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Imagine holding a wrinkled human brain in each hand, dripping with formaldehyde solution. You look at one, then the other. Can you tell which belongs to a woman and which belongs to a man?

You can't.

Since ancient Greek times, humans have been trying to find differences between male and female brains, but most of these efforts have yielded little result. This is partly because there are no two completely distinct forms of the human brain. Dr. Armin Raznahan, director of the Developmental Neurogenomics Section at the U.S. National Institute of Mental Health, says, "I don't think there's any brain measurement that can fully distinguish between males and females."

Nevertheless, studying the differences between male and female brains is still of great significance, as many brain diseases and mental disorders manifest differently between genders. Experts believe that clarifying whether these differences stem from biological or environmental factors may help develop more effective treatments.

"The incidence and manifestation of many mental and neurological diseases vary between genders," says Dr. Yvonne Lui, a clinical scientist and vice - chair of the Department of Radiology at NYU Langone Health. "Understanding these fundamental differences can help us better understand the mechanisms of disease."

Thanks to artificial intelligence, scientists are now able to reliably distinguish between male and female brains - this distinction is based on the microscopic structure of neurons and the subtle differences in neural circuits that play a role in various cognitive tasks such as visual perception, motor control, and emotional regulation. Other studies suggest that some gender - based differences in human brain structure may exist from birth. Additionally, studies on laboratory animals have revealed gender differences in the firing patterns of brain cells at the molecular level.

What remains unclear is how significant these differences are. Do they affect brain function or disease susceptibility? Should doctors develop personalized treatment plans based on these differences? Although scientists are gradually uncovering the subtle differences between male and female brains, their research inevitably involves the complex issue of how gender, physical characteristics, and culture interact to shape human cognition.

Currently, scientists are unable to answer these major questions. However, ongoing and future research - involving laboratory animals, studies of human chromosomes and brain development, and research on subjects tracked from adolescence to adulthood - may begin to reveal how these gender - based brain differences specifically affect cognition and ultimately the development of brain diseases.

Why Study Gender - Based Brain Differences?

Historically, scientists have used so - called brain differences to generalize about the thinking and behavior of men and women, and to support sexist views that women are inherently less intelligent or capable than men.

Although these early studies have been refuted, modern research still finds that there are indeed some cognitive differences between men and women - at least on average. For example, some studies suggest that men perform better on spatial ability tests, while women are better at interpreting others' facial expressions. However, men and women grow up and are treated very differently in society. So, what are the roots of these differences? Are they innate, or are they shaped by the environment, or a combination of both?

"In human studies, it's actually extremely difficult to clearly distinguish whether a gender difference is driven by the social environment or determined by biological factors," says Dr. Raznahan. "Our brains unconsciously absorb various assumptions and biases, which slip in through the back door without our awareness."

Given the many flaws and misleading aspects of past research on brain gender differences, as well as the real challenges of properly researching this issue, many people may wonder: Why do scientists still study it? For many researchers, the answer lies in the fact that neurological and mental diseases manifest differently in men and women, which may be related to both biological and environmental factors.

Data shows that women are more likely to suffer from depression and migraines than men, while men are more prone to schizophrenia and autism. Additionally, the incidence of Parkinson's disease in men is about twice that in women, but the condition in female patients often progresses faster. However, these studies usually do not strictly distinguish between the concepts of "sex" and "gender" - "sex" refers to biological differences, while "gender" involves an individual's self - identity, as well as social roles and external pressures. Confusing these two concepts makes it more difficult to understand the source of a particular difference.

For example, adolescent girls are more likely to suffer from depression than boys of the same age. This may be related to the way their developing brains process stress, or it may be because they experience more stressful events during this period than boys. Conversely, does the male brain make them more resistant to depression? Or are they simply under - diagnosed due to social bias? Different answers to these questions may lead to very different solutions.

Overall Differences in Brain Structure: Trivial Distinctions

Using brain scanning techniques such as magnetic resonance imaging (MRI), scientists have found some subtle differences in the size, shape, and thickness of various brain structures between men and women, as well as differences in the neural networks connecting different brain regions.

However, when considering the average body size differences between men and women, these brain differences are actually very small, even negligible. Lise Eliot, a professor at Rosalind Franklin University of Medicine and Science and author of "Pink Brain, Blue Brain," holds this view.

Eliot and her colleagues recently reviewed about 30 years of research and found that the male brain is on average 6% larger than the female brain at birth and 11% larger in adulthood. This is reasonable because the average brain volume is usually proportional to the average body size, and men generally have larger bodies than women. However, when researchers take into account the overall volume difference, the subtle structural differences between male and female brains almost shrink to an insignificant level.

"Maybe there are some broad gender differences in the human brain, but so far, there's no conclusive evidence to prove their existence," Eliot says. "If these differences do exist, they must be very subtle."

Nevertheless, some scientists have reported gender differences that do not change with body size. For example, a research team analyzed MRI data of more than 40,000 adults collected by the UK Biobank, which stores medical data from 500,000 British adults.

