Sex differences in the human brain: a roadmap for more careful analysis and interpretation of a biological reality

Abstract

Highlights Recent large-scale studies have reached different conclusions regarding the presence of sex differences in human neuroanatomy. We show that these contradictory findings are explained by different methodological choices. While multiple large direct analyses highlight small, highly reproducible sex differences, reviews do not account for methodological heterogeneity across studies (e.g., statistical power/sample size, brain size-correction methods, segmentation, region selection, participant age). This explains many of the apparent inconsistencies reported in recent reviews. We also summarize observations that motivate research on sex differences in human neuroanatomy (including potential causes and effects), review methodological and empirical support for using structural MRI to investigate such patterns, and outline best practices for analyzing and describing neuroanatomical sex differences. Finally, we argue that broader historical and societal contexts make it important to reinforce the scientific method by adopting an actively "anti-sexist" viewpoint when conducting research on sex differences in the human brain.

Keywords

• Sex differences
• Neuroanatomy
• sMRI
• Direct analysis
• Meta-analysis
• Review