Subtypes of brain activation are heritable and genetically linked with behavior in the Human Connectome Project sample

Abstract

Many imaging and genetics studies have aimed to clarify whether the brain acts as an intermediate phenotype mediating the influence of genes in human behaviour. Brain activations in response to task demands are heterogeneous at the individual level, but also follow common patterns at the group level.

Some studies have addressed this tension between heterogeneity and homogeneity by identifying groups of individuals that share the same brain activations patterns, called brain activation subtypes. In this work, we aimed to assess the viability of brain subtypes as endophenotypes intermediate between genes and behavior. We extracted brain activation subtypes separately for seven fMRI tasks, in 842 participants from the Human Connectome Project (HCP). We estimated the heritability of these subtypes and their genetic correlation with behavioral measures obtained inside and outside the scanner. Across all tasks, subtypes ranged from a predominantly ‘deactivating’ pattern towards a more ‘activating’ pattern of brain activity, with a heritability estimate ranging from 0 to 0.62. We observed high
genetic and phenotypic correlation between behavioral measures and brain activation subtypes only for language and working memory tasks. Our results showed a significant genetic grounding of brain activation subtypes and they appear as a simple yet effective technique to tackle heterogeneity into imaging genetics studies.