title: Testosterone affects language areas of the adult human brain.
abstract: Although the sex steroid hormone testosterone is integrally involved in the development of language processing, ethical considerations mostly limit investigations to single hormone administrations. To circumvent this issue we assessed the influence of continuous high-dose hormone application in adult female-to-male transsexuals. Subjects underwent magnetic resonance imaging before and after 4 weeks of testosterone treatment, with each scan including structural, diffusion weighted and functional imaging. Voxel-based morphometry analysis showed decreased gray matter volume with increasing levels of bioavailable testosterone exclusively in Broca's and Wernicke's areas. Particularly, this may link known sex differences in language performance to the influence of testosterone on relevant brain regions. Using probabilistic tractography, we further observed that longitudinal changes in testosterone negatively predicted changes in mean diffusivity of the corresponding structural connection passing through the extreme capsule. Considering a related increase in myelin staining in rodents, this potentially reflects a strengthening of the fiber tract particularly involved in language comprehension. Finally, functional images at resting-state were evaluated, showing increased functional connectivity between the two brain regions with increasing testosterone levels. These findings suggest testosterone-dependent neuroplastic adaptations in adulthood within language-specific brain regions and connections. Importantly, deteriorations in gray matter volume seem to be compensated by enhancement of corresponding structural and functional connectivity. Hum Brain Mapp 37:1738-1748, 2016. © 2016 Wiley Periodicals, Inc.
authors.affiliation: Department of Psychiatry and Psychotherapy, Medical University of Vienna, Austria.
authors.forename: Andreas
authors.initials: A
authors.lastname: Hahn
authors.affiliation: Department of Psychiatry and Psychotherapy, Medical University of Vienna, Austria.
authors.forename: Georg S
authors.initials: GS
authors.lastname: Kranz
authors.affiliation: MR Center of Excellence, Center for Medical Physics and Biomedical Engineering, Medical University of Vienna, Austria.
authors.forename: Ronald
authors.initials: R
authors.lastname: Sladky
authors.affiliation: Department of Obstetrics and Gynecology, Medical University of Vienna, Austria.
authors.forename: Ulrike
authors.initials: U
authors.lastname: Kaufmann
authors.affiliation: Department of Psychiatry and Psychotherapy, Medical University of Vienna, Austria.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Ganger
authors.affiliation: MR Center of Excellence, Center for Medical Physics and Biomedical Engineering, Medical University of Vienna, Austria.
authors.forename: Allan
authors.initials: A
authors.lastname: Hummer
authors.affiliation: Department of Psychiatry and Psychotherapy, Medical University of Vienna, Austria.
authors.forename: Rene
authors.initials: R
authors.lastname: Seiger
authors.affiliation: Department of Psychiatry and Psychotherapy, Medical University of Vienna, Austria.
authors.forename: Marie
authors.initials: M
authors.lastname: Spies
authors.affiliation: Department of Psychiatry and Psychotherapy, Medical University of Vienna, Austria.
authors.forename: Thomas
authors.initials: T
authors.lastname: Vanicek
authors.affiliation: Department of Psychiatry and Psychotherapy, Medical University of Vienna, Austria.
authors.forename: Dietmar
authors.initials: D
authors.lastname: Winkler
authors.affiliation: Department of Psychiatry and Psychotherapy, Medical University of Vienna, Austria.
authors.forename: Siegfried
authors.initials: S
authors.lastname: Kasper
authors.affiliation: MR Center of Excellence, Center for Medical Physics and Biomedical Engineering, Medical University of Vienna, Austria.
authors.forename: Christian
authors.initials: C
authors.lastname: Windischberger
authors.affiliation: Netherlands Institute for Neuroscience, Institute of the Royal Netherlands Academy of Arts and Sciences, Amsterdam, the Netherlands.
authors.forename: Dick F
authors.initials: DF
authors.lastname: Swaab
authors.affiliation: Department of Psychiatry and Psychotherapy, Medical University of Vienna, Austria.
authors.forename: Rupert
authors.initials: R
authors.lastname: Lanzenberger
mesh_terms: D000328:Adult; D001931:Brain Mapping; D065711:Broca Area / Q000000981:diagnostic imaging / Q000187:drug effects* / Q000502:physiology; D005260:Female; D066128:Gray Matter / Q000000981:diagnostic imaging / Q000187:drug effects; D006801:Humans; D007091:Image Processing, Computer-Assisted; D007802:Language; D008297:Male; D059906:Neuroimaging; D013739:Testosterone / Q000494:pharmacology*; D065813:Wernicke Area / Q000000981:diagnostic imaging / Q000187:drug effects* / Q000502:physiology; D066127:White Matter / Q000000981:diagnostic imaging / Q000187:drug effects; D055815:Young Adult
chemical_list: D013739:Testosterone
keywords: functional connectivity; language; neuroplasticity; probabilistic tractography; testosterone; voxel-based morphometry