Whole-Brain c-Fos Connectomics Reveals Biphasic Integration-Distribution Architecture in Valence-Specific Emotional Processing

Emotions emerge from coordinated neural dynamics across distributed brain circuits, but the architectural principles underlying valence-specific emotional processing remain poorly understood. Here, we leverage whole-brain c-Fos connectomics in combination with anatomical projection data to delineate the organizational logic of valence-dependent neural networks in mice responding to ethologically relevant pheromone cues. This approach revealed widespread yet distinct activation patterns, with 13 core nuclei consistently recruited across both valences, spanning olfactory bulb, limbic system, thalamus, and brainstem regions. Critically, network-based analysis uncovered fundamentally different organizational strategies: positive emotional states assembled into compact, highly integrated functional communities, while negative states engaged distributed, multi-modular architectures. Integrating these functional insights with anatomical connectivity data from the Allen Brain Atlas, we uncover a biphasic “integration-distribution” network architecture: positive emotional processing relies on centralized, streamlined hubs anchored in the central amygdala and posterior hypothalamic axis, whereas negative emotional processing employs redundant, parallelized pathways for robust and flexible responses. By bridging cellular-level activation patterns, mesoscale circuit organization, and behavioral relevance, our findings provide a novel conceptual framework for emotion neuroscience and lay the groundwork for understanding the network-level dysfunctions characteristic of psychiatric disorders.