Sex-dependent differences in connectivity patterns are related to episodic memory recall

Previous studies have shown that females typically outperform males on episodic memory tasks. In this study, we investigated if (1) there are differences between males and females in their connectome characteristics, (2) if these connectivity patterns are associated with memory performance, and (3) if these brain connectome characteristics contribute to the differences in episodic memory performance between sexes. In a sample of 655 healthy young subjects (n = 391 females; n = 264 males), we derived brain network characteristics from diffusion-weighted imaging (DWI) data using models of crossing fibers within each voxel of the brain and probabilistic tractography (graph strength, shortest path length, global efficiency, and weighted transitivity). Group differences were analysed with linear models and mediation analyses were used to explore how connectivity patterns might relate to sex-dependent differences in memory performance. Our results show significant sex-dependent differences in weighted transitivity (d = 0.42), with males showing higher values. Further, we observed a negative association between weighted transitivity and memory performance (r = -0.12). Finally, these distinct connectome characteristics partially mediated the observed differences in memory performance (effect size of the indirect effect r = 0.02). Our findings indicate a higher interconnectedness in females compared to males. Additionally, we demonstrate that the sex-dependent differences in episodic memory performance can be partially explained by the differences in this connectome measure. These results further underscore the importance of sex-dependent differences in brain connectivity and their impact on cognitive function.