Stepwise pathways from the olfactory cortex to central hub regions in the human brain.

The human brain is organized as a hierarchical global network. Functional connectivity research reveals that sensory cortices are connected to corresponding association cortices via a series of intermediate nodes linked by synchronous neural activity. These sensory pathways and relay stations converge onto central cortical hubs such as the default-mode network (DMN). The DMN regions are believed to be critical for representing concepts and, hence, language acquisition and use. Although prior research has established that major senses are placed at a similar distance from the DMN-five to six connective steps-it is still unknown how the olfactory system functionally connects to the large-scale cortical hubs of the human brain. In this study, we investigated the connective distance from olfactory seed areas to the DMN. The connective distance involves a series of three to four intermediate steps. Furthermore, we parcellated the olfactory cortical subregions and found evidence of two distinct olfactory pathways. One emerges from the anterior olfactory nucleus and olfactory tubercle; it involves early access to the orbitofrontal cortex, known for processing reward and multisensory signals. The other emerges from the frontal and temporal regions of the piriform cortex, involving the anterior insula, intermediate frontal sulcus, and parietal operculum. The results were confirmed in a replication cohort. Our results provide evidence that olfaction has unique early access to the central cortical networks via dual pathways.