## Protocol Section
### Identification Module
**NCT ID:** NCT06420557

**Acronym:** DecNef

**Brief Title:** Unconscious Reduction of Fear Through Decoded Neuro-Reinforcement

**Official Title:** Unconscious Reduction of Fear Through Decoded Neuro-Reinforcement

#### Organization Study ID Info
**ID:** R33MH135002
**Link:** https://reporter.nih.gov/quickSearch/R33MH135002
**Type:** NIH
#### Organization
**Class:** OTHER
**Full Name:** University of California, Los Angeles
### Status Module
#### Completion Date
**Date:** 2026-09-30

**Type:** ESTIMATED

#### Expanded Access Info
#### Last Update Post Date
**Date:** 2024-05-20

**Type:** ACTUAL

**Last Update Submit Date:** 2024-05-14

**Overall Status:** NOT_YET_RECRUITING

#### Primary Completion Date
**Date:** 2026-09-30

**Type:** ESTIMATED

#### Start Date
**Date:** 2024-06-01

**Type:** ESTIMATED

**Status Verified Date:** 2024-05

#### Study First Post Date
**Date:** 2024-05-20
**Type:** ACTUAL
**Study First Submit Date:** 2024-05-14
**Study First Submit QC Date:** 2024-05-14
### Sponsor Collaborators Module

#### Lead Sponsor

**Class:** OTHER

**Name:** University of California, Los Angeles

#### Responsible Party

**Investigator Affiliation:** University of California, Los Angeles

**Investigator Full Name:** Michelle Craske

**Investigator Title:** Distinguished Professor

**Type:** PRINCIPAL_INVESTIGATOR

### Oversight Module

**Is FDA Regulated Device:** False

**Is FDA Regulated Drug:** False

**Oversight Has DMC:** False

### Description Module

**Brief Summary:** 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.

**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.

### Conditions Module

**Conditions:**

- Phobia

**Keywords:**

- unconscious fear extinction

- anxiety disorders

- decoded neuro-reinforcement

### Design Module

#### Design Info

**Allocation:** RANDOMIZED

**Intervention Model:** PARALLEL

##### Masking Info

**Masking:** TRIPLE

**Who Masked:**

- PARTICIPANT

- INVESTIGATOR

- OUTCOMES_ASSESSOR

**Primary Purpose:** TREATMENT

#### Enrollment Info

**Count:** 60

**Type:** ESTIMATED

**Phases:**

- NA

**Study Type:** INTERVENTIONAL

### Arms Interventions Module

#### Arm Group 1

**Description:** 1 neuro-reinforcement session

**Intervention Names:**

- Behavioral: Unconscious Neuro-reinforcement

**Label:** 1 Session

**Type:** EXPERIMENTAL

#### Arm Group 2

**Description:** 3 neuro-reinforcement sessions

**Intervention Names:**

- Behavioral: Unconscious Neuro-reinforcement

**Label:** 3 Sessions

**Type:** EXPERIMENTAL

#### Arm Group 3

**Description:** 5 neuro-reinforcement sessions

**Intervention Names:**

- Behavioral: Unconscious Neuro-reinforcement

**Label:** 5 sessions

**Type:** EXPERIMENTAL

### Interventions

#### Intervention 1

**Arm Group Labels:**

- 1 Session

**Description:** 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.

**Name:** Unconscious Neuro-reinforcement

**Type:** BEHAVIORAL

#### Intervention 2

**Arm Group Labels:**

- 3 Sessions

**Description:** 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.

**Name:** Unconscious Neuro-reinforcement

**Type:** BEHAVIORAL

#### Intervention 3

**Arm Group Labels:**

- 5 sessions

**Description:** 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.

**Name:** Unconscious Neuro-reinforcement

**Type:** BEHAVIORAL

### Outcomes Module

#### Primary Outcomes

**Description:** 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.

**Measure:** Change in Amygdala Reactivity

**Time Frame:** 10 days (measured at pre-treatment and post-treatment)

**Description:** Subjective Fear Ratings of images of targeted phobic stimuli Minimum score of 0, Maximum score of 180, higher scores mean worse outcome.

**Measure:** Subjective Fear Post-treatment Minus Pre-treatment

**Time Frame:** 10 days (measured at pre-treatment and post-treatment)

#### Secondary Outcomes

**Description:** Skin conductance to image presentation of targeted phobic stimuli post-treatment minus pre-treatment

**Measure:** Skin Conductance Response: Physiological Arousal Post-treatment Minus Pre-treatment

**Time Frame:** 10 days (measured at pre-treatment and post-treatment)

**Description:** Subjective fear ratings of a list of typical phobic stimuli Minimum score of 40, maximum of 200, higher scores mean worse outcome.

