Tag Archives: white matter

Sex Dimorphism of the Brain in Male-to-Female Transsexuals – Review

This study found that trans women (born male) had brains like men’s, at least in terms of gray and white matter volumes and hemispheric asymmetry.

In a few areas, trans women’s brains were different from both men’s and women’s brains.

The authors suggest that the differences they found between trans women and cis people’s brains are related to body perception.

They conclude:

“The present data do not support the notion that brains of MtF-TR are feminized. The observed changes in MtF-TR bring attention to the networks inferred in processing of body perception.”

The study only looked at trans women who were attracted to women. This is both a strength and a limitation of the study.

It is a strength because it avoids confusion between gender identity and sexual orientation. Many recent studies have compared trans women attracted to men to men attracted to women; if you find a difference between the two groups, you can’t be sure if it is due to sexual orientation or gender identity.

This study, however, compared trans women attracted to women with men attracted to women and women attracted to men.

This is also a limitation because it is extremely unrepresentative of trans women. About half of trans women are attracted to men, much more than in the general population. If we want to understand how gender dysphoria works, we need to look at both groups of trans women.

A study looking at just trans women attracted to women was necessary, but clearly we need some follow-up research. Is this result true for trans women who are attracted to men? How do these results compare to cis gay men’s brains?

You can stop here if you want. You now know the main result of the study.

On to the specifics of the study. What exactly did they find?

Ways trans women’s brains were like men’s brains

1. Total brain tissue volume was smaller in heterosexual women (HeW) than in heterosexual men (HeM)  and gyenephillic male to female transsexuals (MtF-TR).*

(Gyenephillic=attracted to women.)

2. Total intracranial volume was smaller in HeW than in HeM or MtF-TR. There was no difference between the groups in total white matter volume or total gray matter volume when you took into account the total intracranial volume.

3. HeM had a larger gray matter volume than HeW in the lingual gyrus, the cerebellum, right putamen, and left amygdala and perirhinal cortex. HeW had larger gray matter and white matter volumes in the precentral gyrus.

None of these differences were reproduced when comparing HeM to MtF-TR.

4. HeW had larger hippocampi compared to both HeM and MtF-TR, mostly due to the left hippocampus. There was no difference between HeM and MtF-TR.

5. HeM and MtF-TR had rightward assymetries in the brain; HeW did not. Specifically:

a. the volume of the right hemisphere was larger than the left for HeM and MtF-TR, but not for HeW;

b. the volume of the thalamus was significantly larger in the right hemisphere for HeM and MtF-TR, but not for HeW – however, there was no significant differences in the groups’ assymetry indices (volume of right side/volume of left side).

c. the volume of the hippocampus was significantly larger in the right hemisphere for HeM, but not for HeW. The volume was also larger for MtF-TR, but this was not statistically significant – although the p-value was 0.065, so it was close. However, the differences in assymetry indices between MtF-TR and HeW and between HeM and HeW were significant.

Ways trans women’s brains were different from cis people’s brains

1. MtF-TR had larger gray matter volumes than either HeM or HeW in the “right temporo-parietal junction (around the angular gyrus and in the posterior portion of the superior temporal gyrus)**, and right inferior frontal and insular cortex.”

2. MtF-TR had a smaller gray matter volume than either HeM or HeW in the thalamus.

3. MtF-TR had smaller thalamuses and putamens than either HeM or HeW; this was a measurement of the regional structural volume. There was no difference between HeM or HeW.

Areas where they found no differences between the groups

1. There were no group differences in the caudate volume.

2. There was no assymtery in the caudate or putamen.

What does all this mean?

First, it does look like the authors are right; the trans women’s brains were more like men’s than women’s. It is possible that trans women’s brains are like women’s brains in some other way than the ones the authors looked at. Nevertheless, the similarities to men’s brains found in this study are fairly large.

What is perhaps, more interesting, is the ways that the trans women’s brains were different from cis people’s brains, whether they were male or female.

The authors of the study point out that these are new findings and they need to be confirmed with larger studies. “Any interpretation must, therefore, proceed cautiously and can at this point only be highly speculative.”

