White Matter Differences in Pre-Op Transsexuals Should NOT be the Basis for Childhood Interventions
Diagram showing principal systems of association fibers in the human brain. The superior longitudinal fasciculus (SLF) is labeled at the center top (marked by purple arrows).
New Scientist covered two journal articles by Rametti and colleagues (2010, 2011), a group of Spanish researchers and clinicians affiliated with Unidad Trastorno Identidad de Género [Gender Identity Disorder Unit]. Using the diffusion tensor imaging (DTI) method, they initially wanted to identify any sex differences in the white mater of the brains of non-transgendered male and female heterosexuals. Then the next step was a prediction that FTM (Female-to-Male) transsexuals would be more like males, while MTF (Male-to-Female) transsexuals would be more like females.
Transsexual differences caught on brain scan12:16 26 January 2011 by Jessica HamzelouIn 5 years of writing this blog, I have come across a multitude of news stories and press releases that make outrageous claims. Here's another one to add to the list. On the basis of two highly variable DTI studies in 36 pre-operative, pre-hormone treatment transgender individuals, now we're supposed to screen children for gender variant behavior and scan them at a young age, so their hormones can be altered before puberty?
Differences in the brain's white matter that clash with a person's genetic sex may hold the key to identifying transsexual people before puberty. Doctors could use this information to make a case for delaying puberty to improve the success of a sex change later.
Returning to the structural imaging experiments, were there any hypotheses at the outset, or were these completely exploratory studies? The authors cite the work of Zhou et al. (1995) on postmortem staining of the bed nucleus of the stria terminalis (BST). This subcortical nucleus connects the amygdala to the septal nuclei, hypothalamus, and thalamus. BST has been shown to play a role in the sexual behavior of male rats. The size of this nucleus in MTF brains was similar to that in female controls, both being smaller than male controls.
However, it's not possible to visualize the BST in living humans, so the authors went with DTI to look for cortical white matter changes. The participants in the first study were 18 FTM transgendered persons (before undergoing hormonal treatment), along with 24 male and 19 female heterosexual controls. The major findings in terms of sex differences between groups were located mainly in 3 fiber tracts:
- anterior and posterior parts of the right superior longitudinal fasciculus - contains connections between the frontal, parietal, occipital, and temporal lobes including language-related areas (Mori et al., 2008).
- forceps minor (anterior forceps) - fiber bundle connecting the lateral and medial surfaces of the frontal lobes, crossing the midline via the genu of the corpus callosum.
- corticospinal tract - connects the cerebral cortex and the spinal cord, contains mostly motor axons.
Fig. 1 (Rametti et al., 2010). Sex differences in fractional anisotropy (FA). FA is lower in female than in male controls in the superior longitudinal fasciculus with a posterior (A) and anterior (B) predominance. Control females also show lower than control male FA values in the forceps minor (C) and the corticospinal tract (D). The group skeleton used for the between group contrast study is green. The red color shows the clusters of significantly decreased FA in female compared to male controls. The threshold for significance was set at p < 0.05 corrected for multiple comparisons.FTM individuals showed greater FA values in all 3 tracts than did the control females. They were similar to control males for anterior and posterior SLF and forceps minor, and in between control male and female FA values for the corticospinal tract.
What does this mean? Basically, at this point, it's like reading tea leaves. We have no indication of other potential differences between the groups in cognitive, emotional, personality, or motor measures, in alcohol use, or in other psychiatric diagnoses. We do know that testosterone levels of the FTM participants were like those of control females, because they had yet to undergo hormone treatment.
Moving right along to the second experiment, which compared MTF individuals to controls (Rametti et al., 2011)... The participants were 18 untreated MTF transsexuals (mean age = 25 yrs), 19 female (mean = 33 yrs) and 19 male controls (mean age = 32 yrs). Yes, the MTF individuals were significantly younger than controls [the human frontal lobe in particular is known to continue maturation processes into the 20's]. Procedures were similar to those used previously. Results in this study showed a greater number of differences in the white matter of male vs. female controls (again, with larger FA values for males):
- left and the right SLF
- forceps minor
- right inferior front-occipital fasciculus (IFOF)
- corticospinal tract
- left cingulum
Nonetheless, what did that comparison show? The MTF individuals showed FA values between those of male and female controls for all tracts (except for IFOF, where they did not differ from males).
