Deciphering How the Sexes Think

Editor's Note: This is the second article in a series on sex-based differences in the biology of males and females. Future articles in the series will cover sex-based differences in genetics, autoimmunity, and drug metabolism. Stereotypes aside, women and men do process information in singular ways. In the past, tests that tried to pinpoint those variations were fraught with inconsistencies and irregularities. But now, by studying the brain itself, researchers are learning that the sexes use different parts of the brain to handle the same input. A growing number of imaging studies reveal that women and men do not process certain cognitive information in the same way. For instance, researchers have found that women, when trying to exit a virtual 3-D maze, activated the right parietal cortex and right prefrontal cortex; men triggered the left hippocampus alone.1 When viewing emotionally disturbing images, women showed an increase in activity on the amygdala's left side; in men, it was the right side.2 The amygdala is a small brain region associated with mood and feelings. Fertile research ground exists for researchers who want to figure out why and how this processing differs, and more specifically, how hormones are involved. And even bigger questions lie ahead in terms of assigning any adaptive significance to these differences. "I think that it's appropriate that we should expect a fair number of proximate processing differences because the ecology of being male and the ecology of being female has been, through our evolutionary history, so different," says evolutionary biologist and behavioral ecologist Bobbi S. Low, University of Michigan, Ann Arbor. Raging Hormones As a developmental psychologist, Sheri Berenbaum is interested in how sex hormones mediate behavior. For her, the big question yet to be tackled is: What goes on in the brain when it is exposed to sex hormones, and how does that translate into conduct? "Given the sex differences in behavior, it's clear that there have to be sex differences in the brain," says Berenbaum of Pennsylvania State University, State College. "But how exposure to androgens or estrogens early in development changes brain function later on is unknown. We don't know yet whether there are more differences than similarities." Berenbaum was a member of an Institute of Medicine (IOM) panel, which last year released a report that discussed sex-based differences and made recommendations strongly urging scientists to incorporate this research into their work.3 Berenbaum studies girls with congenital adrenal hyperplasia (CAH), a genetic enzyme deficiency that causes the embryo to be exposed to high levels of androgens, beginning about the fifth week and continuing through to birth. Her lab has found that CAH girls, as compared to their unaffected sisters, play more with boy's toys as children.4 Jay Giedd, a colleague of Berenbaum's, studies brain anatomy in a host of disorders, including CAH girls. By viewing brain architecture in healthy boys and girls, ages 3 to 19, with MRI scans at two-year intervals, Giedd, chief of brain imaging for the child psychiatry branch at the National Institute of Mental Health, has found that their brains are different in their respective developmental paths. In girls, the brain tends to develop more quickly. The frontal lobes, the executive of the brain so to speak, peak in their thickness of gray matter at age 11 in girls and age 12 in boys. The amygdala is loaded with testosterone receptors and grows more rapidly in teenage boys. The hippocampus—used in memory storage, retrieval, and language—is filled with estrogen receptors, and grows more quickly in girls. Even fewer studies look at brain activity of young children while performing some cognitive task. Erik Everhart, assistant professor of psychology at East Carolina University, and colleagues at the State University of New York at Buffalo, found that boys and girls, 8 through 11, use different parts of their brains to recognize faces and expressions.5 Each sex performed equally well on the cognitive tests. In a face-recognition-memory task, boys used more of their right brain while girls used more of their left, as measured by event-related potentials (ERPs). ERP is a derived measure of the electroencephalogram, which provides gross information about brain electrical activity. The authors speculate that these differences may help girls detect fine changes in facial expression, so therefore they are better at sensing people's moods. Reading someone's mouth or eyes requires finer discrimination, possibly left hemisphere involvement, than does judging emotions in the entire face. This, however, is very difficult to measure. Everhart's team hypothesizes that hormones are responsible for such differences. "Differential exposure to hormones is definitely there prior to puberty," he says. The Verbal-Spatial Dichotomy Courtesy of Sally ShaywitzLanguage Function: Functional magnetic resonance activation patterns of 19 men (left image) and 19 women (right image) obtained while performing a rhyming task. The men activated