MRI of functional connectivity, cortical thickness, surface area, and gray matter volume was carried out in 28 female-to-male transsexuals (FtM-TR) and 68 cis-sexual controls (34 male). FtM-TR displayed thicker mid-frontal, precuneal-parietal, and lingual cortex than both male and female controls, whereas, in regions with reported anatomical sex differences among the controls, FtM-TR followed patterns of the gender assigned at their birth. FtM-TR also displayed weaker functional connections from the pregenual anterior cingulate to the insular cortex, and the temporo parietal junction compared with both control groups. Distinct structural and functional pattern in the own-body image network may represent biological markers for the dysphoric own-body perception in transgender individuals.

Transgender individuals experience incongruence between their gender identity and birth-assigned sex. The resulting gender dysphoria (GD), which some gender-incongruent individuals experience, is theorized to be a consequence of atypical cerebral sexual differentiation, but support for this assertion is inconsistent. We recently found that GD is associated with disconnected networks involved in self-referential thinking and own body perception. Here, we investigate how these networks in trans men (assigned female at birth with male gender identity) are affected by testosterone. In 22 trans men, we obtained T1-weighted, diffusion-weighted, and resting-state functional magnetic resonance imaging scans before and after testosterone treatment, measuring cortical thickness (Cth), subcortical volumes, fractional anisotropy (FA), and functional connectivity. Nineteen cisgender controls (male and female) were also scanned twice. The medial prefrontal cortex (mPFC) was thicker in trans men than controls pretreatment, and remained unchanged posttreatment. Testosterone treatment resulted in increased Cth in the insular cortex, changes in cortico-cortical thickness covariation between mPFC and occipital cortex, increased FA in the fronto-occipital tract connecting these regions, and increased functional connectivity between mPFC and temporo-parietal junction, compared with controls. Concluding, in trans men testosterone treatment resulted in functional and structural changes in self-referential and own body perception areas.

Although frequently discussed in terms of sex dimorphism, the neurobiology of sexual orientation and identity is unknown. We report multimodal magnetic resonance imaging data, including cortical thickness (Cth), subcortical volumes, and resting state functional magnetic resonance imaging, from 27 transgender women (TrW), 40 transgender men (TrM), and 80 heterosexual (40 men) and 60 homosexual cisgender controls (30 men). These data show that whereas homosexuality is linked to cerebral sex dimorphism, gender dysphoria primarily involves cerebral networks mediating self-body perception. Among the homosexual cisgender controls, weaker sex dimorphism was found in white matter connections and a partly reversed sex dimorphism in Cth. Similar patterns were detected in transgender persons compared with heterosexual cisgender controls, but the significant clusters disappeared when adding homosexual controls, and correcting for sexual orientation. Instead, both TrW and TrM displayed singular features, showing greater Cth as well as weaker structural and functional connections in the anterior cingulate-precuneus and right occipito-parietal cortex, regions known to process own body perception in the context of self.

MRI diffusion tensor imaging (DTI) studies of white matter integrity in behavioral variant frontotemporal dementia have consistently shown involvement of frontal and temporal white matter, corresponding to regional loss of cortical volume. Volumetric imaging has a suboptimal sensitivity as a diagnostic tool and thus we wanted to explore if DTI is a better method to discriminate patients and controls than volumetric imaging. We examined the anterior cingulum bundle in 14 patients with behavioral variant frontotemporal dementia and 22 healthy controls using deterministic manual diffusion tensor tractography, and compared DTI parameters with two measures of cortical atrophy, VBM and cortical thickness, of the anterior cingulate cortex (ACC). Statistically significant changes between patients and controls were detected in all DTI parameters, with large effect sizes. ROC-AUC was for the best DTI parameters: 0.92 (fractional anisotropy) to 0.97 (radial diffusivity), 0.82 for the best cortical parameter, VBM of the ACC. Results from the AUC were confirmed with binary logistic regression analysis including demographic variables, but only for fractional anisotropy and mean diffusivity. Ability to classify patient/nonpatient status was significantly better for mean diffusivity vs. VBM (p=0.031), and borderline significant for fractional anisotropy vs. VBM (p=0.062). The results indicate that DTI could offer advantages in comparison with the assessment of cortical volume in differentiating patients with behavioral variant frontotemporal dementia and controls.

Both transgenderism and homosexuality are facets of human biology, believed to derive from different sexual differentiation of the brain. The two phenomena are, however, fundamentally unalike, despite an increased prevalence of homosexuality among transgender populations. Transgenderism is associated with strong feelings of incongruence between one’s physical sex and experienced gender, not reported in homosexual persons. The present study searches to find neural correlates for the respective conditions, using fractional anisotropy (FA) as a measure of white matter connections that has consistently shown sex differences. We compared FA in 40 transgender men (female birth-assigned sex) and 27 transgender women (male birth-assigned sex), with both homosexual (29 male, 30 female) and heterosexual (40 male, 40 female) cisgender controls. Previously reported sex differences in FA were reproduced in cis-heterosexual groups, but were not found among the cis-homosexual groups. After controlling for sexual orientation, the transgender groups showed sex-typical FA-values. The only exception was the right inferior fronto-occipital tract, connecting parietal and frontal brain areas that mediate own body perception. Our findings suggest that the neuroanatomical signature of transgenderism is related to brain areas processing the perception of self and body ownership, whereas homosexuality seems to be associated with less cerebral sexual differentiation.