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Transgender studies in brain anatomy and activity[edit]

Transgender studies concerning the brain often investigate how transgender people's brains differ from that of cisgender people. These studies will often compare the results of transgender men, transgender women, cisgender men and cisgender women to investigate if transgender people's brains are more similar to their sex assigned at birth or their gender identity. Some studies investigate the effects of hormone replacement therapy (HRT) on transgender people's brains, either by comparing pre-HRT transgender people to transgender people on HRT or by conducting a longitudinal study on transgender people starting HRT. Nonbinary people are largely absent from the literature [1].

Techniques employed by this field of study include magnetic resonance imaging, functional magnetic resonance imaging, electroencephalography, structural connectivity, post-mortem studies and functional connectivity [2].

Anatomical findings in pre-HRT transgender people[edit]

Several studies have suggested that pre-HRT transgender people's brains, both men's and women's, exhibit a combination of masculine traits and feminine traits[3][4] in line with the gender mosaic brain hypothesis. The gender mosaic brain hypothesis states that human brains are composed of a mixture of traits that are common in cisgender males and traits that are common in cisgender females regardless of gender or sex assignment[5]. However, what is different in transgender people is the presence of defeminized and demasculinized traits. Pre-HRT transgender women showed differences in the structure of their white matter microstructure that positioned them between what is typical of cisgender men and cisgender women, but closer to cisgender men than women. Transgender men's results were also between cisgender men and women's, but closer to the average for women. The authors refer to such results as demasculinized and defeminized traits respectively. This demasculinization was seen in the white matter microstructures of the right and left superior longitudinal fasciculus, the anterior region of the cingulum, and the fornix minor whilst the defeminization was only seen in the superior longitudinal fasciculus. [3][4]. Later studies have presented similar findings to support the suggestion that pre-HRT transgender people possess a white matter microstructure that is intermediate to cisgender men and cisgender women[6].

Other studies have investigated the volume of pre-HRT transgender people's brains, both the global volume and the volume of specific components such as the grey matter. One study found that pre-HRT transgender men had a significantly increased amount of grey matter in the right posterior cingulate gyrus compared to cisgender women[7]. A mega-analytic study concluded that pre-HRT transgender men's grey matter volumes resemble cisgender women's in the precentral gyrus, the postcentral gyrus, the superior frontal gyrus, the inferior parietal gyrus, the fusiform gyrus, the middle frontal rostral gyrus, the thalamus, the insula, the cerebellum and the pars triangularis [8].

A significant amount more studies have investigated the neuroanatomy of pre-HRT transgender women. These studies present the findings that pre-HRT transgender women have increased global grey matter volumes compared to cisgender women, but have decreased volumes compared to cisgender men [9]; have an increased grey matter volume compared to cisgender men in the right putamen [10]; increased regional grey matter volume in the temporo-parietal junction, inferior frontal cortex and insular cortex of the right hemisphere compared to cisgender people overall [11]; have decreased regional grey matter volumes in the left angular gyrus and inferior parietal lobule compared to cisgender people [12]; have decreased grey matter volumes compared to cisgender men in the middle frontal rostral gyrus and thalamus; that the grey matter volume of pre-HRT transgender women's insula was in-between that of cisgender men as well as cisgender women and that grey matter volumes of pre-HRT transgender women do not differ from that of cisgender men in the cerebellum and pars triangularis[8].

Studies have also investigated components beyond grey matter volumes. Two studies have presented findings suggesting that pre-HRT transgender women have increased cortical thickness compared to cisgender men [13][14]. The results of Savic & Arver's[10] study suggest that pre-HRT transgender women have lower white matter volumes in precentral areas compared to cisgender women.

Two studies employing fractional anisotropy present conflicting results. One's results indicate that the fractional anisotropy of specific fasciculi in pre-HRT transgender women is in between that of cisgender mean and cisgender women[3]. The second study did not find differences in fractional anisotropy between pre-HRT transgender women, cisgender women and cisgender men. However, they present that the mean diffusivity in cisgender women and pre-HRT transgender women is higher than in cisgender men [15].

Connectivity findings in pre-HRT transgender people[edit]

Resting state fMRI studies have been conducted with transgender participants to investigate the connectivity of transgender people's brains. One study presented results suggesting that, when compared with cisgender participants, both pre-HRT transgender men and transgender women had decreased connectivity in anterior as well as posterior regions of the default mode network[8]. Contrary to this, two studies did not find such differences in the default mode network[16][17]. Clemens et al. did however report several novel findings; that pre-HRT transgender women had higher connectivity in the thalamus compared to cisgender women and that pre-HRT transgender women had lower connectivity compared to cisgender men in the dorsolateral prefrontal cortex.

