Structural Connectivity Networks of Transgender People

Abstract

Although previous investigations of transsexual people have focused on regional brain alterations, evaluations on a network level, especially those structural in nature, are largely missing. Therefore, we investigated the structural connectome of 23 female-to-male (FtM) and 21 male-to-female (MtF) transgender patients before hormone therapy as compared with 25 female and 25 male healthy controls. Graph theoretical analysis of whole-brain probabilistic tractography networks (adjusted for differences in intracranial volume) showed decreased hemispheric connectivity ratios of subcortical/limbic areas for both transgender groups. Subsequent analysis revealed that this finding was driven by increased interhemispheric lobar connectivity weights (LCWs) in MtF transsexuals and decreased intrahemispheric LCWs in FtM patients. This was further reflected on a regional level, where the MtF group showed mostly increased local efficiencies and FtM patients decreased values. Importantly, these parameters separated each patient group from the remaining subjects for the majority of significant findings. This work complements previously established regional alterations with important findings of structural connectivity. Specifically, our data suggest that network parameters may reflect unique characteristics of transgender patients, whereas local physiological aspects have been shown to represent the transition from the biological sex to the actual gender identity.

Keywords: graph theory; probabilistic tractography; structural connectivity; transgender.

Figure 1.

Average structural connectivity for female controls, female-to-male transsexuals, male controls, and male-to-female transsexuals for full (i.e., unthresholded connectivity matrices). Increased LCW was found in male-to-female transsexuals^a,b,c between right subcortical (subc.)/limbic and left subcortical/limbic lobes (red, top). Decreased LCW was found in female-to-male transsexuals^a,c,d between right subcortical/limbic and right temporal (temp.) lobes. Line thickness indicates connectivity weighting, whereas only connections with weights of >0.001 are shown (arbitrary choice to remove spurious connections as probabilistic tractography represents the robustness of the modeled tracts against noise). Nodes represent region of interest centers for frontal (green), temporal (blue), parietal (cyan), occipital (magenta), and limbic/subcortical brain regions (yellow). Characters indicate significant differences as compared with female controls (a), female-to-male transsexuals (b), male controls (c), or male-to-female transsexuals (d), see Table 1 for details. Axial images are in radiological view (i.e., left image side is right hemisphere).

Figure 2.

Average structural connectivity for female controls (FC, blue), female-to-male transsexuals (FtM, red), male controls (MC, green), and male-to-female transsexuals (MtF, black) for sparse connectivity matrices thresholded between 10 and 50% network density. Small-worldness was not significantly different between groups (A). In contrast, HCR of right subcortical/limbic connections separated patients from controls (B). The decreased HCR in transsexuals was caused by increased LCW in MtF (C) and decreased LCW in FtM (D). Values show mean ± standard error. See Table 1 for detailed statistics.