Abstract

An improved understanding of the structure-function relationship in the brain is necessary to know to what degree structural connectivity underpins abnormal functional connectivity seen in disorders. We integrated high-field resting-state fMRI-based functional connectivity with high-resolution macro-scale diffusion-based and meso-scale neuronal tracer-based structural connectivity, to obtain an accurate depiction of the structure-function relationship in the rat brain. Our main goal was to identify to what extent structural and functional connectivity strengths are correlated, macro- and meso-scopically, across the cortex. Correlation analyses revealed a positive correspondence between functional and macro-scale diffusion-based structural connectivity, but no significant correlation between functional connectivity and meso-scale neuronal tracer-based structural connectivity. Zooming in on individual connections, we found strong functional connectivity in two well-known resting-state networks: the sensorimotor and default mode network. Strong functional connectivity within these networks coincided with strong short-range intrahemispheric structural connectivity, but with weak heterotopic interhemispheric and long-range intrahemispheric structural connectivity. Our study indicates the importance of combining measures of connectivity at distinct hierarchical levels to accurately determine connectivity across networks in the healthy and diseased brain. Although characteristics of the applied techniques may affect where structural and functional networks (dis)agree, distinct structure-function relationships across the brain could also have a biological basis.

Highlights

  • An improved understanding of the structure-function relationship in the brain is necessary to know to what degree structural connectivity underpins abnormal functional connectivity seen in disorders

  • Since functional connectivity measured with resting-state fMRI relies on synchronous blood oxygenation level-dependent (BOLD) signals, understanding functional connectivity starts with understanding the origin of BOLD signals

  • Functional connectivity strength was positively correlated with diffusion-based structural connectivity strength in cortical connections (ρ = 0.41; p < 0.0001; 95% confidence interval: 0.36–0.46; Fig. 2a)

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Summary

Introduction

An improved understanding of the structure-function relationship in the brain is necessary to know to what degree structural connectivity underpins abnormal functional connectivity seen in disorders. We integrated high-field resting-state fMRI-based functional connectivity with high-resolution macro-scale diffusion-based and meso-scale neuronal tracer-based structural connectivity, to obtain an accurate depiction of the structure-function relationship in the rat brain. Functional connectivity strength correlates with both diffusion- and neuronal tracer-based structural connectivity strength at the whole-brain level[17,18]; for an overview see[19]. More accurate assessment of the structure-function relationships requires integration of functional connectivity with both macro-scale diffusion- and meso-scale neuronal tracer-based structural measures. Rodents are excellent species to study these relationships as resting-state fMRI and diffusion MRI-based tractography are feasible in rodents[28] and comprehensive rodent databases of neuronal tracer-based structural connectivity are available as well[29,30]

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