The authors go on to suggest that their findings might be related to own body perception. As they point out, one of the main symptoms of gender dysphoria is discomfort with your own body. Some studies suggest that the areas of the brain where trans women were different from cis men and women could be part of a network involved in own body perception.

Of course, as in other studies, the parts of the brain involved in this study have multiple functions. For example, the angular gyrus is also involved in language, math, and memory retrieval. So we can’t be sure exactly what it means that trans women have a larger volume of gray matter in those areas.

On the other hand, people with gender dysphoria don’t have problems with language and math, they have problems with dysphoria about their bodies.

More surprisingly, the authors of this study suggest that people with gender dysphoria may have changed their brains by constantly thinking about their bodies. This is possible, but it seems more likely to me that the problem starts with something in the brain causing people to feel uncomfortable with their bodies.

Here is the author’s argument from their conclusion:

“There is no evidence that this feeling [gender dysphoria] is caused by a general sensory deficit in transsexual persons…Several studies propose that own body perception involves networks in the temporo-parietal, inferior parietal cortex, the inferior frontal, and insular cortex, and their connections with the putamen and thalamus. Thus, theoretically, the experience of dissociation of the self from the body may be a result of failure to integrate complex somatosensory and memory processes executed by these networks.

Such disintegration accords with the present findings and could, perhaps, explain recent observation of poorer parietal cortex activation during a spatial orientation task in MtF-TR compared with male controls.

However, it is difficult to explain how such disintergration can be linked to a dysphoria restricted to the own body’s sex characteristics.

Moreover, even if a link exists, it is uncertain whether the here observed morphometric features in transsexual patients underpin their gender identity or are a consequence of being transsexual.

One highly speculative thought is that the enlargement of the GM volume in the insular and inferior frontal cortex and the superior temporal-angular gyrus could derive from a constant rumination about the own body. Brain tissue enlargement has been detected in response to training, and GM enlargement of the insular cortex has been reported in response to meditation, which involves mental focusing on the own body.”

The authors also point out that it might be that something else is causing both gender dysphoria and changes in neuroanatomy.

They stress that we can’t directly connect changes in gray matter volume to effects on the person.

They point out that they did not look at the hypothalamus, so their findings do not contradict earlier studies of it.

Finally, they call for more research, including research which compares trans women attracted to men to trans women attracted to women, and trans women attracted to men to cis gay men. (Yay!)

“Furthermore, they [the results] were generated exclusively from investigations of nonhomosexual, gynephillic MtF-TR. The issue of possible cerebral difference between gynephillic and androphillic (homosexual) MtF-TR and also between androphillic MtF-TR and homosexual healthy men is of special interest and needs to be addressed separately in future studies. Additional studies of the relationship between brain structure and function in transsexual persons and also extending the material to female to male transsexuals are necessary to more precisely interpret the present observations.”

The bottom line: we need more studies confirming these results. Is there a link between gender dysphoria and the network involved in own body perception? If so, which is the cause and which is the effect? Do these results hold true for trans women who are attracted to men? What about trans men?

There were two results the study did not discuss. It may not mean anything, but I think it is worth mentioning.

1. The volume of the amygdala was larger in HeM than HeF; this fits with other studies of sex differences in the brain. For MtF-TR, their amygdalas seems to have been neither bigger nor smaller than males or females. (Table 3)

2. The subcallosum (BA 24, 32) was larger in HeF than HeM. This fits with a study the authors cite showing that women have larger anterior cingulate gyri – the anterior cingulate cortex includes Brodmann Areas 24 and 32. This area seems to have been neither larger nor smaller in MtF-TR.

According to the authors: “Although sex differences have been described also in the amygdala and cingulate gyrus, these structures were not included in the analysis because the identification of anatomical landmarks in these regions is less reliable, especially when using a 1.5-T scanner.”

In other words, they think there could have been an error in the results. Either there was no sex difference in those areas, or they failed to detect differences between trans and cis women in those areas.