Fig. 2 (Rametti et al., 2011). Histograms showing the FA means between control females (black), male to female transsexuals (MtF) (red) and control males (green). MtF transsexuals significantly differed from female and male controls in almost of all the fascicles in which control males differed from control females. (*At least p < 0.01).So the MTF participants showed an intermediate pattern, but FTM individuals were more like biological males. The authors state:
Considering the present work and the data available in the literature, what can we say of the brain of MtF transsexuals? Most importantly, we would suggest that MtF transsexuals do not show a simple feminization of their brain –rather, they present a complex picture in which feminization and incomplete masculinization are present depending on the brain region studied and the kind of measurements taken.So don't scan your little football-playing tomboy or haute couture-loving son just yet...
In the end, I don't doubt that there are differences between the brains of transgendered and non-transgendered people. But these two DTI studies1 do not provide a rationale for initiating treatments in young children.
For an interesting perspective on these studies in relation to gender identity and sexual orientation, I highly recommend Seeing the world in Grey and White…
Footnote
1 I haven't even mentioned criticisms of the DTI technique in general...
References
Mori S, Oishi K, Jiang H, Jiang L, Li X, Akhter K, Hua K, Faria AV, Mahmood A, Woods R, Toga AW, Pike GB, Neto PR, Evans A, Zhang J, Huang H, Miller MI, van Zijl P, Mazziotta J. (2008). Stereotaxic white matter atlas based on diffusion tensor imaging in an ICBM template. Neuroimage 40:570-82.
Rametti, G., Carrillo, B., Gómez-Gil, E., Junque, C., Segovia, S., Gomez, Á., & Guillamon, A. (2011). White matter microstructure in female to male transsexuals before cross-sex hormonal treatment. A diffusion tensor imaging study Journal of Psychiatric Research, 45 (2), 199-204 DOI: 10.1016/j.jpsychires.2010.05.006
Rametti, G., Carrillo, B., Gómez-Gil, E., Junque, C., Zubiarre-Elorza, L., Segovia, S., Gomez, Á., & Guillamon, A. (2010). The microstructure of white matter in male to female transsexuals before cross-sex hormonal treatment. A DTI study Journal of Psychiatric Research DOI: 10.1016/j.jpsychires.2010.11.007
Zhou JN, Hofman MA, Gooren LJ, Swaab DF. (1995). A sex difference in the human brain and its relation to transsexuality. Nature 378:68-70.
Coda:To celebrate the 5 year anniversary of this blog, here are the other entries from Jan 27/28:
2006: Men are Torturers, Women are Nurturers...2007: Gambling On Obscurity2008: Cost of the War in Iraq2009: Voodoo Gurus2010: Mirror Neurons and Magical EFT Therapy Bears
Thanks for reading!
posted by The Neurocritic @ 2:34 PM
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Rationale according to the New Scientist: “Doctors could use this information to make a case for delaying puberty to improve the success of a sex change later.”
Your assessment of the conclusions: “But these two DTI studies do not provide a rationale for initiating treatments in young children.”
I have not read the studies, but based on what you quoted from the New Scientist the goal would not be so much to initiate treatments in young children as to delay major decisions until the children are adults.
Sex reassignment should work best when performed when the individual is young and hasn’t fully developed the secondary sexual characteristics of the wrong sex. Most people feel extremely uncomfortable with the idea of an immature person undergoing this type of major elective surgery, even if they are begging for it. On the other hand, denying it to them so that they can make their own decision at the age of majority may just be delaying the inevitable long enough to guarantee it won’t be very successful.
My interpretation of their rationale is that if your fourteen-year-old is begging you for sex-reassignment surgery, you can have them scanned. If they are clearly transgender according to the scan (not just gay, for instance), then they can be prescribed hormone suppressants to delay puberty until they are old enough to make the surgery decision for themselves.
In this way, parents can buy themselves some time to make a major decision — both saying yes and saying no could have serious consequences if it’s the wrong decision.
I probably agree with you that the results of the studies are not sufficient to guide this decision. A clear shortcoming is that they didn’t scan lesbians or gay men to see whether they were distinguishable from gender-dysphoric people.
Distinguishing the gender-typical from the gender-less-typical is not the issue: if your child were gender-typical they would not be clamouring for sex reassignment. It might be obvious that one’s child is not gender-typical, but that’s not sufficient information. You might have an unhappy teenager who will grow up into a perfectly happy dyke, but who has decided in the meantime that the problem is that she is really a man. So these studies showing that gender-typical people’s brains are different from gender-dysphoric people’s brains are of absolutely no help at all.
