Existing evidence highlights sleep’s critical role in regulating cortisol stress recovery; the underlying neural pathways remain unclear. To address this gap, the current study aims to elucidate the neurobiological pathway linking objective sleep efficiency to cortisol stress recovery using functional magnetic resonance imaging (fMRI), with a focus on the functional connectivity (FC) between prefrontal cortex (PFC) and hippocampus.

Seventy-seven participants completed an acute stress task during a task-dependent and resting-state fMRI scanning. Salivary samples were collected and analyzed as an indicator of cortisol stress recovery. Objective sleep efficiency was measured the night before the fMRI scanning. Using Seed-based gPPI and resting-state FC analysis, we examined the mediating role of PFC-hippocampus FC in the association between objective sleep efficiency and cortisol stress recovery, both during the stress task and in the post-stress resting-state.

Objective sleep efficiency was significantly related to cortisol stress recovery but not with cortisol reactivity. Neurologically, higher sleep efficiency was linked to enhanced prefrontal activity and increased the left dlPFC-hippocampus FC during the acute stress task. Importantly, objective sleep efficiency promoted cortisol stress recovery by the weakened resting-state left dlPFC-hippocampus FC.

This study highlights the pivotal role of left dlPFC-hippocampus regulation underlying sleep’s effect on HPA axis recovery to acute stress. These results suggest a model whereby high objective sleep efficiency promotes adaptive stress recovery through dynamic reallocation of neural resources across acute stress process, characterized by task-dependent coupling and post-stress decoupling of frontal-hippocampal circuitry.