NCT07122739

Neurofeedback to Reduce Spontaneous Recovery of Threat Expectancy

Reducing Spontaneous Recovery Using Functional Connectivity Based Real-time Functional Magnetic Resonance Imaging Neurofeedback Targeting the Memory Control Network

• Status: Recruiting
• Phase: N/A
• Study type: Interventional
• Enrollment: 40 (estimated)
• Sponsor: Trustees of Princeton University · Academic / Other
• Sex: All
• Age: 18 Years – 50 Years
• Healthy volunteers: Accepted

Summary

This study tests the efficacy of a new behavioral intervention with the goal of reducing spontaneous recovery of threat expectancy in healthy adults. This real-time functional magnetic resonance imaging (fMRI) neurofeedback intervention delivers feedback based on a functional connection between the prefrontal cortex and the hippocampus.

Detailed description

Exposure therapy remains the most effective evidence-based treatment for a variety of anxiety related disorders; however, fear often returns over time. Pavlovian conditioning and extinction serve as a laboratory model for threat learning and exposure therapy, respectively. Studies utilizing these tasks can help uncover why exposure therapy fails to prevent the return of fear in some individuals. Pilot data suggest that there are specific behavioral phenotypes that individuals exhibit during a test of spontaneous recovery following Pavlovian acquisition and extinction. Specifically, some participants exhibit high spontaneous recovery, despite previously extinguishing their responses. The investigators hypothesize that individuals that exhibit this behavioral phenotype are also individuals for whom exposure therapy would be ineffective. These distinct phenotypes are also associated with different forms of computational inference, as revealed by fitting latent-cause inference models to behavioral data. In the case of individuals that exhibit high spontaneous recovery, latent cause inference modeling suggests that these participants are reinstating a latent cause associated with initial threat learning, which was protected from updating by the formation of a new cause during extinction. A separate line of work has focused on understanding the behavioral consequences and neural mechanisms of voluntary thought suppression, or inhibitory memory control. This is the process through which an individual can suppress a memory to reduce the influence that it has over future cognition and emotion. The neural mechanisms of retrieval inhibition are well known and involve top-down inhibition from the right dorsal-lateral prefrontal cortex (dlPFC) to the hippocampus. Here, the investigators aim to test the hypothesis that memory control ability is related to latent cause inference during Pavlovian conditioning and extinction, and by extension is related to spontaneous recovery. The goal of this project is to causally test this hypothesis by using real-time fMRI to directly strengthen individuals' memory control ability. Real-time fMRI (rt-fMRI) neurofeedback is a powerful tool that allows participants to modulate their own neural activity based on external cues (akin to biofeedback). Here, the investigators will provide participants feedback designed to help them increase their memory control ability. Specifically, the investigators will give participants positive feedback whenever the investigators detect negative dlPFC-hippocampal functional connectivity, which is the putative neural signature of successful memory inhibition. A control group will also be included, which will involve the delivery of sham placebo neurofeedback. The investigators predict that, following rt-fMRI neurofeedback, participants who received active neurofeedback aimed at increasing memory control will exhibit lower spontaneous recovery in a Pavlovian conditioning task compared to the control group.

Conditions

• Healthy

Interventions

Type	Name	Description
BEHAVIORAL	Active Real-time fMRI Neurofeedback	Active neurofeedback to target a functional connection associated with increased memory control ability
BEHAVIORAL	Sham Real-time fMRI neurofeedback	Sham neurofeedback

Timeline

• Start date: 2025-07-17
• Primary completion: 2027-12-01
• Completion: 2028-06-01
• First posted: 2025-08-14
• Last updated: 2026-02-23

Locations

1 site across 1 country: United States