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.
Highlights
Testosterone exhibits a considerable influence on human behavior through modulation of brain structure and function [Hofer et al, 2013]
Our findings indicate a strong modulatory influence of testosterone on language-specific gray and white matter structures as well as functional connectivity
They affirm that the neuronal organization of languagerelated brain regions is subject to neuroplastic adaptation even in adulthood [Dehaene et al, 2010]
Summary
Testosterone exhibits a considerable influence on human behavior through modulation of brain structure and function [Hofer et al, 2013] This includes, but is not limited to, bargaining and dominant behavior [Eisenegger et al, 2010], neuronal activation in response to visuo-spatial processing and threat [Goetz et al, 2014] as well as size and number of neurons [Bao and Swaab, 2011]. The majority of human studies can only assess the cross-sectional effects of testosterone or the response to a single dose of hormones due to ethical, methodological and practical reasons [Lombardo et al, 2012] In this context, investigation of transsexual subjects offers the unique opportunity to study the influence of high-dose long-term hormone application onto the living human brain in healthy adults. In line with the above mentioned influence of testosterone on behavior, several studies in female-to-male (FtM) transsexuals reported dete-
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