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 'cortico-centric bias'. Here, we consider a large cohort of healthy human subjects of either sex (Human Connectome Project data base) and we perform a dynamic functional connectivity 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, in state 2 with sensorimotor networks. An opposite pattern is observed for thalamus/basal ganglia. Our findings suggest that cortico-subcortical interactions contribute to shaping whole-brain spontaneous functional connectivity patterns, and underline the relevance of including the subcortex in descriptions of large-scale spontaneous brain activity.Significance statement Imaging of the whole brain at rest has shown that distant brain regions engage in transient interactions, giving rise to time-varying coupling patterns. Previous studies analyzing these complex dynamics have generally overlooked subcortical regions. In our study, we analyze functional MRI data of a large cohort of subjects from the Human Connectome Project, demonstrating that the alternation of different coupling patterns is a phenomenon involving cortex and subcortex simultaneously. Limbic regions (hippocampus and amygdala) and subcortical nuclei (thalamus and basal ganglia) form coherent 'blocks', flexibly changing their coupling with cortical regions. Our results suggest that cortical-subcortical interactions might contribute to shaping whole-brain spontaneous activity, emphasizing the importance of including subcortical structures in brain connectivity studies.