Brain Activity Study for Anxiety Disorder

Overseen By Mary R Silvas

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: The University of Texas Health Science Center, Houston

Disqualifiers: Neurologic disease, Seizure, Psychiatric diagnosis, others

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

Compensation: Varies

Number of Visits: 4

150 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to explore how the brain reacts to fear and avoidance using a method called the conditioning and active avoidance paradigm (CAAP). Researchers will examine how different brain activities relate to learning fear, avoiding fear-inducing stimuli, and remembering these experiences. The study is open to individuals who can provide informed consent and have no history of neurological diseases, seizures, or serious psychiatric issues. Participants will contribute to understanding how the brain decides to avoid or not avoid fear-inducing stimuli. As an unphased study, this research offers a unique opportunity to advance scientific understanding without the constraints of traditional clinical trial phases.

Do I need to stop my current medications for the trial?

The trial information does not specify whether you need to stop taking your current medications.

What prior data suggests that this conditioning and active avoidance paradigm is safe?

Research has shown that the conditioning and active avoidance paradigm (CAAP) aids in understanding fear and avoidance behaviors. Studies have explored how people learn to avoid feared stimuli, helping researchers observe the brain's response to fear and safety.

These studies do not directly address the safety of CAAP in humans. However, researchers have used these methods for many years to study behaviors related to fear and anxiety, suggesting that CAAP is generally safe in controlled research settings.

This is a "Not Applicable" phase trial, meaning the study does not test a new drug or treatment's safety. Instead, it aims to explore brain activity related to anxiety. Therefore, no safety concerns are expected for participants in this type of research. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about the conditioning and active avoidance paradigm (CAAP) for anxiety disorder because it offers a unique approach compared to traditional treatments like medication and therapy. Unlike medications that primarily target chemical imbalances in the brain, CAAP aims to modify behavior through learning processes. This method focuses on helping individuals learn to actively avoid anxiety triggers, potentially leading to more sustainable and long-lasting results. The innovative aspect of CAAP is its emphasis on conditioning, which could provide a new avenue for managing anxiety without the reliance on pharmaceuticals.

What evidence suggests that the Conditioning and active avoidance paradigm (CAAP) is effective for anxiety disorder?

Research shows that learning to avoid things plays a significant role in both helpful and unhelpful fear reactions. Studies have found that the way fear is learned is crucial in anxiety and stress-related disorders. Understanding these processes can aid in treating these conditions. This trial uses the Conditioning and Active Avoidance Paradigm (CAAP) to study how fear and avoidance behaviors are learned and unlearned. By examining these patterns, researchers aim to find better ways to manage anxiety by reducing fear and promoting feelings of safety. Early findings suggest that focusing on these fear and safety learning processes can help people manage their anxiety more effectively. ^{1 2 4 6 7}

Who Is on the Research Team?

Mohammed Milad, PhD

Principal Investigator

The University of Texas Health Science Center, Houston

Are You a Good Fit for This Trial?

This trial is for individuals with an anxiety disorder. Participants should be able to undergo fear conditioning and active avoidance tasks while their brain activity is monitored using EEG. Specific inclusion or exclusion criteria are not provided, but typically participants must be healthy enough for the procedures.

Inclusion Criteria

Willing and able to provide informed consent

Exclusion Criteria

High risk of adverse emotional or behavioral reaction, and/or an inability to understand study procedures or the informed consent process, based on investigator/clinician clinical evaluation

Significant suicidal ideation or behaviors

Significant serious psychiatric diagnosis

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Viewing Phase

Participants are presented with images from three different object categories and instructed to passively view them.

15 minutes

1 visit (in-person)

Fear Conditioning Phase

Participants are presented with images used as conditioned stimuli, with some categories reinforced by a mild electrical shock.

18 minutes

1 visit (in-person)

Avoidance Learning Phase

Participants can avoid a shock by pressing a button during the presentation of object categories.

18 minutes

1 visit (in-person)

Memory Recall Phase

Participants are presented with images again and can choose to press a button to avoid a possible shock.

18 minutes

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after the experimental phases.