What you want to know is whether an FTM’s brain scan looks clearly different from a lesbian’s brain scan, and whether an MTF’s brain scan looks clearly different from a gay man’s brain scan. If you had that imformation it might help you decide whether surgery is likely to turn out to be a good idea and whether time should be bought to think about it. But these studies do not provide that information.
Alison,
Thanks for your thoughtful comments. The thing about the NS article that I found speculative and alarming was the "delaying puberty" part. Average onset is 10 for girls and 12 for boys. These children would undergo treatment to block the release of sex hormones, which is controversial.
Compared to the NS article, one of the lead scientists is much more circumspect that DTI would be useful in identifying young trans children:
Guillamon thinks such scans may not help in all cases. "Research has shown that white matter matures during the first 20 to 30 years of life," he says. "People may experience early or late onset of transsexuality and we don't know what causes this difference."
So I think we're all in agreement there.
Since I'm not an expert in trangender issues, I still recommend Seeing the world in Grey and White…
Very interesting post. Like many of the papers you cover, this one makes you wanna SCREAM!!!
You find the delaying of puberty to be alarming?
I would guess that if your body started to produce hormones to cause you to grow breasts and hips and to menstruate, you'd find that even more alarming. Yet, that's what transgender children are often faced with.
I agree that a scan should not be necessary for a transgender child to get treatment. If you read up on this issue from the POV of actual transgender people (and I suggest you do), you will find that there is very little subjective ambiguity as to whether a teen is transgender. To require a kid to get a brain scan to prove that what they are going through is legitimate is appalling.
Delaying puberty via hormones is a recent development, and it is welcome by transgender (not transgenderED) people, who are given at least some time to develop their own identity and autonomy before their bodies go through difficult-to-reverse changes.
Delaying puberty
Not an expert, go to the source - It would be helpful for the readers if you provided a link to the source that describes the welcoming attitude of many transgender people to the delay of puberty with hormones. Thanks.
Transgender Issues 101: transgender or transgendered?
by Matt Kailey
. . .
Today’s 101 deals more with word usage than word meaning — but usage can be just as important, if not more so.
One of the best things about the trans community is that it is not a monolith. Our community is incredibly diverse, and because of this — surprise — we don’t always agree.
And that, I believe, is a strength.
One thing we do not agree upon is the “ed” at the end of transgender.
I have always used the term “transgendered” as an adjective to refer to a person whose gender identity (how that person sees him- or herself in terms of male or female) does not agree with his or her physical body — a transgendered person.
This has been (and will always be) my preferred usage, for a variety of reasons.
However, there are many others who prefer the term “transgender” — a transgender person.
While the difference may seem small, it is meaningful to many of us, and I have spoken to people on both sides of the issue who have very strong feelings about the matter.
But the fact is that “transgender person” has been determined to be the officially correct usage and is the recommended usage in the Gay & Lesbian Alliance Against Defamation (GLAAD) Media Reference Guide. (GLAAD is an incredible organization, by the way, and anyone not familiar with them should check them out. They are an essential part of the LGBT community and work tirelessly for us every day.)
As a member of the media, I have been aware of this recommended usage for quite some time — since the guide was decided upon and printed. I simply have a little bit of a rebellious streak in me.
Both terms are still used by different individuals who prefer one over the other, and for those of you who are new to this topic, you should not consider these two words as different concepts. They are simply different forms of the same word.
But some people who prefer the term “transgender person” can find the use of “transgendered person” to be very offensive. And for this reason, going forward, I will be using the term “transgender person” in my articles.
These don't encompass all that I've read from/about transgender folks, but I think they provide what you are looking for:
http://www.iwanttobeagirl.org/hormone-blockers-trans-girls-nhs.html
http://destrantalk.blogspot.com/2010/04/thanks-to-parents-of-transgender-youth.html
http://www.advocate.com/article.aspx?id=22195
http://www.dailykos.com/story/2010/8/29/895824/-Who-We-Are-And-Why:-Transgender-Science
http://www.secondtype.info/young.htm
To suggest that a decision about delaying puberty would be made solely as a result of a brain scan is not sensible at this stage. For it might be considered that the child in question should have a say in the matter. The implications of such brain scans would however certainly seem to be an avenue which should be further researched.
