Univariate and multivariate sex differences and similarities in gray matter volume within essential language-processing areas

Abstract

Sex differences in language-related abilities have been reported. It is generally assumed that these differences stem from a different organization of language in the brains of females and males. However, research in this area has been relatively scarce, methodologically heterogeneous and has yielded conflicting results. Univariate and multivariate sex differences and similarities in gray matter volume (GMVOL) within 18 essential language-processing brain areas were assessed in a sex-balanced sample (N = 588) of right-handed young adults. Univariate analyses involved location, spread, and shape comparisons of the females’ and males’ distributions and were conducted with several robust statistical methods able to quantify the size of sex differences and similarities in a complementary way. Multivariate sex differences and similarities were estimated by the same methods in the continuous scores provided by two distinct multivariate procedures (logistic regression and a multivariate analog of the Wilcoxon–Mann–Whitney test). Additional analyses were addressed to compare the outcomes of these two multivariate analytical strategies and described their structure (that is, the relative contribution of each brain area to the multivariate effects). When not adjusted for total intracranial volume (TIV) variation, “large” univariate sex differences (males > females) were found in all 18 brain areas considered. In contrast, “small” differences (females > males) in just two of these brain areas were found when controlling for TIV. The two multivariate methods tested provided very similar results. Multivariate sex differences surpassed univariate differences, yielding "large" differences indicative of larger volumes in males when calculated from raw GMVOL estimates. Conversely, when calculated from TIV-adjusted GMVOL, multivariate differences were "medium" and indicative of larger volumes in females. Despite their distinct size and direction, multivariate sex differences in raw and TIV-adjusted GMVOL shared a similar structure and allowed us to identify the components of the SENT_CORE network which more likely contribute to the observed effects. Our results confirm and extend previous findings about univariate sex differences in language-processing areas, offering unprecedented evidence at the multivariate level. We also observed that the size and direction of these differences vary quite substantially depending on whether they are estimated from raw or TIV-adjusted GMVOL measurements. While it is generally assumed that there is a distinct organization of language in the brains of females and males, studies investigating potential sex-based differences in language-related neural circuits have been characterized by their methodological heterogeneity and yielded inconclusive results. In this study, we explored how the brains of men and women differ in a well-defined network of brain areas essential for basic language functions. We found that there are indeed differences in the size of certain brain regions involved in language, with men and women showing varying patterns of these differences. Interestingly, the way these differences were observed depended on whether they are assessed at the whole network or at individual brain regions. Also, when considering the size of these brain regions in relation to overall cranial volume, the differences changed. So, this study highlights that understanding these brain differences requires considering different factors, like existing sex differences in cranial size, and looking at local effects but also their interactions and relationships in the broader context of functional brain networks.