Laboratory of Neuropsychology, National Institute of Mental Health, National Institutes of Health, Bethesda, United States
Sonia G Ruiz
Emotion and Development Branch, National Institute of Mental Health, National Institutes of Health, Bethesda, United States
Andrea L Gold
Emotion and Development Branch, National Institute of Mental Health, National Institutes of Health, Bethesda, United States; Department of Psychiatry and Human Behavior, Brown University Warren Alpert Medical School, Providence, United States
Julia L Napoli
Laboratory of Neuropsychology, National Institute of Mental Health, National Institutes of Health, Bethesda, United States
Jennifer C Britton
Emotion and Development Branch, National Institute of Mental Health, National Institutes of Health, Bethesda, United States; Department of Psychology, University of Miami, Coral Gables, United States
Kalina J Michalska
Emotion and Development Branch, National Institute of Mental Health, National Institutes of Health, Bethesda, United States; Department of Psychology, University of California, Riverside, Riverside, United States
Tomer Shechner
Emotion and Development Branch, National Institute of Mental Health, National Institutes of Health, Bethesda, United States; Psychology Department, University of Haifa, Haifa, Israel
Anderson M Winkler
Emotion and Development Branch, National Institute of Mental Health, National Institutes of Health, Bethesda, United States
Ellen Leibenluft
Emotion and Development Branch, National Institute of Mental Health, National Institutes of Health, Bethesda, United States
Daniel S Pine
Emotion and Development Branch, National Institute of Mental Health, National Institutes of Health, Bethesda, United States
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.