[en] BACKGROUND: Sex differences in performance and regional brain activity during mental rotation have been reported repeatedly and reflect organizational and activational effects of sex hormones. We investigated whether adolescent girls with gender dysphoria (GD), before and after 10 months of testosterone treatment, showed male-typical brain activity during a mental rotation task (MRT). METHODS: Girls with GD underwent fMRI while performing the MRT twice: when receiving medication to suppress their endogenous sex hormones before onset of testosterone treatment, and 10 months later during testosterone treatment. Two age-matched control groups participated twice as well. RESULTS: We included 21 girls with GD, 20 male controls and 21 female controls in our study. In the absence of any group differences in performance, control girls showed significantly increased activation in frontal brain areas compared with control boys (pFWE = 0.012). Girls with GD before testosterone treatment differed significantly in frontal brain activation from the control girls (pFWE = 0.034), suggesting a masculinization of brain structures associated with visuospatial cognitive functions. After 10 months of testosterone treatment, girls with GD, similar to the control boys, showed increases in brain activation in areas implicated in mental rotation. LIMITATIONS: Since all girls with GD identified as gynephilic, their resemblance in spatial cognition with the control boys, who were also gynephilic, may have been related to their shared sexual orientation rather than their shared gender identity. We did not account for menstrual cycle phase or contraceptive use in our analyses. CONCLUSION: Our findings suggest atypical sexual differentiation of the brain in natal girls with GD and provide new evidence for organizational and activational effects of testosterone on visuospatial cognitive functioning.
Disciplines :
Neurosciences & behavior
Author, co-author :
Burke, Sarah M.
Kreukels, Baudewijntje P. C.
Cohen-Kettenis, Peggy T.
Veltman, Dick J.
Klink, Daniel T.
Bakker, Julie ; Université de Liège > Département des sciences biomédicales et précliniques > Biologie de la différenciation sexuelle du cerveau
Language :
English
Title :
Male-typical visuospatial functioning in gynephilic girls with gender dysphoria - organizational and activational effects of testosterone.
Publication date :
2016
Journal title :
Journal of Psychiatry and Neuroscience
ISSN :
1180-4882
eISSN :
1488-2434
Publisher :
Canadian Medical Association/Association Medical Canadienne, Ottawa, Canada
Shepard RN, Metzler J. Mental rotation of three-dimensional objects. Science 1971;171:701-3.
Vandenberg SG, Kuse AR. Mental rotations, a group test of three-dimensional spatial visualization. Percept Mot Skills 1978;47:599-604.
Linn MC, Petersen AC. Emergence and characterization of sex differences in spatial ability: a meta-analysis. Child Dev 1985;56:1479-98.
Voyer D, Voyer S, Bryden MP. Magnitude of sex differences in spatial abilities: a meta-analysis and consideration of critical variables. Psychol Bull 1995;117:250-70.
Hugdahl K, Thomsen T, Ersland L. Sex differences in visuo-spatial processing: an fMRI study of mental rotation. Neuropsychologia 2006;44:1575-83.
Phoenix CH, Goy RW, Gerall AA, et al. Organizing action of prenatally administered testosterone propionate on the tissues mediating mating behavior in the female guinea pig. Endocrinology 1959;65:369-82.
Manson JE. Prenatal exposure to sex steroid hormones and behavioral/cognitive outcomes. Metabolism 2008;57:S16-21.
Puts DA, McDaniel MA, Jordan CL, et al. Spatial ability and prenatal androgens: meta-analyses of congenital adrenal hyperplasia and digit ratio (2D:4D) studies. Arch Sex Behav 2008;37:100-11.
Berenbaum SA, Bryk KLK, Beltz AM. Early androgen effects on spatial and mechanical abilities: evidence from congenital adrenal hyperplasia. Behav Neurosci 2012;126:86-96.
Mueller SC, Temple V, Oh E, et al. Early androgen exposure modulates spatial cognition in congenital adrenal hyperplasia (CAH). Psychoneuroendocrinology 2008;33:973-80.
Hier DB, Crowley WF. Spatial ability in androgen-deficient men. N Engl J Med 1982;306:1202-5.
van Hemmen J, Veltman DJ, Hoekzema E, et al. Neural activation during mental rotation in complete androgen insensitivity syndrome: the influence of sex hormones and sex chromosomes. Cereb Cortex 2016;26:1036-45.
Grimshaw GM, Sitarenios G, Finegan JA. Mental rotation at 7 years: relations with prenatal testosterone levels and spatial play experiences. Brain Cogn 1995;29:85-100.
Kerns KA, Berenbaum SA. Sex differences in spatial ability in children. Behav Genet 1991;21:383-96.
Levine SC, Huttenlocher J, Taylor A, et al. Early sex differences in spatial skill. Dev Psychol 1999;35:940-9.
Clements-Stephens AM, Rimrodt SL, Cutting LE. Developmental sex differences in basic visuospatial processing: Differences in strategy use? Neurosci Lett 2009;449:155-60.
