Genetic Architecture Underlying Differential Resting-state Functional Connectivity of Subregions Within the Human Visual Cortex

Abstract The human visual cortex is a heterogeneous entity that has multiple subregions showing substantial variability in their functions and connections. We aimed to identify genes associated with resting-state functional connectivity (rsFC) of visual subregions using transcriptome-neuroimaging spatial correlations in discovery and validation datasets. Results showed that rsFC of eight visual subregions were associated with expression measures of eight gene sets, which were specifically expressed in brain tissue and showed the strongest correlations with visual behavioral processes. Moreover, there was a significant divergence in these gene sets and their functional features between medial and lateral visual subregions. Relative to those associated with lateral subregions, more genes associated with medial subregions were found to be enriched for neuropsychiatric diseases and more diverse biological functions and pathways, and to be specifically expressed in multiple types of neurons and immune cells and during the middle and late stages of cortical development. In addition to shared behavioral processes, lateral subregion associated genes were uniquely correlated with high-order cognition. These findings of commonalities and differences in the identified rsFC-related genes and their functional features across visual subregions may improve our understanding of the functional heterogeneity of the visual cortex from the perspective of underlying genetic architecture.