The ups and downs of brain stress: Extending the triple network hypothesis

Background : This pre-registered functional magnetic resonance imaging study aimed to test and possibly extend the triple network hypothesis of psychosocial stress processing, positing that responses in the salience (SN) and default mode network (DMN) dominate at the expense of the central executive network (CEN). Methods : We reviewed psychosocial stress studies and conducted a mega-analysis of N=459 ScanSTRESS-datasets (222 women) with harmonized preprocessing (ENIGMA HALFpipe). Results : Our findings disconfirmed the original hypothesis, revealing activations and deactivations across all three networks, related in a complex way to hormonal, cardiac, subjective, and performance parameters. Additionally, we replicated an exposure-time effect of decreasing activation, identified a novel age effect of increasing DMN-activation, sex-specific patterns, and confirmed the involvement of all networks by task-based connectivity. Conclusions : These results suggest a new, extended triple network hypothesis of psychosocial stress processing, describing that SN- and DMN-structures orchestrate hormonal, cardiac, and subjective stress responses, while CEN- and DMN-structures process the stress-eliciting tasks.