Sex differences in cognition and structural covariance-based morphometric connectivity: evidence from 28,000+ UK Biobank participants

Abstract

There is robust evidence for sex differences in domain-specific cognition, where females typically show an advantage for verbal memory, whereas males tend to perform better in spatial memory. Sex differences in brain connectivity are well documented and may provide insight into these differences. In this study, we examined sex differences in cognition and structural covariance, as an index of morphometric connectivity, of a large healthy sample (n = 28,821) from the UK Biobank. Using T1-weighted magnetic resonance imaging scans and regional cortical thickness values, we applied jackknife bias estimation and graph theory to obtain subject-specific measures of structural covariance, hypothesizing that sex-related differences in brain network global efficiency, or overall covariance, would underlie cognitive differences. As predicted, females demonstrated better verbal memory and males showed a spatial memory advantage. Females also demonstrated faster processing speed, with no observed sex difference in executive functioning. Males showed higher global efficiency, as well as higher regional covariance (nodal strengths) in both hemispheres relative to females. Furthermore, higher global efficiency in males mediated sex differences in verbal memory and processing speed. Findings contribute to an improved understanding of how biological sex and differences in cognition are related to morphometric connectivity as derived from graph-theoretic methods.