical Analysis plan, and informed consent form will be made public on the project site on Open Science Framework (https://osf.io/4yjev/)
• IPD Sharing Supporting Information Type: SAP; ICF

Drug and device information, study documents

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