You may find you you obtain a more rounded picture of this issue by reading this paper:
Transgender children: more than a theoretical difference
http://www.gjss.org/images/stories/volumes/7/2/3.%20Kennedy%20and%20Hellen.pdf
Certainly the opinion of trans people on delay of puberty is relevant - and in my experience and conversations (as a trans man who's active in both local and online trans communities), I think the majority of trans people consider the potential availability of delayed puberty an amazing tool for questioning youth. And certainly, no small number of us wish that such an option had been available in our own childhoods.
However, it would also be interesting (though likely far more difficult to survey) to know how former gender questioning youth who wound up identifying with their assigned gender think of the idea. (I know a couple people who might fit in this category who still think it could be a useful tool.)
Far more divisive, certainly, in trans communities is the opinion on etiological research on trans people. If transsexuality could be objectively tested, would we be further discriminated against? Would attempts be made to cure us? What if you are trans but fail to test positively as trans? Would you be denied access to hormones/surgery? I think it has the potential to be fascinating, personally (if so much of the research didn't display a questionable understanding of trans experiences...), but I understand others' concerns.
@Alison - while you are correct that comparing trans people to heterosexuals would only give part of the picture, you're making a similar oversight - the orientation of the trans people. There are gay, lesbian, bisexual and queer trans people (I should know - I am one ;).
Interesting subject. I was totally ignorant in the topic until you brought it up.
Happy anniversary!!! and please keep writing. It is always informing to read you and the comments your posts generate.
I'd just like to respond to your footnote in which you say that you "haven't even mentioned criticisms of DTI in general" and link to an article critiquing probabilistic tractography analyses of DTI data. I'd like to note that, just as there are multiple ways to analyze fMRI data (all with limitations, but some pretty rigorous, some middling, some appalling), there are multiple ways to analyze diffusion tensor data.
Probabilistic tractography is one of the "fuzzier" methods; however, it's not the one used here. This group used FSL's TBSS (Tract Based Spatial Statistics), which is a more rigorous approach. Because group-level analyses of differences in white matter can be complicated by individual variability in the structure of tracts, TBSS first aligns subjects' FA images to a common space and then extracts only the aligned centers of these tracts for use in statistical analyses. Creating this "mean FA skeleton" reduces the likelihood that differences identified in voxelwise analyses are due to comparison of non-equivalent regions. You can then run a nonparametric two-sample t-test on the skeletons for the different groups (FSL lets you do this using permutation methods). Thereafter, you can back-project regions identified as having significantly differing FA values (at the group level) into individual subject space and look at the original location of the skeletonized voxels for each participant. This final step can provide a nice check for any individual-level funkiness in the data disguised by the group-level approach.
I agree with you that probabilistic tractography is a relatively "squishy" technique -- more exploratory -- it's not what's in play in this study.
In response to:
Neurocritic: These children would undergo treatment to block the release of sex hormones, which is controversial."
The link you posted here is a story about a doctor who provides these treatments. There's no discussion of any professional "controversy", only a brief use of the word in the interviewer's own commentary in the introduction. Quote:
Interviewer: So do groups say you should not do this treatment?
Dr. Norman Spack: There's been very little criticism. If anything, it's been totally opposite to what I expected.
So you and the interviewer both need to check your own knee jerk prejudicial responses: this treatment is not "controversial" just because it squicks you out.
My guess is that any controversy surrounding this treatment is among people who simply feel that trans identities are themselves controversial, instead of seeing them as one of several legitimate and almost-always life-long ways of relating to gender.
(& check out that Kennedy & Hellen (2010) paper SarahL linked to for the life-longness.)
Thanks to SarahL and Not an expert for the links, to Allison J for the clarification on probabilistic tractography vs. TBSS methods for analyzing DTI data, and to kami for the compliment.
Alex - I appreciate your perspective on the issue of delaying puberty. It's interesting too that you raised the issue of former gender questioning youth and what they might think of such treatment, given their ultimate decision to remain as their original gender.
Rebecca - I'd appreciate it if you don't make a knee jerk response of your own. You really have no idea about what "squicks [me] out."
