In vivo cartography of state-dependent signal flow hierarchy in the human cerebral cortex

Understanding the principle of information flow across distributed brain networks is of paramount importance in neuroscience. Here, we introduce a novel neuroimaging framework, leveraging integrated effective connectivity (iEC) and unconstrained signal flow mapping for data-driven discovery of the human cerebral functional hierarchy. Simulation and empirical validation demonstrated the high fidelity of iEC in recovering connectome directionality and its potential relationship with histologically defined feedforward and feedback pathways. Notably, the iEC-derived hierarchy displayed a monotonously increasing level along the axis where the sensorimotor, association, and paralimbic areas are sequentially ordered – a pattern supported by the Structural Model of laminar connectivity. This hierarchy was further demonstrated to flexibly reorganize according to brain states, flattening during an externally oriented condition, evidenced by a reduced slope in the hierarchy, and steepening during an internally focused condition, reflecting heightened engagement of interoceptive regions. Our study highlights the unique role of macroscale directed functional connectivity in uncovering a neurobiologically grounded, state-dependent signal flow hierarchy.