Unconscious Reduction of Fear Through Decoded Neuro-Reinforcement (DecNef)

This application investigates the efficacy of a novel method of neuro-reinforcement based on decoded fMRI activity to reduce fear responses in individuals with phobias (e.g., spiders, snakes). This method works unconsciously in the brain, without the need for participants to endure repeated conscious exposures to their feared stimuli. Fear-related disorders such as specific phobia, post-traumatic stress disorder (PTSD), and other anxiety disorders present a major challenge, as effective treatment options usually involve repeated exposures to feared stimuli, leading to high levels of distress, fear, and panic that can motivate premature treatment termination. Consequently, there is an unmet need for treatment that minimizes subjective discomfort and attrition in order to maximize efficacy. Recent developments in computational neuroimaging have enabled a method that can deliver unconscious exposure to feared stimuli, resulting in effective fear reduction while bypassing a primary cause of treatment attrition. Because this treatment method happens unconsciously in the brain, changes in behavior outcomes are potentially more likely to generalize to different contexts, thereby overcoming a limitation of traditional treatments.

Study Overview

• Status: Recruiting
• Conditions: Phobia
• Intervention / Treatment: Behavioral: Unconscious Neuro-reinforcement; Behavioral: Unconscious Neuro-reinforcement; Behavioral: Unconscious Neuro-reinforcement

Detailed Description

The gold standard treatment for specific phobias is exposure therapy, wherein the individual repeatedly faces the object of their fear. However, for many patients, the level of distress prohibits them from either starting or completing exposure therapy. The objective of this application is to use focal neuro-reinforcement based on decoded fMRI information (from the ventral temporal temporal cortex) to reduce fear responses to feared animal stimuli (e.g., spiders, birds) in individuals with phobias, directly and unconsciously in the brain, without repeatedly consciously exposing participants to their feared stimuli. Because the induced representations are unconscious, participants do not experience negative emotional responses and the procedure is double-blind placebo-controlled, thus providing a level of experimental rigor not afforded to standard psychological therapies. Extending from our pilot data, we are positioned to test the mechanisms and behavioral outcomes of a novel treatment for phobias that at the same time advances our understanding of the role of consciousness in fear responses and their change over time. The specific aims are to: (1) confirm that our method engages the neurobiological target (amygdala reactivity to images of feared animals) in a population of individuals with specific phobias of animals; (2) quantify how changes in amygdala reactivity with neuro-reinforcement mediate changes in behavioral outcomes, as measured by attentional capture, approach/avoidance behavior, or subjective fear ratings, immediately post neuro-reinforcement; (3) assess the longer term effects four weeks after neuro-reinforcement; and (4) explore the impact of three dosage levels of neuro-reinforcement to identify the optimal dosage for future research. If proven effective, the results will inform applications for other fear related disorders, such as posttraumatic stress disorder, social anxiety disorder and panic disorder.

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

Contacts and Locations

• Study Contact: Name: Kainoa R MacDonald, B.A.; Email: macdonald@psych.ucla.edu
• Study Contact Backup: Name: Gabriel J Fiol, B.A.; Phone Number: 7252228834; Email: gfiol@psych.ucla.edu

Study Locations

• United States
  • California
    • Los Angeles, California, United States, 90095
      • Recruiting
      • University of California, Los Angeles
      • Contact: Michelle G Craske, PhD; Phone Number: 310-206-9191; Email: MCraske@mednet.ucla.edu
      • Principal Investigator: Michelle G. Craske, Ph.D

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Individual has normal or corrected to normal vision
2. Individual has normal or corrected to normal hearing
3. Individual is competent to understand informed consent
4. Individual must meet the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) diagnostic criteria for specific phobias, animal subtype

Exclusion Criteria:

1. Individual is unable to fill in consent form correctly
2. Individual is unable to respond adequately to screening questions
3. Individual is unable to maintain focus or to sit during assessment
4. Individual has history of: neurological disease or defect (e.g., stroke, traumatic brain injury, schizophrenia or other psychological disorders, or seizures) Individual has vision problems (including cataracts, amblyopia, or glaucoma) Individual presents with: Obsessive Compulsive Disorder, Substance Use Disorder, Bipolar Disorder, Psychosis, neurologic diagnoses or unstable serious medical conditions
5. Participant receives an elevated score on the PHQ-9
6. Individual does not present with more than one object of specific phobia
7. Individual can touch the phobic object category during the pre-treatment Behavioral Approach Test without presenting significant distress
8. Individual is currently prescribed psychotropic medication

