Functional connectome analyses reveal a highly optimized human olfactory network

Abstract

The olfactory system is uniquely heterogeneous, performing multifaceted functions (beyond basic sensory processing) across diverse, widely distributed neural substrates. While knowledge of human olfaction continues to grow, it remains unclear how the olfactory network is organized to serve this unique set of functions. Leveraging a large and high-quality resting-state functional magnetic resonance imaging (rs-fMRI) dataset of nearly 900 participants from the Human Connectome Project (HCP), we identified a human olfactory network encompassing cortical and subcortical regions across the temporal and frontal lobes. Highlighting its reliability and generalizability, the connectivity matrix of this olfactory network mapped closely onto that extracted from an independent rs-fMRI dataset. Graph theoretical analysis further explicated the organizational principles of the network. The olfactory network exhibits a functionally advantageous modular composition of three (i.e., the sensory, limbic, and frontal) subnetworks and demonstrates strong small-world properties, high in both global integration and local segregation (i.e., circuit specialization). This network organization thus ensures the segregation of local circuits, which are nonetheless integrated via connecting hubs (i.e., amygdala and anterior insula), thereby enabling the specialized, yet integrative, functions of olfaction. In particular, the degree of local segregation positively predicted olfactory discrimination performance in the independent sample. In sum, an olfactory functional network has been identified through the large HCP dataset, affording a representative template of the human olfactory functional neuroanatomy. Importantly, the topological analysis of the olfactory network provides network-level insights into the remarkable functional specialization and spatial segregation of the olfactory system. Significance StatementOlfaction is an intriguing multifunctional system, playing key roles in regulating emotions, autonomic tone, and feeding, beyond basic sensory perception. However, it is unclear how the neuroanatomy of olfaction is organized in humans to subserve these functions. Functional connectivity analysis of the HCP dataset combined with graph theoretical analysis revealed an optimized large-scale network consisting of three subnetworks-the sensory, limbic, and frontal subnetworks. Distributed across frontal and temporal lobes in well segregated fashion, these olfactory structures are also highly integrated, linked through hub nodes of the amygdala and anterior insula. Our independent dataset replicated the HCP-derived olfactory network and, importantly, highlighted a direct association between the degree of network segregation and olfactory perception.

Anchoring the human olfactory system to a functional gradient

“…The fifth gradient involves a set of regions that likely corresponds to the olfactocentric system and is classically activated in fMRI studies during olfactoryspecific tasks. The olfactocentric system is traditionally divided into the primary olfactory cortex and the secondary olfactory cortex (Purves and Williams, 2001) with a high modularity (Arnold et al, 2019). The primary olfactory cortex is represented by the piriform cortex that projects to various cortical (e.g.…”