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Sammy Profile picture
@NeuroSGS
Aug 28 • 14 tweets • 6 min read • Read on X
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? Image
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…Image
Later in 2022, this was "replicated" () in adolescent trans girls (mean age = 15.4). However, no sex-reversal was seen in dysphoric pre-pubescent children (mean age = 10.4).

Importantly, this sample overlapped with the study cited above. pmc.ncbi.nlm.nih.gov/articles/PMC10…Image
In the previous study, the adolescent trans girls had been exposed to puberty blockers (GnRHa).

The authors noted a negative correlation (pre-multiple comparison correction) between the dosage of GnRHa and the microstructural integrity of the IFOF (i.e., reduced FA value). Image
The confounded data above make causal conclusions difficult. Further, we don't fully understand regular sex differences in the IFOF to be confident enough that the IFOF in transgender individuals is sex-atypical.
While it's typically assumed that males have greater white matter integrity (increased FA values) compared to females in the majority of white matter tracts, there still lie many inconsistencies.

pubmed.ncbi.nlm.nih.gov/27226438/

pmc.ncbi.nlm.nih.gov/articles/PMC33…

annas-archive.org/scidb/10.1016/…
In this paper (), the authors statistically accounted for the sex differences in intracranial volume (ICV) via adding it as a covariate in their statistical model. In doing so, sex differences in all major tracts disappeared. onlinelibrary.wiley.com/doi/epdf/10.10…Image
Interestingly, the integrity of the IFOF tends to decrease around the age of 30, and higher FA values during development are associated with greater global cognitive functioning. The impact of age is thus another important consideration.
pmc.ncbi.nlm.nih.gov/articles/PMC44…Image
In a larger cohort, and while accounting for both age and brain size via both statistical modelling and/or by using brain-size matched men & women, these authors found that it's actually females who show increased FA in the IFOF:
onlinelibrary.wiley.com/doi/epdf/10.10…Image
It's important to note that in the transgender studies, the authors did not account for brain size, had a small and confounded sample, didn't "replicate" previous data, and the data on regular sex differences in the IFOF are inconsistent (perhaps due to methodological reasons).
Now even consider the fact that other transgender studies investigating white matter integrity (using FA metrics) did not report IFOF sex-reversal.
pmc.ncbi.nlm.nih.gov/articles/PMC46…
The function of IFOF is much debated (academic.oup.com/brain/article/…), but in transgender individuals some authors have claimed that it's involved in body image distortions (similar reductions in IFOF integrity have also been found in anorexia): pmc.ncbi.nlm.nih.gov/articles/PMC67…
Based on all the data above, I don't find it convincing enough to claim that "gender identity" is located within the IFOF, nor that it being related to sexual dimorphism implicates it in GD aetiology.
Perhaps an overall reduction in IFOF integrity may at the very least 'predispose' one to some form of body distortion (but even then, causal conclusions are a long way away).

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More from @NeuroSGS

Sammy Profile picture
Mar 21
A thread of mis-information here…
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.
You then go onto talk about a few papers (vaguely) that include functional brain activity, neuroimaging (looking at cortical thickness), and various responses.

You fail to mention the impact that homosexuality may have on the results and make the assumption of causality (again)
Read 8 tweets
Sammy Profile picture
Aug 23, 2024
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: Image
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).
However, both sets of transsexual subjects did show some differences in relation to both male and female controls (see figure below): Image
Read 8 tweets
Sammy Profile picture
Dec 7, 2023
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/
Image
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: Image
As expected, trans participants subjectively rated their bodies morphed toward the opposite sex as being more like "me", whereas male and female controls rated their natal sexed body images as being more like "me": Image
Read 9 tweets
Sammy Profile picture
Dec 5, 2023
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: Image
After TTV correction + multiple comparisons, 65.8% of the human brain showed statistically significant sex differences, of which 63.8% were female-bias & 36.3% were male-bias.

In mice, 58.6% of all regions were sexually dimorphic, with 53% being female-bias & 47% male-bias.
Read 12 tweets
Sammy Profile picture
Dec 1, 2023
@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
@hanksfolly @SimpForSowell @HermanSonofHerm @Anna11Ebiza @RoisinMichaux The pre-pubescent trans participants showed no sex-atypicality (their sexual orientation, as a group, was considerably more varied). The adolescent participants showed a cross-sex shift (the vast majority were homosexual).
Read 19 tweets
Sammy Profile picture
Aug 1, 2023
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/
The BSTc in males was 44% larger than in females. In MtFs (who were all on cross-sex hormone treatment), the volume of the BSTc was found to be within the female range and seemed independent of sexual orientation (as seen by homosexual males being sex-typical): Image
Read 16 tweets

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