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

Trial Summary

What is the purpose of this trial?

The purpose of this study is to examine which event-related potentials (ERPs) and event-related oscillations (EROs) are associated with fear conditioning, avoidance learning, and memory recall for fear and avoidance, where are the source generators of the observed scalp EEG activity, the impact of fear and avoidance learning on the decision to avoid or not to avoid conditioned stimuli , to examine the large-scale functional connectivity across distributed brain regions across experimental phases, and to examine whether spontaneous EEG data during resting-state correlate with the EEG measures during experimental tasks.

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 data supports the effectiveness of the treatment Conditioning and active avoidance paradigm (CAAP) for anxiety disorder?

Research shows that fear conditioning, a component of CAAP, is linked to specific brain activity patterns that are consistent across studies, suggesting it plays a role in anxiety disorders. Additionally, studies on fear extinction, which is related to CAAP, indicate that learning to reduce fear responses can help manage anxiety. ^{1 2 3 4 5}

Is the Conditioning and Active Avoidance Paradigm (CAAP) safe for humans?

The research on fear conditioning and safety signal learning suggests that these paradigms can reduce fear responses and are generally safe, even for individuals with trauma exposure. However, the neural processes involved may vary based on trauma history, indicating the need for further research to fully understand safety in diverse populations. ^{2 6 7 8 9}

How is the Conditioning and Active Avoidance Paradigm (CAAP) treatment different from other anxiety disorder treatments?

The Conditioning and Active Avoidance Paradigm (CAAP) treatment is unique because it uses a learning-based approach to help patients anticipate and avoid anxiety triggers by conditioning their responses, which is different from traditional therapies like medication or cognitive-behavioral therapy that focus on altering brain chemistry or thought patterns. ^{2 3 10 11 12}

Research Team

Mohammed Milad, PhD

Principal Investigator

The University of Texas Health Science Center, Houston

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

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]

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]

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]

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]

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]

References

1. Germany pubmed.ncbi.nlm.nih.gov

A new paradigm (Westphal-Paradigm) to study the neural correlates of panic disorder with agoraphobia. [2021]

2. England pubmed.ncbi.nlm.nih.gov

Neural signatures of human fear conditioning: an updated and extended meta-analysis of fMRI studies. [2022]

3. United States pubmed.ncbi.nlm.nih.gov

Test-retest reliability of a functional MRI anticipatory anxiety paradigm in healthy volunteers. [2008]

4. Germany pubmed.ncbi.nlm.nih.gov

Neural correlates of aversive conditioning: development of a functional imaging paradigm for the investigation of anxiety disorders. [2021]

5. Germany pubmed.ncbi.nlm.nih.gov

Neuroimaging of Fear Extinction. [2023]

6. England pubmed.ncbi.nlm.nih.gov

The learned safety paradigm as a mouse model for neuropsychiatric research. [2021]

7. England pubmed.ncbi.nlm.nih.gov

Measuring maladaptive avoidance: from animal models to clinical anxiety. [2022]

8. United States pubmed.ncbi.nlm.nih.gov

Neural circuitry involved in conditioned inhibition via safety signal learning is sensitive to trauma exposure. [2023]

9. United States pubmed.ncbi.nlm.nih.gov

Fear but not awareness predicts enhanced sensory processing in fear conditioning. [2019]

10. United States pubmed.ncbi.nlm.nih.gov

Dynamic neural activity recorded from human amygdala during fear conditioning using magnetoencephalography. [2007]

11. Netherlands pubmed.ncbi.nlm.nih.gov

Pathological anxiety and function/dysfunction in the brain's fear/defense circuitry. [2016]

12. United States 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. [2018]