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 1 Session; 1 neuro-reinforcement session	Behavioral: Unconscious Neuro-reinforcement; Individuals will complete an implicit fmri neuro-reinforcement task where real-time brain activity is matched to a desired activation. Individuals will also receive financial reward for activating the desired activation. Visual feedback will be presented to indicate how well individuals' brain activity matches the desired activation. Individuals will complete 1 session of neuro-reinforcement.; Behavioral: Unconscious Neuro-reinforcement; Individuals will complete an implicit fmri neuro-reinforcement task where real-time brain activity is matched to a desired activation. Individuals will also receive financial reward for activating the desired activation. Visual feedback will be presented to indicate how well individuals' brain activity matches the desired activation. Individuals will complete 3 sessions of neuro-reinforcement.; Behavioral: Unconscious Neuro-reinforcement; Individuals will complete an implicit fmri neuro-reinforcement task where real-time brain activity is matched to a desired activation. Individuals will also receive financial reward for activating the desired activation. Visual feedback will be presented to indicate how well individuals' brain activity matches the desired activation. Individuals will complete 5 sessions of neuro-reinforcement.
Experimental: 3 Sessions; 3 neuro-reinforcement sessions	Behavioral: Unconscious Neuro-reinforcement; Individuals will complete an implicit fmri neuro-reinforcement task where real-time brain activity is matched to a desired activation. Individuals will also receive financial reward for activating the desired activation. Visual feedback will be presented to indicate how well individuals' brain activity matches the desired activation. Individuals will complete 1 session of neuro-reinforcement.; Behavioral: Unconscious Neuro-reinforcement; Individuals will complete an implicit fmri neuro-reinforcement task where real-time brain activity is matched to a desired activation. Individuals will also receive financial reward for activating the desired activation. Visual feedback will be presented to indicate how well individuals' brain activity matches the desired activation. Individuals will complete 3 sessions of neuro-reinforcement.; Behavioral: Unconscious Neuro-reinforcement; Individuals will complete an implicit fmri neuro-reinforcement task where real-time brain activity is matched to a desired activation. Individuals will also receive financial reward for activating the desired activation. Visual feedback will be presented to indicate how well individuals' brain activity matches the desired activation. Individuals will complete 5 sessions of neuro-reinforcement.
Experimental: 5 sessions; 5 neuro-reinforcement sessions	Behavioral: Unconscious Neuro-reinforcement; Individuals will complete an implicit fmri neuro-reinforcement task where real-time brain activity is matched to a desired activation. Individuals will also receive financial reward for activating the desired activation. Visual feedback will be presented to indicate how well individuals' brain activity matches the desired activation. Individuals will complete 1 session of neuro-reinforcement.; Behavioral: Unconscious Neuro-reinforcement; Individuals will complete an implicit fmri neuro-reinforcement task where real-time brain activity is matched to a desired activation. Individuals will also receive financial reward for activating the desired activation. Visual feedback will be presented to indicate how well individuals' brain activity matches the desired activation. Individuals will complete 3 sessions of neuro-reinforcement.; Behavioral: Unconscious Neuro-reinforcement; Individuals will complete an implicit fmri neuro-reinforcement task where real-time brain activity is matched to a desired activation. Individuals will also receive financial reward for activating the desired activation. Visual feedback will be presented to indicate how well individuals' brain activity matches the desired activation. Individuals will complete 5 sessions of neuro-reinforcement.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Amygdala Reactivity	The neural measure of difference in amygdala reactivity (measured by fMRI) to target phobic animals compared to control phobic animals from pre-treatment to post-treatment. Lower numbers (i.e. more negative numbers) indicate greater amygdala decrease and and better outcomes.	14 days (measured at pre-treatment and 2 weeks)
