HealthyNCT07122739
Neurofeedback to Reduce Spontaneous Recovery of Threat Expectancy
A study testing Active Real-time fMRI Neurofeedback in people with Healthy, run by Trustees of Princeton University at 1 site in United States.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 to 50 yearsHealthy volunteers can take part
- Conditions the study is for
- Healthy
- What is being tested?
- Active Real-time fMRI Neurofeedback
- Type of treatment
- Lifestyle or therapy programme
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 40 participants
- Where
- 1 siteUnited States
- Study dates
- 17 Jul 2025to Jun 2028
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 50 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- 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
Show all 9Show fewer
- 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
Who cannot join
- 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
Show all 9Show fewer
- 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 locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
Princeton Neuroscience Institute
Princeton, New Jersey, 08540
Augustin C. Hennings, Ph.D., gus.hennings@princeton.edu
About this study
Official title: Reducing Spontaneous Recovery Using Functional Connectivity Based Real-time Functional Magnetic Resonance Imaging Neurofeedback Targeting the Memory Control Network
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.
Read the 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
- Being tested
- Active Real-time fMRI Neurofeedback, Sham Real-time fMRI neurofeedback
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Active Real-time fMRI NeurofeedbackBehavioural
Active neurofeedback to target a functional connection associated with increased memory control ability
Sham Real-time fMRI neurofeedbackBehavioural
Sham neurofeedback
| Study group | Role | What they receive |
|---|---|---|
| Active Neurofeedback | Experimental | Active neurofeedback will reinforce negative dlPFC-hippocampal functional connectivity, as this is expected to increase memory control ability. Receives: Behavioral: Active Real-time fMRI Neurofeedback |
| Control Neurofeedback | Sham comparator | Participants in the control neurofeedback group will receive the same instructions as the experimental group, but will receive sham neurofeedback. Receives: Behavioral: Sham Real-time fMRI neurofeedback |
What is being measured
The primary outcome is the main question the study is designed to answer.
Spontaneous recovery behavior
The investigators will assess neurofeedback related changes in behavioral threat expectancy ratings in a discriminatory Pavlovian conditioning task. Spontaneous recovery is taken as the difference in responding to the conditioned stimulus that was paired with an outcome (CS+) vs. the conditioned stimulus that was not paired with an outcome (CS-) during a test of extinction recall following acquisition and extinction learning.
Measured: Baseline and fourth fMRI session (out of four total fMRI sessions). At most 60 days will elapse between the start of data collection for a participant and their final fMRI session.
Secondary outcomes (1)
Neurofeedback learning
The investigators will assess the overall trend in neurofeedback scores over the course of the intervention. If neurofeedback learning is successful, the investigators expect participants in the experimental group to increase the number of positive neurofeedback instances as the experiment progresses.
Measured: Second and third fMRI sessions (out of four total fMRI sessions). At most 60 days will elapse between the start of data collection for a participant and their final fMRI session.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Aug 2025
- Study start17 Jul 2025
- Primary completionDec 2027 (estimated)
- Study completionJun 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for HealthyStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Participant
- Enrolment
- 40 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Trustees of Princeton University
- Sponsor type
- University, hospital or other
- Collaborators
- National Institute of Mental Health (NIMH)
- Responsible party
- Sponsor
- Investigators
- Kenneth A. Norman, Ph.D., Principal investigator, Princeton University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07122739
- Sponsor's protocol ID
- 14852
- Other IDs
- P50MH136296
- Status last verified
- Feb 2026
- First submitted
- 1 Aug 2025
- Last updated
- 23 Feb 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: Anonymized data will be uploaded to the NIMH Data Archive (NDA).
Study at a glance
From the registry record, last updated by the sponsor on 23 Feb 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Reducing Spontaneous Recovery Using Functional Connectivity Based Real-time Functional Magnetic Resonance Imaging Neurofeedback Targeting the Memory Control Network
- ClinicalTrials.gov ID
- NCT07122739
- Acronym / sponsor ID
- 14852
- Conditions
- Healthy
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 40 participants (estimated)
- Lead sponsor
- Trustees of Princeton UniversityUniversity, hospital or other
- Collaborators
- National Institute of Mental Health (NIMH)
- Study start
- 17 Jul 2025 (actual)
- Primary completion
- Dec 2027 (estimated)
- Study completion
- Jun 2028 (estimated)
- First posted
- 14 Aug 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (participant)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Active Neurofeedback | Experimental | Behavioral: Active Real-time fMRI NeurofeedbackActive neurofeedback will reinforce negative dlPFC-hippocampal functional connectivity, as this is expected to increase memory control ability. |
| Control Neurofeedback | Sham comparator | Behavioral: Sham Real-time fMRI neurofeedbackParticipants in the control neurofeedback group will receive the same instructions as the experimental group, but will receive sham neurofeedback. |
Who may qualify
- Ages
- 18 to 50 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (9 listed)
- 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
Key exclusion criteria (9 listed)
- Pregnancy (female participants)
- Outside of age range
- History of psychiatric or neurological disease
- Currently taking psychoactive medication or drugs of abuse
- Color blindness
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Active Real-time fMRI NeurofeedbackActive neurofeedback to target a functional connection associated with increased memory control ability | Behavioural | Active Neurofeedback |
| Sham Real-time fMRI neurofeedbackSham neurofeedback | Behavioural | Control Neurofeedback |
Primary outcome
Spontaneous recovery behavior
Time frame: Baseline and fourth fMRI session (out of four total fMRI sessions). At most 60 days will elapse between the start of data collection for a participant and their final fMRI session.
The investigators will assess neurofeedback related changes in behavioral threat expectancy ratings in a discriminatory Pavlovian conditioning task. Spontaneous recovery is taken as the difference in responding to the conditioned stimulus that was paired with an outcome (CS+) vs. the conditioned stimulus that was not paired with an outcome (CS-) during a test of extinction recall following acquisition and extinction learning.
1 secondary outcome
Neurofeedback learning
Time frame: Second and third fMRI sessions (out of four total fMRI sessions). At most 60 days will elapse between the start of data collection for a participant and their final fMRI session.
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Feb 2026.
- Individual participant dataSharing planned: No. Anonymized data will be uploaded to the NIMH Data Archive (NDA).
Related trials for Healthy
Recruiting
THE EFFECTS OF GAME-BASED EXERCISE PROGRAMS
Physical Activity, Body Image
Not yet recruitingPhase 1
A Phase I Study of GLR2053 Tablets in Chinese Healthy Adult Participants
Atopic Dermatitis
Recruiting
Colon-delivered Riboflavin and Gut Microbiota Composition
Microbiome Dysbiosis, Gut Health
Not yet recruiting
Neuroergonomic Analysis of a Brain-Computer Interface Device (BCI)
Healthy Volunteers - Male and Female
RecruitingPhase 1
First-in-Human Trial to Assess REGN20423 in Healthy Adult Participants and Adult Participants With Atopic Dermatitis
Healthy Volunteer, Atopic Dermatitis
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Kenneth A. Norman, Ph.D. principal investigator
Princeton University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Active Real-time fMRI Neurofeedback in people with Healthy, run by Trustees of Princeton University at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 23 Feb 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Augustin C. Hennings, Ph.D. (609-258-5032, gus.hennings@princeton.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Spontaneous recovery behavior (time frame: Baseline and fourth fMRI session (out of four total fMRI sessions). At most 60 days will elapse between the start of data collection for a participant and their final fMRI session.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 Feb 2026.