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Brains Are Not Binary

April 16, 2022

Brains Are Not Binary
Both in humans and in nonhuman animals, biological sex characteristics are diverse. They refuse to be forced into two categories, male and female. There are combinations of typically male and typically female body parts and there are body parts that are intermediate between typically male and typically female. But what about brains?

To reproduce as female or male, most animals must exhibit a particular set of behaviors, and behaviors are controlled by the brain. For example, animals that fertilize externally lay eggs or squirt sperm onto the eggs. In species that fertilize internally, typically a male mounts a female and the female adopts a suitable posture to allow mounting. In many animals, there are elaborate pre-fertilization courting rituals–different for females and males–that must be followed for reproduction to succeed. 

It seems likely that brains differ to control all these sexual behaviors. But do brains fit into a binary classification–are there female brains and male brains? And is this true for humans, or just for nonhuman animals?
Some brain regions show sex differences on average
In songbirds and rodents, at least, there is strong evidence that a few brain regions differ in size according to sex. In species of songbirds in which males sing and females largely don’t, singing-related brain areas are much larger in males, at least during the breeding season. In rodents, a small structure called the hypothalamus, which regulates fundamental physiological processes like eating, drinking, body temperature, blood pressure, and sexual behaviors, has a few subdivisions of subdivisions that show sex-related size differences on average.

There is strong experimental evidence that gonadal hormones during early development—especially androgens (like testosterone) and estrogens—largely cause these brain sex differences and accompanying differences in adult sexual behaviors in rodents: adding or blocking a hormone at the right time in development can reverse some brain sex differences and some adult sexual behaviors. These behaviors include the frequency of mounting another rodent– more common in typical males (though all rodents do it)–and the frequency of adopting a typically female sexual posture that facilitates such mounting.  

But hormones are not the whole story. This was first shown in a songbird called a zebra finch that had female plumage on the left side and male plumage on the right, likely due to an early merger of genetically male and genetically female embryos. The animal’s brain had corresponding left-right differences. Hormones circulate through the entire bloodstream, so they cannot create left-right differences. This finding indicated that genes can directly cause some brain sex differences, in addition to those caused by gonadal hormones. 

This is not just a bird thing. Something similar was shown in mice in which the Sex-determining Region of the Y chromosome (SRY) gene was experimentally moved to a different chromosome, creating some mice with testes (and testicular hormones) but no Y chromosome and other mice with a Y chromosome but no testes. This also showed some direct genetic effects on the brain, in addition to hormonal effects.

All of this indicates that our sex chromosomes and our prenatal hormones together might create sex-related brain differences in people, too. But do they?
Some evidence suggests that there are a few human hypothalamic regions and connected structures that show a sex difference on average, though the functions of these brain regions are unknown. Some of these structures may correspond to regions previously shown to have a sex difference on average in rodents. 

Simon LeVay, then at the University of California, San Diego, wondered if the size of such brain regions might also be correlated with sexual orientation in people. In a small sample of postmortem brains, he examined one hypothalamic region that is on average larger in men than women. He found that in gay men, this region is about the same size as in women–smaller than in men presumed to be heterosexual. (Since all the people were dead, he could not be sure about their sexual orientation.) He hypothesized that lower levels of prenatal androgens caused XY people to be sexually attracted to men, in addition to causing other behavioral characteristics he considered typically feminine. One later study pointed in the same direction as LeVay’s, but without a statistically significant difference between groups. 

In addition, recent studies on small numbers of transgender and cisgender people have found that the sizes of some hypothalamic regions or connected structures are correlated with the person’s felt gender, not with their sex assigned at birth. This might have occurred because circulating androgen levels changed between early prenatal genital development and later prenatal brain development, but there is no direct evidence of this, because one can’t go back and measure prenatal hormone levels at each time point.

Brain regions don’t have predictable sex-related features in individual people
There is much uncertainty and disagreement in the field of human brain sex differences. One reason is that the difference in any brain region between women on average and men on average is typically very small. Another reason is that studies of humans, in contrast to nonhuman animals, generally must rely on noninvasive approaches like magnetic resonance imaging (MRI) to make measurements in living people and these methods have limited spatial resolution, making the measurements “fuzzy.”

