Switching Patterns of Cortical–Subcortical Interaction in the Human Brain

It is still poorly understood how subcortical structures contribute to spontaneous infraslow brain activity. In fact, cortical spontaneous activity is often analyzed in isolation, possibly a result of a long-standing “corticocentric bias”. Here, we consider a large cohort of healthy human subjects of either sex (Human Connectome Project database), and we perform a dynamic functional connectivity (FC) analysis to investigate fluctuations of cortical–subcortical interactions. Our analysis shows that FC shifts in the cortex and the subcortex are synchronized. Two core subcortical “clusters” comprising, respectively, limbic regions (hippocampus and amygdala) and subcortical nuclei (thalamus and basal ganglia) show a temporally flexible coupling with cortical regions. Correspondingly, we consistently observe two recurring FC patterns (states). In State 1, limbic regions couple with the default mode network, and in State 2, they couple with sensorimotor networks. An opposite pattern is observed for the thalamus/basal ganglia. Our findings suggest that cortical–subcortical interactions contribute to shaping whole-brain spontaneous FC patterns and underline the relevance of including the subcortex in descriptions of large-scale spontaneous brain activity.