**Measure:** Fear Survey Schedule

**Time Frame:** 10 days (measured at pre-treatment and post-treatment)

**Description:** Measure of preferential allocation of attentional resources measured in reaction time (seconds) for visual presentation of the targeted phobic stimulus

**Measure:** Stroop Task Post-treatment Minus Pre-treatment

**Time Frame:** 10 days (measured at pre-treatment and post-treatment)

**Description:** Maximal approach distance will be assessed in a behavioral avoidance test conducted in a virtual reality context. The Behavioral Approach Task (BAT) 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 BAT include a) maximal approach distance and b) subjective fear ratings at each distance.

**Measure:** Approach/Avoidance Behavior in VR Post-treatment Minus Pre-treatment

**Time Frame:** 10 days (measured at pre-treatment and post-treatment)

**Description:** Subjective fear ratings will be assessed at each distance in a behavioral avoidance test conducted in a virtual reality context. The BAT 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.

**Measure:** Subjective Fear Ratings in Virtual Reality (VR) Post-treatment Minus Pre-treatment

**Time Frame:** 10 days (measured at pre-treatment and post-treatment)

**Description:** Self-reported depression severity. Scores range from 0-27, with higher scores indicating greater severity.

**Measure:** Patient Health Questionnaire (PHQ-9)

**Time Frame:** 10 days (measured at pre-treatment and post-treatment)

**Description:** Self-reported anxiety severity. Scores range from 0-21, with higher scores indicating greater severity.

**Measure:** Generalized Anxiety Disorder-7 (GAD-7)

**Time Frame:** 10 days (measured at pre-treatment and post-treatment)

### Eligibility Module

**Eligibility Criteria:** 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: PTSD, Obsessive Compulsive Disorder, Substance Use Disorder, Current Major Depression, Bipolar Disorder, Psychosis, neurologic diagnoses or unstable serious medical conditions
5. Individual does not present with more than one object of specific phobia
6. Individual can touch the phobic object category during the pre-treatment Behavioral Approach Test without presenting significant distress
7. Individual is currently prescribed psychotropic medication

**Maximum Age:** 65 Years

**Minimum Age:** 18 Years

**Sex:** ALL

**Standard Ages:**

- ADULT

- OLDER_ADULT

### Contacts Locations Module

#### Central Contacts

**Contact 1:**

**Email:** shawnwang@psych.ucla.edu

**Name:** Shawn Wang, B.A.

**Phone:** 916-792-1756

**Role:** CONTACT

**Contact 2:**

**Email:** brookecullen@psych.ucla.edu

**Name:** Brooke Cullen, B.A.

**Phone:** 310-990-4459

**Role:** CONTACT

#### Locations

**Location 1:**

**City:** Los Angeles

**Country:** United States

**Facility:** University of California, Los Angeles

**State:** California

**Zip:** 90095

## Derived Section

### Condition Browse Module - Ancestors

- ID: D000003244

- Term: Consciousness Disorders

- ID: D000019954

- Term: Neurobehavioral Manifestations

- ID: D000009461

- Term: Neurologic Manifestations

- ID: D000009422

- Term: Nervous System Diseases

### Condition Browse Module - Browse Branches

- Abbrev: BXM

- Name: Behaviors and Mental Disorders

- Abbrev: All

- Name: All Conditions

- Abbrev: BC10

- Name: Nervous System Diseases

- Abbrev: BC23

- Name: Symptoms and General Pathology

### Condition Browse Module - Browse Leaves

- ID: M4324

- Name: Anxiety Disorders

- Relevance: LOW

- As Found: Unknown

- ID: M17224

- Name: Unconsciousness

- Relevance: HIGH

- As Found: Unconscious

- ID: M13603

- Name: Phobic Disorders

- Relevance: LOW

- As Found: Unknown

- ID: M6468

- Name: Consciousness Disorders

- Relevance: LOW

- As Found: Unknown

- ID: M21826

- Name: Neurobehavioral Manifestations

- Relevance: LOW

- As Found: Unknown

- ID: M12404

- Name: Neurologic Manifestations

- Relevance: LOW

- As Found: Unknown

### Condition Browse Module - Meshes

- ID: D000014474

- Term: Unconsciousness

### Misc Info Module

- Version Holder: 2024-05-31