Another possibility is that trans women and cis women were not different in those areas because trans women’s volumes were intermediate between cis men’s and cis women’s.

If this is so, there are many possible explanations. It might have something to do with sex hormones, although it is hard to see why trans women’s brains would have developed like cis men’s in most parts of the brain if they weren’t exposed to sex hormones. You would have to assume that there was something different about how their amygdala and cingulate gyrus responded to sex hormones.

Another possibility is that trans women’s amygdalas were as large as men’s amygdalas, but something made them shrink.

Studies have linked a smaller amygdala to obsessive-compulsive disorder (OCD), anxiety, PTSD, sociopathy, and early life stress (abuse, neglect, or poverty). [Click through to see the studies.]

Trans people have higher rates of anxiety than other groups, but this study excluded people with any psychiatric disorders.

Trans people also suffer higher rates of abuse and trauma than most people which might have affected their amygdalas.

A final, hypothetical possibility might be that gender dysphoria is in some way related to OCD.

In the case of the cingulate gyrus, we would have to assume that something happened to trans women’s brains to make the volume of their cingulate gyrus increase to be intermediate between cis women and cis men. This is harder to understand, since OCD, anorexia, and body dysmorphic disorder are all correlated with decreases in the size of the anterior cingulate cortex.

However, there is one study suggesting that a large right anterior cingulate “is related to a temperamental disposition to fear and anticipatory worry.” No doubt the experience of being transgender in our society causes people to worry and feel fear; perhaps this changes the brain. Alternatively, it might be that a tendency to worry is somehow linked to developing gender dysphoria.

Original Study:

Sex Dimorphism of the Brain in Male-to-Female Transsexuals by Savic I, Arver S. in Cereb Cortex. 2011 Nov;21(11):2525-33.

A few fun facts:

You can induce out-of-body experiences by stimulating either the temporo-parietal junction or the angular gyrus. (Read more here and here).

The right temporo-parietal junction is also involved in thinking about thoughts. It, or an area close to it, is involved in directing your attention. (Read more here and here.)

The superior temporal gyrus is involved in recognizing your own face, identifying emotions in other people’s faces, and social cognition.

Information about the self may be processed in the right hemisphere; however, not everyone agrees on this theory. (Read more here.)

Increased volume in the left inferior frontal gyrus and right amygdala are associated with worse symptoms in body dysmorphic disorder. The trans women in this study had increased volumes in the right inferior frontal gyrus only. This does, however, suggest that these areas of the brain are important to perceptions of the body. (Read more here.)

*I am using the language of the study now.

** The original text refers to the superior temporal gurus. A cool idea, but probably a typo.

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.

The microstructure of white matter in male to female transsexuals before cross-sex hormonal treatment. A DTI study – Review

This study compared the white matter in the brains of males, females, and 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.

MtF transsexuals were similar to males, not females, in the volume of gray matter, white matter, and cerebrospinal fluid in their brains.

In five fasciculi (bundles of nerve fibers), MtF transsexuals had white matter that was different from both males and females. MtF transsexuals’ white matter microstructure pattern fell halfway between the pattern of male and female controls.

The study does not say if there were any other ways in which MtF 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 MtF 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 MtF transsexuals were all sexually attracted to males while the males were all attracted to females and the females were all attracted to males.

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 volumes of gray matter and white matter in the brain as well as the volume of cerebrospinal fluid (CSF); males have larger volumes than females. They found that the MtF transsexuals had volumes similar to the males and significantly different from the females. In this respect, MtF transsexuals have brains more like male’s than female’s.

The study also find sex differences in the fractional anisotropy (FA) values of white matter in six bundles of nerves with males having a higher FA value. The white matter structures with a higher FA value were the left and the right superior longitudinal fasciculus, the right inferior front-occipital fasciculus, the left cingulum, the forceps minor, and the corticospinal tract.

An earlier, related study of white matter in FtM transsexuals found a sex difference in the white matter in three of the same bundles of nerves: the right superior longitudinal fasciculus, the forceps minor, and the corticospinal tract. They did not report a sex difference in the left superior longitudinal fasciculus, the right inferior front-occipital fasciculus, or the left cingulum. (The earlier study was done by the same people using the same methodology but different control groups.)