If you scroll down further in the NPR article, you'll find a Q&A with Dr. Polly Carmichael:
"Carmichael is a psychologist at the Portman Clinic in London, where national guidelines say hormonal treatment of transgender teenagers should take place only after puberty. Carmichael has worked with dozens of kids with gender identity issues. In 2000, the Portman Clinic, which specializes in gender issues, published a study of all the children treated at the clinic who had been diagnosed with gender identity disorders. There were 124 children in all."
I understand that you have done a study of all 124 children who have gone through your clinic, and that 80 percent of those under 12 chose not to pursue sexual reassignment as adults. The kids who didn't continue — what were their reasons?
"It's very tempting to be looking for similarities that might predict it, but there's a very wide range. I can think of one [boy] who came first at 6 or 7 and we saw on a regular basis. And over that time, he felt more comfortable being the sort of boy he was: having female friends, being very theatrical. At first, he really wanted to wear pink — and the mother was torn between wanting her child to choose his own clothes and the teasing. That changed, and at a later stage he said he just felt OK as he was — that he still sometimes had those feelings, but he felt happy being a boy. And that's how he wanted to continue."
. . .
How do you feel about giving hormone treatments to young transgender individuals?
"There are debates to be had around the impact of giving hormone blockers at an early stage. One of the debates is, indeed, does one's own sex hormones have an impact on identity development in adolescence? So if one intervenes, is that affecting the final outcome? I think that's just one part of the debate, but important to debate."
Reproductive organs aren't the only thing that develop during puberty. Wouldn't delaying its onset have a huge effect on many body systems? Including the brain's development?
Anonymous of January 31, 2011 3:40 PM - I find it remarkable that you can speak for all 99 of those children...
I did not mean that every child was that way, I was just pissed off. But look at this: http://pn.psychiatryonline.org/content/38/14/32.full
"A. A strong and persistent cross-gender identification (not merely a desire for any perceived cultural advantages of being the other sex). In children, the disturbance is manifested by four (or more) of the following:
1.repeatedly stated desire to be, or insistence that he or she is, the other sex
2.in boys, preference for cross-dressing or simulating female attire; in girls, insistence on wearing only stereotypical masculine clothing
3.strong and persistent preferences for cross-sex roles in make-believe play or persistent fantasies of being the other sex
4.intense desire to participate in the stereotypical games and pastimes of the other sex
5.strong preference for playmates of the other sex"
I actually recall there being more than that, but maybe it's just my bad memory. But look at it! You have to fall under at least 4! The only thing that should be required for a diagnosis should be number 1, but the way this is set up assures that merely gender-nonconforming kids get slapped with the diagnosis (and not trans kids like myself who would have not fit 4 of those). That criteria seem perfect for picking up kids like the doctor mentioned, who sometimes think they would (eh, how do I phrase this?) "work" better as the other gender but then feel that that is not who they are. How different do you think his clinic's statistics would be if this criteria were less ...sexist?
It's also playing on the rather transphobic assumption that transgender people just wanna act/dress like the other gender which means that gatekeepers think your not really trans if you don't act like a walking stereotype of the other gender. I have heard of some clinics requiring dress codes or else you get sent away. But I digress...
You're absolutely right - I did not read the NPR article beyond my confirmatory bias. It's a well-founded confirmatory bias, however.
Even in the UK hormone blockers are considered best practice (according to the British Society of Pediatric Endocrinology & Diabetes, who are the folks who draft such things) in a situation where gender dysphoria is causing significant distress (so not based on white matter changes, sure, but still not controversial).
This is notable because these same guidelines specifically denied treatment for GID until after the completion of puberty (so this is the 2005 BSPED guidelines, which were themselves controversial, actually drafted by members of the Portman clinic [to which Polly Carmichael belongs, and which has a long history of doing involuntary things to intersex people], redacted in 2007, and revised in 2009 to include the use of hormone blockers at Tanner stage 2 [about 10-12 years old]) (Giordano, J Medical Ethics, 2008 - has most of this info, other stuff is on BSPED's website, Wikipedia for the Tanner stage ages).
Admittedly, this strategy is only accepted as best practice by the reigning national endocrine societies in a few countries: the UK, United States, and the Netherlands (are the only ones I know about), but it is the current best practices given by the World Professional Association for Transgender Health (formerly Harry Benjamin).
These are the standards of care observed by every medical doctor and psychotherapist I know - they're pretty much the only standards of care for the treatment of transsexual people. They've also been adopted by the International Endocrine Society.