Kucian K, von Aster M, Loenneker T, et al. Brain activation during mental rotation in school children and adults. J Neural Transm 2007;114:675-86.
Roberts JE, Bell MA. Sex differences on a mental rotation task: variations in electroencephalogram hemispheric activation between children and college students. Dev Neuropsychol 2000;17:199-223.
Roberts JE, Bell MA. The effects of age and sex on mental rotation performance, verbal performance, and brain electrical activity. Dev Psychobiol 2002;40:391-407.
Nagel BJ, Barlett VC, Schweinsburg AD, et al. Neuropsychological predictors of BOLD response during a spatial working memory task in adolescents: What can performance tell us about fMRI response patterns? J Clin Exp Neuropsychol 2005;27:823-39.
Titze C, Jansen P, Heil M. Mental rotation performance and the effect of gender in fourth graders and adults. Eur J Dev Psychol Routledge 2010;7:432-44.
Comasco E, Sundström-Poromaa I. Neuroimaging the menstrual cycle and premenstrual dysphoric disorder. Curr Psychiatry Rep 2015;17:77.
Toffoletto S, Lanzenberger R, Gingnell M, et al. Emotional and cognitive functional imaging of estrogen and progesterone effects in the female human brain: a systematic review. Psychoneuroendocrinology 2014;50:28-52.
American Psychiatric Association. Diagnostic and statistical manual of mental disorders (5th ed.). Arlington, VA: American Psychiatric Publishing. Arlington, VA: American Psychiatric Publishing; 2013.
Swaab DF. Sexual differentiation of the brain and behavior. Best Pract Res Clin Endocrinol Metab 2007;21:431-44.
Cohen-Kettenis PT, Van Goozen SHM, Doorn CD. Cognitive ability and cerebral lateralization in transsexuals. Psychoneuroendocrinology 1998;23:631-41.
van Goozen SHM, Gooren LJG, Sanders G, et al. Organizing and activating effects of sex hormones in homosexual transsexuals. Behav Neurosci 2002;116:982-8.
Slabbekoorn D, van Goozen SH, Megens J, et al. Activating effects of cross-sex hormones on cognitive functioning: a study of short-term and long-term hormone effects in transsexuals. Psychoneuroendo crinology 1999;24:423-47.
Van Goozen SHM, Cohen-Kettenis PT, Gooren LJG, et al. Gender differences in behaviour: activating effects of cross-sex hormones. Psychoneuroendocrinology 1995;20:343-63.
Van Goozen SH, Cohen-Kettenis PT, Gooren LJ, et al. Activating effects of androgens on cognitive performance: causal evidence in a group of female-to-male transsexuals. Neuropsychologia 1994;32:1153-7.
Haraldsen IR, Opjordsmoen S, Egeland T, et al. Sex-sensitive cognitive performance in untreated patients with early onset gender identity disorder. Psychoneuroendocrinology 2003;28:906-15.
Haraldsen IR, Egeland T, Haug E, et al. Cross-sex hormone treatment does not change sex-sensitive cognitive performance in gender identity disorder patients. Psychiatry Res 2005;137:161-74.
Wisniewski AB, Prendeville MT, Dobs AS. Handedness, functional cerebral hemispheric lateralization, and cognition in male-to-female transsexuals receiving cross-sex hormone treatment. Arch Sex Behav 2005;34:167-72.
Carrillo B, Gómez-Gil E, Rametti G, et al. Cortical activation during mental rotation in male-to-female and female-to-male transsexuals under hormonal treatment. Psychoneuroendocrinology 2010;35:1213-22.
Schöning S, Engelien A, Bauer C, et al. Neuroimaging differences in spatial cognition between men and male-to-female transsexuals before and during hormone therapy. J Sex Med 2010;7:1858-67.
Sommer IEC, Cohen-Kettenis PT, van Raalten T, et al. Effects of cross-sex hormones on cerebral activation during language and mental rotation: an fMRI study in transsexuals. Eur Neuropsychopharmacol 2008;18:215-21.
de Vries ALC, Cohen-Kettenis PT. Clinical management of gender dysphoria in children and adolescents: the Dutch approach. J Homosex 2012;59:301-20.
Kreukels BPC, Cohen-Kettenis PT. Puberty suppression in gender identity disorder: the Amsterdam experience. Nat Rev Endocrinol 2011;7:466-72.
Hembree WC, Cohen-Kettenis P, Delemarre-van de Waal HA, et al. Endocrine treatment of transsexual persons: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab 2009;94:3132-54.
Burke SM, Cohen-Kettenis PT, Veltman DJ, et al. Hypothalamic response to the chemo-signal androstadienone in gender dysphoric children and adolescents. Front Endocrinol (Lausanne) 2014;5:60.
Wechsler D. Wechsler intelligence scale for children, WISC-III-NL. third ed. Pearson Assessment and Information B.V.; 2005.
Wechsler D. Wechsler adult intelligence scale, WAIS-III-NL. third ed. Pearson Assessment and Information B.V.; 2005.
