Influence of Wiring Cost on the Large-Scale Architecture of Human Cortical Connectivity

Abstract

In the past two decades some fundamental properties of cortical connectivity have been discovered: small-world structure, pronounced hierarchical and modular organisation, and strong core and rich-club structures. A common assumption when interpreting results of this kind is that the observed structural properties are present to enable the brain's function. However, the brain is also embedded into the limited space of the skull and its wiring has associated developmental and metabolic costs. These basic physical and economic aspects place separate, often conflicting, constraints on the brain's connectivity, which must be characterized in order to understand the true relationship between brain structure and function. To address this challenge, here we ask which, and to what extent, aspects of the structural organisation of the brain are conserved if we preserve specific spatial and topological properties of the brain but otherwise randomise its connectivity. We perform a comparative analysis of a connectivity map of the cortical connectome both on high- and low-resolutions utilising three different types of surrogate networks: spatially unconstrained (‘random’), connection length preserving (‘spatial’), and connection length optimised (‘reduced’) surrogates. We find that unconstrained randomisation markedly diminishes all investigated architectural properties of cortical connectivity. By contrast, spatial and reduced surrogates largely preserve most properties and, interestingly, often more so in the reduced surrogates. Specifically, our results suggest that the cortical network is less tightly integrated than its spatial constraints would allow, but more strongly segregated than its spatial constraints would necessitate. We additionally find that hierarchical organisation and rich-club structure of the cortical connectivity are largely preserved in spatial and reduced surrogates and hence may be partially attributable to cortical wiring constraints. In contrast, the high modularity and strong s-core of the high-resolution cortical network are significantly stronger than in the surrogates, underlining their potential functional relevance in the brain.

Author Summary

Macroscopic regions in the grey matter of the human brain are intricately connected by white-matter pathways, forming the extremely complex network of the brain. Analysing this brain network may provide us insights on how anatomy enables brain function and, ultimately, cognition and consciousness. Various important principles of organization have indeed been consistently identified in the brain's structural connectivity, such as a small-world and modular architecture. However, it is currently unclear which of these principles are functionally relevant, and which are merely the consequence of more basic constraints of the brain, such as its three-dimensional spatial embedding into the limited volume of the skull or the high metabolic cost of long-range connections. In this paper, we model what aspects of the structural organization of the brain are affected by its wiring constraints by assessing how far these aspects are preserved in brain-like networks with varying spatial wiring constraints. We find that all investigated features of brain organization also appear in spatially constrained networks, but we also discover that several of the features are more pronounced in the brain than its wiring constraints alone would necessitate. These findings suggest the functional relevance of the ‘over-expressed’ properties of brain architecture.