Subjective Fear Post-treatment Minus Pre-treatment	Subjective Fear Ratings of images of targeted phobic stimuli Minimum score of 0, Maximum score of 180, higher scores mean worse outcome.	14 days (measured at pre-treatment and 2 weeks)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Skin Conductance Response: Physiological Arousal Post-treatment Minus Pre-treatment	Skin conductance to image presentation of targeted phobic stimuli post-treatment minus pre-treatment	14 days (measured at pre-treatment and 2 weeks)
Fear Survey Schedule	Subjective fear ratings of a list of typical phobic stimuli Minimum score of 40, maximum of 200, higher scores mean worse outcome.	14 days (measured at pre-treatment and 2 weeks)
Stroop Task Post-treatment Minus Pre-treatment	Measure of preferential allocation of attentional resources measured in reaction time (seconds) for visual presentation of the targeted phobic stimulus	14 days (measured at pre-treatment and 2 weeks)
Approach/Avoidance Behavior in VR Post-treatment Minus Pre-treatment	Maximal approach distance will be assessed in a behavioral approach test conducted in a virtual reality context. The Behavioral Approach Test follows a ten-step procedure of increasing difficulty to approach a feared animal (e.g. snakes), beginning with a first step such as standing in the same room as the feared animal. Then, participants approach the feared animal step-by-step, taking time at each step, until a final step such as holding the feared animal or having it touch you is reached. Behavioral outcomes that will be measured from the Behavioral Approach Test include a) maximal approach distance and b) subjective fear ratings at each distance. Minimum score for approach distance is 1, and highest is 10 (numbers represent steps taken toward fearful stimulus). Higher scores represent a better outcome on this task.	14 days (measured at pre-treatment and 2 weeks)
Subjective Fear Ratings in Virtual Reality (VR) Post-treatment Minus Pre-treatment	Subjective fear ratings will be assessed at each distance in a behavioral approach test conducted in a virtual reality context. The Behavioral Approach Test follows a ten-step procedure of increasing difficulty to approach a feared animal (e.g. snakes), beginning with a first step such as standing in the same room as the feared animal. Then, participants approach the feared animal step-by-step, taking time at each step, until a final step such as holding the feared animal or having it touch you is reached. Minimum score for subjective fear is 1, and maximum is 8. Higher scores represent a worse outcome on this task.	14 days (measured at pre-treatment and 2 weeks)
Patient Health Questionnaire (PHQ-9)	Self-reported depression severity. Scores range from 0-27, with higher scores indicating greater severity.	14 days (measured at pre-treatment and 2 weeks)
Generalized Anxiety Disorder-7 (GAD-7)	Self-reported anxiety severity. Scores range from 0-21, with higher scores indicating greater severity.	14 days (measured at pre-treatment and 2 weeks)
Severity of Phobias questionnaire	Self-report severity of phobias rating; 10 items. Scores range from "Never" to "All of the time," with a higher score indicating greater severity.	14 days/6 weeks (measured at pre-treatment, 2 weeks, and 6 weeks)
Behavioral Inhibition/Behavioral Activation Scales (BIS/BAS)	Self-report behavioral inhibition/activation rating; 20 items. Scores range from "Very true for me" to "Very false for me," with a higher score indicating greater severity.	0 days (measured at pre-treatment)
Vividness of Visual Imagery Questionnaire (VVIQ)	Self-report vividness of visual imagery; 16 items. Scores range from "No image at all, you only "know" that you are thinking of the object" to "Perfectly real and vivid as real seeing," where higher scores indicate greater vividness of imagery.	0 days (measured at pre-treatment)

Collaborators and Investigators

• Sponsor: University of California, Los Angeles
• Collaborators: National Institute of Mental Health (NIMH)
• Investigators: Principal Investigator: Michelle G Craske, PhD, University of California, Los Angeles

Study record dates

Study Major Dates

• Study Start (Actual): September 9, 2024
• Primary Completion (Estimated): September 30, 2026
• Study Completion (Estimated): September 30, 2026

Study Registration Dates

• First Submitted: May 14, 2024
• First Submitted That Met QC Criteria: May 14, 2024
• First Posted (Actual): May 20, 2024

Study Record Updates

• Last Update Posted (Estimated): October 2, 2025
• Last Update Submitted That Met QC Criteria: September 26, 2025
• Last Verified: September 1, 2025

More Information

Terms related to this study

• Keywords: anxiety disorders; unconscious fear extinction; decoded neuro-reinforcement
• Additional Relevant MeSH Terms: Mental Disorders; Anxiety Disorders; Phobic Disorders
• Other Study ID Numbers: 23-001604; R33MH135002 (U.S. NIH Grant/Contract)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No