Computational Modeling of Threat Learning Reveals Links with Anxiety and Neuroanatomy in Humans

Rany Abend, Diana Burk, Sonia G. Ruiz, Andrea L. Gold, Julia L. Napoli, Jennifer C. Britton, Kalina J. Michalska, Tomer Shechner, Anderson M. Winkler, Ellen Leibenluft, Daniel S. Pine, Bruno B. Averbeck

Research output: Contribution to journalArticlepeer-review

Abstract

Influential theories implicate variations in the mechanisms supporting threat learning in the severity of anxiety symptoms. We use computational models of associative learning in conjunction with structural imaging to explicate links among the mechanisms underlying threat learning, their neuroanatomical substrates, and anxiety severity in humans. We recorded skin-conductance data during a threat-learning task from individuals with and without anxiety disorders (N=251; 8-50 years; 116 females). Reinforcement-learning model variants quantified processes hypothesized to relate to anxiety: threat conditioning, threat generalization, safety learning, and threat extinction. We identified the best-fitting models for these processes and tested associations among latent learning parameters, whole-brain anatomy, and anxiety severity. Results indicate that greater anxiety severity related specifically to slower safety learning and slower extinction of response to safe stimuli. Nucleus accumbens gray-matter volume moderated learning-anxiety associations. Using a modeling approach, we identify computational mechanisms linking threat learning and anxiety severity and their neuroanatomical substrates.

Original languageEnglish
Article numbere66169
JournaleLife
Volume11
DOIs
StatePublished - Apr 2022

Bibliographical note

Funding Information:
This research was supported (in part) by the NIMH IRP (ZIAMH002781-15; DSP), NIH

Funding Information:
We thank the participants and families, as well as the staff of the Intramural Research Program of the National Institute of Mental Health (IRP, NIMH), National Institutes of Health. We also thank Emily Ronkin, Elizabeth Steuber, Madeline Farber, Jessica Sachs, Brigid Behrens, Carolyn Spiro, and Omri Lily for their contribution to data collection. This research was supported (in part) by the NIMH IRP (ZIAMH002781-15; DSP), NIH grant K99/R00MH091183 (JCB), and a NARSAD Young Investigator Grant from the Brain & Behavior Research Foundation (RA).

Publisher Copyright:
© 2022, eLife Sciences Publications Ltd. All rights reserved.

ASJC Scopus subject areas

  • Neuroscience (all)
  • Biochemistry, Genetics and Molecular Biology (all)
  • Immunology and Microbiology (all)

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