Is there really such a thing as a “male” or “female” brain? Sex certainly seems to affect a person’s risk of developing various psychiatric and other brain-related conditions—but scientists aren’t entirely sure why. Attention-deficit/hyperactivity disorder for example, is more commonly diagnosed in individuals who were assigned male at birth (AMAB), whereas those assigned female at birth (AFAB) are more likely to exhibit symptoms of anxiety. It’s unclear, however, whether these differences are actually driven by sex, or have more to do with how people are perceived and treated based on their sex or gender.
Now, new research suggests sex and gender are associated with distinct brain networks. Published today in Science Advances, the findings draw on brain imaging data from nearly 5000 children to reveal that gender and sex aren’t just distinct from one another in society—they also play unique roles in biology.
In science, the term “biological sex” encompasses a variety of genetic, hormonal, and anatomical characteristics. People are typically assigned “male” or “female” as their sex at birth, although the medical establishment in recent years has begun to acknowledge that sex doesn’t always fall neatly into binary categories. Indeed, about 0.05% of children born in the United States are assigned intersex at birth. Gender, by contrast, has more to do with a person’s attitudes, feelings, and behavior—and may not always align with the sex they were assigned at birth.
These nuances often go unrecognized in neuroscience, says Sheila Shanmugan, a reproductive psychiatrist at the University of Pennsylvania who wasn’t involved in the new study. Sex and gender-based differences in the brain “have historically been understudied,” she explains, “and terms describing each are often conflated.”
“I don’t think anyone’s looked at this question of how brain networks are related to sex versus how they’re related to gender,” says Lucina Uddin, a professor of psychiatry and biobehavioral sciences at the Semel Institute for Neuroscience and Human Behavior at the University of California, Los Angeles who wasn’t involved in the study. In fact, many previous studies, “just never bothered to ask about gender.”
And yet both sex and gender are important to study because they’re “essential components of identity,” says Elvisha Dhamala, a neuroscientist at the Feinstein Institutes for Medical Research and the Zucker Hillside Hospital and lead author on the new study. “It’s becoming more and more clear that just looking at sex itself is not enough,” she says. “It’s not going to give us all the answers.”
To disentangle the effects of sex on brain activity from those of gender, Dhamala and her colleagues analyzed brain imaging data collected as part of the Adolescent Brain Cognitive Development (ABCD) Study—the largest long-term study of brain development and child health in the U.S. The team looked at functional magnetic resonance imaging (fMRI) scans from 4727 children ages 9 and 10, all of whom were either assigned female (2315 children) or male (2442) at birth.
Collecting gender data was a little more complicated. The ABCD Study takes a nuanced approach by asking participants four questions centered on gender, including whether they feel satisfied with the gender they were assigned at birth, explains Uddin, who serves as the ABCD Study’s justice, equity, diversity, and inclusion associate director.
Because 9- and 10-year-olds may not have a completely developed sense of their own gender identity, the ABCD Study also asks participants’ parents a larger set of questions about certain behaviors in their child and signs of gender dysphoria. For example, whether they’ve noticed that their AMAB child imitates female characters on TV, or that their AFAB child consistently expresses a wish to be a boy or a man. “We’re hoping we get the questions right in order to capture this complex construct of gender,” Uddin says.
During fMRI scanning, ABCD Study participants were asked to do a set of neurocognitive tests—related to things like memory and emotional processing—to see how different brain regions and networks communicate with one another. Dhamala and her colleagues then fed those scans to machine learning algorithms to determine whether these patterns of activity in a child’s brain could be used to identify their sex and gender.
Although the algorithms accurately predicted a participant’s assigned sex at birth, they had a harder time determining gender. The models couldn’t predict self-reported gender for either sex, but did identify some brain activity patterns that were consistently associated with parent-reported gender—possibly because this latter measurement captured multiple dimensions of gender identity.
These gender-associated brain networks were distinct from those associated with assigned sex at birth. Networks that showed patterns of connectivity associated with sex included those that play a role in sensory processing and motor control, whereas the networks associated with gender were more widely distributed throughout the brain and tended to be involved in cognitive abilities such as attention, social cognition, and emotional processing.
Dhamala and her team are also careful to note that their findings should not be misinterpreted as evidence that men and women are born with distinctly different brains that drives them to behave in distinct ways. “Nothing in our work establishes any aspect of causality,” she explains. The effects of both sex and gender on the brain may also arise because of social and environmental factors, including gender roles and stereotypes.
But the team’s findings do suggest neuroscientists need to consider sex and gender separately in biomedical research, Dhamala and her colleagues argue. It’s possible, Uddin notes, that lumping study participants together by sex might cause researchers to overlook the influence of other variables, such as gender, on human health and behavior. The discovery that sex and gender influence the brain in different ways, she adds, “could change the way we do science.”
A major limitation of the study is that it includes data only from people who haven’t reached puberty, says Tobias Kaufmann, a neuroscientist with joint appointments at the University of Tübingen and the University of Oslo who wasn’t involved in the work. “The mapping between sex and gender might change” during puberty, he explains—along with how these two characteristics show up in the brain. Gender norms can also vary widely across cultures, so the ABCD Study—which only includes children in the U.S.—doesn’t reflect the global population, he and others note in a related article.
This particular type of research also runs a risk of being exaggerated or misconstrued, Kaufmann adds, noting that work on sex differences in the brain has been used to reinforce harmful gender stereotypes. In the 19th century, for example, scientists used the difference in average brain weight between men and women to argue that the latter were less intelligent. And as recently as 2003, clinical psychologist Simon Baron-Cohen claimed that men are naturally better at understanding and building systems, whereas women’s brains are hard-wired for empathy. “Taken out of context or put in the wrong light,” Kaufmann says, “results can easily be used to support or to diminish viewpoints, or to stigmatize.”
The best way to avoid such misconceptions and perform rigorous science, Dhamala says, is to invite transgender and gender-nonconforming people, whose bodies and identities have historically been excluded or treated as abnormal by scientists and may have unique insights into the nature of sex and gender, into the process—both as participants and collaborators. “You can’t necessarily do research on a population,” she adds, “if you’re not including that population in your research team.”
