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

Background 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.Methods Univariate and multivariate sex differences and similarities in gray matter volume (GM(VOL)) 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).Results 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 GM(VOL) estimates. Conversely, when calculated from TIV-adjusted GM(VOL), 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 GM(VOL) shared a similar structure and allowed us to identify the components of the SENT_CORE network which more likely contribute to the observed effects.Conclusions 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 GM(VOL) measurements.