Still another reason is that the distributions of measurements from women and men overlap considerably. That is, even if a brain region is larger in men than in women on average, for example, there are still many women in which that region is larger than it is in many men. As an analogy, consider height: men are taller than women on average, but some women are taller than some men. The amount of overlap between sex-related distributions of the size of any brain region is much greater than the overlap between sex-related distributions of height. 

Even if these sex-related brain differences are small on average, in principle they still might be consistent within a person. For example, let’s imagine there are 10 sex-related brain regions–5 of them larger in men and 5 larger in women. One might expect that in most men, the first 5 regions will all be larger than in the average woman and the second 5 will all be smaller than in the average woman. In most women, the reverse would be true. One might also imagine that some people will be intermediate across all 10 regions and thus have a consistently intermediate “brain sex.”

But Daphna Joel and colleagues at Tel Aviv University found that this is not the case. Using large, human brain-imaging datasets, they examined just the brain regions with the largest sex/gender differences on average. For each such region, they divided the set of measurements into thirds: the male-typical end, the female-typical end, and the middle. They found that for 23-53% of people (depending on analysis method), at least one brain region was at the male-typical end while at least one other was at the female-typical end. In contrast, only 0- 8% of people were consistently at either the male-typical or the female-typical end. (Still others were a mix of one end and the middle third.) Thus, it is much more common for people to have brains that are “mosaics” of sex-related features than to have brain features consistently at one end of a sex/gender continuum. 

Even if human brains do not divide neatly into female and male, there must be brain differences that account for our differences in skills, habits, preferences, etc. After all, our brains are what allow us to feel, think, and move. 
But such brain differences may be quite subtle. Important differences in cognition and behavior might be produced by microscopic differences in the connections between nerve cells, which are currently undetectable in living people. We have billions of brain cells and trillions of connections between them, so there is tremendous room for variation. The things we learn and the events that change us alter these connections.

It is important to note that if or when we do find differences in human brains, there is usually no way to know whether the cause was genes, prenatal hormones, postnatal hormones, nutrition, upbringing, education, life events, habits, medications, or some complex interacting tangle of these factors. Everything that changes who we are does so by changing our brains and there is no easy way to trace the causes of brain differences found in adult humans.

We are mosaics of sex-related biological characteristics
One way of looking at sex-related variation in the brain and the rest of the body is to say that chromosomes, gonads, and genitals are typically either female or male, but brains and behaviors are instead a mosaic of typically female, typically male, and intermediate regions. This view asserts a kind of dichotomy between genitals and brains: most people have binary genitals but mosaic brains.

But the difference between brain and genital diversity is quantitative, not qualitative. We might estimate that about 53% of people have mosaic brains and up to 6% of people are born with some kind of intersex characteristics of their chromosomes, gonads, and/or genitals. 
Perhaps a more precise description of human biological variation would be to say that typical people are mosaics of all biological sex characteristics–from brains to genitals–though the degree of mosaicism differs across individual people and organs. Each of our biological structures might be described as more typically female, more typically male, or intermediate. In this view, each of us combines anatomical, physiological, and behavioral characteristics in a unique way and the biological characteristics of the human population defy binary sex categorization. 

In any case, as we have seen, our biology is not binary–not in people and not in nonhuman animals. Animals, particularly sexual species, have evolved a rich diversity of biological characteristics, including characteristics related to sex. This is not a political point. It is just accurate biology.
Many people think that each of us is biologically either male or female. If that’s true, then anyone who feels that they are not either male or female, or feels that their gender does not match their sex assigned at birth, essentially has a conflict between their psychology and their biology. 

But if biology is not binary, then there is not a conflict between our diverse psychology on the one hand and our binary biology on the other. Instead, there is a conflict between our diverse biological characteristics and psychological characteristics–mediated by our brains–and our largely binary culture, which often tries to place biologically diverse people into one of two categories.

A version of this post appeared on Medium.


Human brains do not fit well into female and male categories.

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Some brain regions show sex differences on average, especially regions of the hypothalamus in some nonhuman animals.
Sex differences in human brain regions are small and inconsistent, even in the hypothalamus.
People typically are mosaics of sex-related anatomical, physiological, and behavioral characteristics.

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Author: aberkowitz

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