Background Studies assessing volumetric sex differences have provided contradictory results. Total intracranial volume (TIV) is a major confounding factor when estimating local volumes of interest (VOIs). We investigated how the number, size, and direction of sex differences in gray matter volume (GMv) vary depending on how TIV variation is statistically handled. Methods Sex differences in the GMv of 116 VOIs were assessed in 356 participants (171 females) without correcting for TIV variation or after adjusting the data with 5 different methods (VBM8 non-linear-only modulation, proportions, power-corrected-proportions, covariation, and the residuals method). The outcomes obtained with these procedures were compared to each other and to those obtained in three criterial subsamples, one comparing female-male pairs matched on their TIV and two others comparing groups of either females or males with large/small TIVs. Linear regression was used to quantify TIV effects on raw GMv and the efficacy of each method in controlling for them. Results Males had larger raw GMv than females in all brain areas, but these differences were driven by direct TIV-VOIs relationships and more closely resembled the differences observed between individuals with large/small TIVs of sex-specific subsamples than the sex differences observed in the TIV-matched subsample. All TIV-adjustment methods reduced the number of sex differences but their results were very different. The VBM8- and the proportions-adjustment methods inverted TIV-VOIs relationships and resulted in larger adjusted volumes in females, promoting sex differences largely attributable to TIV variation and very distinct from those observed in the TIV-matched subsample. The other three methods provided results unrelated to TIV and very similar to those of the TIV-matched subsample. In these datasets, sex differences were bidirectional and achieved satisfactory replication rates in 19 VOIs, but they were “small” ( d < ∣0.38∣) and most of them faded away after correcting for multiple comparisons. Conclusions There is not just one answer to the question of how many and how large the sex differences in GMv are, but not all the possible answers are equally valid. When TIV effects are ruled out using appropriate adjustment methods, few sex differences (if any) remain statistically significant, and their size is quite reduced. Electronic supplementary material The online version of this article (10.1186/s13293-019-0245-7) contains supplementary material, which is available to authorized users.

Sex differences in 116 local gray matter volumes (GMVOL) were assessed in 444 males and 444 females without correcting for total intracranial volume (TIV) or after adjusting the data with the scaling, proportions, power-corrected proportions (PCP), and residuals methods. The results confirmed that only the residuals and PCP methods completely eliminate TIV-variation and result in sex-differences that are “small” (∣d∣ < 0.3). Moreover, as assessed using a totally independent sample, sex differences in PCP and residuals adjusted-data showed higher replicability ($$\approx $$ ≈ 93%) than scaling and proportions adjusted-data $$( \approx $$ ( ≈ 68%) or raw data ($$\approx $$ ≈ 45%). The replicated effects were meta-analyzed together and confirmed that, when TIV-variation is adequately controlled, volumetric sex differences become “small” (∣d∣ < 0.3 in all cases). Finally, we assessed the utility of TIV-corrected/ TIV-uncorrected GMVOL features in predicting individuals’ sex with 12 different machine learning classifiers. Sex could be reliably predicted (> 80%) when using raw local GMVOL, but also when using scaling or proportions adjusted-data or TIV as a single predictor. Conversely, after properly controlling TIV variation with the PCP and residuals’ methods, prediction accuracy dropped to $$\approx $$ ≈ 60%. It is concluded that gross morphological differences account for most of the univariate and multivariate sex differences in GMVOL

It is a common belief that males have superior visuospatial abilities and that differences in this and other cognitive domains (e.g., math) contribute to the reduced interest and low representation of girls and women in STEM education and professions. However, previous studies show that gender-related implicit associations and explicit beliefs, as well as situational variables, might affect cognitive performance in those gender-stereotyped domains and produce between-gender spurious differences. Therefore, the present study aimed to provide information on when, how and who might be affected by the situational reactivation of stereotypic gender-science beliefs/associations while performing a 3D mental rotation chronometric task (3DMRT). More specifically, we assessed the explicit beliefs and implicit associations (by the Implicit Association Test) held by female and male students of humanities and STEM majors and compared their performance in a 3DMRT after receiving stereotype- congruent, incongruent and nullifying experimental instructions. Our results show that implicit stereotypic gender-science associations correlate with 3DMRT performance in both females and males, but that inter-gender differences emerge only under stereotype-reactivating conditions. We also found that changes in self-confidence mediate these instructions’ effects and that academic specialization moderates them, hence promoting 3DMRT performance differences between male and female humanities, but not STEM, students. Taken together, these observations suggest that the common statement “males have superior mental rotation abilities” simplifies a much more complex reality and might promote stereotypes which, in turn, might induce artefactual performance differences between females and males in such tasks.

Background/Objective. To explore the effectiveness of a specific working memory (WM) training program in MS patients and healthy controls (HC). Method. 29 MS patients and 29 matched HC were enrolled in the study. MS and HC were randomly split into two groups: nontraining groups (15HC/14 MS) and training groups (14 HC/15 MS). Training groups underwent adaptive n-back training (60 min/day; 4 days). Functional magnetic resonance imaging (fMRI) was used to monitor brain activity during n-back performance (conditions: 0-back, 2-back, and 3-back) at 3 time points: (1) baseline, (2) post-training (+7days), and (3) follow-up (+35days). Results. In post-training and follow-up fMRI sessions, trained groups (HC and MS patients) exhibited significant reaction time (RT) reductions and increases in Correct Responses (CRs) during 2-back and 3-back performance. This improvement of task performance was accompanied by a decrease in brain activation in the WM frontoparietal network. The two effects were significantly correlated. Conclusions. After WM training, both cognitively preserved MS patients and HC participants showed task performance improvement made possible by neuroplastic processes that enhanced neural efficiency.

The present study aimed to investigate altered grey matter (GM) and functional connectivity (FC) in deep subcortical areas, such as the thalamus and basal ganglia, and their relationship with cognitive impairment (CI) in multiple sclerosis (MS). Thirty-six patients were neuropsychologically assessed, classified as cognitive preserved (CP) and CI, and were compared with 18 healthy controls. GM atrophy and FC were observed in 10 predefined functional areas of the thalamus and in six of basal ganglia. GM atrophy was prominent in the basal ganglia in CI patients compared with CP MS patients. Increased FC was observed between the right caudate and the bilateral orbitofrontal cortex in CI versus CP patients. The discriminant and correlation analyses showed that the enhanced FC observed between the right caudate and the orbitofrontal cortex was closely associated with CI in MS patients. In conclusion, reduced GM volume and enhanced frontobasal ganglia connectivity are related to cognition in MS patients.