Long-range functional connections mirror and link microarchitectural and cognitive hierarchies in the human brain

Background Higher-order cognition is hypothesized to be implemented via distributed cortical networks that are linked via long-range connections. However, it is unknown how computational advantages of long-range connections reflect cortical microstructure and microcircuitry. Methods We investigated this question by (i) profiling long-range cortical connectivity using resting-state functional magnetic resonance imaging (MRI) and cortico-cortical geodesic distance mapping, (ii) assessing how long-range connections reflect local brain microarchitecture, and (iii) examining the microarchitectural similarity of regions connected through long-range connections. Results Analysis of 2 independent datasets indicated that sensory/motor areas had more clustered short-range connections, while transmodal association systems hosted distributed, long-range connections. Meta-analytical decoding suggested that this topographical difference mirrored shifts in cognitive function, from perception/action towards emotional/social processing. Analysis of myelin-sensitive in vivo MRI as well as postmortem histology and transcriptomics datasets established that gradients in functional connectivity distance are paralleled by those present in cortical microarchitecture. Notably, long-range connections were found to link spatially remote regions of association cortex with an unexpectedly similar microarchitecture. Conclusions By mapping covarying topographies of long-range functional connections and cortical microcircuits, the current work provides insights into structure-function relations in human neocortex.

Automated summary

This study used resting-state functional magnetic resonance imaging (MRI) to investigate long-range cortical connectivity and its relationship with cortical microstructure and microcircuitry. The results revealed that long-range connections reflected different cognitive functions and were associated with similar microarchitecture in spatially remote regions. This work provides valuable insights into the structure-function relations in the human neocortex.