Is there such a thing as a male or female brain?

As a girl who learned how to use tools from her mother and how to cook from her father, I’ve always been skeptical about alleged gender differences in the brain. The stereotype is that males have better motor skills and spatial abilities, and that females have a better memory and are more adept in social situations (Ingalhalikar et al., 2014).

Watching my father try to put all the pieces of the vacuum back onto the vacuum one day very closely resembled a toddler trying to fit the right shape into the appropriate hole of the box. However, give the man a chicken or a computer and keyboard and he will create art. My mother always took care of the finances in our house. Which made sense, seeing as she’s the one with the MBA. However, I would not say that communication is exactly her forte. Neither of us has a particularly good memory either. For some reason we often ask each other to remind the other of something. This is like asking a squirrel to remember where he buried his acorns last year.

I therefore decided to investigate whether the concept of a “female brain” and a “male brain” holds any water.

This issue is difficult to navigate, especially when you have such contrasting information from so many different studies and sources. Note these two opposing headlines from the same journal- Science Magazine, considered one of the leading scientific publications in the world. If Science can’t even make up their mind on the issue, then what hope do the rest of us have on understanding the facts and coming to a reasonable conclusion?

Luckily for you, I have enough time and coffee on my hands to wade through the methods and results of many studies and present the conclusions and my own analysis of the issue.

First of all, what is sexual dimorphism? The definition according to Britannica is “the differences in appearance between males and females of the same species, such as in colour, shape, size, and structure, that are caused by the inheritance of one or the other sexual pattern in the genetic material.” Other sources, such as biologyonline.com and The International Encyclopedia of Biological Anthropology, additionally specify that sexual dimorphism refers to only the secondary sexual characteristics, and not those directly relation to reproduction. For example, the difference in color between the sexes in some species of birds, or antlers on deer. Humans show about 15% sexual dimorphism between the sexes (for example size differences and hair growth), whereas gorillas and orangutans are more than 50% sexually dimorphic (Larsen, 2003). So what about the brain? Could you analyze a brain and be able to successfully determine whether it’s from a man or a woman? And if not, what is the level of similarity between the brains? Would you be able to guess correctly 75% of the time? 50% of the time?

There is definitely sexual dimorphism in the brains of certain animals. In species of birds where only the males sing, like canaries and zebra finches, the vocal control areas of the brain are up to 6 times larger in the males (Eliot et al., 2021).

The sexually dimorphic nucleus of the preoptic area (SDN-POA), a small, sexually dimorphic brain region in the medial preoptic area of the hypothalamus was first discovered in rats, and is larger in males of at least 8 other species, including macaques and humans (Greenberg and Trainor, 2016). The medial POA regulates parental and sex specific behaviors differently in females and males through hormones in all species studied (Wei et al., 2018), so the difference in size in certain animals is definitely significant.

There are certain differences in women and men that indicate that there could be differences in the brain. For example women have higher rates of Alzheimer’s disease and major depressive disorder (Rutter et al. 2003; Gobinath et al. 2017), while men are more likely to be diagnosed with autism spectrum disorder, schizophrenia, and dyslexia (Ritchie et al., 2018).

All studies performed have found differences in size and volume between men and women, though this is not particularly surprising. If larger people didn’t have larger brains, there’d be a lot of empty space in their skulls for their brains to rattle around in. They also found differences between the volume of gray matter, which contains the neural cell bodies, and the white matter, which is made up of the nerve fibers, or axons which transfer signals and messages to the next cell.

In a large study published by Stuart Ritchie of the University of Edinburgh, they analyzed the brain volumes of 5,216 men and women, adjusting each measure for age and ethnicity (unclear how one adjusts brain volume for ethnicity) and then compared grey and white matter volumes. They presented this data in graphs, conveniently labeled in pink for women, and blue for men. Unsurprisingly, men had larger brains on average, although there was a lot of overlap. They then looked at different regions of the brain, and after adjusting them to the general larger size of men, still found most of them to be larger than women’s. However, women had a thicker cortex. They also tested network connections of the brain in its resting state and found that 54.7% of these network connections were different on average between men and women, although again, there was great overlap between the sexes (Ritchie et al., 2018). In short, there was definitely a trend detected, but you wouldn’t necessarily be able to tell whether a brain scan picked at random came from a man or a woman.

