Molecular basis underlying functional connectivity of fusiform gyrus subregions: A transcriptome-neuroimaging spatial correlation study

Abstract

The fusiform gyrus (FG) subserves a range of visual cognitive functions likely arising from its distinct subregions that present different connectivity profiles. Nevertheless, the molecular basis underlying such connectivity variability across FG subregions is still an open question. Resting-state functional magnetic resonance imaging (fMRI) data were collected from a discovery dataset (361 healthy subjects) and two independent cross-race, cross-scanner validation datasets (103 and 329 healthy subjects). We adopted a newly developed standardized pipeline to process gene expression data from the Allen Human Brain Atlas. Fine-grained FG subregions derived from the Human Brainnetome Atlas were utilized to measure seed-based resting-state functional connectivity (rsFC). Then, transcriptome-neuroimaging spatial association analyses were conducted to identify genes related to rsFC of each FG subregion. Results showed that rsFC of the left A37mv was associated with expression measures of 1063 genes, while there were no expression-rsFC correlations for the other subregions. The 1063 genes were mainly enriched for biological functions and pathways related to synaptic transmission, neurons, and neurotransmitter systems as well as for autism spectrum disorder. Specific expression analyses revealed that these rsFC-related genes were specifically expressed in brain tissue, in cortical neurons and immune cells, and during nearly all developmental periods. In addition, these genes were associated with multiple behavioral domains such as vision, language, and sensation. Finally, protein–protein interaction (PPI) analysis demonstrated that the genes could construct a PPI network with 37 hub genes. These findings may offer unique insights into the molecular basis underlying the functional heterogeneity of the FG.