Instrumental Avoidance Promotes Safety Learning Across Distributed Neural Circuits

Authors

• Zhenfu Wen
• Lihan Cui
• Muhammad Badarnee
• Kai Zhang
• Isabel Moallem
• Hannah McManus
• Zakiya Atiyah
• Joseph Borrelli
• Wen Li
• L Elliot Hong
• Peter Kochunov
• Mohammed R Milad

Language

English

Publication Date

4-1-2026

Journal

Biological Psychiatry: Cognitive Neuroscience and Neuroimaging

DOI

10.1016/j.bpsc.2026.03.018

PMID

41932578

Abstract

Background: Instrumental avoidance is a coping strategy that plays a critical role in anxiety and trauma-related disorders. Yet, the neural mechanisms supporting instrumental avoidance and its interaction with extinction learning remain incompletely understood.

Methods: Fifty-nine healthy adults completed a two-day fMRI paradigm including Pavlovian threat conditioning, avoidance learning, extinction, and memory recall. Subjective reports measuring the 'fear ratings' for each CS were administered and analyzed across all experimental phases. Neural responses were analyzed using univariate general linear modeling and multivariate pattern analysis with a validated threat/safety decoder. To assess generalizability, the analysis pipeline was repeated in an independent cohort (n=59) using a variant design.

Results: Subjective 'fear ratings' indicated successful fear acquisition, instrumental avoidance learning and extinction learning. During extinction recall, fear ratings to the CS+ Avoidable were significantly lower compared to those for the CS+ Non-avoidable. As for the neural correlates, instrumental avoidance learning engaged the ventromedial prefrontal cortex, amygdala, and striatum. Multivariate decoding revealed a dynamic shift from threat- to safety-like neural representations for CS+A, emerging after only two successful avoidance trials. This avoidance-related neural shift predicted reduced neural recruitment during subsequent extinction learning. During memory recall, participants were charged a monetary cost for avoidance responses, yet still showed reduced threat expression to CS+A-supporting consolidation of safety representations. All key findings were replicated in the independent cohort.

Conclusions: Our findings show that controllable avoidance can promote adaptive regulation of threat and support long-term safety learning-offering implications for anxiety and trauma-related disorders.

Published Open-Access

yes

Recommended Citation

Wen, Zhenfu; Cui, Lihan; Badarnee, Muhammad; et al., "Instrumental Avoidance Promotes Safety Learning Across Distributed Neural Circuits" (2026). Faculty, Staff and Student Publications. 3648.
https://digitalcommons.library.tmc.edu/uthmed_docs/3648