Multiscale neural dynamics reveal how striatal subregions shape stress vulnerability and resilience

Effective stress coping relies on neural and endocrine coordination, with the mesostriatal system serving as a central substrate. However, how striatal subregions contribute to stress vulnerability versus resilience remains unclear. Here, we show dissociable roles of the nucleus accumbens (NAC) and dorsal caudate (dCA) and their associated brain networks in shaping stress responses. We identify neural stability (NS)—capturing stress-induced changes in state-switching frequency over the course of stress responses—as a marker: task-state NS correlates positively with stress-related NAC activity, whereas resting-state NS correlates inversely with stress-related dCA activity. NAC-mediated networks and associated NS further predict faster cortisol recovery. Intriguingly, NAC-related functional connectivity patterns spatially covary with dopamine D 2 receptor distributions and gene expression in inhibitory neurons and glia, whereas dCA-related patterns covary with μ-opioid receptor distributions. Together, these findings reveal striatal subregional heterogeneity in stress coping and characterize resilience as a multisystem homeostatic process integrating neural, endocrine, and molecular layers.