Abstract

The white matter is made of anatomical fibres that constitute the highway of long-range connections between different parts of the brain. This network is referred to as the brain’s structural connectivity and lays the foundation of network interaction between brain areas. When analysing the architectural principles of this global network most studies have mainly focused on cortico-cortical and partly on cortico-subcortical connections. Here we show, for the first time, how the integrated cortical, subcortical, and cerebellar brain areas shape the structural architecture of the whole brain. We find that dense clusters vertically transverse cortical, subcortical, and cerebellar brain areas, which are themselves centralised by a global rich-club consisting similarly of cortical and subcortical brain areas. Notably, the most prominent hubs can be found in subcortical brain regions, and their targeted in-silico lesions proved to be most harmful for global signal propagation. Individually, the cortical, subcortical, and cerebellar sub-networks manifest distinct network features despite some similarities, which underline their unique structural fingerprints. Our results, exposing the heterogeneity of internal organisation across cortex, subcortex, and cerebellum, and the crucial role of the subcortex for the integration of the global anatomical pathways, highlight the need to overcome the prevalent cortex-centric focus towards a global consideration of the structural connectivity.