Hubs and interaction: the brain's meta-loop

We must reconcile the needs of the internal world and the demands of the external world to make decisions relevant to homeostasis, well-being, and flexible behavior. Engagement with the internal (eg interoceptive) world is linked to medial brain systems, whereas the extrapersonal space (eg exteroceptive) is associated with lateral brain systems. Using Human Connectome Project data, we found three association tracts connecting the action-related frontal lobe with perception-related posterior lobes. A lateral dorsal tract and a medial dorsal tract interact independently with a ventral tract at frontal and posterior hubs. The two frontal and the two posterior hubs are interconnected, forming a meta-loop that integrates lateral and medial brain systems. The four anatomical hubs correspond to the common nodes of the intrinsic cognitive brain networks such as the default mode network. These functional networks depend on the integration of both realms. Thus, the positioning of functional cognitive networks can be understood as the intersection of long anatomical association tracts. The strength of structural connectivity within lateral and medial brain systems correlates with performance on behavioral tests assessing theory of mind. The meta-loop provides an anatomical framework to associate neurological and psychiatric symptoms with functional and structural changes.