Cortical activation during mental rotation in male-to-female and female-to-male transsexuals under hormonal treatment Beatriz Carrillo b , Esther Go ´mez-Gil c , Giuseppina Rametti b , Carme Junque b , A ´ ngel Gomez d , Kazmer Karadi e , Santiago Segovia a , Antonio Guillamon a, * a Departamento de Psicobiologı ´a, UNED, Madrid, Spain b Departamento de Psiquiatrı ´a y Psicobiologı ´a Clı ´nica, Universidad de Barcelona, Spain c Unidad de Identidad de Ge ´nero, Hospital Clinic, Barcelona, Spain d Departamento de Psicologı ´a Social y de las Organizaciones, UNED, Madrid, Spain e Institute of Behavioral Science, Medical University of Pecs, Hungary Received 7 October 2009; received in revised form 8 February 2010; accepted 11 February 2010 Psychoneuroendocrinology (2010) 35, 1213—1222 KEYWORDS Transsexualism; Gender identity disorders; Cross-sex hormonal treatment; Mental rotation; Parietal cortex; Occipital cortex; Frontal cortex; fMRI Summary 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 activa- tion 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 * Corresponding author at: Psicobiologı ´a, UNED C/Juan del Rosal, 10, 28040 Madrid, Spain. Tel.: +34 91 938 62 72. E-mail address: aguillamon@psi.uned.es (A. Guillamon). available at www.sciencedirect.com journal homepage: www.elsevier.com/locate/psyneuen 0306-4530/$ — see front matter # 2010 Elsevier Ltd. All rights reserved. doi:10.1016/j.psyneuen.2010.02.010