The relationship between interhemispheric homotopic functional connectivity and left-right difference of intrahemispheric functional integration in the human brain

Abstract

Abstract The brain comprises left and right hemispheres, with notable distinctions in intrahemispheric functional integration observed between homotopic regions of each hemisphere. Previous studies have shown these left-right differences may be induced by interhemispheric connectivity between homotopic regions. However, no research has comprehensively investigated the relationship between lateralization of intrahemispheric functional integration and interhemispheric homotopic functional connectivity in the resting state. Based on resting-state functional connectivity, we identified two brain functional organization properties named lateralization of intrahemispheric functional integration (LI) and interhemispheric homotopic functional connectivity (HoFC), hypothesizing the former was modulated by the latter in healthy individuals. Results showed a widespread significant negative correlation between LI and HoFC among the whole brain, which could be affected by age and task state presenting a still negative pattern but with weaker strength, especially in heteromodal regions. Furthermore, two mediation models showed that HoFC significantly mediated the age and brain state effect on LI, suggesting age and task state might influence lateralization of intrahemispheric functional integration via interhemispheric homotopic functional connectivity in adults. Lastly, these two intrinsic organization properties with different heritability together correlated with the general intelligence factor in an antagonistic manner. In summary, our findings offer important and valuable insight into functional lateralization, functional homotopy, and their relationship from the perspective of intrinsic functional architecture, together with influential factors such as age and task state. These results provide direct evidence to further understand the link between the left and right hemispheres of the human brain, along with the relation to cognitive functions.