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Cereb Cortex. 2016 Mar;26(3):1036-45. doi: 10.1093/cercor/bhu280. Epub 2014 Dec 1.

Neural Activation During Mental Rotation in Complete Androgen Insensitivity Syndrome: The Influence of Sex Hormones and Sex Chromosomes.

Author information

1
Netherlands Institute for Neuroscience, Amsterdam, The Netherlands Department of Medical Psychology, Neuroscience Campus Amsterdam.
2
Department of Psychiatry, VU University Medical Center, Amsterdam, The Netherlands.
3
Department of Medical Psychology, Neuroscience Campus Amsterdam.
4
Department of Child and Adolescent Psychiatry, Erasmus Medical Center-Sophia, Rotterdam, The Netherlands.
5
Netherlands Institute for Neuroscience, Amsterdam, The Netherlands Department of Medical Psychology, Neuroscience Campus Amsterdam Group Interdisciplinaire de Genoproteomique appliquee, University of Liège, Liège, Belgium.

Abstract

Sex hormones, androgens in particular, are hypothesized to play a key role in the sexual differentiation of the human brain. However, possible direct effects of the sex chromosomes, that is, XX or XY, have not been well studied in humans. Individuals with complete androgen insensitivity syndrome (CAIS), who have a 46,XY karyotype but a female phenotype due to a complete androgen resistance, enable us to study the separate effects of gonadal hormones versus sex chromosomes on neural sex differences. Therefore, in the present study, we compared 46,XY men (n = 30) and 46,XX women (n = 29) to 46,XY individuals with CAIS (n = 21) on a mental rotation task using functional magnetic resonance imaging. Previously reported sex differences in neural activation during mental rotation were replicated in the control groups, with control men showing more activation in the inferior parietal lobe than control women. Individuals with CAIS showed a female-like neural activation pattern in the parietal lobe, indicating feminization of the brain in CAIS. Furthermore, this first neuroimaging study in individuals with CAIS provides evidence that sex differences in regional brain function during mental rotation are most likely not directly driven by genetic sex, but rather reflect gonadal hormone exposure.

KEYWORDS:

CAIS; fMRI; sexual differentiation; spatial cognition; testosterone

PMID:
25452569
DOI:
10.1093/cercor/bhu280
[Indexed for MEDLINE]

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