Heritability of human directed functional connectome

IntroductionThe functional connectivity patterns in the brain are highly heritable; however, it is unclear how genetic factors influence the directionality of such information flows. Studying the directionality of the brain functional connectivity and assessing how heritability modulates it can improve our understanding of the human connectome. MethodsHere, we investigated the heritability of directed functional connections using a state-space formulation of Granger causality (GC), in conjunction with blind deconvolution methods accounting for local variability in the hemodynamic response function. Such GC implementation is ideal to explore the directionality of functional interactions across a large number of networks. Resting-state functional magnetic resonance imaging data were drawn from the Human Connectome Project (total n = 898 participants). To add robustness to our findings, the dataset was randomly split into a discovery and a replication sample (each with n = 449 participants). The two cohorts were carefully matched in terms of demographic variables and other confounding factors (e.g., education). The effect of shared environment was also modeled. ResultsThe parieto- and prefronto-cerebellar, parieto-prefrontal, and posterior-cingulate to hippocampus connections showed the highest and most replicable heritability effects with little influence by shared environment. In contrast, shared environmental factors significantly affected the visuo-parietal and sensory-motor directed connectivity. ConclusionWe suggest a robust role of heritability in influencing the directed connectivity of some cortico-subcortical circuits implicated in cognition. Further studies, for example using task-based fMRI and GC, are warranted to confirm the asymmetric effects of genetic factors on the functional connectivity within cognitive networks and their role in supporting executive functions and learning.

Automated summary

This study investigated the heritability of directed functional connections in the brain using the state-space formulation of Granger causality (GC) method. The results showed that the directed connectivity of certain cortico-subcortical circuits is strongly influenced by genetic factors, while other connections are less affected.