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

Cereb Cortex. 2023 Feb 20;33(5):1782-1798. doi: 10.1093/cercor/bhac172.

Abstract

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.

Keywords: connectome; cortical gradients; cortical microstructure; functional connectivity; neuroimaging.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Brain Mapping / methods
  • Cognition
  • Connectome* / methods
  • Emotions
  • Humans
  • Magnetic Resonance Imaging / methods
  • Neocortex*
  • Neural Pathways

Grants and funding