It's often been stated that a particular white matter tract in the human brain, the inferior fronto-occipital fasciculus (IFOF; see below), is altered in gender dysphoria (GD) and may even be the neurological location/substrate for "gender identity".

But what does the data say? The first report of an altered IFOF in GD comes from this 2017 paper (), in which they found reduced white matter structural integrity (FA values) in transgender women (not trans men), and appeared independent of sexual orientation. pmc.ncbi.nlm.nih.gov/articles/PMC57…

A thread of mis-information here…

https://twitter.com/sportingnest/status/1903076704525930784

You make the claim that the hypothalamic nuclei (the BSTc in the cited Zhou et al., 1995 study), in transwomen is similar to that of natal women. However, you fail to mention that the BSTc doesn’t become dimorphic until 30-35 years of age and instead assume causality.

This paper suggests that untreated male-to-female transsexuals (MtF; n = 18) and FtMs (n = 24) show signs of feminisation and masculinisation, respectively, in relation to cortical thickness (CTh).

Let’s take a look: In their whole-brain comparison on CTh in relation to sexual dimorphism, the authors found that FtMs did not differ from female controls (thus having a CTh pattern congruent with their biological sex). Similarly, MtFs also did not differ to female controls (thus having a CTh pattern reflective of the opposite sex).

Brain activation patterns (those involved in self-referential/own body-perception processing) in trans men (n=14) & women (n=16) are similar to those of male (n=15) & female (n=15) controls, except when viewing their bodies morphed to the opposite sex:
pubmed.ncbi.nlm.nih.gov/31813993/
Participants wore a skin-tight suit which was virtually morphed to appear more masculine or feminine, representing images that are associated with either their natal sex or the opposite sex.

They then view these images in different increments in an fMRI scanner:

NEW STUDY: This is the first attempt to assess the translational potential for utilizing mice as a model for investigating human sex differences in the brain, focusing on regional grey matter volume (GMV).

Let's take a look 👀 Using a large cohort from the Human Connectome Project (597 females & 496 males) and mice (213 females & 216 males), total tissue volume (TTV; i.e., brain size) was assessed.

Human males showed a 13.5% larger TTV, whereas mice showed no such sex difference:

@hanksfolly @SimpForSowell @HermanSonofHerm @Anna11Ebiza @RoisinMichaux There is 100% research that demonstrates the impact of homosexuality on the cross-sex shift.

Let’s see some examples: @hanksfolly @SimpForSowell @HermanSonofHerm @Anna11Ebiza @RoisinMichaux In this paper, transgender participants (pre-pubescent and adolescent) smelled a pheromone (androstenedione; AND) which is known to cause a sex difference in hypothalamic activation via fMRI.

ncbi.nlm.nih.gov/pubmed/24904525

This is a thread reviewing two papers that are cited in support of the ‘brain-sex’ theory of gender dysphoria regarding the central subdivision of the bed nucleus of the stria terminalis (BSTc). The two studies in question are Zhou et al., 1995 and Kruijver et al., 2000: The first paper (Zhou et al) investigated the volume of the BSTc via the staining of vasoactive intestinal polypeptide (VIP) fibre innovation arising from the amygdala in 6 male-to-female transsexuals (MtFs):
pubmed.ncbi.nlm.nih.gov/7477289/

Using MRI to assess gray matter volume in trans women (TW; n=33), trans men (TM; n=33), males (n=24), and females (n=25), these authors identified the putamen as a marker associated with “gender identity”:
https://t.co/61TZdmQpuMpubmed.ncbi.nlm.nih.gov/33916288/
Comparing trans participants vs controls, it was observed that the volume of the putamen was greater in the transgender cohort in both the left and right hemispheres:

Incorrect. Specifically, homosexual men & women show less sexually differentiated brains (on average), and this is what's reflected in studies identifying a cross-sex shift in transgender participants.

https://twitter.com/AnnasisLizKelly/status/1667856686315618305

Citations:

pubmed.ncbi.nlm.nih.gov/21467211/

Testosterone (T) in males shows a homeostatic rhythmic expression though out the day, in so much that continued wakefulness decreases T whereas sleep increases it. Further, the T rhythm peaks just prior to REM sleep:
ncbi.nlm.nih.gov/pubmed/15914523

Large study investigating sex differences in gray matter volume (GMV) in a large sample (n=2,838) of men and women between the ages of 21-90 years old: Women, on average, showed larger GMV in various frontal regions, such as the ventrolateral and dorsolateral prefrontal cortex, medial and lateral orbitofrontal cortex, and anterior cingulate cortex.

