Abstract
The brain’s functional connectivity architecture (functional connectome) is dynamic, constantly reconfiguring in an individual-specific manner and contributing to inter-individual variability in cognitive performances. However, to what extent genetic effects shape the dynamic reconfigurations of the functional connectome is largely unknown. This paper assesses whether dynamic connectome features are heritable, quantifies their heritability, and explores their association with cognitive phenotypes. We identified discrete connectome states from resting-state fMRI data (n = 1003 including twins and non-twin siblings) and obtained multivariate features, each describing temporal or spatial characteristics of connectome dynamics. We found strong evidence that the temporal features, particularly fractional occupancy (FO) and transition probability (TP), were heritable. Importantly, a substantial proportion of phenotypic variance of these features (35% of FO and 41% of TP) was explained by genetic effects. The effect was stable after adjusting for head motion, independent of global signal regression and the chosen number of states, and absent in surrogate data. Contrarily, the data did not provide robust support for heritability of spatial features suggesting that genetic effects primarily contribute to how the connectome transitions across states, rather than the precise way in which the states are spatially instantiated. Notably, temporal phenotypes also captured variability in cognitive performance. Overall, our findings demonstrate a link between genetic makeup and temporal reconfigurations of the functional connectome, suggesting that dynamic features may act as endophenotypes for cognitive abilities. In conclusion, we propose that connectome dynamics offer considerable potential as a theoretical, conceptual, and practical framework for linking genetics to behavior.
Competing Interest Statement
The authors have declared no competing interest.
Footnotes
Author Contributions: SJ and SS designed research; SJ performed research; SJ analyzed data; SJ and SS wrote the paper; and SS, THA and AA contributed analytic expertise, theoretical guidance, paper revisions, and informed interpretation of the results.