Cortisol awakening response prompts dynamic reconfiguration of brain networks in emotional and executive functioning.

Emotion and cognition involve an intricate crosstalk of neural and endocrine systems that support dynamic reallocation of neural resources and optimal adaptation for upcoming challenges, an active process analogous to allostasis. As a hallmark of human endocrine activity, the cortisol awakening response (CAR) is recognized to play a critical role in proactively modulating emotional and executive functions. Yet, the underlying mechanisms of such proactive effects remain elusive. By leveraging pharmacological neuroimaging and hidden Markov modeling of brain state dynamics, we show that the CAR proactively modulates rapid spatiotemporal reconfigurations (state) of large-scale brain networks involved in emotional and executive functions. Behaviorally, suppression of CAR proactively impaired performance of emotional discrimination but not working memory (WM), while individuals with higher CAR exhibited better performance for both emotional and WM tasks. Neuronally, suppression of CAR led to a decrease in fractional occupancy and mean lifetime of task-related brain states dominant to emotional and WM processing. Further information-theoretic analyses on sequence complexity of state transitions revealed that a suppressed or lower CAR led to higher transition complexity among states primarily anchored in visual-sensory and salience networks during emotional task. Conversely, an opposite pattern of transition complexity was observed among states anchored in executive control and visuospatial networks during WM, indicating that CAR distinctly modulates neural resources allocated to emotional and WM processing. Our findings establish a causal link of CAR with brain network dynamics across emotional and executive functions, suggesting a neuroendocrine account for CAR proactive effects on human emotion and cognition.