Heritability and interindividual variability of regional structure-function coupling

Zijin Gu,Mert Rory Sabuncu,Keith Wakefield Jamison,Amy Kuceyeski

doi:10.1038/s41467-021-25184-4

Abstract

White matter structural connections are likely to support flow of functional activation or functional connectivity. While the relationship between structural and functional connectivity profiles, here called SC-FC coupling, has been studied on a whole-brain, global level, few studies have investigated this relationship at a regional scale. Here we quantify regional SC-FC coupling in healthy young adults using diffusion-weighted MRI and resting-state functional MRI data from the Human Connectome Project and study how SC-FC coupling may be heritable and varies between individuals. We show that regional SC-FC coupling strength varies widely across brain regions, but was strongest in highly structurally connected visual and subcortical areas. We also show interindividual regional differences based on age, sex and composite cognitive scores, and that SC-FC coupling was highly heritable within certain networks. These results suggest regional structure-function coupling is an idiosyncratic feature of brain organisation that may be influenced by genetic factors.

Highlights

White matter structural connections are likely to support flow of functional activation or functional connectivity
In this paper, we quantified the strength of coupling between the structural and functional connectivity profiles of cortical, subcortical and cerebellar brain regions in a large sample of healthy young adults
We demonstrate that structural connectome (SC)–functional connectome (FC) coupling is strongest in visual and subcortical areas, weakest in limbic and default mode network regions and is consistent across time and different sample populations

Summary

Introduction

White matter structural connections are likely to support flow of functional activation or functional connectivity. Some of the main goals in joint structure–function connectome modeling are to understand how neural populations communicate via the SC backbone[7], how functional activation spreads through the structural connectome[8], to increase the accuracy of noisy connectivity measurements, to identify function-specific subnetworks[10], to predict one modality from the other[1] or to identify multi-modal mechanisms of recovery after injury[11,12] While useful, these modeling approaches are global in nature and ignore the regional variability in the structure–function relationship that, to date, has not been adequately quantified in adult populations. In one of the few studies to date of regional SC–FC coupling, Baum et al.[24] studied a large number of developing subjects (N = 727, aged 8−23 years old) and showed that the relationship between age and SC–FC coupling varied across brain regions, with some regions showing positive and fewer regions showing negative relationships They showed that stronger SC–FC coupling in rostro-lateral prefrontal cortex was associated with development-related increases in executive function. Another of regional SC–FC coupling analyzed data from a group of around 100 young adults and showed that, overall, regional SC–FC coupling was stronger in females than in males and that there were sex-specific correlations of SC–FC coupling with cognitive scores[25]

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Results

Conclusion