Many people suggest that trans people have brains more inline with their desired gender, and this causes feelings of gender incongruence.

However, if we take a closer look, we see some important underlying issues.

In a famous study, the authors compared prepubertal and adolescent children, then suggest sex atypical cerebral differentiation occurs within these individuals [1].

The authors found sex atypical differences in the adolescent cohort, but the majority of that cohort is homosexual:

- Homosexuality = 23% of trans boys + 44% of trans girls (prepubertal cohort)

- Homosexuality = 100% of trans boys + 78% of trans girls (adolescent cohort)

The only non-sex typical finding which was specific to gender dysphoria was in visual network-1 (VN-1; via fMRI). It was suggested that alterations in this network may disrupt body perception in gender dysphoric individuals.

In another study by some of the same authors, they tested whether transgender people (with gender dysphoria) would have sex atypical hypothalamic activation to androstenedione, a steroid hormone in human sweat that causes sex-specific olfactory responses [2].

But similar to the previous study, sexual orientation was not accounted for. Why is this important? Well, the same sex atypical hypothalamic response is observed in homosexual men [3] and in homosexual women [4].

It's becoming increasingly clear that the only people with any sort of sex atypical cerebral differentiation occurs in homosexual individuals (on average).

This is further supported by functional connectivity studies of sex atypical amygdala co-variance. You can see this in Figure 1 of this paper: [5]. Notice the high similarity in amygdala activity (at rest) between heterosexual females and homosexual males (and vice versa).

Interestingly, in an effort to bring all of this together, this study examined the brains of heterosexual transgender people in order to control for sexual orientation: [6]. As Figure 1 of this paper shows, the authors found sexual dimorphism in various gray matter parameters in control male and females. However, these findings were not found in the heterosexual transgender population.

So rather than sex atypical brain structure/function, what is specific to gender dysphoria itself?

It's been shown that individuals with gender dysphoria show weaker structural and functional connectivity within the default mode network (DMN) of the brain, which is vital for body perception/image and self-referential processing [7]. Findings which have been replicated in [8] and [9].

The DMN consists of cerebral midline structures, including the medial prefrontal cortex (mPFC) and the posterior cingulate cortex (PCC). Interestingly, it's been shown that trans individuals (with GD) show a stronger activation pattern within these DMN structures when viewing pictures of their body morphed to the opposite sex: [10]. You can see the results in Figure 5 of this paper.

It's important to note that correlation is not causation. Just because we observe a different pattern in gender dysphoric subjects compared to neuro-typical controls, does not suggest it's innate (born with) or a product of post-natal experience. We simply do not know.

Also, transgender people tend to have lots of co-morbidities from depression, anxiety, anorexia, autism, and a homosexual orientation. All of this needs to be considered when looking at neuroscience studies on this population.

[1] Nota, N. M., Kreukels, B. P. C., den Heijer, M., Veltman, D. J., Cohen-Kettenis, P. T., Burke, S. M., & Bakker, J. (2017). Brain functional connectivity patterns in children and adolescents with gender dysphoria: Sex-atypical or not? https://pubmed.ncbi.nlm.nih.gov/28972892/

[2] Burke, S. M., Cohen-Kettenis, P. T., Veltman, D. J., Klink, D. T., & Bakker, J. (2014). Hypothalamic response to the chemo-signal androstadienone in gender dysphoric children and adolescents. https://pubmed.ncbi.nlm.nih.gov/24904525/

[3] Savic, I., Berglund, H., & Lindström, P. (2005). Brain response to putative pheromones in homosexual men. https://pubmed.ncbi.nlm.nih.gov/15883379/

[4] Berglund, H., Lindström, P., & Savic, I. (2006). Brain response to putative pheromones in lesbian women. https://pubmed.ncbi.nlm.nih.gov/16705035/

[5] Savic, I., & Lindström, P. (2008). PET and MRI show differences in cerebral asymmetry and functional connectivity between homo- and heterosexual subjects. https://pubmed.ncbi.nlm.nih.gov/18559854/

[6] Savic, I., & Arver, S. (2011). Sex dimorphism of the brain in male-to-female transsexuals. https://pubmed.ncbi.nlm.nih.gov/21467211/

[7] Burke, S. M., Manzouri, A. H., & Savic, I. (2017). Structural connections in the brain in relation to gender identity and sexual orientation. https://pubmed.ncbi.nlm.nih.gov/29263327/

[8] Uribe, C., Junque, C., Gómez-Gil, E., Abos, A., Mueller, S. C., & Guillamon, A. (2020). Brain network interactions in transgender individuals with gender incongruence. https://pubmed.ncbi.nlm.nih.gov/32057995/

[9] Feusner, J. D., Lidström, A., Moody, T. D., Dhejne, C., Bookheimer, S. Y., & Savic, I. (2017). Intrinsic network connectivity and own body perception in gender dysphoria. https://pubmed.ncbi.nlm.nih.gov/27444730/

[10] Majid, D. S. A., Burke, S. M., Manzouri, A., Moody, T. D., Dhejne, C., Feusner, J. D., & Savic, I. (2020). Neural Systems for Own-body Processing Align with Gender Identity Rather Than Birth-assigned Sex. https://pubmed.ncbi.nlm.nih.gov/31813993/