Duke PM, Litt IF, Gross RT. Adolescents’ self-assessment of sexual maturation. Pediatrics 1980;66:918-20.
Marshall WA, Tanner JM. Variations in the pattern of pubertal changes in boys. Arch Dis Child 1970;45:13-23.
Marshall WA, Tanner JM. Variations in pattern of pubertal changes in girls. Arch Dis Child 1969;44:291-303.
Riling JK, Worthman CM, Campbell BC, et al. Ratios of plasma and salivary testosterone throughout puberty: production versus bioavailability. Steroids 1996;61:374-8.
Bui HN, Schagen SEE, Klink DT, et al. Salivary testosterone in female-to-male transgender adolescents during treatment with intra-muscular injectable testosterone esters. Steroids 2013;78:91-5.
Peters M, Battista C. Applications of mental rotation figures of the Shepard and Metzler type and description of a mental rotation stimulus library. Brain Cogn 2008;66:260-4.
Lemieux L, Salek-Haddadi A, Lund TE, et al. Modelling large motion events in fMRI studies of patients with epilepsy. Magn Reson Imaging 2007;25:894-901.
Brett M, Anton J, Valabregue R, et al. Region of interest analysis using an SPM toolbox [abstract]. Present 8th Int Conf Funct Mapp Hum Brain Sendai, Japan; 2002.
Zacks JM. Neuroimaging studies of mental rotation: a meta-analysis and review. J Cogn Neurosci 2008;20:1-19.
Nielsen F, Hansen L. Automatic anatomical labeling of Talairach coordinates and generation of volumes of interest via the BrainMap database. Present. 8th Int. Conf. Funct. Mapp. Hum. Brain. S; 2002.
Ankarberg-Lindgren C, Norjavaara E. Changes of diurnal rhythm and levels of total and free testosterone secretion from pre to late puberty in boys: testis size of 3 ml is a transition stage to puberty. Eur J Endocrinol 2004;151:747-57.
Davis SR, Davison SL, Gavrilescu M, et al. Effects of testosterone on visuospatial function and verbalfluency in postmenopausal women: results from a functional magnetic resonance imaging pilot study. Menopause 2014;21:410-4.
Zubiaurre-Elorza L, Junque C, Gómez-Gil E, et al. Effects of cross-sex hormone treatment on cortical thickness in transsexual individuals. J Sex Med 2014;11:1248-61.
Rametti G, Carrillo B, Gómez-Gil E, et al. Effects of androgenization on the white matter microstructure of female-to-male transsexuals. A diffusion tensor imaging study. Psychoneuroendocrinology 2012;37:1261-9.
Kimura D. Sex hormones influence human cognitive pattern. Neuroendocrinol Lett 2002;23:67-77.
Jordan K, Wüstenberg T, Heinze HJ, et al. Women and men exhibit different cortical activation patterns during mental rotation tasks. Neuropsychologia 2002;40:2397-408.
Aleman A, Bronk E, Kessels RPC, et al. A single administration of testosterone improves visuospatial ability in young women. Psychoneuroendocrinology 2004;29:612-7.
McCormick CM, Teillon SM. Menstrual cycle variation in spatial ability: relation to salivary cortisol levels. Horm Behav 2001;39:29-38.
Silverman I, Phillips K. Effects of estrogen changes during the menstrual cycle on spatial performance. Ethol Sociobiol 1993; 14:257-69.
Schöning S, Engelien A, Kugel H, et al. Functional anatomy of visuo-spatial working memory during mental rotation is influenced by sex, menstrual cycle, and sex steroid hormones. Neuropsychologia 2007;45:3203-14.
Peters M, Manning JT, Reimers S. The effects of sex, sexual orientation, and digit ratio (2D:4D) on mental rotation performance. Arch Sex Behav 2007;36:251-60.
Maylor EA, Reimers S, Choi J, et al. Gender and sexual orientation differences in cognition across adulthood: Age is kinder to women than to men regardless of sexual orientation. Arch Sex Behav 2007;36:235-49.
Nieder TO, Herff M, Cerwenka S, et al. Age of onset and sexual orientation in transsexual males and females. J Sex Med 2011; 8:783-91.
Lawrence AA. Sexual orientation versus age of onset as bases for typologies (subtypes) for gender identity disorder in adolescents and adults. Arch Sex Behav 2010;39:514-45.
Cerwenka S, Nieder TO, Briken P, et al. Intimate partnerships and sexual health in gender-dysphoric individuals before the start of medical treatment. Int J Sex Health 2014;26:52-65.
Rahman Q, Wilson GD. Large sexual-orientation-related differences in performance on mental rotation and judgment of line orientation tasks. Neuropsychology 2003;17:25-31.
Sanders G, Ross-Field L. Sexual orientation and visuo-spatial ability. Brain Cogn 1986;5:280-90.
Hall JA, Kimura D. Sexual orientation and performance on sexually dimorphic motor tasks. Arch Sex Behav 1995;24:395-407.