I think it's important to mentally separate the use of hormone blockers (which WPATH lists as "reversible interventions" because puberty will resume normally if they are stopped) from the often irreversible effects of treatment with desired-gender hormones.
It'd also be worth your time to read that J Med Ethics paper I cited above. It's a good read with a lot of insight into why [pre-]pubertal hormone blockers make clinical sense.
I also think it's worth noting that journalists sometimes choose interview subjects to tell the story they want to tell. Or to paint the picture of a controversy when it's really just prejudice. It's better news.
Also that the "study" cited here is 10 years old, that the screening criteria involved in that study were probably even older - perhaps even dating back to before the 1989 date given as the start of the study.
I cannot find the study they reference (only an allusion to a sample of some 124 people in an praxis piece written by a member of the Portman clinic in 2000 [& I'm a pretty good lit searcher, but have at if you'd like]).
I did, however, find the 80% remission figure cited elsewhere, this time with two concrete citations to back it up (& this was in "[...] Endocrine Society Clinical Practice Guideline, J Clin Endocrinol Metab, 2009). So the two studies (minus the review articles they also cite):
Wallien & Cohen-Kettenis (2008). Psychosexual Outcome of Gender-Dysphoric Children. Child & Adolescent Psychiatry.
Drummond et al (2008). A Follow-Up Study of Girls With Gender Identity Disorder. Developmental Psychology.
Neither of which I've read, but both of which say in their abstract that their initial samples included subclinical adolescent GID presentations and that post-hoc analyses in both cases found that among their GID-persisting adults, more "symptoms" were observed in adolescence. Lends some credence to the Dutch study, don't you think?
And as a personal note - prejudice against trans people is rampant and uncritically accepted in our culture. Perhaps this is the well-trained antiracist in me speaking - but I feel that to not acknowledge your own internalization of a widespread cultural prejudice is to express it. I'm trans and, god help me, I'm transphobic too.
Men are torturers, women are nurturers?!! LOL!!! I have to read it.I can't wait til I finish studying all this basic level science stuff so I can get to neurology. UGh the not understanding is maddening. Thanks for breaking it down for those of us who want to understand neurology but have a ways to go. (In my case... thousands of leagues)
It makes me really upset when people get over zealous with diagnosing kids with "whatever ailment" without hard evidence to do so.
"Anonymous of January 31, 2011 3:40 PM - I find it remarkable that you can speak for all 99 of those children..."
Anonymous didn't say they (sorry for the misgendering, I'm not sure how to address you) spoke for all these children, but as a trans person, Anonymous certainly has more right to voice an opinion concerning trans issues than you do. You may be abler to critique the study, or the criteria of GID, or whatever is under discussion, from a scientific point of view, but where it comes to opinionating, a trans person certainly has more right to speak up than a cis person does.
I think scanning gender-dysphoric children is a terrible idea because I'm certain there is plenty of variation in transgender brains (just as there is with any example of "sex dimorphism") and it would be incredibly tragic to base a child's future on whether their brain "proved" their assertion that they were transsexual. But I think the way you've presented this is really problematic. Do you understand how puberty blockers work? Your statement about altering peoples' hormones before puberty is plain inaccurate and reminds me of the scaremongering I see on this issue all the time. As other commenters have explained, blockers delay the onset of puberty, giving young people more time to understand their gender identity and their options for the future, rather than potentially being forced into a nonconsensual puberty that might be traumatic and have irreversible effects (like unwanted masculinization, or the development of breasts that would later need to be surgically removed). There are no long-term downsides to blockers, unless you privilege cisgender identity over transgender identity to the point of risking the child's future detriment. And again, as other commenters have said, the large number of people who are diagnosed with childhood GID who never transition is the result of the absolutely absurd criteria for childhood GID that make it a diagnosis for boys who act girly and girls who act boyish (though especially boys who act girly, a cultural anxiety reflected in the DSM). We don't need brain scans or contrived and misleading diagnostic criteria to provide this invaluable treatment to transgender kids; we need to actually listen to what they are saying. That means recognizing the difference between a boy who wears dresses and a "boy" who unceasingly insists that she's female.
Again, I think brain scans should absolutely stay out of this issue, but I think your reasons for saying so are based on inaccurate beliefs and probably also on a lack of faith in or comfort with transgender people. That's understandable -- many people have the same issue -- but if (as I hope) you're interested in thinking and writing compassionately and accurately about transgender issues, you may want to do some soul-searching.
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