White matter microstructure in female to male transsexuals before cross-sex hormonal treatment. A diffusion tensor imaging study – Review

This study compared the white matter in the brains of males, females, and female to male transsexuals (FtM).*

This is one of a set of studies; another one looked at the white matter in the brains of male to female transsexuals (MtF) .

White matter is the stuff in your brain that transmits signals from one area to another. It is mostly made up of glial cells and axons. Glial cells are cells in the brain that aren’t nerve cells; they’re like a support system for the nerve cells. Axons are the long skinny part of your nerve cells that transmit information.

In three fasciculi (bundles of nerve fibers), FtM transsexuals had white matter that was like males and different from females.

In the corticospinal tract, FtM transsexuals’ white matter microstructure pattern was between the pattern of the male and female controls.

The study does not say if there were any other ways in which FtM transsexuals’ white matter was different from both males and females without gender dysphoria. I think they did not look at the question; they seem to have analyzed the data first to find sex differences and then to compare FtM transsexuals to the other groups in those areas.

It would be beyond interesting and relevant to find any areas of the brain in which people with gender dysphoria were different from people without gender dysphoria.

It is worth noting that the FtM transsexuals were all sexually attracted to females while the females were all attracted to males and the males were all attracted to females.

Thus the study was also comparing the brains of two groups of people attracted to males and one group of people attracted to females. The differences they found could be related to sexual orientation.

It is not clear what these differences mean, what caused them, or what their significance would be in brain function.

You can stop here if you just want the gist of the results. Otherwise, back to the study:

The study found sex differences in the fractional anisotropy (FA) values of white matter in four bundles of nerves with males having a higher FA value. The white matter structures with a higher FA value for males were the anterior** and posterior parts of the right superior longitudinal fasciculus, the forceps minor (right), and the corticospinal tract.***

In three of these four nerve areas, FtM transsexuals had FA values that were significantly larger than females and not significantly different from males.

In the inferior corticospinal tract, FtM transsexuals had FA values that were significantly larger than females and significantly smaller than males.

The authors conclude:

“…the main result of our study is that untreated FtM transsexuals differed from control females in two associative fasciculi (superior longitudinal fasciculus and forceps minor) and in the corticospinal tract. In contrast they only differed from control males in the corticospinal tract. These findings indicates that prior to hormonal cross-sex treatment the white matter microstructure of associative fascicles in untreated FtM transsexuals is more like that of individuals with the same gender identity than of individuals with the same biological sex.”

Their fascicles are also more like that of individuals with the same sexual orientation. We can not conclude that the cause is their gender identity, at least not from this data. We need more research in this area.

It is worth noting that we do not know what exactly made the white matter microstructures develop the way they did. It could be due to hormones or experience or an interaction of the two.

In addition, the microstructure in FtMs might have been affected by a different factor than the microstructure in males.

Finally, in the case of the corticospinal tract, it is possible that FtM transssexuals had white matter that developed like the control males, but then something caused their FA values to decrease. Changes in FA values can be due to age or illnesses, including depression or excessive alcohol consumption.

What do the differences they found mean practically?

This study found a sex difference in the FA values for the following fasciculi (bundles of nerves):

Superior longitudinal fasciculus (right, anterior and posterior) – a pair of long bundles of neurons connecting the front and back of the cerebrum (cerebrum=most of your brain). It is connected to many parts of the brain. One of its functions is to integrate auditory and speech nuclei.

Forceps minor (right) – a fiber bundle that connects that lateral and medial surfaces of the frontal lobes of the brain. It is part of the corpus collosum. The corpus collosum is responsible for interhemispheric sensory and auditory connectivity.

Corticalspinal tract (right) – connects the brain to the spinal cord. It is responsible for voluntary movement.

Looking at these descriptions, this study found sex differences in the nerves that connect the front and back of the brain, the nerves that connect the two hemispheres, and nerves that connect the brain to the spinal column.

It’s hard to predict how differences in these parts of the brain would affect men’s and women’s cognitive abilities and personalities.

The difference was found only on the right side of the brain. Does this mean anything? Maybe. According to the authors:

“Regarding brain laterality, we found that all the FA value decreases in women compared to men are seen in the right hemisphere. Similar asymmetries are also reported by Schmithorst et al. (2008), they described lower FA values in girls than in boys, and although there were decreases on both sides, the largest lost FA value clusters were on the right, indicating a right hemispheric predominance in sex differences. More recently Huster et al. (2009), focusing on the midcingulum bundle, found lower FA values in the right hemisphere than in the left and in women than in men.”

What specifically is the difference they observed in these bundles of nerves? What are FA values?

In another study, the authors say that FA values are “related to the ordered arrangement of myelinated fibers” and “an indication of white matter coherence and axonal integration.” Wikipedia says that FA is thought to reflect fiber density, axonal diameter, and myelination in white matter.

So finding higher FA values for males in certain bundles of nerves could mean that they have more dense nerve connections there or that those nerve connections are fatter or that they have more or fatter myelin sheaths. It might mean that the nerve connections in those bundles are more orderly, coherent, and integrated.

The next question, of course, is what does it mean if you have more or fatter or more coherent nerve connections between the front and back of your brain? between the two hemispheres? going to your spine?