When watching erotic stimuli (male-female intercourse), males show greater activation in the thalamus, amygdala, orbitofrontal and insular cortex compared to females. Male-to-female transsexuals showed a remarkably similar profile to females:
ncbi.nlm.nih.gov/pubmed/18761592 You can see this here:

Fact? 🤔

Trans women’s brains only show a cross-sex shift when they are homosexual, on average. Heterosexual trans women’s brains show NO signs of “feminisation”. ncbi.nlm.nih.gov/pmc/articles/P…

Important data to consider when investigating the sociological and biological elements of female-typical gendered behaviour:
researchgate.net/publication/24… Notice how females exposed to the lowest levels of testosterone in utero (top line) show more and more “female-typical” behaviour in adulthood with more and more encouraged femininity from their mothers (sociological effects of increasing certain behaviours)

Study showing the impact of cross-sex hormone therapy on brain volume in male-to-female (MFs) and female-to-male (FMs) transsexuals.
eje.bioscientifica.com/view/journals/… Specific to the hypothalamus, control males had a significantly larger volume compared to control females (remaining after controlling for intracranial volume)

MFs had hypothalamic volume inline with control males (pre-HRT). Similarly, FMs had hypothalamic volume inline with control females (pre-HRT).

This article is often cited as evidence that the brains of transgender women (TW) resemble the brains of natal women. However, once looking at the data, we see that this may not be the case.
ncbi.nlm.nih.gov/pmc/articles/P… The study included 48 controls (24=male; 24=female) and 24 TW (mean age = 45 for all participants).

All subjects underwent MRI and then the authors implemented a multivariate classifier to these MR images, in which a brain sex index (BSI) was derived. The BSI ranges between “0”… twitter.com/i/web/status/1…

Let’s review this paper:

The participants included 10 male-to-female (MtF) and 7 female-to-male (FtM) individuals diagnosed with gender dysphoria (pre-treatment). All trans participants were homosexual (i.e., attracted to people of their same natal sex; assessed by self-report).

https://twitter.com/IanCopeland5/status/1631177601057161223

The authors implemented voxel-based morphology (VBM) to identify changes in local gray matter volume (GMV), in relation to sexual dimorphism, and compare with healthy age-matched control male and females.

Study showing that homosexuality is related to less cerebral sex dimorphism:
ncbi.nlm.nih.gov/pmc/articles/P… Study participants (mean age = 29)

30 homosexual men (HoM)
40 heterosexual men (HeM)
40 heterosexual females (HeF)
30 homosexual females (HoF)

There is NO evidence that gender dysphoria is caused by a brain of the opposite sex, as sex-atypicality correlates with the individuals sexual orientation.

https://twitter.com/Mama_LuluVT/status/1620684914386690048

Here’s a few examples:

When the transgender cohort is 100% homosexual, their brains white matter resemble those of the opposite sex (on average), but when controlling for sexuality, their white matter resembles their natal sex
nature.com/articles/s4159…

An interesting study investigating sex differences in the molecular rhythms of the cerebral cortex in humans:
pubmed.ncbi.nlm.nih.gov/33934884/ Using post-mortem brain tissue, the authors were able to specifically assess the circadian rhythmicity of the entire transcriptome (mRNA) in the dorsolateral prefrontal cortex (DLPFC) and the anterior cingulate cortex (ACC); locations of which are shown below, respectively:

Are there sex differences in the circadian timing system within the brain?

The circadian system orchestrates all of our daily rhythms in behavior (sleep/wake cycle), body temperature, hormone secretion, immunity, and many others. Quick background:

Nearly all of our cells within the body demonstrate a genetic oscillation every 24 hours (seen below), which controls the rhythmic expression of many clock-controlled genes (CCGs).