There is strong evidence of sex differences in mental rotation tasks. Transsexualism is an extreme gender identity disorder in which individuals seek cross-gender treatment to change their sex. The aim of our study was to investigate if male-to-female (MF) and female-to-male (FM) transsexuals receiving cross-sex hormonal treatment have different patterns of cortical activation during a three-dimensional (3D) mental rotation task. An fMRI study was performed using a 3-T scan in a sample of 18 MF and 19 FM under chronic cross-sex hormonal treatment. Twenty-three males and 19 females served as controls. The general pattern of cerebral activation seen while visualizing the rotated and non-rotated figures was similar for all four groups showing strong occipito-parieto-frontal brain activation. However, compared to control males, the activation of MF transsexuals during the task was lower in the superior parietal lobe. Compared to control females, MF transsexuals showed higher activation in orbital and right dorsolateral prefrontal regions and lower activation in the left prefrontal gyrus. FM transsexuals did not differ from either the MF transsexual or control groups. Regression analyses between cerebral activation and the number of months of hormonal treatment showed a significant negative correlation in parietal, occipital and temporal regions in the MF transsexuals. No significant correlations with time were seen in the FM transsexuals. In conclusion, although we did not find a specific pattern of cerebral activation in the FM transsexuals, we have identified a specific pattern of cerebral activation during a mental 3D rotation task in MF transsexuals under cross-sex hormonal treatment that differed from control males in the parietal region and from control females in the orbital prefrontal region. The hypoactivation in MF transsexuals in the parietal region could be due to the hormonal treatment or could reflect a priori cerebral differences between MF transsexual and control subjects.
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