Establishing a link between sex-related differences in the structural connectome and behaviour

Abstract

Recent years have witnessed an increased attention to studies of sex differences, partly because such differences offer important considerations for personalized medicine. While the presence of sex differences in human behaviour is well documented, our knowledge of their anatomical foundations in the brain is still relatively limited. As a natural gateway to fathom the human mind and behaviour, studies concentrating on the human brain network constitute an important segment of the research effort to investigate sex differences. Using a large sample of healthy young individuals, each assessed with diffusion MRI and a computerized neurocognitive battery, we conducted a comprehensive set of experiments examining sex-related differences in the meso-scale structures of the human connectome and elucidated how these differences may relate to sex differences at the level of behaviour. Our results suggest that behavioural sex differences, which indicate complementarity of males and females, are accompanied by related differences in brain structure across development. When using subnetworks that are defined over functional and behavioural domains, we observed increased structural connectivity related to the motor, sensory and executive function subnetworks in males. In females, subnetworks associated with social motivation, attention and memory tasks had higher connectivity. Males showed higher modularity compared to females, with females having higher inter-modular connectivity. Applying multivariate analysis, we showed an increasing separation between males and females in the course of development, not only in behavioural patterns but also in brain structure. We also showed that these behavioural and structural patterns correlate with each other, establishing a reliable link between brain and behaviour.

Keywords: behaviour; connectome; diffusion imaging; gender; sex; structural connectivity.

Figure 1.

An illustration of structurally cohesive subnetworks, with 10 subnetworks (a), and a set of example group differences between males and females, with mean connectivity within and between subnetworks being compared (b). Females show higher connectivity in the inter-hemispheric connections, and males have higher connectivity in the intra-hemispheric connections. The complete set of group differences is given in table 1. (Online version in colour.)

Figure 2.

Classification accuracy (y-axis) with different age groups in years (x-axis), when using (a) structural connectivity patterns and (b) behavioural patterns. Box plots depict the range of the classification accuracy as estimated using 10-fold cross-validation, repeated by 100 randomization. For both cases, the average classification accuracy increases steadily across development, although the structural scores show a higher increase. (Online version in colour.)

Figure 3.

Construction of the structural connectome. The nodes of the connectome are the anatomical regions of interest. Edges are generated by seeding probabilistic tractography from WM–GM boundaries of regions. The final network representation defines the connectome. (Online version in colour.)