The default-mode network, a coherent resting-state brain network, is thought to characterize basal neural activity. Aberrant default-mode connectivity has been reported in a host of neurological and psychiatric illnesses and in persons at genetic risk for such illnesses. Whereas the neurophysiologic mechanisms that regulate default-mode connectivity are unclear, there is growing evidence that genetic factors play a role. In this report, we estimate the importance of genetic effects on the default-mode network by examining covariation patterns in functional connectivity among 333 individuals from 29 randomly selected extended pedigrees. Heritability for default-mode functional connectivity was 0.424 ± 0.17 (P = 0.0046). Although neuroanatomic variation in this network was also heritable, the genetic factors that influence default-mode functional connectivity and gray-matter density seem to be distinct, suggesting that unique genes influence the structure and function of the network. In contrast, significant genetic correlations between regions within the network provide evidence that the same genetic factors contribute to variation in functional connectivity throughout the default mode. Specifically, the left parahippocampal region was genetically correlated with all other network regions. In addition, the posterior cingulate/precuneus region, medial prefrontal cortex, and right cerebellum seem to form a subnetwork. Default-mode functional connectivity is influenced by genetic factors that cannot be attributed to anatomic variation or a single region within the network. By establishing the heritability of default-mode functional connectivity, this experiment provides the obligatory evidence required before these measures can be considered as endophenotypes for psychiatric or neurological illnesses or to identify genes influencing intrinsic brain function.
Fig. 1 (A) Group-ICA map of the default-mode network derived from resting state scans of 333 individuals from large extended pedigrees. (B) Significant genetic correlations for functional connectivity between heritable regions in the default-mode network. The left parahippocampal gyrus (green) was genetically correlated with the posterior cingulate/precuneus (yellow), medial prefrontal (blue), right cerebellar (red), and right temporal-parietal (pink) regions. In addition, the posterior cingulate/precuneus, medial prefrontal, and right cerebellar regions form a circuit influenced by the same genetic factors. (C) Significant environmental correlations between these same regions.
The pattern of significant environmental correlations differed dramatically from those of the genetic correlations (Fig. 1C). Environmental correlations typically result from unmeasured aspects of the environment or correlated measurement errors. The right temporal–parietal region was significantly correlated with the posterior cingulate/precuneus and medial prefrontal cortex. Neither of these regions showed significant genetic correlations. In addition, the right cerebellum and medial prefrontal cortex had a significant environmental correlation.