There’s no inconsistency in the two findings. It’s a difference of perspective: Are you interested in similarities between male and female brains or differences? The topic of this chapter is differences.
So much for the preliminaries. The next three sections describe some of the most important and securely known biological sex differences in the brain: the activational effects of the sex hormones, sex differentiation during fetal and neonatal brain development, and the generally greater lateralization of the male brain. I then discuss differences in emotional cognition and their links to specific regions of the brain.
I have consigned discussion of two other securely documented and substantial sex differences to Appendix 3: “Sex Differences in Brain Volumes and Variance.” Both types of difference will presumably play into the story of sex differences in cognitive repertoires eventually, but as I write they represent important findings with undetermined or uncertain effects on the phenotype.
The Activational Effects of Sex Hormones
Almost everyone has heard about sex hormones. Both sexes have all of the major sex hormones to some degree, but androgens are the ones most identified with males (testosterone being the most famous) and estrogens are the ones most identified with females. Their effects on mood and behavior are part of the popular culture. Some of the stereotypes are exaggerated, but not all of them. Journalist Andrew Sullivan once underwent a medically prescribed regimen of testosterone injections. Here is his description of what an injection did to him:
Within hours, and at most a day, I feel a deep surge of energy. It is less edgy than a double espresso, but just as powerful. My attention span shortens. In the two or three days after my shot, I find it harder to concentrate on writing and feel the need to exercise more. My wit is quicker, my mind faster, but my judgment is more impulsive. It is not unlike the kind of rush I get before talking in front of a large audience, or going on a first date, or getting on an airplane, but it suffuses me in a less abrupt and more consistent way. In a word, I feel braced. For what? It scarcely seems to matter.22
Nor were those effects limited to Sullivan’s mood. When he began his series of testosterone injections, he weighed 165 pounds.
I now weigh 185 pounds. My collar size went from a 15 to a 17 1/2 in a few months; my chest went from 40 to 44. My appetite in every sense of that word expanded beyond measure. Going from napping two hours a day, I now rarely sleep in the daytime and have enough energy for daily workouts and a hefty work schedule. I can squat more than 400 pounds. Depression, once a regular feature of my life, is now a distant memory. I feel better able to recover from life’s curveballs, more persistent, more alive. These are the long-term effects. They are almost as striking as the short-term ones.23
These effects of hormones are akin to those of alcohol—powerful but varying with their level in the bloodstream, which changes over time. The technical term for these effects is activational. Hormones have many such effects on phenotypic differences between males and females, and the hormones are not limited to estrogen and testosterone. For example:
The female advantage in social cognition. A single administration of testosterone in women significantly altered connectivity of the network in the brain (technically known as the IFG-ACC-SMA network) that underlies the integration and selection of sensory information during empathic behavior. This finding suggests a neural mechanism by which testosterone can impair the recognition of emotions.24
In a double-blind, placebo-controlled study, testosterone administered to women diminished their accuracy in inferring mental states. Estrogen administered to men increased their emotional reactivity when watching a distressed person.25
In a placebo-controlled study, administration of oxytocin to males improved their ability to infer the mental state of others from social cues. The effect was pronounced for difficult items.26
The female advantage in prosocial behavior. In a double-blind and placebo-controlled experiment, pharmacologically blocking dopaminergic transmission reduced prosociality in women and selfishness in men. The authors concluded that in females the dopaminergic reward system is more sensitive to shared rewards than to selfish rewards, while the opposite is true for males. Their conclusion is supported both by pharmacological and neuroimaging data.27
The higher male level of impulsive behavior. In a placebo-controlled experiment, testosterone administered to males diminished their performance on the Cognitive Reflection Test, which measures capacity to override intuitive judgments with deliberated answers. The independent effect of the testosterone persisted after controls for background variables and 14 other hormones.28
The higher female level of risk aversion. Variations in salivary concentrations of testosterone were analyzed in MBA students. Higher levels of testosterone in women were associated with lower levels of risk aversion, with collateral evidence suggesting that testosterone has nonlinear effects on risk aversion. Persons high in testosterone and low in risk aversion were also more likely to choose risky careers in finance.[29]
The higher female level of emotional arousal. Neuroimaging studies have shown that measures of fear and arousal are associated with changes in estradiol levels across the menstrual cycle and correlate with changes in the functional reactivity of the amygdala and hippocampus.30
I will leave the discussion of the activational effects of hormones with these examples. The even bigger story about hormones and sex differences is not their temporary activational effects, but their permanent organizational effects on the fetal and neonatal brain.
Sex Differentiation During Fetal and Neonatal Brain Development
The discovery that testosterone permanently changes brain tissue was made 60 years ago but remains remarkably little known among the lay public. What follows is a simplified description. A more complete description (for example, discussing important changes that occur during and after puberty) would include yet other ways in which brains develop differently in males and females.
