Spatiotemporal Patterns of White Matter Maturation after Pre-Adolescence: A Diffusion Kurtosis Imaging Study.

Diffusion tensor imaging (DTI) enables the assessment of changes in brain tissue microstructure during maturation and ageing. In general, patterns of cerebral maturation and decline render non-monotonic lifespan trajectories of DTI metrics with age, and, importantly, the rate of microstructural changes is heterochronous for various white matter fibres. Recent studies have demonstrated that diffusion kurtosis imaging (DKI) metrics are more sensitive to microstructural changes during ageing compared to those of DTI. In a previous work, we demonstrated that the Cohen's d of mean diffusional kurtosis (dMK) represents a useful biomarker for quantifying maturation heterochronicity. However, some inferences on the maturation grades of different fibre types, such as association, projection, and commissural, were of a preliminary nature due to the insufficient number of fibres considered. Hence, the purpose of this follow-up work was to further explore the heterochronicity of microstructural maturation between pre-adolescence and middle adulthood based on DTI and DKI metrics. Using the effect size of the between-group parametric changes and Cohen's d, we observed that all commissural fibres achieved the highest level of maturity, followed by the majority of projection fibres, while the majority of association fibres were the least matured. We also demonstrated that dMK strongly correlates with the maxima or minima of the lifespan curves of DTI metrics. Furthermore, our results provide substantial evidence for the existence of spatial gradients in the timing of white matter maturation. In conclusion, our data suggest that DKI provides useful biomarkers for the investigation of maturation spatial heterogeneity and heterochronicity.

Cortical Structure Differences in Relation to Age, Sexual Attractions, and Gender Dysphoria in Adolescents: An Examination of Mean Diffusivity and T1 Relaxation Time.

Recent research found that the combination of masculine gender identity and gynephilia was associated with cortical T1 relaxation time, which is considered to reflect gray matter density. We hypothesized that mean diffusivity (MD), a diffusion tensor imaging metric that reflects the degree to which water movement is free versus constrained, in combination with T1 relaxation time would provide further insight regarding cortical tissue characteristics. MD and T1 relaxation time were measured in 76 cortical regions in 15 adolescents assigned female at birth who experience gender dysphoria (GD AFAB) and were not receiving hormone therapy, 17 cisgender girls, and 14 cisgender boys (ages 12-17 years). Sexual orientation was represented by the degree of androphilia-gynephilia and the strength of sexual attraction. In multivariate analyses, cortical T1 relaxation time showed a weak but statistically significant positive association with MD across the cortex, suggesting that macromolecule-rich cortical tissue also tends to show water movement that is somewhat more constrained. In further multivariate analyses, in several left frontal, parietal, and temporal regions, the combination of shorter T1 relaxation time and faster MD was associated with older age and greater gynephilia in GD AFAB individuals and cisgender boys and with stronger attractions in cisgender boys only. Thus, for these cortical regions in these groups, older age, gynephilia, and stronger attractions (cisgender boys only) were associated with macromolecule-rich tissue in which water movement was freer-a pattern that some prior research suggests is associated with greater cell density and size. Overall, this study indicates that investigating T1 relaxation time and MD together can further inform how cortical gray matter tissue characteristics relate to age and psychosexuality.

A Multi-Modal MRI Analysis of Cortical Structure in Relation to Gender Dysphoria, Sexual Orientation, and Age in Adolescents.

Gender dysphoria (GD) is characterized by distress due to an incongruence between experienced gender and sex assigned at birth. Sex-differentiated brain regions are hypothesized to reflect the experienced gender in GD and may play a role in sexual orientation development. Magnetic resonance brain images were acquired from 16 GD adolescents assigned female at birth (AFAB) not receiving hormone therapy, 17 cisgender girls, and 14 cisgender boys (ages 12-17 years) to examine three morphological and microstructural gray matter features in 76 brain regions: surface area (SA), cortical thickness (CT), and T1 relaxation time. Sexual orientation was represented by degree of androphilia-gynephilia and sexual attraction strength. Multivariate analyses found that cisgender boys had larger SA than cisgender girls and GD AFAB. Shorter T1, reflecting denser, macromolecule-rich tissue, correlated with older age and stronger gynephilia in cisgender boys and GD AFAB, and with stronger attractions in cisgender boys. Thus, cortical morphometry (mainly SA) was related to sex assigned at birth, but not experienced gender. Effects of experienced gender were found as similarities in correlation patterns in GD AFAB and cisgender boys in age and sexual orientation (mainly T1), indicating the need to consider developmental trajectories and sexual orientation in brain studies of GD.