A large portion of connectivity studies have focused on transgender men, yielding a large body of findings. One study investigating connectivity between regions in pre-HRT transgender men found that they had similar connectivity to cisgender women between the left amygdala, right amygdala, motor cortex and hypothalamus. The same study also presented findings to suggest that pre-HRT transgender men have weaker connectivity than both cisgender men and cisgender women in the tracts between the amygdala, posterior cingulate, fusiform cortex and extra striatal body[18]. A different study's results indicate that pre-HRT transgender men may have stronger connectivity between the right temporo-parietal regions and the bilateral insula when compared to a group of cisgender people composed of both women and men [19] whilst another presents that the intrahemispheric connectivity of subcortical limbic areas of pre-HRT transgender men is decreased.[20].

Several studies have investigated the connectivity of both pre-HRT transgender men and pre-HRT transgender women's brains. Results from these studies suggest that pre-HRT transgender men have decreased connectivity compared to cisgender men in the left supramarginal gyrus of the executive control network, but have increased connectivity bilaterally in the frontal pole and supramarginal regions of the salience network. Meanwhile, pre-HRT transgender women are suggested to have decreased connectivity in the salience network compared to cisgender men in the left superior parietal gyrus, supramarginal gyrus and parietal operculum. Small regions of the right angular gyrus showed increased connectivity when comparing pre-HRT transgender women with cisgender women. [21] [22].

Anatomical findings in transgender people on HRT[edit]

Similar to pre-HRT transgender people, it is suggested that transgender people on HRT may have a mixture of masculine, feminine and defeminized traits (for transgender men) or a combination of feminine, masculine and demasculinized traits (for transgender women)[23].

An early post-mortem study found that the bed nucleus of the stria terminalis of transgender women was similar to that of cisgender women in regards to size[24]. Since then, studies have used neuroimaging techniques to search for similar changes in vivo.

The earliest changes a study has presented evidence for happened after 1 month in transgender mean. Reductions in mean diffusivity were shown in the lateral hypothalamus, but only in one hemisphere. These were demonstrated in both hemispheres after 4 months[15]

Studies suggest that after four months on HRT, transgender women may experience brain volume reductions towards the average of cisgender women; particularly in the hypothalamus. They may also experience an increase in ventricle volumes. Opposite to this, transgender men on HRT may experience an increase in total brain and hypothalamic volumes as well as a decrease in ventricle volumes towards typical male proportions [25]. A second study demonstrated grey matter decreases in the right hippocampal regions of transgender women after four months, concurrent with increases in the ventricles and correlated with changes in progesterone levels[26].

After six months, cortical thickness may be reduced in cortical and subcortical structures for transgender women on HRT whilst transgender men may experience an increase in cortical thickness <[23]>.

A study suggested that transgender men on 7 months of HRT may show changes to their white matter microstructure as the fractional anisotropy of their right superior longitudinal fasciculus increases compared to pre-HRT measurements [3]

References[edit]