In this study, men had a larger thalamus - the thalamus is a relay station in the brain that transmits sensory information. Additionally, men had a larger putamen, a structure that helps control movement and is involved in a feedback loop to help individuals judge whether an action is performed correctly. In contrast, women had a larger left nucleus accumbens on average, which is part of the brain's reward system. At the same time, women also had a larger hippocampus, which not only stores short - term memories of facts and events but also converts this information into long - term memories.

However, neither this study nor other related studies have found a feature that can reliably distinguish between male and female brains. Raznahan and his colleagues pointed out in a letter responding to this study that the volume ranges of male and female brains largely overlap, so it's impossible to clearly distinguish gender based solely on subtle structural differences.

For these small volume differences that exist, it's currently unclear whether they explain certain gender - related cognitive differences. On the contrary, it's also possible that these differences make men and women more similar in cognitive function. The researchers wrote in the letter that perhaps the male and female brains operate slightly differently but ultimately achieve the same cognitive output - this process may be a "counterbalance" to the influence of hormonal or genetic differences on brain function.

"When we're just describing a difference in a measurement, it doesn't mean it has any practical significance in terms of function," Raznahan emphasizes.

Artificial Intelligence Reveals Subtle Differences

Although large - scale brain structural features cannot clearly distinguish between male and female brains, artificial intelligence is helping scientists discover more subtle differences. Some of these differences are at the microscopic structure level of the brain, that is, the level of individual neurons and their components.

For example, a study published in May 2024 used different AI models to analyze brain scan data of 1030 young adults aged between 22 and 37. This study mainly focused on white matter - which consists of a large number of myelinated nerve fibers and is responsible for transmitting information between neurons. "I think we're the first research team to detect microscopic structural differences between male and female brains," says Yvonne Lui, a co - author of the study.

The AI models analyzed local landmark structures in the brain (such as the corpus callosum that connects the left and right hemispheres) and neural pathways connecting distant cells. The study also examined the way white matter is bound, its density, and the integrity of the myelin sheath.

The results showed that these AI algorithms could predict the biological sex of the individual whose brain scan image belonged to with an accuracy of 92% to 98%. Dr. Lui points out that the remaining errors are likely due to "the huge variability among human individuals."

Notably, no single brain region can be used independently to predict gender. One of the models relied on 15 different white matter regions for classification. However, all models showed some consistent patterns, especially the corpus callosum - the largest white matter structure in the brain that spans the left and right hemispheres - which was particularly crucial in distinguishing gender.

Brain Differences from Birth

Dr. Lui and her colleagues' study was not designed to explore how an individual's growth experience or environment shapes the brain, nor did it attempt to distinguish which brain differences stem from biology and which are related to gender.

By scientific definition, sex refers to the biological differences in anatomical structure, physiological characteristics, hormone levels, and chromosomes. Generally, sex characteristics are classified as male or female, but not everyone's gender characteristics can be fully classified into these two categories. Gender belongs to the cultural realm, involving an individual's self - identity and expression, as well as society's expectations and treatment of them. Gender includes not only "male" and "female" but also other identities, such as non - binary genders and genders unique to specific cultures, such as māhū in Hawaiian culture.

Historically, many studies have confused sex and gender. The most effective way to clarify the specific manifestations of these two factors in the brain is to track an individual's brain development process over a long period - and the latest research is starting to move in this direction.

For example, a study published in 2024 analyzed the average brain volume of more than 500 newborns and found that even after considering the difference in birth weight, the male infants' brains were still 6% larger than the female infants'. At the same time, female infants had a higher ratio of gray matter to white matter. (Note: Gray matter is mainly composed of neuron cell bodies and is mainly distributed in the outer cortex of the brain.) Interestingly, this average gender difference in the gray matter ratio also exists in adult brains. This also makes sense - because a larger brain requires more white matter to transmit signals between distant neurons.

Statistically, these overall brain differences are more significant than some small - scale structural differences. The study also found that women have a relatively larger corpus callosum, more gray matter around the hippocampus, and more gray matter in the left anterior cingulate gyrus (ACG) - a key emotion - processing area. Men have more gray matter in some areas of the temporal lobe (involved in sensory processing) and the subthalamic nucleus (responsible for motor control). However, gender factors can only explain a small part of these brain structure changes.

The study authors point out that some of these brain differences exist from the earliest stages after birth and persist into adulthood. These differences are mainly reflected in the overall brain structure, but some smaller local differences may also be persistent. For example, some studies (but not all) suggest that the left anterior cingulate gyrus is also larger in adult women than in men, not just in infancy.

For the differences that exist from birth and persist, they are likely related to sex - related biological characteristics. However, those differences that appear or disappear later in life (such as changes in the hippocampus) may be influenced by environmental factors or reflect sex - related developmental processes, including hormonal changes during puberty.

Gender and Sex

This type of research helps clarify the independent and interactive effects of sex and gender on the brain. However, there is still a huge gap in the scientific community's understanding of how these two factors shape the brain. Elvisha Dhamala, an assistant professor of psychiatry at the Feinstein Institutes for Medical Research in New York, says, "There's still a 'huge gap' in our knowledge in this area."

