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.

Gender dysphoria (GD) is characterized by incongruence between onés gender assigned at birth and the gender that one identifies with. The biological mechanisms of GD are unclear, especially in female-to-male transsexuals (FtM-TR). Here, we investigate whether distinct structural and functional patterns along cerebral midline networks processing own-body perception may constitute a biological correlate.METHOD: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.

BACKGROUND AND PURPOSE: Volumetric measurements on structural MR images are an established method to investigate pathology-related volume changes in cortex. Manual volumetric methods have sometimes been referred to as the reference standard for quality control of automatic volumetric methods. While some automatic methods, like VBM, may rely on a template, manual methods use sulci as indirect landmarks for the subdivision of cortex. The purpose of this study was to compare volumetric data generated by MM and VBM on 4 multimodal regions in the frontal lobe. MATERIALS AND METHODS: We investigated 4 multimodal frontocortical regions by MM and VBM in patients with frontotemporal lobar degeneration and Alzheimer disease and controls. RESULTS: MM and VBM results were highly correlated for dorsolateral prefrontal cortex, orbitofrontal cortex, and hippocampus, but not for the dorsal and rostral anterior cingulate. VBM results were more consistent with results from previous studies on cingulate in frontotemporal lobar degeneration. Our results may potentially be explained by 2 factors. First, the volume of small cortical regions may be more affected by anatomic variability than large regions in the MM. Second, it has been shown that the location of multimodal cytoarchitectonic areas, such as the cingulate cortex, may be difficult to predict by the appearance of sulci and gyri. CONCLUSIONS: While both VBM and the MM may do equally poorly in predicting cytoarchitecture, the MM may add additional unrelated variance caused by anatomic variability. Thus, paradoxically, the higher anatomic precision of the MM may potentially cause a weaker relation to cytoarchitecture.