By the end of week eight, a human embryo’s brain and central nervous system already contain their rudimentary structures. By week 26, the primary ridges, folds, and furrows of the human brain have emerged. Most of the 100 billion neurons in the adult human brain have already been created.31 These basic changes happen for both sexes, driven by processes that are believed to be unrelated (or nearly so) to the embryo’s sex.32
But long before week 26, sex has entered the picture. Even at the end of the embryonic phase, the embryo’s testicles or ovaries have been developing for two weeks. By week 12, the differentiation of the sexual organs is settled, and the differentiation of the brain begins. Specifically, testosterone surges in human males occur twice before birth, during weeks 12–18 and again during weeks 34–41. Another testosterone surge in males, often called mini-puberty , occurs in the first three months after birth.33
The confirmation of this role for hormones dates to 1959 and a seminal article by Charles Phoenix and his colleagues.34 Before then, biologists knew about the role of the sex hormones in stimulating mating behavior. The Phoenix study presented the first evidence that hormones also had organizational effects that permanently altered the structure of the nervous system. “No other idea in behavioral neuroendocrinology has so transformed how we think about the genesis of masculine and feminine behavior,” wrote neuroendocrinologist Kim Wallen. “The notion that hormones at circumscribed times in life predictably and permanently alter the function, and we now know, the structure, of a living being to become phenotypically male, is one of the truly powerful ideas of the twentieth century.”35
Since 1959, thousands of experiments have been conducted on nonhuman mammals, primarily rodents and primates, in which the experimental animals are exposed to hormone manipulations during critical periods of prenatal and neonatal development.36 These experiments have established that certain regions of the brain (but not others) have receptors (in different proportions) that accept chemical signals from hormones. These signals can affect a ce
ll’s survival, its anatomical connectivity, and its neurochemicals.
It has been found that the default is female—in the absence of a spike in testosterone at the appropriate times during gestation and neonatal life, the brain takes on female characteristics. Feminization is not an entirely passive process, however. Just as some receptors accept chemical signals from testosterone, others accept signals from estrogen. But it is through the spike in testosterone that the brain is both masculinized and defeminized (the testosterone prevents the development of female characteristics).37 For both males and females, changes that develop during the fetal and neonatal phases also have delayed effects. Some of the circuits that are already formed by three months after birth are quiescent until activated by sex hormones at puberty.38
What does masculinized mean? Neuroscientist Margaret McCarthy summarized aspects of masculinization in rodents as follows:
Collections of cells that constitute nuclei or subnuclei of the brain differ in overall size due to differences in cell number and/or density, as well as in the number of neurons expressing a particular neurotransmitter. The length and branching patterns of dendrites and the frequency of synapses also vary between males and females—in specific ways in specific regions—as does the number of axons that form projections between nuclei and across the cerebral hemispheres. Even nonneuronal cells are masculinized. Astrocytes in parts of the male brain are more “bushy,” with longer and more frequent processes than those in the same regions of the female brain. And microglia, modified macrophages that serve as the brain’s innate immune system, are more activated in parts of the male brain and contribute to the changes seen in the neurons.39
Indisputably, a variety of physiological and measurable sex differences exist in the brains of rodents. What about in the brains of humans?
WHY RODENT STUDIES, THOUGH IGNORED HERE, ARE REALLY IMPORTANT
The quote from Margaret McCarthy gives you only a glimpse of the many ways in which studies of rodents and primates have documented that the mammalian brain is a highly sexed organ. My approach is akin to going into a fight with one hand voluntarily tied behind my back. One of the largest and most sophisticated bodies of knowledge about biological sex differences in the brain is based on nonhuman mammals, primarily rodents and some species of monkey. I am ignoring it here for the same reason I draw so little from evolutionary psychology. Like the accusation that “Evolutionary psychology is nothing more than just-so stories,” the dismissive response that “Knowing something about rats doesn’t mean humans work that way” is more effective than it should be. The proper question is not “Why should we think humans are the same as rats?” but rather “Why should we think that one mammalian brain was immune from the evolutionary forces that produced highly sexed brains in other mammals?”
Exploring the Organizational Effects of Prenatal Hormones in Humans
A genetic disorder of the adrenal glands known as congenital adrenal hyperplasia (CAH) has been recognized for more than a century. It can result in the production of too little cortisol or aldosterone, with effects having nothing to do with sexual identity. But it also can result in overproduction of androgens, especially testosterone. Starting in the late 1960s, researchers began to explore the possibility that girls with CAH might be more likely to engage in male sex-typed behavior in their choices of toys and games.40 In the 1980s, researchers also began to explore the possibility that the organizational effects of prenatal hormones in animal studies applied to humans as well.41 In 1995, sociologist and demographer J. Richard Udry and his colleagues put that possibility to the test and found that the model used for animal research did in fact apply to humans: “It is concluded that gendered behavior is not entirely socially constructed, but partly built on a biological foundation.”42 It was a landmark article in the development of an alternative to the social-construction orthodoxy.