  1. ^ Nguyen, H. B., Loughead, J., Lipner, E., Hantsoo, L., Kornfield, S. L., & Epperson, C. N. (2018). What has sex got to do with it? The role of hormones in the transgender brain. Neuropsychopharmacology, 44(1), 22-37. doi: 10.1038/s41386-018-0140-7
  2. ^ Kiyar, M., Collet, S., T'Sjoen, G., & Mueller, S. C. (2020). Neuroscience in transgender people: an update. Neuroforum, 26(2). 85-92. doi: 10.1515/nf-2020-007
  3. ^ Rametti, G., Carrillo, B., Gómez-Gil, E., Junque, C., Segovia, S., Gomez, Á. and Guillamon, A. (2011a). White matter microstructure in female to male transsexuals before cross-sex hormonal treatment. A diffusion tensor imaging study. Journal of Psychiatric Research, 45 (2), 199-204. doi:10.1016/j.jpsychires.2010.05.006
  4. ^ Rametti, G., Carrillo, B., Gómez-Gil, E., Junque, C., Zubiarre-Elorza, L., Segovia, S., Gomez, Á. and Guillamon, A. (2011b) The microstructure of white matter in male to female transsexuals before cross-sex hormonal treatment. A DTI study. Journal of Psychiatric Research, 45(7), 949-954. doi: 10.1016/j.jpsychires.2010.11.007
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  12. ^ Simon, L., Kozak, L. R., Simon, v., Czobor, P., Unoka, Z., Szabo, A., & Csukly, G., (2013). Regional Grey Matter Structure Differences between Transexuals and Healthy Controls. pLos ONE, 8(12),e83947. doi:10.1371/journal.pone 0093847
  13. ^ Zubiaurre-Elorza, L., Junque, C., Gomez-Gil, E., Segovia, S., Carrillo, B., Rametti, G., & Guillamon, A., (2013). Cortical Thickness in Untreated Transexuals. Cerebral Cortex, 23(12), 2855-2862. doi: 10.1093/cercor/bhs267.
  14. ^ Luders, E., Sanchez, F. J., Tosun, D., Shattuck, D. W., Gaser, C., Vilain, E., & Toga, A. W. (2012). Increased Cortical Thickness in Male-to-Female Transsexualism. Journal of Behavioral and Brain Science, 2(3), doi:10.4236/jbbs.2012.23040.
  15. ^ Kranz, G. S., Hahn, A., Kaufmann, U., Küblböck, M., Hummer, A., Ganger, S., Seiger, R., Winkler, D., Swaab, D. F., Windischberger, C., Kasper, S., & Lanzenberger, R. (2014). White matter microstructure in transsexuals and controls investigated by diffusion tensor imaging. The Journal of neuroscience : the official journal of the Society for Neuroscience, 34(46), 15466–15475. doi:10.1523/JNEUROSCI.2488-14.2014
  16. ^ Clemens, B., Junger, J., Pauly, K., Neulen, J., Neuschaefer-Rube, C., Frolich, D., Mingoia, G., Derntl, B., & Habel, U. (2017). Male-to-female gender dysphoria: gender-specific differences in resting-state networks. Brain and Behavior, 7(1), e00691. doi:10.1002/brb3.691.
  17. ^ Nota, N.M., Burke, S.M., Heijer, M., Soleman, R. S., Lambal, C.B., Cohen-Kettenis, P. T., Veltman, D. J., Kreukels, B. P., (2017). Brain sexual differentiation and effects of cross-sex hormone therapy in transpeople: a resting-state functional magnetic resonance study. Neurophysiol, 47(1), 361-370. doi:10.1016/j.neucli.2017.09.001.
  18. ^ Manzouri, A., Kosidou, K. & Savic, I. (2017). Anatomical and functional fidnings in female-to-male transexuals:testing a new hypothesis. Cerebral Cortex, 1991(27),998-1010. doi:10.1093/cercor/bhv278
  19. ^ Burke, S. M., Manzouri, A. H., Dhejne, C., Bergström, K., Arver, S., Feusner, J. D., & Savic-Berglund, I. (2018). Testosterone Effects on the Brain in Transgender Men. Cerebral cortex ), 28(5), 1582–1596. doi: 10.1093/cercor/bhx054
  20. ^ Hahn, A., Kranz, G. S., Kublock, M., Kayfmann, U., Ganger, S., Hummer, A., Seiger, R., Spies, M... Lanzenberger, R. (2015). Structural connectivity networks of transgender people. Cerebral Cortex,25(10),3527-3534. doi:10.1093/cercor/bhu194.
  21. ^ Feusner, J. D., Lidstrom, A., Moody, T. D., Dhejne, C., Bookheimer, S. Y., & Savic, I. (2016) Intrinsic network connectivity and own body perception in gender dysphoria. Brain Imaging and Behavior, 11, 964-976. doi: 10.1007/s11682-016-9578-6
  22. ^ Uribe, C., Junque, C., Gomez-Gil, E., Abos, A., Mueller, S. C. & Guillamon, A. (2020). Brain network interactions in transgender indivudals with gender incongruence. NeuroImage, 211(1), 116613. doi:1-.1-16/j.neuroimage.2020.116613.
  23. ^ Zubiaurre-Elorza, L., Junque, C., Gómez-Gil, E., & Guillamon, A. (2014). Effects of cross-sex hormone treatment on cortical thickness in transsexual individuals. The journal of sexual medicine, 11(5), 1248–1261. doi:10.1111/jsm.12491
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  26. ^ Seiger, R., Hahn, A., Hummer, A., Kranz, G. S., Ganger, S., Woletz, M., Kraus, C., Sladky, R., Kautzky, A., Kasper, S., Windischberger, C., & Lanzenberger, R. (2016). Subcortical gray matter changes in transgender subjects after long-term cross-sex hormone administration. Psychoneuroendocrinology, 74, 371–379. doi:10.1016/j.psyneuen.2016.09.028
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