1-2 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Conditioning and active avoidance paradigm (CAAP)

Trial Overview The study investigates how certain brain wave patterns (ERPs and EROs) relate to learning about fear and making decisions to avoid things that cause fear. It uses a special task called CAAP while recording brain activity with EEG, looking at memory recall related to fear and avoidance.

How Is the Trial Designed?

Group I: Conditioning and active avoidance paradigm (CAAP) Experimental Treatment 1 Intervention

Who Is Running the Clinical Trial?

The University of Texas Health Science Center, Houston

Lead Sponsor

Trials

974

Recruited

361,000+

Published Research Related to This Trial

Cognitive-behavioral therapy (CBT) significantly reduces hyperactivation in brain areas associated with fear, such as the amygdala and anterior cingulate cortex, in patients with spider phobia, indicating its efficacy in treating anxiety disorders.

While CBT effectively alters brain responses to consciously perceived threats, it does not significantly affect the brain's automatic responses to subliminal threats, suggesting that different neural mechanisms are involved in anxiety maintenance.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of cognitive-behavioral therapy on brain responses to subliminal and supraliminal threat and their functional significance in specific phobia. Lipka, J., Hoffmann, M., Miltner, WH., et al.[2018]

The study introduces a novel behavioral paradigm called conditioned inhibition of fear, which focuses on how animals learn to feel safe rather than just how they learn to fear, providing insights into emotional regulation crucial for mental health.

This learned safety training, conducted over 3 days with one session per day, can help researchers explore the molecular mechanisms behind interventions for depression, enhancing our understanding of emotional behavior dysregulation in various neuropsychiatric conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The learned safety paradigm as a mouse model for neuropsychiatric research. Pollak, DD., Monje, FJ., Lubec, G.[2021]

The study demonstrated that a specific fMRI paradigm effectively induces reproducible anticipatory anxiety in healthy volunteers, as evidenced by consistent brain activation in areas related to anxiety, such as the frontal cortex and insula.

The results indicate that this method can be used to accelerate the evaluation and development of new anxiolytic medications, providing a reliable way to assess anxiety responses in clinical research.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Test-retest reliability of a functional MRI anticipatory anxiety paradigm in healthy volunteers. Schunck, T., Erb, G., Mathis, A., et al.[2008]

Maladaptive avoidance, a behavior seen in anxiety disorders, PTSD, and OCD, is driven by altered neurobehavioral processes including threat appraisal, habitual avoidance, and trait avoidance tendency, which complicates its measurement.

The authors propose a new framework to better understand and measure maladaptive avoidance by adapting existing paradigms, aiming to develop targeted interventions for clinical populations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Measuring maladaptive avoidance: from animal models to clinical anxiety. Ball, TM., Gunaydin, LA.[2022]

Conditioned safety signals can effectively reduce fear responses in individuals with trauma exposure, as shown by decreased skin conductance responses during a functional MRI task.

Higher trauma exposure is linked to reduced activation in key brain areas (hippocampus, amygdala, and dorsolateral prefrontal cortex) during safety signal learning, indicating that trauma may affect the neural mechanisms involved in fear reduction.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neural circuitry involved in conditioned inhibition via safety signal learning is sensitive to trauma exposure. Kribakaran, S., Odriozola, P., Cohodes, EM., et al.[2023]

Participants who experienced heart rate acceleration showed increased sensory processing in the visual and parietal cortex when exposed to reinforced stimuli (CS+), indicating a link between autonomic responses and cortical activation during fear conditioning.

Simply being aware of the relationship between stimuli (CS-US contingencies) does not guarantee enhanced visual processing, suggesting that activation of the fear system plays a crucial role in how we respond to potential threats.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fear but not awareness predicts enhanced sensory processing in fear conditioning. Moratti, S., Keil, A., Miller, GA.[2019]

A new fMRI paradigm called the 'Westphal-Paradigm' was developed to study agoraphobia-specific stimuli, showing high reliability and validity in distinguishing responses between patients with panic disorder and agoraphobia and healthy controls.