In five of these six nerve bundles, the MtF transsexuals had white matter that was significantly different from both males and females. Their FA values fell in-between the values for males and females. In the inferior frontooccipital fasciculus their FA values were also different, but the difference was not statistically significant.

What does this mean?

First of all, it is important to note that for three of the six nerve bundles, the sex difference was not found in another closely related study. It may be that only the sex differences in the right superior longitudinal fasciculus, the forceps minor, and the corticospinal tract are real. The authors do not address this question (they should have).

In any case, the authors conclude that “the white matter microstructure pattern in untreated MtF transsexuals falls halfway between the pattern of male and female controls. The nature of these differences suggests that some fasciculi do not complete the masculinization process in MtF transsexuals during brain development.”

There are other possible explanations, however:

1. MtF transsexuals who are attracted to males might have had different experiences from both males and females. For example, they might have played soccer more than most girls but less than most boys. Similarly, the observed sex differences might have been caused by differences in experiences for girls and boys. This article argues that the superior longitudinal fasciiculus is changed by musical expertise.

2. MtF transsexuals might have had fasciculi 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. In this model, a lower FA value for females could be due to sex differences, while the lower value for MtF transsexuals might be due to later problems damaging the white matter.

3. There might be two completely separate pathways that cause males and MtF transsexuals to have higher FA values than females – or that cause females and MtF transsexuals to have lower FA values than males.

4. There might be some other confounding variable like left-handedness that affects white matter. The authors do not say if their subjects were right- or left-handed, but transsexuals are more likely to be non-right-handed than the general population.

5, The differences in the white matter in different nerve bundles might have different causes. For example, males might have a higher FA value for white matter connecting the brain to the spinal column due to playing sports, while their white matter in another region was affected by hormones.

We can’t conclude anything about what it means that the MtF transsexuals had FA values between males and females. We don’t know what caused the differences. What we do know is that MtF transsexuals were different from both males and females.

We also don’t know what the sex differences they found mean at a practical level.

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

Superior longitudinal fasciculus (right and left) – 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. An earlier study only found a sex difference in the right superior longitudinal fasciculus.

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.

Inferior fronto-occipital fasciculus (right) – a nerve bundle that goes from the frontal lobe along the caudate nucleus and corona radiata, it also goes into the occipital and temporal lobes. One of its functions is to integrate auditory and visual association cortices with the prefontal cortex.  An earlier study by the same authors did not find a sex difference in this fasciculus. This is also the nerve bundle that was not significantly different for MtF transsexuals.

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

Cingulum (right) – a collection of white matter fibers that go from the cingulate gyrus to the entorhinal cortex. One of its functions is to integrate executive function nuclei. It allows the parts of the limbic system to communicate with each other. The limbic system is involved in emotion, behavior, motivation, long-term memory, and the sense of smell. An earlier very similar study did not find a sex difference in the cingulum.

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, nerves that go from the front lobe into the occipital and temporal lobes, nerves that connect the brain to the spinal column, and nerves that connect the parts of the limbic system.

The difference does not seem to be related to any particular part of the brain.

The difference was found mostly on the right side of the brain. Does this mean anything?

If we only include the sex differences that were found in both this and the earlier study of FtM transsexuals, all of the sex differences were on the right side of the brain. We would still be looking at nerves that connect the front and back of the brain, nerves that connect the two hemispheres, and nerves that connect the brain and spinal cord.

It’s hard to predict how a difference in so many parts of the brain would affect men’s and women’s cognitive abilities and personalities.

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

They 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 of the study don’t see it that way. They try to connect what they’ve found to sex differences in spatial abilities and verbal fluency, because the superior longitudinal fasciculus “connects complex cortical regions that subserve higher cognitive functions.” The problem with that logic is that there are a lot of cognitive functions being processed in the cortex.

I think they are overreaching a great deal there.

