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Sex on the Brain

Lecture preview: neurobiologist Cynthia Forehand



You think you have gender identity issues? You've got nothing on the gynandromorph. "It's a mosaic, an animal that might have some female parts and some male parts," says Cynthia Forehand, a professor of anatomy and neurobiology in the University of Vermont College of Medicine. She demonstrates with a photo of a zebra finch that sports pimped-out male plumage on one side of its body and drab female feathers on the other. The bird's not a hermaphrodite with ambiguous equipment; it's split 50/50, inside and out.

To the layperson, the gynandromorph is a curiosity. To Forehand and other neuroscientists, the bird is a clue with the potential to unlock mysteries about sex differences in the human brain. She'll be discussing some of those differences in an upcoming lecture for the UVM Community Medical School. The program gives the public a chance to explore the cutting-edge research covered in the med school's curriculum. Forehand's talk is called "Sex and the Brain: How Do Male and Female Brains Become Different?" And yes, attendees will get a chance to scrutinize real human brains in jars.

Forehand, 53, is originally from Nebraska; she's been at UVM since 1987, when she arrived with a doctorate from the University of North Carolina at Chapel Hill. Her main research area is the development of the human spinal cord. For the talk, though, she'll be taking on a larger issue that's daunting in more ways than one.

Sex differences in the brain are a topic that everyone, scientist or layperson, seems to have an opinion about. In the old days, curious doctors weighed male and female brains, found that men's were bigger, and left it at that - their prejudices confirmed.

Nowadays it's more complicated. There are the academics who firmly believe that any apparent differences between the thinking or feeling styles of the two sexes are a product of social conditioning. And then there are the beer commercials that portray women as chattering social networkers and men as uncommunicative, football-worshipping cavemen. Economist Lawrence Summers resigned the presidency of Harvard last year after he sparked a furor by suggesting that women might be underrepresented in science because their brains are wired for nurturing, not nuclear physics.

Can a look inside the brain confirm our preconceptions about gender - or shatter them? Forehand reveals that it's far from that simple. The results of two large National Institute of Health studies published in 2001 confirm that sex differences in human beings are real and pervasive. But it's not easy to connect clear differences in brain structure or chemistry with subtler differences in intelligence or behavior. "When you're asking how something alters behavior, it depends on how you ask the question," Forehand says.

Take the issue of brain size - does it matter? "You hear about men's brains being bigger, which is true," Forehand says. "But it turns out, if you look at the cortex, in a lot of areas in the female brain, the cells are more packed in; there are actually more cells. There's some very specific regions, often associated with language, that have more cells in the female brain."

There are consistent size differences among parts of the brain, too. The hippocampus, which is involved in learning and memory, tends to be larger in women; the amygdala, which plays some role in processing emotional reactions, is generally larger in men. The corpus callosum, which connects the brain's two hemispheres, has some areas, "probably associated with language function, where females have a relatively larger connection than males," Forehand says.

But function is just as important as size. For instance, a study found that men respond to emotional stimuli with the right side of their amygdalae, women with their left. "You might have something bigger, but it might not function any differently, or something the same size functions entirely differently," Forehand points out. "There are so many data points."

Sex differences start in the womb. If you have an XX chromosome pair - the "default body" - you become female, Forehand explains. "If you have a Y chromosome, you make that default body into a male. That means you can make gonads." From gonads come sex hormones, which "make the rest of the secondary sex characteristics, including the brain."

The process isn't over, though. Sex hormones are active soon after birth, and again - as we all know too well - during puberty and adolescence. "It's critical when you look," Forehand says. For instance, take the fraught issue of girls and mathematics. Through seventh or eighth grade, "they don't learn that differently," Forehand says. Only at about age 14 do boys pull ahead in numbers, while girls tend to outperform them in verbal tasks.

What's to blame for girls' math setback in puberty - estrogen or social expectations? Forehand believes it's both. "I think you have to step back from the time when people wanted to believe that all differences were from social pressures," she says. "It's just not true. Male and female brains are different. If you don't give your boys guns, they will turn sticks into guns. If you don't give your daughters dolls, on average, your daughters will make babies out of other things. The question is: Do those differences reflect innate ability, or do they reflect environmental niches that we have grown up in, as a species? I think it's more likely the latter."

Forehand points to changes over time in how the sexes act: "Because work is no longer all hard labor, women do a lot more work than they did in generations before." She also doesn't discount the influence of social bias in keeping women out of fields like math and the sciences.

Forehand cites the example of Ben Barres, a neuroscientist who had a sex change and wrote about being treated differently in his new identity as a man. "He'd been a neuroscientist throughout his sex change operation, always working in the same area. He gave a seminar, and he heard somebody in the hallway say something about how that was a really fantastic seminar, and it was amazing how much better his work was than his sister's," she says. The "sister" was pre-op Barres.

Neuroscience, being a fairly young specialty - the term was coined in 1975 - may actually be less biased than others. Forehand says she feels lucky to be in a field that "grew up after the realization that women could be major contributors to science."

One of the problems with mapping brain anatomy directly onto sex roles is that it's hard to see inside the working brain. The classic approach is to study rats, manipulating their brains in various ways and then watching how the changes affect their behavior. "But rats are still not people," Forehand says.

That obstacle is being overcome through imaging. Using new techniques like functional magnetic resonance imaging, scientists can see which parts of your brain you're using when you respond to a visual stimulus or remember something that makes you emotional. Another technique, positron emission tomography, uses a radioactive tracer to reveal the distribution of different chemicals in the brain.

These studies have shown, for instance, that men synthesize the neurotransmitter serotonin more quickly than women. Serotonin depletion is thought to be the major factor in clinical depression. And who suffers disproportionately from depression? Women. This example shows how useful sex-and-the-brain studies can be to the practice of medicine.

Since the 2001 NIH studies, "The Heart Association has been really good at getting the public to recognize that females feel heart attacks completely differently from men," Forehand says. "But all medicine is like that. A lot of mental illnesses are sexually dimorphic" - that is, they play out differently in the two sexes. "So we're really interested in looking at, how does your sex affect how you handle diseases?"

Understanding the sex-specific factors in disease could improve both diagnosis and treatment. So why has it taken us so long to start studying them? "It wasn't that long ago that all the research subjects at NIH were 70-kilogram males - white males at that," Forehand points out. Fearful of inadvertently harming a fetus, scientists used to exclude women of childbearing age from their studies. "That's changed dramatically, though it's been slow," Forehand says. "Two-thousand-one seems pretty late to me to finally say we've done this study and sex matters."

Even the quirky gynandromorph can contribute something to our understanding of sex and the human brain. Despite being split down the middle, the bird has hormones of both types circulating throughout its body. Its "mosaic" appearance suggests that factors besides hormones contribute to sex expression. Forehand speculates that those other factors might help account for human transsexualism, in which a person with all the anatomy and hormones of one sex nonetheless feels as if he or she belongs on the other side of the divide.

Fascinating as brain science is in its complexity, it tempts people to ask simple questions. Will studies of the brain give girls an excuse for chatting on the phone instead of tackling their calculus homework? Or guys a justification for playing video games instead of "talking about the relationship"?

Forehand doesn't think so. "You have an entire repertoire of behaviors that are based on your genotype and your relationship with the environment from the time you were born," she points out. Some factors, like your IQ, may be a lot more empowering or limiting than any sexual characteristic. As for the pop psychology of Mars and Venus, that's all well and good, she suggests - as "cocktail party conversation."

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