# Project 3: Latent-cause inference in anxiety

> **NIH NIH P50** · PRINCETON UNIVERSITY · 2024 · $403,247

## Abstract

Exposure therapy is the most effective evidence-based treatment for a variety of anxiety disorders, but relapse
is common. Failures of exposure therapy can be explained in part by laboratory studies using aversive
conditioning and extinction, where the extinction phase can be viewed as a model of exposure therapy. These
studies show that the “safe” association learned during extinction is tenuous, and the original negative
association can sometimes return – a process known as spontaneous recovery. Recent work from our group
shows that during extinction, some participants update the original association from fear to safety while others
remember the fear association. The latter participants show spontaneous recovery (relapse) of fear at a later test.
The overall goal of Project 3 is to understand these individual differences in spontaneous recovery, their
relationship to transdiagnostic mental health symptoms of anxiety and to generalized anxiety disorder, and
their neural underpinnings. To accomplish this goal, we will leverage the computational framework of latent
cause inference; according to this framework, spontaneous recovery arises when an old latent cause associated
with an aversive outcome is inferred to be active in a harmless situation, a form of overgeneralization. We will
fit a model (from Core C) to behavior of individual participants to precisely quantify individual differences in
the computational process underlying spontaneous recovery and correlate these to symptoms. We will also
identify the neurocognitive systems that are implicated in this overgeneralization: we hypothesize that
participants show spontaneous recovery because of deficient memory-control processes – these participants
are failing to suppress retrieval of the original memory, even in the presence of evidence that the situation is
now “safe”. We will relate this to clinical symptoms: based on prior work, we hypothesize that spontaneous
recovery will be associated with low memory-control ability and high clinical symptoms of anxiety.
Using Core B, Aim 3.1 will test for relationships between memory control, spontaneous recovery, anxiety
symptoms and parameters of latent cause inference, taking a dimensional approach in a large-scale online
study and also comparing a clinical sample with generalized anxiety disorder to healthy controls. Aim 3.2 will
leverage Core D to identify the neural correlates of spontaneous recovery using multivariate predictive
modeling of fMRI, focusing on brain networks previously established to relate to memory control, and also
using data-driven methods to identify new biomarkers. Last, Aim 3.3 will causally test our hypotheses about
brain networks that mediate spontaneous recovery by intervening on these networks with real-time fMRI
neurofeedback, with the goal of reducing spontaneous recovery in individuals who are prone to it. Taken
together, these studies will substantially advance our understanding of why spontaneous recovery occurs an...

## Key facts

- **NIH application ID:** 10862340
- **Project number:** 1P50MH136296-01
- **Recipient organization:** PRINCETON UNIVERSITY
- **Principal Investigator:** KENNETH A NORMAN
- **Activity code:** P50 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $403,247
- **Award type:** 1
- **Project period:** 2024-08-12 → 2029-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10862340

## Citation

> US National Institutes of Health, RePORTER application 10862340, Project 3: Latent-cause inference in anxiety (1P50MH136296-01). Retrieved via AI Analytics 2026-06-12 from https://api.ai-analytics.org/grant/nih/10862340. Licensed CC0.

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