While this is an unusually large sample size (most studies use fewer than 100 brains. One study I read and immediately discarded after laughing for a good minute or two compared brain tissue samples from 5 males and 1 female), which in general means that statistically significant differences are more credible, my main issue with this study is that the scans were taken from participants aged 44–77, with the average age being 62. Not to be ageist, but the brain you have at 50 is not the same brain you had at 25, so the most one can reliably conclude from this study is that brains age differently in men and women. Additionally, hormonal changes, like those that occur during menopause, have been shown to affect brain structures (Price, 2017).

A study by Ingalhalikar et al. published in 2014 compared the connectivity between male and female brains in 949 youths between the ages of 8 and 22 and found that male brains have stronger intrahemisheric connections in most of the brain and that females have stronger interhemispheric connections, except in the cerebellum where the pattern is reversed. From this they conclude that “male brains are structured to facilitate connectivity between perception and coordinated action, whereas female brains are designed to facilitate communication between analytical and intuitive processing modes,” basically confirming the stereotype that they themselves proposed (as stated in my first paragraph). Figure 2 shows the connections which are stronger in males and the connections which are stronger in females.

However, in a letter to PNAS published a month later, Joel and Tarrasch point out that this figure obviously doesn’t represent realistic connectivity in the brain since it doesn’t show all the connections, and both females and males have both types of connections. They also don’t share the actual numbers of connections that were different in males and females so it’s impossible to tell how large the differences were between the sexes (Joel and Tarrasch, 2014). In short, if they only show you the number of connections that were different but not the number of connections that were the same, it’s impossible to get an idea of how big the difference is. Is every 1 out
of 5 connections different? 1 out of every 5,000 connections? 1 out of every 500,000?

In addition, 2 subsequent studies (Hänggi et al., 2014; Martínez et al., 2017) showed that these differences in connectivity are related to the difference in brain size, not sex, and that the larger the brain, the higher the intra-hemispheric connectivity.

Therefore, normalizing brain size is really the key to being able to compare between male and female brains. However, normalizing brain structure volume based on brain size is tricky. Using different methods yields different results. The better the method of normalization, the fewer the differences in volume between different sized brains, if any (Jäncke et al., 2015; Sanchis-Segura et al., 2019; Voevodskaya et al., 2014). When they compared the same sized brains taken from both men and women, they found no differences in white and gray matter volume (Luders et al., 2009).

In a study performed by Joel et al. (yes, the same Daphna Joel from before, of Tel Aviv University), even without normalizing for brain size they found that each individual person’s brain was a mosaic between more characteristically “male” structures and more characteristically “female” structures (volume, thickness, and connectivity). Other studies looked at the averages of all the brains and brain regions in the study, but not the individual structures in individual brains. This study found that very few brains have perfect internal structural consistency (Joel et al., 2015).

In a letter published by Marek Glezerman (incidentally also of Tel Aviv University. Lunch breaks must have gotten awkward after this), he points out that morphology doesn’t necessarily equal functionality and that still images from an MRI can’t present the whole picture (Glezerman, 2016).

We know that men and women are different, physically, emotionally, and psychologically. The question is, what is the cause of these differences? Our chromosomal makeup (the presence or absence of a Y chromosome) leads to different hormonal environments in utero. But how much of that influences our brain structure? How much of nature vs. nurture influences brain development as children grow up and are influenced by their parents and the culture around them? Aside from the brain regions dedicated to sexual reproduction and secondary sex differences, I’m not convinced that there is a morphological or functional difference between male and female brains. While there is definitely a difference between men and women, I think that most of it is due to either hormonal or cultural reasons, not any intrinsic difference in the brain.

References:

Eliot, L., Ahmed, A., Khan, H., and Patel, J. (2021). Dump the “dimorphism”: Comprehensive synthesis of human brain studies reveals few male-female differences beyond size. Neurosci. Biobehav. Rev. 125, 667–697.

