ORIGINAL RESEARCH—INTERSEX AND GENDER IDENTITY DISORDERS: Neuroimaging Differences in Spatial Cognition between Men and Male-to-Female Transsexuals Before and During Hormone Therapy

ABSTRACT Introduction Neuropsychological abnormalities in transsexual patients have been reported in comparison with subjects without gender identity disorder (GID), suggesting differences in underlying neurobiological processes. However, these results have not consistently been confirmed. Furthermore, studies on cognitive effects of cross-sex hormone therapy also yield heterogeneous results. Aim We hypothesized that untreated transsexual patients differ from men without GID in activation pattern associated with a mental rotation task and that these differences may further increase after commencing of hormonal treatment. Method The present study investigated 11 male-to-female transsexual (MFTS) patients prior to cross-sex hormone therapy and 11 MFTS patients during hormone therapy in comparison with healthy men without GID. Using functional magnetic resonance imaging at 3-Tesla, a mental rotation paradigm with proven sexual dimorphism was applied to all subjects. Data were analyzed with SPM5. Main Outcome Measures Patterns of brain activation associated with a mental rotation task. Results The classical mental rotation network was activated in all three groups, but significant differences within this network were observed. Men without GID exhibited significantly greater activation of the left parietal cortex (BA 40), a key region for mental rotation processes. Both transsexual groups revealed stronger activation of temporo-occipital regions in comparison with men without GID. Conclusions Our results confirmed previously reported deviances of brain activation patterns in transsexual men from men without GID and also corroborated these findings in a group of transsexual patients receiving cross-sex hormone therapy. The present study indicates that there are a priori differences between men and transsexual patients caused by different neurobiological processes or task-solving strategies and that these differences remain stable over the course of hormonal treatment.