# Generalized Fear-Conditioning & Avoidance: Neurobiology & Transdiagnostic Import

> **NIH NIH R01** · UNIVERSITY OF MINNESOTA · 2020 · $196,739

## Abstract

Project Summary:
The objective of this project is to neurally, behaviorally, psychologically, and clinically characterize fundamental
Pavlovian and instrumental dimensions of potential threat through which emotional and behavioral responses to
threat cues generalize to resembling, safe stimuli. Such generalization is aligned with the potential threat
construct due to the threat ambiguity, or uncertain threat value, inherent in these safe `generalization' stimuli.
The Pavlovian dimension of interest is generalization of conditioned fear: a fundamental Pavlovian process
through which fear transfers, or generalizes, to safe stimuli resembling a conditioned threat-cue (CS+). The
targeted instrumental dimension is generalized avoidance: active decisions to withdraw from safe stimuli
resembling the CS+ that are motivationally prompted by Pavlovian generalization. Given lab-based findings
have linked heightened Pavlovian generalization to a variety of traditional anxiety disorders (PTSD, GAD,
panic), overgeneralization represents a promising dimension of potential threat with transdiagnostic relevance
to anxiety pathology. One central aspect of this project is testing personality and psychiatric factors (e.g., trait
fear, internalizing, externalizing) that may account for the relevance of generalization and its neurobiology
across traditional anxiety disorders. A second key aspect, is studying neural processes by which Pavlovian
generalization evokes instrumental generalized avoidance of benign stimuli (resembling danger cues), which,
when excessive, is likely to impair day-to-day functioning in anxiety patients. Unfortunately, human fear-
conditioning experiments in clinical samples, have focused almost exclusively on passive-emotional, Pavlovian
conditioning, to the virtual exclusion of studying active-behavioral, instrumental avoidance. The current fMRI
project fills this gap by applying a novel Pavlovian-instrumental generalization paradigm to neurally and
behaviorally elucidate Pavlovian processes leading to generalized instrumental avoidance. Personality
moderators (e.g., dispositional resilience) of relations between Pavlovian and instrumental generalization will
also be examined. The studied adult samples will display a wide range of symptom severity across traditional
anxiety disorders and will include trauma survivors (N=114), and anxiety-clinic patients and healthy
comparisons (N=159). Central goals of this proposal include: 1) elucidating the neurobiology of Pavlovian and
instrumental generalization and their interaction, 2) testing relations between neural substrates of Pavlovian and
instrumental generalization and broad psychiatric dysfunction (Aims2-3); and 3) assessing the degree to which
relations between these dimensions of generalization and broad dysfunction are driven by transdiagnostic,
psychometrically validated personality traits. This third and final goal is critical to the project, because individual
difference measures capturi...

## Key facts

- **NIH application ID:** 9942503
- **Project number:** 5R01MH107382-05
- **Recipient organization:** UNIVERSITY OF MINNESOTA
- **Principal Investigator:** Shmuel Mordechai Lissek
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $196,739
- **Award type:** 5
- **Project period:** 2016-07-20 → 2022-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9942503

## Citation

> US National Institutes of Health, RePORTER application 9942503, Generalized Fear-Conditioning & Avoidance: Neurobiology & Transdiagnostic Import (5R01MH107382-05). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/9942503. Licensed CC0.

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