Glezerman, M. (2016). Yes, there is a female and a male brain: Morphology versus functionality. Proc Natl Acad Sci USA 113, E1971–E1971.

Greenberg, G.D., and Trainor, B.C. (2016). Sex Differences in the Social Behavior Network and Mesolimbic Dopamine System. In Sex Differences in the Central Nervous System, (Elsevier), pp. 77–106.

Hänggi, J., Fövenyi, L., Liem, F., Meyer, M., and Jäncke, L. (2014). The hypothesis of neuronal interconnectivity as a function of brain size-a general organization principle of the human connectome. Front. Hum. Neurosci. 8, 915.

Ingalhalikar, M., Smith, A., Parker, D., Satterthwaite, T.D., Elliott, M.A., Ruparel, K., Hakonarson, H., Gur, R.E., Gur, R.C., and Verma, R. (2014). Sex differences in the structural connectome of the human brain. Proc. Natl. Acad. Sci. USA 111, 823–828.

Jäncke, L., Mérillat, S., Liem, F., and Hänggi, J. (2015). Brain size, sex, and the aging brain. Hum. Brain Mapp. 36, 150–169.

Joel, D., and Tarrasch, R. (2014). On the mis-presentation and misinterpretation of gender-related data: the case of Ingalhalikar’s human connectome study. Proc. Natl. Acad. Sci. USA 111, E637.

Joel, D., Berman, Z., Tavor, I., Wexler, N., Gaber, O., Stein, Y., Shefi, N., Pool, J., Urchs, S., Margulies, D.S., et al. (2015). Sex beyond the genitalia: The human brain mosaic. Proc. Natl. Acad. Sci. USA 112, 15468–15473.

Larsen, C.S. (2003). Equality for the sexes in human evolution? Early hominid sexual dimorphism and implications for mating systems and social behavior. Proc. Natl. Acad. Sci. USA 100, 9103–9104.

Luders, E., Gaser, C., Narr, K.L., and Toga, A.W. (2009). Why sex matters: brain size independent differences in gray matter distributions between men and women. J. Neurosci. 29, 14265–14270.

Martínez, K., Janssen, J., Pineda-Pardo, J.Á., Carmona, S., Román, F.J., Alemán-Gómez, Y., Garcia-Garcia, D., Escorial, S., Quiroga, M.Á., Santarnecchi, E., et al. (2017). Individual differences in the dominance of interhemispheric connections predict cognitive ability beyond sex and brain size. Neuroimage 155, 234–244.

Price, M. (2017). Study finds some significant differences in brains of men and women. Science.

Ritchie, S.J., Cox, S.R., Shen, X., Lombardo, M.V., Reus, L.M., Alloza, C., Harris, M.A., Alderson, H.L., Hunter, S., Neilson, E., et al. (2018). Sex Differences in the Adult Human Brain: Evidence from 5216 UK Biobank Participants. Cereb. Cortex 28, 2959–2975.

Sanchis-Segura, C., Ibañez-Gual, M.V., Adrián-Ventura, J., Aguirre, N., Gómez-Cruz, Á.J., Avila, C., and Forn, C. (2019). Sex differences in gray matter volume: how many and how large are they really? Biol. Sex Differ. 10, 32.

Voevodskaya, O., Simmons, A., Nordenskjöld, R., Kullberg, J., Ahlström, H., Lind, L., Wahlund, L.-O., Larsson, E.-M., Westman, E., and Alzheimer’s Disease Neuroimaging Initiative (2014). The effects of intracranial volume adjustment approaches on multiple regional MRI volumes in healthy aging and Alzheimer’s disease. Front. Aging Neurosci. 6, 264.

Wei, Y.-C., Wang, S.-R., Jiao, Z.-L., Zhang, W., Lin, J.-K., Li, X.-Y., Li, S.-S., Zhang, X., and Xu, X.-H. (2018). Medial preoptic area in mice is capable of mediating sexually dimorphic behaviors regardless of gender. Nat. Commun. 9, 279.