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

Yuan Zhang, Zhongxiang Dai, Jianping Hu, Shaozheng Qin, Rongjun Yu, Yu Sun, Yuan Zhang, Zhongxiang Dai, Jianping Hu, Shaozheng Qin, Rongjun Yu, Yu Sun

Abstract

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.

Keywords: Functional connectivity; Graph theory; Modularity; Resting-state fMRI; Stress.

© 2020 The Authors.

Figures

Fig. 1
Fig. 1
Experimental procedure and manipulation check. (A) After acclimation period of 20 min following arrival, participants were required to go through the Trier Social Stress Test (TSST) which consists of preparation (5 min) and formal tasks (10 min). The formal tasks were performed either with (stress condition) or without (control condition) social evaluative processes. After the formal tasks, resting-state fMRI were collected. Saliva samples were collected at T1, T3, T4, T5, and T6. Affective ratings were collected at T1, T2, T3, T4, T5, and T6. (B) Cortisol and positive/negative emotional responses under control and stress condition. Compared with control condition, stress induced higher cortisol responses at T3, T4, T5, and T6, as well as lower positive and higher negative emotional responses at T2 and T3. *p < 0.05, **p < 0.01, ***p < 0.001.
Fig. 2
Fig. 2
Modular structure of condition-average brain functional network for both control and stress condition at sparsity level of 13%. Five connected modules were identified in both control (A) and stress (B) conditions, including the frontoparietal module (Module I), the default mode module (Module II), the occipital module (Module III), the subcortical module (Module IV), and the central-opercular module (Module V). Topological roles of brain regions (i.e., connector hub, connector non-hub, provincial hub, or provincial non-hub) in each module were presented for control (C) and stress (D) conditions. Shape stands for connector (square) or provincial (circle) nodes whereas size stands for hub (large) or non-hub (small) nodes.

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