Beckman Institute for Advanced Science and Technology, University of Illinois at Urbana-Champaign, Urbana, Illinois, 618201; Psychology Department, University of Illinois at Urbana-Champaign, Urbana, Illinois 61801.
Beckman Institute for Advanced Science and Technology, University of Illinois at Urbana-Champaign, Urbana, Illinois, 618201.
Neuroimage. 2022 Aug 1;256:119274. doi: 10.1016/j.neuroimage.2022.119274. Epub 2022 Apr 30.
The brain's functional connectome is dynamic, constantly reconfiguring in an individual-specific manner. However, which characteristics of such reconfigurations are subject to genetic effects, and to what extent, is largely unknown. Here, we identified heritable dynamic features, quantified their heritability, and determined their association with cognitive phenotypes. In resting-state fMRI, we obtained multivariate features, each describing a temporal or spatial characteristic of connectome dynamics jointly over a set of connectome states. We found strong evidence for heritability of temporal features, particularly, Fractional Occupancy (FO) and Transition Probability (TP), representing the duration spent in each connectivity configuration and the frequency of shifting between configurations, respectively. These effects were robust against methodological choices of number of states and global signal regression. Genetic effects explained a substantial proportion of phenotypic variance of these features (h=0.39, 95% CI= [.24,.54] for FO; h=0.43, 95% CI=[.29,.57] for TP). Moreover, these temporal phenotypes were associated with cognitive performance. Contrarily, we found no robust evidence for heritability of spatial features of the dynamic states (i.e., states' Modularity and connectivity pattern). Genetic effects may therefore primarily contribute to how the connectome transitions across states, rather than the precise spatial instantiation of the states in individuals. In sum, genetic effects impact the dynamic trajectory of state transitions (captured by FO and TP), and such temporal features may act as endophenotypes for cognitive abilities.
大脑的功能连接组是动态的,以个体特有的方式不断重新配置。然而,这种重新配置的哪些特征受遗传影响,以及受遗传影响的程度如何,在很大程度上尚不清楚。在这里,我们确定了可遗传的动态特征,量化了它们的遗传性,并确定了它们与认知表型的关联。在静息状态 fMRI 中,我们获得了多元特征,每个特征描述了连接组动力学在一组连接组状态下的时间或空间特征。我们发现,时间特征,尤其是分数占据(Fractional Occupancy,FO)和转换概率(Transition Probability,TP)具有很强的遗传性,分别代表了在每个连通性配置中花费的持续时间以及在配置之间转换的频率。这些效应在状态数量和全局信号回归的方法选择方面具有稳健性。遗传效应解释了这些特征的表型方差的很大一部分(FO 的 h=0.39,95%CI=[.24,.54];TP 的 h=0.43,95%CI=[.29,.57])。此外,这些时间表型与认知表现相关。相反,我们没有发现动态状态的空间特征(即状态的模块性和连通模式)具有遗传性的可靠证据。因此,遗传效应可能主要影响连接组在状态之间的转换动态轨迹,而不是个体中状态的精确空间实例化。总之,遗传效应影响状态转换的动态轨迹(由 FO 和 TP 捕获),并且这些时间特征可能作为认知能力的内表型。