The heritability and structural correlates of brain entropy

Brain entropy (BEN) quantifies the temporal complexity of spontaneous neural activity, which has been increasingly recognized as providing important insights into cognitive functions and psychiatric disorders. However, its heritability and structural underpinnings are not well understood. Here, we utilize sample entropy to calculate BEN in healthy young adults using resting-state fMRI from the Human Connectome Project. We show that BEN is significantly heritable in broad brain regions. Heritability estimates exhibit regional variability, with lower heritability in the limbic and subcortical networks than in other networks. We further relate BEN to structural features including surface area (SA), cortical myelination (CM), cortical thickness (CT), and subcortical volumes (SV). We find that BEN is negatively correlated with SA in most cortical regions, but is positively correlated with CM in the prefrontal cortex, lateral temporal lobe, precuneus, lateral parietal cortex, and cingulate cortex. Only a few cortical regions show significant correlations between BEN and CT. By decomposing correlations into genetic and environmental components, we observe that most of BEN-SA correlations are associated with shared genetic and environmental effects. BEN-CM correlations are mainly attributed to shared environmental effects. BEN-CT correlations are partly related to shared environmental effects. We find no significant associations between BEN and SV. Collectively, our work establishes the genetic basis and structural correlates of resting-state fMRI-based BEN, supporting its potential application as an endophenotype for psychiatric disorders.