Reconfiguration of default mode metabolic demands and network organization during acute stress

Psychosocial stress engages coordinated physiological and neural responses that enable adaptation to environmental challenges. Maladaptive stress responses and reduced resilience are major risk factors for psychiatric and neurodegenerative disorders. As the brain's metabolic response to stress remains largely unexplored, we used simultaneous [18F]FDG PET/MRI during performance of the Montreal Imaging Stress Task to assess cerebral glucose metabolism, BOLD activation and functional connectivity. Multimodal data analysis identified the posterior cingulate cortex (PCC) as hub of stress processing beyond cognitive input, with increased glucose metabolism and attenuated BOLD deactivations. This was accompanied by reduced PCC connectivity within the default mode network and increased influence onto frontoparietal and dorsal attention networks. Endocrine stress responsivity was further reflected in lower resilience sub scores, failure to downregulate anterior cingulate cortex (ACC) metabolism during stress, and an inverse relationship between ACC glucose metabolism and anterior insula functional connectivity. These results indicate that acute psychosocial stress does not merely increase overall energy demand but reconfigures the relationship between regional metabolism and large-scale network organization, which further differs with individual endocrine stress responsivity. Our findings unify the roles of stress and the DMN in brain disorders, providing a multimodal framework for assessment in patient populations.