期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2022
卷号：119
期号：26
DOI：10.1073/pnas.2204066119
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：Significance
Pavlovian threat learning is a primary translational model for understanding the brain systems that underlie anxiety and trauma-related psychopathology. The amygdala has traditionally played a central role in this important form of learning across species. However, recent human neuroimaging work has revealed inconsistent findings regarding the role of human amygdala in threat and safety learning. To address this discrepancy, we examined amygdala responses to threat-predictive cues in a large sample of human participants. We found robust evidence for amygdala responses during threat conditioning and, further, that these responses occurred in a temporally and anatomically specific manner. Our results reveal clear evidence of human amygdala involvement in associative learning and offer insight into why some neuroimaging work has yielded equivocal findings.
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.
