Treating Phobia With Multivoxel Neuro-reinforcement

Specific phobias and other anxiety disorders represent a major mental health problem, and present a significant challenge to researchers because effective treatment usually involves repeated exposure to feared stimuli, and the high levels of associated distress can lead to termination of treatment. Recent advances in computational functional magnetic resonance imaging (fMRI) provide a method by which individuals may be unconsciously exposed to fearful stimuli, leading to effective fear reduction while eliminating a primary cause of attrition.

The objective of the current study is to use the novel approach of neuro-reinforcement based on decoded fMRI information to reduce fear responses to fearful stimuli (e.g., spiders, heights) in individuals with phobias, directly and unconsciously in the brain, without repeatedly exposing participants to their feared stimuli.

Participants will be randomized into one of three groups of varying neuro-reinforcement sessions (1, 3, or 5). They will complete tests of subjective fear and directed attention while being scanned by fMRI to measure engagement of amygdala activity to fearful stimuli as well as measured through other indicators of fear such as skin conductance response.

Study Overview

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

Detailed Description

Anxiety disorders, the most common group of mental disorders in the United States, represent a major mental health problem. Phobias, in which fear and anxiety are triggered by a specific stimulus or situation, are the largest category of anxiety disorders and affect 5 - 12% of the world's population.

Exposure-based therapies are effective in reducing symptoms, but their effectiveness depends on the individual's capacity or willingness to consciously confront their feared object. The associated distress can be so extreme that it prevents patients from seeking treatment, and contributes to attrition from exposure once treatment begins. As a result, there is an unmet need for treatment that minimizes attrition and subjective patient discomfort.

The current study uses a novel technique of neuro-reinforcement based on decoded fMRI information to reduce fear responses to fearful stimuli directly and unconsciously without repeatedly exposing participants to those stimuli. The goals are to (1) confirm that our method decreases amygdala reactivity to images of phobic stimuli as well as (2) determine dosage-response optimization.

• Study Type: Interventional
• Enrollment (Actual): 23
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • California
    • Los Angeles, California, United States, 90095
      • University of California, Los Angeles

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Individual has normal or corrected to normal vision
• Individual has normal or corrected to normal hearing
• Individual is competent to understand informed consent

Exclusion Criteria:

• Individual is unable to fill in consent form correctly
• Individual is unable to respond adequately to screening questions
• Individual is unable to maintain focus or to sit during assessment
• 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
• Individual does not present with more than one object of specific phobia
• Individual can touch the phobic object category during the pre¬treatment Behavioral Approach Test without presenting significant distress
• 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 x day(s) 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 x day(s) 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 x day(s) of neuro-reinforcement.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	10 days (measured at pre-treatment and post-treatment)
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.	10 days (measured at pre-treatment and post-treatment)

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	10 days (measured at pre-treatment and post-treatment)
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.	10 days (measured at pre-treatment and post-treatment)
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	10 days (measured at pre-treatment and post-treatment)

Collaborators and Investigators

• Sponsor: University of California, Los Angeles

Study record dates

Study Major Dates

• Study Start (Actual): October 1, 2018
• Primary Completion (Actual): June 30, 2022
• Study Completion (Actual): June 30, 2022

Study Registration Dates

• First Submitted: August 28, 2018
• First Submitted That Met QC Criteria: August 29, 2018
• First Posted (Actual): August 31, 2018

Study Record Updates

• Last Update Posted (Actual): February 2, 2024
• Last Update Submitted That Met QC Criteria: January 31, 2024
• Last Verified: January 1, 2024

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: R61MH113772 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No