Quantifying Multi-step Avoidance in Anxiety

Official title

Quantifying Neural Signatures of Multi-step Avoidance Behavior in Anxiety

Overview

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.

Interventions

• Behavioral 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 av

Primary outcome measures

• Ecological momentary assessment (EMA) [Time frame: Baseline, week 1, week 2, week 3, and week 4]
• Avoidance Severity Based on Location Entropy [Time frame: Baseline, week 1, week 2, week 3, and week 4]
• Change in Location Entropy [Time frame: Baseline, week 1, week 2, week 3, and week 4]

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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: Yes

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Basic science

Study locations

United States · 2 centers

• Emory College — Atlanta
• Facility for Education and Research in Neuroscience (FERN) — Atlanta

Identifiers

NCT: NCT07203027 · STUDY00009403 · 1R01MH139780

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