A Neurocognitive Shift in Midlife: Linking Cognitive Flexibility and Functional-Metabolic Adaptation with the SENECA model

Cognitive flexibility in the human brain engages dynamic interactions between the Default Mode Network (DMN) and the Fronto-Parietal Network (FPN), a functional architecture that is metabolically demanding and thus potentially susceptible to age-related decline. How the aging brain reorganizes its functional architecture to sustain cognitive flexibility under metabolic constraints remains an open question. In this study, we modeled resting-state functional flexibility across the adult lifespan (ages 18–88) using structural balance theory. Our findings align with the predictions of the SENECA model ( Synergistic, Economical, Nonlinear, Emergent, Cognitive Aging ), revealing a midlife neurocognitive transition: (i) from a metabolically costly, flexible DMN-FPN architecture, toward (ii) a more redundant configuration dominated by low-cost, sensory-driven interactions. The medio-parietal DMN and the Cingulo-Opercular Network (CON) are crucial to this transition, contributing to maintain global brain activity near a critical dynamic regime in older adulthood that optimizes for cognitive flexibility in face of declining metabolic resources. These findings advance a theoretical and methodological framework for understanding neurocognitive flexibility in aging and underscore the importance of multimodal fMRI-PET studies in midlife. They also open promising avenues for translational applications in neuropathology.