The fMRI pilot study demonstrated significant brain activations in areas related to fear, such as the amygdala and insula, indicating that this paradigm can effectively characterize the neural mechanisms underlying panic disorder and agoraphobia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A new paradigm (Westphal-Paradigm) to study the neural correlates of panic disorder with agoraphobia. Wittmann, A., Schlagenhauf, F., John, T., et al.[2021]

The study successfully established a short paradigm for examining classical aversive conditioning in healthy subjects, using fMRI and skin conductance measurements to assess behavioral and neural responses.

During the acquisition phase, significant activation was observed in brain regions associated with emotional processing, such as the amygdala and insula, indicating that the paradigm effectively engages the fear circuit, which could be useful for studying anxiety disorders and cognitive-behavioral interventions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neural correlates of aversive conditioning: development of a functional imaging paradigm for the investigation of anxiety disorders. Reinhardt, I., Jansen, A., Kellermann, T., et al.[2021]

Neuroimaging tools are crucial for understanding the brain mechanisms involved in extinguishing fear responses, which can help reduce anxiety and stress-related disorders.

Recent advances in multivariate data analysis have improved our ability to explore complex brain-behavior relationships, enhancing our understanding of fear extinction beyond what was established in rodent studies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neuroimaging of Fear Extinction. LaBar, KS.[2023]

This meta-analysis of 27 fMRI studies involving 677 participants reveals a consistent pattern of brain activation during fear conditioning, highlighting the central autonomic-interoceptive network, which is crucial for understanding how humans process fear.

The study also identifies a coordinated brain response related to processing 'safety signals', suggesting that understanding both fear and safety responses can enhance our knowledge of anxiety disorders and inform future research in both healthy and clinical populations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neural signatures of human fear conditioning: an updated and extended meta-analysis of fMRI studies. Fullana, MA., Harrison, BJ., Soriano-Mas, C., et al.[2022]

Research indicates that the startle reflex, which is linked to fear processing in the brain, varies among patients with different anxiety disorders, suggesting that anxiety can be viewed as a spectrum of brain dysfunction.

Preliminary fMRI studies support the idea that dysfunction in brain circuits related to fear and motivation is associated with the severity of anxiety disorders, and future research aims to explore ways to enhance these circuits using real-time fMRI feedback.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pathological anxiety and function/dysfunction in the brain's fear/defense circuitry. Lang, PJ., McTeague, LM., Bradley, MM.[2016]

Using magnetoencephalography (MEG) to study fear conditioning in humans, researchers found that the amygdala shows distinct activation patterns when responding to conditioned stimuli (CS+) compared to unconditioned stimuli (CS-), particularly at the onset of the CS+.

The study revealed that the amygdala not only reacts to stimuli but also anticipates them based on learned associations, indicating its role in processing both the presence and absence of expected stimuli, which could influence future learning and responses.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dynamic neural activity recorded from human amygdala during fear conditioning using magnetoencephalography. Moses, SN., Houck, JM., Martin, T., et al.[2007]

Citations

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Avoidance learning: a review of theoretical models and recent ... Avoidance is a key characteristic of adaptive and maladaptive fear. Here, we review past and contemporary theories of avoidance learning.

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The birth, death and resurrection of avoidance - PubMed Central Research on avoidance conditioning began in the late 1930s as a way to use laboratory experiments to better understand uncontrollable fear and anxiety.

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Avoiding negative outcomes: tracking the mechanisms of ... The goal of this study was to investigate the physiological and neural correlates underlying avoidance learning in humans.

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Avoidance of learnt fear: Models, potential mechanisms ... The current overview proposes potential behavioral mechanisms and neural circuits of avoidance of learnt fear in humans, and discusses findings and paradigms ...

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Avoiding Negative Outcomes: Tracking the Mechanisms of ... The goal of this study was to investigate the physiological and neural correlates underlying avoidance learning in humans.

7. nature.com nature.com/articles/mp2016166

The birth, death and resurrection of avoidance Research on avoidance conditioning began in the late 1930s as a way to use laboratory experiments to better understand uncontrollable fear and anxiety.