Unconscious Neuro-reinforcement for Anxiety Disorders

(DecNef Trial)

Overseen By Gabriel J Fiol, B.A.

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: University of California, Los Angeles

Must not be taking: Psychotropic medication

Disqualifiers: Neurological disease, Vision problems, OCD, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 2

60 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new method to help people with phobias, such as fear of spiders or snakes, by using brain activity decoded from MRI scans to reduce fear without direct exposure. The goal is to determine the effectiveness of this method, called Unconscious Neuro-reinforcement (also known as Decoded Neuro-reinforcement or Multi-voxel Neuro-reinforcement), in lowering fear responses and its potential to aid anxiety disorders like PTSD. The trial includes groups receiving one, three, or five sessions of this treatment. Suitable participants have normal vision and hearing, can understand consent forms, and have specific animal-related phobias. As an unphased trial, this study offers a unique opportunity to contribute to innovative research that could transform phobia treatment.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but it excludes individuals who are currently prescribed psychotropic medication (drugs that affect mood, perception, or behavior).

What prior data suggests that this neuro-reinforcement method is safe for anxiety disorders?

Research has shown that a new method called unconscious neuro-reinforcement can reduce fear without direct confrontation. This technique uses brain imaging to engage the brain's fear centers without causing distress. Studies have found that this method effectively lowers fear responses, and participants generally tolerated the treatment well. No major side effects were reported, indicating safety. By avoiding direct exposure to feared stimuli, this method reduces the stress and discomfort often associated with traditional treatments. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about unconscious neuro-reinforcement for anxiety disorders because it offers a fresh approach compared to traditional treatments like cognitive-behavioral therapy or medication. Unlike these standard methods that require conscious effort or chemical intervention, neuro-reinforcement works by subtly retraining the brain's response to anxiety triggers without the patient needing to be actively engaged. This technique is also promising because it can potentially show benefits with a minimal number of sessions, ranging from just one to five, making it a more time-efficient option. By tapping directly into the brain's unconscious processes, this method could provide a quicker, more targeted way to alleviate anxiety symptoms.

What evidence suggests that Unconscious Neuro-reinforcement is effective for anxiety disorders?

Research shows that a technique called unconscious neuro-reinforcement can help reduce fear in people with phobias, such as fear of spiders or snakes. This method uses a special brain scan to change how the brain reacts to scary things without requiring people to face their fears directly. Studies have found that it can lower activity in the amygdala, the part of the brain that handles fear, making it less sensitive to fear-inducing stimuli. The trial will explore different treatment arms, with participants receiving either 1, 3, or 5 neuro-reinforcement sessions. This approach helps avoid the stress and panic often associated with traditional treatments, which can lead to early dropout. Overall, early findings suggest that this method could be a promising alternative for treating anxiety disorders without the usual discomfort. ^{1 2 3 4 6}

Who Is on the Research Team?

Michelle G. Craske, Ph.D

Principal Investigator

University of California, Los Angeles

Are You a Good Fit for This Trial?

This trial is for individuals with phobias or anxiety disorders like PTSD, who are looking for a treatment that doesn't involve consciously facing their fears. Participants should be comfortable undergoing fMRI scans and not have conditions that exclude them from such procedures.

Inclusion Criteria

Individual must meet the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) diagnostic criteria for specific phobias, animal subtype

My hearing is normal or corrected to normal.

I understand the details and implications of the clinical trial.

Exclusion Criteria

Individual is unable to fill in consent form correctly

I have vision problems like cataracts, lazy eye, or glaucoma.

Individual does not present with more than one object of specific phobia

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Neuro-reinforcement Treatment

Participants undergo neuro-reinforcement sessions using decoded fMRI activity to reduce fear responses

2 weeks

1-5 sessions (in-person)

Follow-up

Participants are monitored for changes in amygdala reactivity and behavioral outcomes post-treatment

4 weeks

1 visit (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• Unconscious Neuro-reinforcement

Trial Overview The study tests an innovative neuro-reinforcement method using decoded fMRI to reduce fear responses without conscious exposure to the feared subject. It aims to provide a less distressing alternative to traditional treatments by working unconsciously.

How Is the Trial Designed?

Group I: 5 sessions Experimental Treatment 1 Intervention

5 neuro-reinforcement sessions

Group II: 3 Sessions Experimental Treatment 1 Intervention

3 neuro-reinforcement sessions

Group III: 1 Session Experimental Treatment 1 Intervention

1 neuro-reinforcement session

Who Is Running the Clinical Trial?

University of California, Los Angeles

Lead Sponsor

Trials

1,594

Recruited

10,430,000+

National Institute of Mental Health (NIMH)

Collaborator

Trials

3,007

Recruited

2,852,000+

Published Research Related to This Trial

In a study involving 45 individuals with spider phobia, exposure therapy was found to be significantly more effective than progressive muscle relaxation, with a large effect size (Cohen's d = 0.90) in reducing symptoms.

Neural activation in the ventromedial prefrontal cortex (vmPFC) during early extinction learning, particularly related to prediction errors, was a strong predictor of how well participants responded to exposure therapy, suggesting that these neural processes are crucial for effective treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neural responses during extinction learning predict exposure therapy outcome in phobia: results from a randomized-controlled trial. Lange, I., Goossens, L., Michielse, S., et al.[2021]

The study used fMRI to explore how healthy volunteers respond to fearful faces, revealing that unconscious processing activates the basolateral amygdala, while conscious processing activates the dorsal amygdala.

