“To some appreciable degree, these brain differences have to translate to behavioral differences,” says Cahill. Numerous studies show that they do, sometimes with medically meaningful implications.

A 2017 study in JAMA Psychiatry imaged the brains of 98 individuals ages 8 to 22 with autism spectrum disorder and 98 control subjects. Both groups contained roughly equal numbers of male and female subjects. The study confirmed earlier research showing that the pattern of variation in the thickness of the brain’s cortex differed between males and females. But the great majority of female subjects with ASD, the researchers found, had cortical-thickness variation profiles similar to those of typical non-ASD males.

In other words, having a typical male brain structure, whether you’re a boy or a girl, is a substantial risk factor for ASD. By definition, more boys’ than girls’ brains have this profile, possibly helping explain ASD’s four- to fivefold preponderance among boys compared with girls.

Why our brains differ

But why are men’s and women’s brains different? One big reason is that, for much of their lifetimes, women and men have different fuel additives running through their tanks: the sex-steroid hormones. In female mammals, the primary additives are a few members of the set of molecules called estrogens, along with another molecule called progesterone; and in males, testosterone and a few look-alikes collectively deemed androgens. Importantly, males developing normally in utero get hit with a big mid-gestation surge of testosterone, permanently shaping not only their body parts and proportions but also their brains. (Genetic defects disrupting testosterone’s influence on a developing male human’s cells induce a shift to a feminine body plan, our “default” condition.)

In general, brain regions that differ in size between men and women (such as the amygdala and the hippocampus) tend to contain especially high concentrations of receptors for sex hormones.

Another key variable in the composition of men versus women stems from the sex chromosomes, which form one of the 23 pairs of human chromosomes in each cell. Generally, females have two X chromosomes in their pair, while males have one X and one Y chromosome. A gene on the Y chromosome is responsible for the cascade of developmental events that cause bodies and brains to take on male characteristics. Some other genes on the Y chromosome may be involved in brain physiology and cognition.

Scientists routinely acknowledge that the presence or absence of a single DNA base pair can make a medically important difference. What about an entire chromosome? While the genes hosted on the X chromosome and the Y chromosome (about 1,500 on the X, 27 on the Y) may once have had counterparts on the other, that’s now the case for only a few of them. Every cell in a man’s body (including his brain) has a slightly different set of functioning ​sex-​chromosome genes from those operating in a woman’s.

Sex-based differences in brain structure and physiology reflect the alchemy of these hormone/receptor interactions, their effects within the cells, and the intermediating influence of genetic variables — particularly the possession of an XX versus an XY genotype, says Cahill.

Zeroing in on neural circuits

Shah’s experiments in animals employ technologies enabling scientists to boost or suppress the activity of individual nerve cells — or even of single genes within those nerve cells — in a conscious, active animal’s brain. These experiments have pinpointed genes whose activity levels differ strongly at specific sites in male versus female mice’s brains.

What would happen, Shah’s team wondered, if you knocked out of commission one or another of these genes whose activity level differed between male and female brains? They tried it with one of their candidate genes, turning off one that was normally more active in females.

Doing this, they found, totally shredded mouse moms’ willingness to defend their nests from intruders and to retrieve pups who had wandered away — maternal mandates that normal female mice unfailingly observe — yet had no observable effect on their sexual behavior. Torpedoing a different gene radically reduced a female mouse’s mating mood, but males in which the gene has been trashed appear completely normal.

All this points to a picture of at least parts of the brain as consisting of modules. Each module consists of a neural or genetic pathway in charge of one piece of a complicated behavior, and responds to genetic and hormonal signals. These modules — or at least some of them — are masculinized or feminized, respectively, by the early testosterone rush or its absence. The mammalian brain features myriad modules of this sort, giving rise to complex combinations of behavioral traits.

Which is not to say every man’s or woman’s brain looks the same. Our multitudinous genetic variations interact with some of our genes’ differential responsiveness to estrogens versus androgens. This complicated pinball game affects goings-on in at least some of the brain’s neural circuits and in whatever little piece of behavior each of these neural circuits manages.

“We think gender-specific behavior is a composite of all these modules, which, added up, give you your overall degree of maleness and femaleness,” says Shah.

Consider the genes Shah has isolated whose activity levels differ significantly in the brains of male and female mice. “Almost all of these genes have human analogues,” he says. “We still don’t completely understand their function in human social behavior. But when we looked at publicly available databases to find out what we do know about them, we found a surprising number that in humans have been linked with autism, alcoholism and other conditions.”

Bigger imaging studies and imaginative animal research now in the works promise to reveal much more about humanity’s inherent — although by no means uniform, and often not substantial — sex-associated cognitive differences and vulnerability to diseases.

Trying to assign exact percentages to the relative contributions of “culture” versus “biology” to the behavior of free-living human individuals in a complex social environment is tough at best. Halpern offers a succinct assessment: “The role of culture is not zero. The role of biology is not zero.”