The relationship between glymphatic system, multi-level stress response, and psychological resilience

Stress promotes affective, neural, endocrine, and immune responses. The glymphatic system, essential for waste clearance and immune homeostasis, protects the brain against adverse neurobiological changes. However, it remains unclear how the glymphatic system changes during acute stress, coordinates with multi-level stress responses, and relates to psychological resilience in humans.

We recruited 84 healthy middle-aged adults (mean age 29.26 ± 2.91, 50 males) without major physical, neurological, or psychological conditions. Glymphatic system function was assessed via the coupling between global blood-oxygen-level-dependent and cerebrospinal fluid signals (gBOLD-CSF coupling) before, immediately after, and 60 min after the Montreal Imaging Stress Task. Mood states, neural responses (BOLD signal changes), acute and awakening cortisol responses, and psychological resilience (Connor-Davidson Resilience Scale) were measured. We compared gBOLD-CSF coupling changes over time using repeated-measures ANOVA, and investigated their associations with affective, neural, endocrine responses, and resilience with linear models and network analysis.

gBOLD-CSF coupling was stronger at baseline and after recovery compared to immediately after stress. Changes in gBOLD-CSF coupling were associated with stress-related negative affect and prefrontal neural response. The cortisol response to acute stress was related to gBOLD-CSF coupling response to stress, depending on the level of the cortisol awakening response. The glymphatic system emerged as a central mediator of multi-organ stress response. Finally, post- to pre-stress changes in gBOLD-CSF coupling were associated with psychological resilience.

The glymphatic system transiently fluctuates during acute stress, synergizing with affective, neural, and endocrine networks, playing significant roles in stress response and psychological resilience.