Anyhow, here is part of their discussion of their results and how they relate to the brain:

“MtF transsexuals differed from male and female controls in the right and the left superior longitudinal fasciculus. The SLF connects complex cortical regions that subserve higher cognitive functions and that are sexually dimorphic. Sex differences in cognition are consistently found in spatial abilities and verbal fluency ( Kimura, 1999); males outshine females in the former but the females outshine males in the latter. It has been reported that the performance of untreated MtF transsexuals in mental rotation tasks is consistent with that of their biological sex ( Haraldsen et al., 2003 Slabbekoorn et al., 1999 ). Schöning et al. (2010) studied spatial cognition using fMRI and found that untreated and treated MtF transsexuals had increased activation in the temporo-occipital regions and decreased activation in the left parietal lobe compared to control men. We have investigated brain activation during mental rotation in chronically hormone treated MtF transsexuals. These MtF transsexuals present less activation than male controls in the superior parietal lobe (Brodman’s area 7) and higher activation than females in the superior part of the gyrus frontalis (Brodman’s area 9) ( Carrillo et al., 2010). Interestingly, these two cerebral regions are connected by the SLF ( Makris et al., 2005Hua et al., 2009 ).

We found significant differences between MtF transsexuals and male and female controls in the forceps minor and the anterior region of the cingulum, both in the right hemisphere. The forceps minor connects orbitofrontal regions ( Park et al., 2008) and the cingulum is an associative bundle that runs from the anterior temporal gyrus to the orbitofrontal cortex ( Catani and Thiebaut de Schotten, 2008) and both form part of the emotional networks ( Kober et al., 2008 ). There is evidence that the orbitofrontal cortex and anterior cingulate cortices are involved in reinforcement processing and the reward value of reinforcers and punishers ( Cohen, 2008 Kringelbach and Rolls, 2004 ). Moreover, it has been suggested that the anterior cingulated cortex relates current information with an extended history of reward ( Walton et al., 2007).

The FA values of the corticospinal tract in MtF transsexuals also differed from male and female controls. Studies performed in non-human primates ( Lemon, 2008) have shown that this tract is a descending motor pathway originated from several cortical regions (primary motor cortex, premotor cortices, supplementary motor area and cingulate motor area, primary somatosensory cortex, posterior parietal cortex and the parietal operculum). Limb movements that require a high degree of skill and flexibility are controlled by these motor fibers. Lesions of this tract affect fine sensoriomotor function of the hand ( Lemon and Griffith, 2005). The maturation of the corticospinal tract depends on motor experience and genetic factors ( Cheeran et al., 2009 Martin et al., 2007).”

 

Original Article:

The microstructure of white matter in male to female transsexuals before cross-sex hormonal treatment. A DTI study by Rametti G, Carrillo B, Gómez-Gil E, Junque C, Zubiarre-Elorza L, Segovia S, Gomez Á, Guillamon A. in J Psychiatr Res. 2011 Jul;45(7):949-54. 

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

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

Regional gray matter variation in male-to-female transsexualism – Review

This article found that trans women’s brains are more similar to men’s brains than cis women’s brains, at least in terms of the pattern of gray matter variation.

They also found that trans women’s brains had more gray matter in the putamen than both cis men and cis women, although the difference was only significant for cis men.*

The authors found 20 areas of the brain where women had more gray matter than men. The male-to-female transsexuals (trans women) had the smallest volume of gray matter in these areas, but their data spectrum mostly overlapped with the men’s.

In two areas of the brain, the left and right putamen, male-to-female transsexuals had the largest volume of gray matter.**

“…the gray matter volume of this particular structure in the MTF transsexual group was both larger than in males and within the average range of females.”

Gray matter, in case you’re wondering, contains more neuronal cell bodies. White matter is mostly made up of axons that transmit signals within the brain. Previous studies have found that there are sex differences in the distribution of gray matter in the brain.

The authors describe the putamen as being “feminized” in MTF transsexuals. That might be, but it might also be that their putamens are simply different from cis people’s for some other reason.