Individual differences in trait anxiety influenced how the basolateral amygdala responded to unconscious stimuli, suggesting a biological basis for the heightened emotional vigilance seen in anxiety, which could inform future anxiety treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Individual differences in trait anxiety predict the response of the basolateral amygdala to unconsciously processed fearful faces. Etkin, A., Klemenhagen, KC., Dudman, JT., et al.[2019]

A brief computerized intervention targeting anxiety sensitivity (AS) was effective in reducing AS symptoms, anxiety, and depression in participants, with 67 receiving the treatment and 60 in a control group.

Lower occipital alpha power, a neurophysiological measure of attentional control, was linked to faster reductions in AS and lower anxiety and depression levels at a 1-month follow-up, suggesting that attentional control may influence treatment efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A multimethod investigation of the impact of attentional control on a brief intervention for anxiety and depression. Allan, NP., Albanese, BJ., Judah, MR., et al.[2020]

Subliminal exposure to phobic stimuli can trigger physiological responses such as cardiac defense reactions and specific brain activations, particularly in the amygdala, without causing the distress associated with traditional exposure therapies.

While subliminal exposure does not significantly reduce subjective fear levels, it can effectively lead to the extinction of psychophysiological and behavioral responses, suggesting a potential new approach to exposure therapy that incorporates subliminal stimulation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Systematic Review of Studies on Subliminal Exposure to Phobic Stimuli: Integrating Therapeutic Models for Specific Phobias. Frumento, S., Menicucci, D., Hitchcott, PK., et al.[2021]

The integration of neuroscience with psychological models enhances our understanding of exposure therapy, particularly how attention to emotional content can help regulate the amygdala through prefrontal control.

Neuroimaging research suggests that adding new emotional context during exposure therapy can improve treatment outcomes for anxiety and depression by facilitating inhibitory signals from the hippocampus.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Does neuroscience hold promise for the further development of behavior therapy? The case of emotional change after exposure in anxiety and depression. De Raedt, R.[2021]

Very brief exposure (VBE) to masked phobic stimuli, like spiders, activated brain regions associated with emotion regulation and fear extinction in women with spider phobia, indicating a potential mechanism for reducing fear without conscious awareness.

Participants who underwent VBE showed a significant reduction in avoidance behavior towards a live tarantula, demonstrating the efficacy of this method in treating specific phobias without any reported adverse effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Brain-based mediation of non-conscious reduction of phobic avoidance in young women during functional MRI: a randomised controlled experiment. Siegel, P., Wang, Z., Murray, L., et al.[2021]

Recent advancements in cognitive neuroscience, particularly through techniques like Decoded Neural-Reinforcement, allow for the manipulation of unconscious processes in psychological treatments without engaging conscious awareness.

This innovative approach can enhance the design of double-blind placebo-controlled studies and reduce patient dropouts during fear treatment, suggesting potential benefits for other survival-related physiological processes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Unconscious Psychological Treatments for Physiological Survival Circuits. Taschereau-Dumouchel, V., Liu, KY., Lau, H.[2020]

A novel method using functional MRI decoding allows for the reprogramming of physiological fear responses to naturally feared animals without conscious exposure, potentially reducing the aversive nature of traditional exposure therapy.

This approach, which pairs monetary rewards with unconscious representations of fear, has shown reliable reductions in physiological fear responses, suggesting a new avenue for treating anxiety disorders in a double-blind, placebo-controlled manner.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Towards an unconscious neural reinforcement intervention for common fears. Taschereau-Dumouchel, V., Cortese, A., Chiba, T., et al.[2019]

In a study of 28 unmedicated patients with panic disorder, just four sessions of exposure-based cognitive-behavioral therapy (CBT) significantly reduced anxiety symptoms, with 71% of participants achieving recovery compared to only 7% in the control group.

CBT not only improved symptoms but also normalized brain hyperactivity in key areas associated with anxiety, suggesting that effective treatment may require fewer sessions than previously believed and highlighting early neural changes that could be crucial for recovery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Early effects of exposure-based cognitive behaviour therapy on the neural correlates of anxiety. Reinecke, A., Thilo, KV., Croft, A., et al.[2022]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT03655262

Treating Phobia With Multivoxel Neuro-reinforcement 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 ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11312662/

A double-blind trial of decoded neurofeedback intervention ... A new closed-loop fMRI method called multi-voxel neuro-reinforcement has the potential to alleviate the subjective aversiveness of exposure-based interventions.

3. ucla.clinicaltrials.researcherprofiles.org ucla.clinicaltrials.researcherprofiles.org/trial/NCT06420557

Unconscious Reduction of Fear Through Decoded Neuro ... This method works unconsciously in the brain, without the need for participants to endure repeated conscious exposures to their feared stimuli.

4. clinicaltrials.gov clinicaltrials.gov/study/NCT06420557?term=AREA%5BInterventionSearch%5D(desired)%20AND%20AREA%5BStudyType%5D(INTERVENTIONAL)&rank=9&checkSpell=

Unconscious Reduction of Fear Through Decoded Neuro- ... This application investigates the efficacy of a novel method of neuro-reinforcement based on decoded fMRI activity to reduce fear responses in individuals ...

5. reporter.nih.gov reporter.nih.gov/project-details/9507597

Treating Phobia with Multivoxel Neuro-reinforcement Pilot Data demonstrate that the proposed method can effectively reduce amygdala reactivity to feared stimuli (target engagement). The R61 Phase will confirm ...

6. withpower.com withpower.com/trial/phase-unconsciousness-5-2024-81c83

Unconscious Neuro-reinforcement for Anxiety Disorders Unconscious Neuro-reinforcement is unique because it reduces fear without the need for conscious exposure to feared situations, using brain imaging techniques ...