Also beginning in the late 1960s, neurologist Norman Geschwind had been studying anatomical asymmetries in the brain. By the early 1980s, Geschwind had integrated diverse empirical evidence to reach a specific hypothesis that would explain links between maleness and the right hemisphere. Along with one of his students, Albert Galaburda, he presented his hypothesis in another landmark article, “Cerebral Lateralization,” in 1985:
It is the intent of this hypothesis to account for the following: (1) Left-handedness is usually found to be more common in men than women. (2) The developmental disorders of language, speech, cognition, and emotion, e.g., stuttering, dyslexia, and autism are strongly male predominant. (3) Women are on the average superior in verbal talents while men tend on the average to be better at spatial functions. (4) Left-handers of both sexes and those with learning disabilities often exhibit superior right-hemisphere functions. (5) Left-handedness and ambidexterity are more frequent in the developmental disorders of childhood. (6) Certain diseases are more common in non-right-handers, e.g., immune disorders.43
Simplified, Geschwind’s hypothesis was that the prenatal testosterone surge in males led to earlier and faster growth of the male’s right hemisphere.44
In the late 1990s, Simon Baron-Cohen, whom you met in chapter 1, was inspired by Geschwind’s hypothesis to test its validity. To infer levels of prenatal testosterone, Baron-Cohen and his colleagues measured testosterone levels in amniotic fluid.[45] In The Essential Difference, Baron-Cohen recalled his reaction to the initial results:
We found that the toddlers (at twelve and twenty-four months of age) who we had identified as having lower fetal testosterone, now had higher levels of eye contact and a larger vocabulary; or, putting it the other way around, the higher your levels of prenatal testosterone, the less eye contact you now make and the smaller your vocabulary. This is exactly as Geschwind had predicted. When we got those results, I had one of those strange feelings, like a shiver down the spine. A few drops more of this little chemical could affect your sociability or your language ability. I found it extraordinary.46
In the first two decades of the twenty-first century, these beginnings have been augmented by an array of additional evidence for the role of androgens in masculinizing the human brain.
Evidence from natural variation in prenatal testosterone. Baron-Cohen’s Autism Research Centre has generated most of the studies documenting the relationships between prenatal testosterone levels and various measures of male-typical and female-typical behavior. These include visuospatial ability,47 autism,48 the empathy quotient,49 systemizing quotient,50 social relationships,51 and interest in children.52 The pattern of results linking testosterone to the phenotype has been striking but not dispositive. A 2015 review of the literature on early androgen exposure and sex development (first author was Melissa Hines) indicates that the underlying problem may be the use of amniotic fluid: The within-sex variation in testosterone in amniotic fluid may not be sufficient to serve as a reliable measure of natural variation in prenatal exposure to testosterone.53 It can point research in the right direction, but seldom can conclusively pin down relationships. Measures of neonatal testosterone (which can be tested directly) and studies of people with sexual disorders are producing more robust evidence.
DISSENTING VOICES
The best-known and most detailed critiques of the organizational role of testosterone in particular and biological explanations of phenotypic sex differences in general are Rebecca Jordan-Young’s Brain Storm (2010), Cordelia Fine’s pair of books, Delusions of Gender (2010) and Testosterone Rex (2017), and Gina Rippon’s The Gendered Brain (2019).54 All four books are directed at the general reader and are entertainingly written. They draw attention to some problems that are indeed common such as small samples, inconsistent results, and scarce replications.
The reviews in the mainstream press have been uniformly and sometimes gushingly enthusiastic.[55] Testosterone Rex also won the 2017 Royal Society Insight Investment Science Book Prize, awarded by the oldest scientific society in the world.56 And yet none of these books has had a visible effect on neuroscientists worki
ng on sex differences. There were a few critical reviews in the technical literature, and other academics have had scathing things to say in blogs, but that’s it.[57] A neuroscientist whom I asked about the lack of reaction to Testosterone Rex replied, “One reason you don’t find many critiques of Fine’s book is that people in the field really don’t care. It’s so evidently nonsense.” In their view, Jordan-Young, Fine, and Rippon are guilty of cherry-picking (they’re good at attacking weak studies; they don’t come to grips with the strong ones), fail to acknowledge the weaknesses of their favored studies, and set up straw men, demolishing positions that neuroscientists working on sex differences don’t take (e.g., treating male and female brains as binary).[58]
If you want to compare the arguments side by side, I recommend a pair of articles easily obtainable online. The first is by Cordelia Fine, Daphna Joel, and Gina Rippon: “Eight Things You Need to Know About Sex, Gender, Brains, and Behavior: A Guide for Academics, Journalists, Parents, Gender Diversity Advocates, Social Justice Warriors, Tweeters, Facebookers, and Everyone Else.”59 The second is a response by Marco Del Giudice, David Puts, David Geary, and David Schmitt: “Sex Differences in Brain and Behavior: Eight Counterpoints.”60
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