Stress-induced changes in modular organizations of human brain functional networks

Humans inevitably go through various stressful events, which initiates a chain of neuroendocrine reactions that may affect brain functions and lead to psychopathological symptoms. Previous studies have shown stress-induced changes in activation of individual brain regions or pairwise inter-regional connectivity. However, it remains unclear how large-scale brain network is reconfigured in response to stress. Using a within-subjects design, we combined the Trier Social Stress Test and graph theoretical method to characterize stress-induced topological alterations of brain functional network. Modularity analysis revealed that the brain network can be divided into frontoparietal, default mode, occipital, subcortical, and central-opercular modules under control and stress conditions, corresponding to several well-known functional systems underpinning cognitive control, self-referential mental processing, visual, salience processing, sensory and motor functions. While the frontoparietal module functioned as a connector module under stress, its within-module connectivity was weakened. The default mode module lost its connector function and its within-module connectivity was enhanced under stress. Moreover, stress altered the capacity to control over information flow in a few regions important for salience processing and self-referential metal processing. Furthermore, there was a trend of negative correlation between modularity and stress response magnitude. These findings demonstrate that acute stress prompts large-scale brain-wide reconfiguration involving multiple functional modules.