White matter microstructure in transmasculine and cisgender adolescents: A multiparametric and multivariate study.

Adolescence is a sensitive developmental period for neural sex/gender differentiation. The present study used multiparametric mapping to better characterize adolescent white matter (WM) microstructure. WM microstructure was investigated using diffusion tensor indices (fractional anisotropy; mean, radial, and axial diffusivity [AD]) and quantitative T1 relaxometry (T1) in hormone therapy naïve adolescent cisgender girls, cisgender boys, and transgender boys (i.e., assigned female at birth and diagnosed with gender dysphoria). Diffusion indices were first analyzed for group differences using tract-based spatial statistics, which revealed a group difference in AD. Thus, two multiparametric and multivariate analyses assessed AD in conjunction with T1 relaxation time, and with respect to developmental proxy variables (i.e., age, serum estradiol, pubertal development, sexual attraction) thought to be relevant to adolescent brain development. The multivariate analyses showed a shared pattern between AD and T1 such that higher AD was associated with longer T1, and AD and T1 strongly related to all five developmental variables in cisgender boys (10 significant correlations, r range: 0.21-0.73). There were fewer significant correlations between the brain and developmental variables in cisgender girls (three correlations, r range: -0.54-0.54) and transgender boys (two correlations, r range: -0.59-0.77). Specifically, AD related to direction of sexual attraction (i.e., gynephilia, androphilia) in all groups, and T1 related to estradiol inversely in cisgender boys compared with transgender boys. These brain patterns may be indicative of less myelination and tissue density in cisgender boys, which corroborates other reports of protracted WM development in cisgender boys. Further, these findings highlight the importance of considering developmental trajectory when assessing the subtleties of neural structure associated with variations in sex, gender, and sexual attraction.

Researchers' sex/gender identity influences how sex/gender question is investigated in neuroscience: an example from an OHBM meeting.

Gender inequality and diversity in STEM is a challenging field of research. Although the relation between the sex/gender of the researcher and the scientific research practices has been previously examined, less interest has been demonstrated towards the relation between sex/gender of the researcher and the way sex/gender as a variable is explored. Here, we examine, from a neurofeminist perspective, both questions: whether sex/gender identity is related to the examination of sex/gender as a variable and whether different approaches towards examining sex/gender are being used in different topics of study within neuroscience. Using the database of submitted posters to the Organization of Human Brain Mapping 2022 annual conference, we identified abstracts examining a sex/gender-related research question. Among these target abstracts, we identified four analytical categories, varying in their degree of content-related complexity: (1) sex/gender as a covariate, (2) sex/gender as a binary variable for the study of sex/gender differences, (3) sex/gender with additional biological information, and (4) sex/gender with additional social information. Statistical comparisons between sex/gender of researcher and the target abstract showed that the proportion of abstracts from Non-binary or Other first authors compared to both Women and Men was lower for all submitted abstracts than for the target abstracts; that more researchers with sex/gender-identity other than man implemented analytical category of sex/gender with additional social information; and, for instance, that research involving cognitive, affective, and behavioural neuroscience more frequently fit into the sex/gender with additional social information-category. Word cloud analysis confirmed the validity of the four exploratorily identified analytical categories. We conclude by discussing how raising awareness about contemporary neurofeminist approaches, including perspectives from the global south, is critical to neuroscientific and societal progress.

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.

Inter-Network Brain Functional Connectivity in Adolescents Assigned Female at Birth Who Experience Gender Dysphoria.

Gender dysphoria (GD) is characterized by distress due to an incongruence between experienced gender and sex assigned at birth. Brain functional connectivity in adolescents who experience GD may be associated with experienced gender (vs. assigned sex) and/or brain networks implicated in own-body perception. Furthermore, sexual orientation may be related to brain functional organization given commonalities in developmental mechanisms proposed to underpin GD and same-sex attractions. Here, we applied group independent component analysis to resting-state functional magnetic resonance imaging (rs-fMRI) BOLD timeseries data to estimate inter-network (i.e., between independent components) timeseries correlations, representing functional connectivity, in 17 GD adolescents assigned female at birth (AFAB) not receiving gender-affirming hormone therapy, 17 cisgender girls, and 15 cisgender boys (ages 12-17 years). Sexual orientation was represented by degree of androphilia-gynephilia and sexual attractions strength. Multivariate partial least squares analyses found that functional connectivity differed among cisgender boys, cisgender girls, and GD AFAB, with the largest difference between cisgender boys and GD AFAB. Regarding sexual orientation and age, the brain's intrinsic functional organization of GD AFAB was both similar to and different from cisgender girls, and both differed from cisgender boys. The pattern of group differences and the networks involved aligned with the hypothesis that brain functional organization is different among GD AFAB (vs. cisgender) adolescents, and certain aspects of this organization relate to brain areas implicated in own-body perception and self-referential thinking. Overall, brain functional organization of GD AFAB was generally more similar to that of cisgender girls than cisgender boys.

Mental rotation task performance in relation to sexual and gender diversity in Thailand.

Neurohormonal theory argues that organizational effects of hormone exposure influence sexual orientation and gender identity, as well as sex differences in visuospatial cognition. This study examined mental rotation task (MRT) performance in a diverse Thai sample (N = 980). Thai culture has several third genders: individuals assigned male at birth (AMAB) who are feminine and attracted to cis men (i.e., sao praphet song); individuals assigned female at birth (AFAB) who are masculine and attracted to feminine individuals (i.e., toms); AFAB individuals who are feminine and attracted to toms (i.e., dees); and sexual orientation categories similar to Western culture (e.g., gay, lesbian, bi). On the MRT, straight cis men outperformed straight cis women. Results were consistent with organizational effects among AMAB individuals, with straight cis men outperforming gay cis men and sao praphet song. Among AFAB individuals, however, only bi and lesbian cis women outperformed dees. Overall, support for neurohormonal theory was limited among AFAB individuals, but MRT performance among AMAB individuals was consistent with organizational effects. This study informs our understanding of visuospatial sex/gender differences and the applicability of neurohormonal theory across cultures.

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.