Sex-related human brain asymmetry in hemispheric functional gradients

The left and right hemispheres of the human brain are two connected but relatively independent functional modules; they show multidimensional asymmetries ranging from particular local brain unit properties to entire hemispheric connectome topology. To date, however, it remains largely unknown whether and how hemispheric functional hierarchical structures differ between hemispheres. In the present study, we adopted a newly developed resting-state (rs) functional connectivity (FC)-based gradient approach to evaluate hemispheric functional hierarchical structures and their asymmetries in right-handed healthy young adults. Our results showed an overall mirrored principal functional gradient between hemispheres, with the sensory cortex and the default-mode network (DMN) anchored at the two opposite ends of the gradient. Interestingly, the left hemisphere showed a significantly larger full range of the principal gradient in both males and females, with males exhibiting greater leftward asymmetry. Similarly, the principal gradient component scores of two regions around the middle temporal gyrus and posterior orbitofrontal cortex exhibited similar hemisphere × sex interaction effects: a greater degree of leftward asymmetry in males than in females. Moreover, we observed significant main hemisphere and sex effects in distributed regions across the entire hemisphere. All these results are reproducible and robust between test-retest rs-fMRI sessions. Our findings provide evidence of functional gradients that enhance the present understanding of human brain asymmetries in functional organization and highlight the impact of sex on hemispheric functional gradients and their asymmetries.