In addition, the putamen has more gray matter in women than in men, but the trans women’s putamens had more gray matter than either, although the difference between trans women and cis women was probably not significant.**

The authors conclude:

“Overall, our study provides evidence that MTF transsexuals possess regional gray matter volumes mostly consistent with control males. However, the putamen was found to be “feminized” in MTF transsexuals….”

“Taken together, these findings lend support to the hypothesis that specific neuroanatomical features are associated with transsexual identity, where the particular role of the putamen requires investigation in future studies.”

The study results also support the idea that trans women’s brains are more similar to men’s brains than to cis women’s brains. Most of the time when men’s and women’s brains differ, the trans women’s brains were like men’s.

In addition, the authors briefly mention a few areas where women’s and men’s brains were similar, but trans women’s brains were different from cis women’s (see details of study below).

On the other hand, we definitely need more studies of the putamen and gender dysphoria.

As the authors point out, we do not know if the differences in the putamen are the cause or result of gender dysphoria – or if the differences are caused by another factor that also causes gender dysphoria.

It is also possible that the observed differences are caused by sexual orientation, not gender identity. The authors explain that their sample included 6 male-oriented people (25%) and 18 female-oriented people (75%). They did not know the sexual orientation of their control groups, but it is likely that 95% of the males were attracted to females and 95% of the females were attracted to males.

Their sample also included more left-handed people than the control groups. It is possible that handedness affects the size of the putamen in some way.

Another huge issue is that we have no flipping idea what the results mean. The putamen is an area of the brain that is believed to be involved in many different functions including motor skills, memory, and processing sensory information. If it is involved in gender dysphoria, we need studies to figure out how.

Hopefully we will see some studies confirming this result, this time with a control group that includes gay men and lesbians. The study should also control for handedness.

Then we will need more studies looking at exactly what is going on.

Original Article:

Regional gray matter variation in male-to-female transsexualism by Luders E, Sánchez FJ, Gaser C, Toga AW, Narr KL, Hamilton LS, Vilain E. in Neuroimage. 2009 Jul 15;46(4):904-7.

Some details of the study:

The authors looked at 24 trans women recruited through the community organizations and professionals who serve trans people. Their average age was 43 (range 23-72). They were genetic males (they had the SRY gene),*** they were free of psychoses, and they passed a physical and neurological exam. 76% of them were right-handed, compared to 90% or more of the controls.

None of them were on hormones, although they all intended to take them.

More about the results:

“females had more gray matter than males in large portions of the brain… Similarly, females had more gray matter than MTF transsexuals… Although the differences between females and MTF transsexuals did partly overlap with the difference between females and males…, they were spatially more extended, and also evident in a few regions where females and males did not differ… There was no region where females had significantly less gray matter than males… or MTF transsexuals… Similarly, there was no region where MTF transsexuals had significantly less gray matter than males… MTF transsexuals, however, showed significantly more gray matter than males in the right putamen… MTF transsexuals also showed significantly more gray matter than males in the left putamen when findings were not corrected for multiple comparisons (p<0.001, maps not shown).”

I am intrigued by the mention of a few regions where females and males did not differ but females had more gray matter than MTF transsexuals. I wish the authors had discussed these areas. Perhaps they would shed some additional light on gender dysphoria.

*The box plot data on the trans women’s putamen looks pretty different from the cis women’s data. Their median value is higher and their range seems to be much bigger and go up higher. However, the difference is probably not significant since the authors say elsewhere that there was no area where females had significantly less gray matter than trans women.

** It may be that the difference was only statistically significant in the right putamen. Elsewhere in the study the authors say that trans women had significantly more gray matter than males in the left putamen only when the findings were not corrected for multiple comparisons. Because brain scans involve collecting so many data points, the chances of finding correlations by chance are much greater. Thus you have to make corrections. On the other hand, in this case, the other half of the putamen was different at a stastically significant level.

*** Zoe Brain has pointed out that someone could have the SRY gene, but still have unusual chromosomes, if they had Kleinfelter’s syndrome (47xxy) or mosaicism (46xx/46xy). Her interpretation of this study is quite different from mine, but well worth reading.