KIBRA gene variants are associated with synchronization within the default-mode and executive control networks

Abstract

Genetic variation at the KIBRA rs17070145 polymorphism has been linked to episodic memory, executive function, and Alzheimer's disease (AD), which are related to the structural and functional integrity of the default-mode network (DMN) and executive control network (ECN). We hypothesize that the KIBRA polymorphism could modulate the structure and function of the DMN and ECN in healthy young subjects, which might underlie the association between this gene and cognitive function. To test our hypothesis, we analyzed the resting-state synchronization in the DMN and ECN in 288 young, healthy Chinese Han subjects. We found that carriers of the KIBRA C-allele demonstrated an increased synchronization in the posterior cingulate cortex (PCC) and medial prefrontal cortex (MPFC) of the DMN and in the right anterior insula, bilateral caudate nuclei, and bilateral dorsal anterior cingulate cortices (dACC) of the ECN compared to individuals with a TT genotype. Moreover, KIBRA C-allele carriers also showed a smaller gray matter volume (GMV) in the MPFC and bilateral dACCs than TT individuals. In contrast, there were no significant genotype differences in the synchronization of either the visual network or the sensorimotor network. These findings suggest that the polymorphism in the KIBRA gene affects GMV and the function of the DMN and ECN. This increased synchronization is likely a reflection of compensation for the regional gray matter deficits in these networks in young healthy subjects. The association between KIBRA polymorphisms and the DMN and ECN should be further explored in a healthy older population and in patients with AD.