Dhamala and her colleagues recently tried to fill this gap by using data from the Adolescent Brain Cognitive Development (ABCD) study - a large - scale U.S. study aiming to explore children's brain development and health. The research team analyzed functional magnetic resonance imaging (fMRI) scan data of nearly 4800 children. (Note: fMRI provides an indirect measurement of brain activity by detecting changes in brain blood flow.) These children joined the study at the age of 9 or 10 and will be continuously tracked for the next 10 years, providing the possibility for future longitudinal studies.

In the study, fMRI recorded the activity patterns of different brain regions, especially which neural networks were activated when the children performed various tasks (such as memory tests, recalling multiple pictures). Additionally, the researchers asked the children and their parents to fill out questionnaires, answering questions about the children's feelings about their own gender and their tendencies in daily games and expressions.

Dhamala explains, "This doesn't involve any clinical diagnosis. It's just used to measure a behavioral characteristic that reflects your gender identity."

The research team used the answers from these questionnaires to generate "gender scores" and then input them into an AI algorithm as data points to explore the relationship between gender identity and brain activity.

Finally, the AI algorithm revealed two largely independent sets of brain networks, related to sex and gender respectively. The brain differences related to sex are mainly concentrated in neural networks involved in processing visual information, body perception, motor control, decision - making, and emotional regulation. The brain differences related to gender are more scattered, involving connections between multiple regions of the cerebral cortex.

After identifying these brain networks, the researchers used an AI training algorithm to try to predict the children's sex or gender based on brain activity. The accuracy of predicting sex was very high, similar to the results of Dr. Lui's study. Predicting gender was more challenging: based on the questionnaires filled out by the children themselves, the AI could not accurately predict their position on the gender identity spectrum. Based on the questionnaires filled out by the parents, the AI's prediction ability was slightly better than random, but still far lower than the accuracy of predicting sex.

Nevertheless, Dr. Dhamala says that this study highlights a long - neglected concept: gender shapes the brain in a different way from sex.

Interestingly, although Dr. Lui and Dr. Dhamala used different AI research methods and focused on different brain features, there are still some interrelated clues between them. Dr. Dhamala says that the key white matter pathways identified by AI in Dr. Lui's study overlap to some extent with the functional brain networks found in her study.

For example, the cingulum bundle - a white matter pathway surrounding the corpus callosum, was identified as a key predictor in Dr. Lui's study. In Dr. Dhamala's study, multiple functional neural networks connected by the cingulum bundle were also identified by AI, including circuits related to emotion processing. This indicates that gender differences may exist in both the physical structure of these neural networks and their activation patterns, Dr. Dhamala concludes.

The Future of Gender Difference Research

Scientists have made some progress in exploring gender differences in the brain, but to truly understand these differences, more animal experiments are needed to better control variables. Dr. Raznahan pointed out in a paper co - authored in 2020 that this is crucial for future research.

Currently, studies on laboratory rats have found some gender - related brain differences, such as differences in the way male and female individuals form connections between neurons and differences in the way they process fear memories.

In human research, scientists can collect more brain data when newborns are born to determine whether there are baseline differences before an individual is exposed to any cultural influence, and then track them over the long term. Dr. Raznahan and his colleagues point out that this method can help us more accurately analyze which differences stem from biology and which are influenced by the environment.

Another research idea is to analyze human genes unique to the X and Y chromosomes. For example, studying individuals with extra or missing sex chromosomes can help scientists reveal how certain genes affect the increase or decrease in the volume of brain structures and thus create gender differences. Additionally, chromosomes may also affect disease risk. For example, an extra Y chromosome increases the incidence of autism, while an extra X chromosome does not. This may help explain why men (usually carrying one X and one Y) are more likely to suffer from autism than women (usually carrying two Xs).

However, gender research in the United States is currently facing uncertainty.

Affected by an executive order from the new government, the U.S. National Science Foundation (NSF) is reviewing existing research projects to check if they contain certain "sensitive words" such as "woman," "female," and "gender." At the same time, the U.S. National Institutes of Health (NIH) seems to have archived a long - term policy that originally required all studies to use both female and male experimental animals.

"Everything is full of uncertainty now," she worries. If the worst - case scenario occurs, "removing gender factors or making gender difference research more difficult will only make us go backward, not forward."

But if this research field can continue to develop, future research can learn from the method of the ABCD study, such as using questionnaires to generate gender scores. Dr. Dhamala says that as a starting point, scientists can at least ask research participants about their gender identity, which will help more accurately distinguish between sex and gender in research. Other experts also support this view.

If these strategies are implemented, scientists will be able to greatly advance this research field that has existed since the time of Aristotle. Their research may provide a new perspective on the "nature versus nurture" debate, reveal gender - related brain differences, and thus promote personalized treatment for diseases such as depression and Alzheimer's disease, or ultimately prove that the so - called "opposite sexes" are actually more similar than we think.