Sex differences in Variability of Brain Structure Across the Lifespan

Abstract

Several brain disorders exhibit sex differences in onset, presentation, and prevalence.Increased understanding of the neurobiology of sex-based differences across the lifespan can provide insight into potential disease risk and protective mechanisms. We focused on sex-related differences in variability, which may be indicative of both disease vulnerability and resilience. In n=3,069 participants, from 8-95 years of age, we first analyzed the variance ratio in females vs. males of cortical surface area and global and subcortical volumes for discrete brain regions, and found widespread greater variability in males. In contrast, variance in cortical thickness was similar for males and females. Multivariate analysis that accounts for structural covariance supported variance ratio findings. Findings were present from early life and stable with age. We then examined variability among brain regions by sex. We found significant age-by-sex interactions across neuroimaging metrics, whereby in very early life males had reduced among-region variability compared to females, while in very late life this was reversed. Overall, our findings of greater regional variability but less among-region variability in males in early life may aid our understanding of sex-based risk for neurodevelopmental disorders. In contrast, our findings in late life may provide a potential sex-based risk mechanism for dementia.

Individualized Spatial Network Predictions Using Siamese Convolutional Neural Networks: A Resting-State fMRI Study of over 11,000 Unaffected Individuals

“…Further analysis of our results revealed that the performance of our model depends on subjects’ age and sex. From the sex-based assessments, we observed in most cases (71%) the model performed better in males corroborating the previous studies’ findings, which showed that males’ brain networks have larger variability (i.e., more distinct patterns) than females’ [51,52]. Especially for the first time, we showed functional activity in the SPL network varies more within males than females.…”

“…This suggests that male functional networks have more uniquely identifying individual patterns, especially in the cerebellar domain, compared to females. This finding is consistent with studies of brain structure that maintain males’ brains have more variability than females [51,52]. Indeed, higher variability in brain structure is conducive to the existence of more distinct patterns in males that help characterize male subjects’ identities more accurately.…”

Greater male than female variability in regional brain structure across the lifespan

“…In this study, we analyzed a large lifespan sample of neuroimaging data from 16,683 participants spanning nine decades of life starting at birth. Results confirmed the hypothesis of greater male variability in brain structure (Forde et al 2019;Ritchie et al 2018;Wierenga et al 2017;. Variance differences were more pronounced for subcortical volumes and regional cortical surface area than for regional cortical thickness.…”

“…body weight and height, blood parameters) already detectable at birth. Recent studies suggest greater male variability also in brain structure and its development (Forde et al 2019;Ritchie et al 2018; Wierenga et al 2017;, but studies with larger samples that cover both early childhood and old age are critically needed. Specifically, we do not know when sex differences in variability in brain structure emerge and whether they change with development and throughout life.…”

“…Our first aim was to replicate previous findings of greater male variability in brain structure in a substantially larger sample. Based on prior studies (Forde et al 2019;Ritchie et al 2018; Wierenga et al 2017; and reports of somewhat greater genetic effect on surface area than thickness (Eyler et al 2011;Kremen et al 2013), we hypothesized that greater male variance would be more pronounced for subcortical volumes and cortical surface area than for cortical thickness, and that greater male variance would be observed at both upper and lower ends of the distribution. Our second aim was to test whether observed sex differences in variability of brain structure are stable across the lifespan from birth until 90 years of age, or e.g.…”