Establishing the resting state default mode network derived from functional magnetic resonance imaging tasks as an endophenotype: A twins study

The resting state default mode network (DMN) has been shown to characterize a number of neurological and psychiatric disorders. Evidence suggests an underlying genetic basis for this network and hence could serve as potential endophenotype for these disorders. Heritability is a defining criterion for endophenotypes. The DMN is measured either using a resting-state functional magnetic resonance imaging (fMRI) scan or by extracting resting state activity from task-based fMRI. The current study is the first to evaluate heritability of this task-derived resting activity. 250 healthy adult twins (79 monozygotic and 46 dizygotic same sex twin pairs) completed five cognitive and emotion processing fMRI tasks. Resting state DMN functional connectivity was derived from these five fMRI tasks. We validated this approach by comparing connectivity estimates from task-derived resting activity for all five fMRI tasks, with those obtained using a dedicated task-free resting state scan in an independent cohort of 27 healthy individuals. Structural equation modeling using the classic twin design was used to estimate the genetic and environmental contributions to variance for the resting-state DMN functional connectivity. About 9-41% of the variance in functional connectivity between the DMN nodes was attributed to genetic contribution with the greatest heritability found for functional connectivity between the posterior cingulate and right inferior parietal nodes (P<0.001). Our data provide new evidence that functional connectivity measures from the intrinsic DMN derived from task-based fMRI datasets are under genetic control and have the potential to serve as endophenotypes for genetically predisposed psychiatric and neurological disorders.