Quantifying Multi-step Avoidance in Anxiety

NCT ID: NCT07203027

Last Updated: 2025-10-02

Basic Information

• Recruitment Status: NOT_YET_RECRUITING
• Total Enrollment: 163 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2027-01-31
• Study Completion Date: 2030-06-30

Brief Summary

This study aims to learn more about avoidance behavior in people with anxiety, using mathematical models of decision-making processes and decoded neural signals of threat imminence.

Researchers are investigating anxiety-related behavior and brain function in people with and without anxiety. Investigators are also looking at how behavior and brain function during tasks in the lab relate to avoidance in their daily lives. The investigators will also test whether changing how people avoid things in a behavioral task affects how people avoid things in their everyday life.

Detailed Description

Current learning theories of anxiety propose that disrupted fear learning underlie anxiety disorders. This suggests that treatments like exposure therapy work by changing learned threat values. However, empirical data does not support these models where changes in fear conditioning lead to symptom changes and later reductions of avoidance behavior. Instead, recent findings suggest that avoidance behavior can be a mechanism on its own, and reductions in avoidance behavior both precede and predict improvements in anxiety symptoms. To target avoidance, a working theory of the processes underlying avoidance behavior is needed. Recently, Markov Decision Process (MDP) models have been used to measure threat expectancy, which has the advantage of capturing the difference between avoidance and fear learning as mechanisms in anxiety disorders. Initial MDP models that demonstrate the rise of avoidance behavior show promise; however, additional non-behavioral information is needed to fit these models in humans.

The researcher's main hypothesis is that MDP models, augmented with decoded neural signals of threat imminence, can characterize and modify anxiety disorder-related avoidance behavior in and outside of the laboratory.

Aim 1: Adults unselected for psychopathology (120, assessed twice): develop a brain signature of threat imminence (from a predictive model independently trained on fMRI data from other threat imminence tasks) and combine with task behavior to create an MDP model of avoidance behavior.

Aims 2 and 3: A separate set of participants with clinical anxiety and maladaptive avoidance (N=163, assessed four times) will complete an MDP-based learning task assessing avoidance during fMRI scanning and quantify differences in MDP-modeled behavior and test if the magnitude of these task-based differences predicts between-and within-person differences in the severity of real-world avoidance behavior.

Multivariate predictors of functional magnetic resonance imaging (fMRI) data can decode latent values and enhance the computational fit of the MDP models. To identify these latent values, previously validated neural signatures of a threat-imminence model will be used. In the threat-imminence model, the same brain regions (e.g., amygdala, vmPFC), but different ensembles and neural populations, are involved in different stages of threat imminence, and these patterns do not differ between humans with different levels of clinical anxiety, allowing for a neurobiologically supported approach to creating latent values of threat. Therefore, researchers aim to use MDP models, augmented with decoded neural signals of threat imminence, to characterize and support a new mechanism (avoidance behavior) of symptom change in anxiety and modify anxiety disorder-related avoidance behavior.

Conditions

Anxiety; Anxiety Disorders

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: PROSPECTIVE

Study Groups

Anxiety and impairing levels of avoidance

Participants are screened for anxiety and impairing levels of avoidance and will complete questionnaires, a clinical interview, behavioral tasks, scanning, ecological momentary assessment (EMA), and passive sensing. Participants will complete four visits total.

Behavioral Tasks with imaging

Intervention Type: BEHAVIORAL

Participants will complete the MDP task only during 3 separate fMRI scanning sessions.

After each session, they will complete one week of ambulatory assessment of real-world avoidance behavior (self-reported avoidance behavior) via Emory Qualtrics surveys. In a fourth scanning session, the brain signature of threat imminence constructed in the first set of participants (Aim 1) will be used to predict and modify avoidance behavior (on the task and in a further week of ambulatory assessment of avoidance) in these participants. During their last visit, the behavioral task will be modified to decrease the availability of avoidance choices; subsequent effects on EMA and passive sensing measures will be assessed.

Interventions

Behavioral Tasks with imaging

Participants will complete the MDP task only during 3 separate fMRI scanning sessions.

After each session, they will complete one week of ambulatory assessment of real-world avoidance behavior (self-reported avoidance behavior) via Emory Qualtrics surveys. In a fourth scanning session, the brain signature of threat imminence constructed in the first set of participants (Aim 1) will be used to predict and modify avoidance behavior (on the task and in a further week of ambulatory assessment of avoidance) in these participants. During their last visit, the behavioral task will be modified to decrease the availability of avoidance choices; subsequent effects on EMA and passive sensing measures will be assessed.

Intervention Type: BEHAVIORAL

Other Intervention Names

Investigational

Eligibility Criteria

Inclusion Criteria

• Ability to comprehend written and spoken English
• Ability to provide informed consent
• Estimated intelligence quotient (IQ) >70.
• Clinically significant anxiety symptoms (scoring above clinical cutoff on at least one Inventory of Depression and Anxiety Symptoms (IDAS) anxiety-related subscale and/or OASIS total)
• Significant anxiety-related avoidance (scoring 2 or above on a 0-4 scale, indicating at least "occasional" avoidance) on the avoidance-related question on the Overall Anxiety Severity and Impairment Scale (OASIS)
• Functional impairment, defined as at least moderate impairment in one WHO Disability Assessment Schedule (WHODAS 2.0) domain related to anxiety.

Exclusion Criteria

• Individuals younger than 22 or older than 55,
• Individuals with an IQ < 70,
• A lifetime history of neurological disorder or brain damage,
• Contraindications for undergoing MRI scanning,
• A lifetime history or diagnosis of psychosis or bipolar disorder,
• Current substance use intoxication or withdrawal,
• Severe risk of suicide, or
• Recent (<3 months) changes in psychotropic medicine or psychotherapy treatment,
• Ineligible at the PI's discretion, are excluded.

• Minimum Eligible Age: 22 Years
• Maximum Eligible Age: 55 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

National Institute of Mental Health (NIMH)

NIH

Sponsor Role: collaborator

Emory University

OTHER

Sponsor Role: lead

Responsible Party

Vanessa M. Brown

Assistant Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Vanessa M Brown, PhD

Role: PRINCIPAL_INVESTIGATOR

Emory University

Locations

Emory College

Atlanta, Georgia, United States

Facility for Education and Research in Neuroscience (FERN)

Atlanta, Georgia, United States

Countries

United States

Central Contacts

Vanessa M. Brown, PhD

Role: CONTACT

vanessa.m.brown@emory.edu

404-727-5454

Other Identifiers

1R01MH139780

Identifier Type: NIH

Identifier Source: secondary_id

View Link

STUDY00009403

Identifier Type: -

Identifier Source: org_study_id