The study investigates the distributed neural representations of conditioned threat in the human brain using functional MRI data from 1465 participants across various threat conditioning and negative affect paradigms. The researchers employed multivariate pattern analysis to develop sensitive and specific decoders for distinguishing between threat and safety cues. The results show that the 'threat circuit'—comprising the amygdala, hippocampus, insular cortex, and medial prefrontal cortices—successfully decodes threat from safety cues across multiple datasets. However, the classification accuracies were higher when including neural patterns from other distributed neural systems beyond the 'threat circuit'. The study constructs an 'extended threat detection and responding circuit' that integrates the 'threat circuit' with sensory and cognitive nodes, demonstrating its sensitivity and reproducibility across different experimental paradigms and MRI scanners. The findings highlight the importance of considering multiple neural systems in concert for a comprehensive understanding of threat processing.The study investigates the distributed neural representations of conditioned threat in the human brain using functional MRI data from 1465 participants across various threat conditioning and negative affect paradigms. The researchers employed multivariate pattern analysis to develop sensitive and specific decoders for distinguishing between threat and safety cues. The results show that the 'threat circuit'—comprising the amygdala, hippocampus, insular cortex, and medial prefrontal cortices—successfully decodes threat from safety cues across multiple datasets. However, the classification accuracies were higher when including neural patterns from other distributed neural systems beyond the 'threat circuit'. The study constructs an 'extended threat detection and responding circuit' that integrates the 'threat circuit' with sensory and cognitive nodes, demonstrating its sensitivity and reproducibility across different experimental paradigms and MRI scanners. The findings highlight the importance of considering multiple neural systems in concert for a comprehensive understanding of threat processing.