4.8 Article

Temporally and anatomically specific contributions of the human amygdala to threat and safety learning

Publisher

NATL ACAD SCIENCES
DOI: 10.1073/pnas.2204066119

Keywords

amygdala; threat conditioning; fMRI

Funding

  1. National Institute of Mental Health [R01MH097964, R01MH097880, R01MH109638, 1R01AT006344-01]

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This study examines the involvement of the amygdala in threat conditioning and safety learning by combining data from multiple studies. The findings reveal that two subregions of the amygdala track the conditioned stimulus with aversive shock during early conditioning, while only one subregion demonstrates delayed responding to a stimulus not paired with shock.
Neural plasticity in subareas of the rodent amygdala is widely known to be essential for Pavlovian threat conditioning and safety learning. However, less consistent results have been observed in human neuroimaging studies. Here, we identify and test three important factors that may contribute to these discrepancies: the temporal profile of amygdala response in threat conditioning, the anatomical specificity of amygdala responses during threat conditioning and safety learning, and insufficient power to identify these responses. We combined data across multiple studies using a well-validated human threat conditioning paradigm to examine amygdala involvement during threat conditioning and safety learning. In 601 humans, we show that two amygdala subregions tracked the conditioned stimulus with aversive shock during early conditioning while only one demonstrated delayed responding to a stimulus not paired with shock. Our findings identify cross-species similarities in temporal- and anatomical-specific amygdala contributions to threat and safety learning, affirm human amygdala involvement in associative learning and highlight important factors for future associative learning research in humans.

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