Neurofeedback to Reduce Spontaneous Recovery of Threat Expectancy

Trustees of Princeton University

Status: Enrolling

Conditions: Healthy

Treatments: Behavioral: Sham Real-time fMRI neurofeedback; Behavioral: Active Real-time fMRI Neurofeedback

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT07122739

P50MH136296-8441-33a

P50MH136296 (U.S. NIH Grant/Contract)

Details and patient eligibility

About

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.

Full 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.

Enrollment: 40 estimated patients

Sex: All

Ages: 18 to 50 years old

Volunteers: Accepts Healthy Volunteers

Inclusion criteria

• Adults aged 18-50
• No history of psychiatric disorders or neurological disorders affecting the central nervous system.
• Are not currently taking psychoactive medication or drugs of abuse.
• Must be eligible to enter an MRI (i.e., no permanent metal or medical implants)
• Normal color vision
• Right-handed
• Full reading and writing English comprehension
• Must exhibit spontaneous recovery behavior as determined by an experimenter in a prescreening experimental session
• Must be able to provide informed consent

Exclusion criteria

• Pregnancy (female participants)
• Outside of age range
• History of psychiatric or neurological disease
• Currently taking psychoactive medication or drugs of abuse
• Color blindness
• Primary left-handedness
• Less than full reading and writing English comprehension
• Do not exhibit spontaneous recovery behavior as determined by an experimenter in a prescreening experimental session
• Refusing to provide informed consent

Trial design

Primary purpose: Basic Science

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Single Blind

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40 participants in 2 patient groups

Active Neurofeedback

Experimental group

Description:

Active neurofeedback will reinforce negative dlPFC-hippocampal functional connectivity, as this is expected to increase memory control ability.

Treatment:

Behavioral: Active Real-time fMRI Neurofeedback

Control Neurofeedback

Sham Comparator group

Description:

Participants in the control neurofeedback group will receive the same instructions as the experimental group, but will receive sham neurofeedback.

Treatment:

Behavioral: Sham Real-time fMRI neurofeedback