Or, to look at it in terms of function, if the white matter responsible for voluntary movement is more coherent in males, it might give them faster reflexes. On the other hand, what does it mean if the white matter that connects auditory and speech nuclei is more coherent in males? It sounds like it ought to make it easier for males to process language.

My basic conclusion from all this is that we have found a sex difference in the brain, but we don’t really know what it means.

The authors try to connect their findings to differences in spatial abilities and verbal fluency, because the superior longitudinal fasciculus is “involved in the integration of inputs from multiple modalities and is a component of the network for spatial awareness that plays a major role in the visual and oculomotor aspects of spatial function such as spatial attention and spatial working memory.”

It might be, but there are a lot of other cognitive functions that use the integrations of inputs from multiple modalities. We have no way of knowing if the connections they observed were for spatial ability or giving a speech or cooking dinner without burning yourself.

I think they are overreaching in their conclusion here.

The authors also discuss the difference they found in the forceps minor. Again, I think it’s hard to know what exactly a sex difference here would mean; the forceps minor connects the two halves of the prefrontal cortex which controls our behavior. Does having more connectivity on the right make men better at controlling themselves or integrating their emotions?

The forceps is part of the corpus collosum. Another study found differences related to sexual orientation in this area of the brain. It is important to make sure that any differences found in this study are not due to sexual orientation.

The authors refer to a study which found that the shape of the corpus collousm in transsexual individuals matched their gender identity not their biological sex. I can only see the abstract of that study, so I don’t know if they looked at the sexual orientation of the people in that study.

Anyhow, here is the discussion of the forceps minor by the authors:

“The forceps minor connects, via the genu of the CC, orbitofrontal regions ( Park et al., 2008) involved in emotional functions and behavioral control. Kringelbach and Roll (2004), suggested that orbital cortex activity is related to the reward value of reinforcers and punishers.

The forceps minor is a part of the anterior region of the corpus callosum. The CC is the major interhemispheric pathway in the human brain and integrates sensory, motor, cognitive and emotional functions from both hemispheres; the isthmal area of the CC is larger in homosexual than in heterosexual males ( Witelson et al., 2008). FA values in the anterior part of the CC change during development ( Lebel et al., 2008). In a sample of children and adolescents, it was reported that girls have lower FA values than boys in the anterior CC region ( Schmithorst et al., 2008). In addition, the boys had lower FA values than girls in a small region of the splenium. We did not observe differences in the splenium between adult male and female controls.

There are only a couple of studies on the transsexual CC. Studying the CC shape, it was concluded that the shape in transsexuals is more similar to their gender identity than to their biological sex ( Yokota et al., 2005). However, when the whole CC surface was studied no differences in CC -regardless of genetic sex or gender- were reported (Emory et al., 1991). Our results cannot be compared to these works, which used surface measurements, while we have used FA analysis, which seems to be a more suitable technique for detecting microstructural white matter differences.”

The authors say less about the corticospinal tract, but they mention that genes and motor experience interact in its development. This is an area where FtM transsexuals were in-between male and female controls, so perhaps they are suggesting that the males had more practice at motor skills.

Of course all of the sex differences found in this study could be related to experience or an interaction of genes and experiences.

The authors of this study imply that the sex differences they found were caused by hormones early in development, but we can’t actually know that.

This study had a couple of serious weaknesses.

1. They did not look for any general differences between the brains of trans and cis people, they only looked at how trans men compared to males and females in areas where they found a sex difference. This assumes that gender dysphoria is caused by something related to hormones – which is what the authors want to prove.

It would be helpful if future studies look at both issues – sex differences and general differences between cis and trans people. Perhaps the authors could of this study would be able to use the data they collected to do this.

2. They did not include any cis lesbians as control groups, although all of the FtM transsexuals were attracted to women. Without doing this, we can not be sure if the similarities between the FtM transsexuals and cis men attracted to women are caused by gender identity or sexual orientation.

The study also has some strengths.

1. They used only trans men who had not yet taken hormones. We know that taking cross-sex hormones changes your brain. (Early studies of gender identity and the brain used people who had already been on hormones.)

2. They tested the actual hormone levels of the FtMs before the brain scans. A Japanese study found that many of the trans men who came to their clinic had poly-cystic ovarian syndrome (PCOS). PCOS can lead to elevated levels of androgens which would confuse the results.

3. Everyone in the study was right-handed.

Original Article:

White matter microstructure in female to male transsexuals before cross-sex hormone treatment. A diffusion tensor imaging study by Rametti G, Carrillo B, Gómez-Gil E, Junque C, Segovia S, Gomez Á, Guillamon A in J Psychiatr Res. 2011 Feb;45(2):199-204.

* I am following the language used in the study to refer to trans men and control subjects.

** The abstract says that the white matter was different in the medial and posterior parts of the superior longitudinal fasciculus, but  in the text of the study, the results discuss the anterior and posterior parts. Anterior and posterior refer to front and back while medial means in the middle, so it makes more sense to talk about the anterior and posterior parts of the nerve bundle. I think they made an error in the abstract.

***A later study of white matter in MtF transsexuals found a sex difference in the same three bundles of nerves. They found a sex difference in three additional areas as well: the left superior longitudinal fasciculus, the right inferior front-occipital fasciculus, and the left cingulum. It’s not clear why one study found more sex differences in white matter than the other did. (The earlier study was done by the same people using the same methodology but different control groups.)

 

P.S. A fun link on the map of the connections of white matter in young men’s brains.

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