the left inferior frontal gryrus while the women activated both the left and the right inferior frontal gyri. Before the mid-1990s, language-skill imaging studies primarily enrolled male subjects. Pediatrics professor Sally Shaywitz, Yale University School of Medicine, studies sex differences in the brain using functional MRI (fMRI). She codirects, along with husband Bennett Shaywitz, the National Institute of Child Health and Development, Yale Center for Learning and Attention. Together, they study phonological processing, a word's sound structure. Subjects view pairs of nonsense words such as "jeat" and "lete" and are asked whether they rhyme or not. Sally Shaywitz decided to include women in this type of work. In doing so, her team found significant differences in the parts of the brain men and women used to perform these tasks, although both sexes carried out the test with equal speed and accuracy. fMRI scans showed that male subjects activated the left inferior frontal gyrus (bocha's region), which is involved in processing speech; females activated both the left and right regions.6 Shaywitz, who was also an IOM panel member, says this new knowledge helps to explain the observation that only men typically suffer decrements in verbal function following a left hemisphere stroke. It also answers why women seem to be more resilient to the effects of such injury. Architecture Counts Differences in how the brain is utilized is not the only factor, its architecture also matters. Several years ago, Raquel Gur, professor of psychiatry and neurology, and husband Ruben Gur, professor of psychology in psychiatry, both at the University of Pennsylvania School of Medicine, found through MRI that the proportions of gray and white matter in the brain differ between men and women, and that this difference is associated with cognitive performance.7 The Gurs learned that women have more gray matter, which is comprised of the neuronal cells and their dendrite extensions that communicate with other neurons. Men have more cerebral fluid and white matter, the axons that reach out to distant areas of the brain. In short, they believe that women are more efficient at central processing of information, and men at transferring information between distant regions. In addition, it might mean that women are better at communicating between hemispheres and men within those hemispheres. Of the top spatial test performers, nine were men and one was a woman. Of the men, seven had greater white matter volumes than the women. They also found that women have a larger corpus callosum than men. But the corpus callosum consists of white matter, so the question becomes why would women have more white matter only here? The Gurs suggest that women are more efficient at moving between different ways of relating to the world, and men are better at working within one mode at a time. More recently the Gurs, using fMRI, found a difference in the regions of the brain activated during verbal and spatial tests.8 During difficult verbal tasks, women activated more brain regions than did men. During difficult spatial tasks, men mobilized their brains in a more concentrated way; only their right parietal cortexes were activated. Women used more brain regions during the spatial task, "almost as if they were doing a verbal test," says Ruben Gur. Much of the brain imaging work may have implications for treating stroke or victims of brain injury. If a person has a left hemisphere stroke, men are more likely than women to have aphasia, or language deficits, notes Everhart. So, knowing how injury affects the brain, as well as how men and women use these areas differently, might help in understanding how they recover. Donald Stein, an Asa G. Candler professor in psychobiology, emergency medicine, and neurology at Emory University in Atlanta, has found a profound effect of hormone status and recovery.9 About 10 years ago, using spatial learning tests, he noted that his female lab rats recovered from traumatic brain injury better than males. But this depended on the status of the females' estrus cycle at the time of the injury. Animals in the luteal phase, when progesterone predominates, recovered better than if the same injury occurred during the follicular phase, when estrogen is on the rise. Stein found that in injured rats, progesterone reduces cerebral edema while preventing further cell death and inflammatory damage to brain cells. But how this is accomplished is still unknown. "That's the big question," he says. Stein surmises that progesterone, which is made in both the brain's glial cells and in the peripheral nervous system's Schwann cells, stems the flow of immune-presenting cells entering the compromised blood-brain barrier. This squelches the excitotoxicity of neurons, which essentially fire themselves to death after a head trauma. Progesterone is also a potent anti-inflammatory and antioxidant, both of which help reduce neuronal loss caused by brain injury. Armed with these data, Stein and colleagues Arthur Kellerman and David Wright are starting a National Institutes of Health Phase II safety and efficacy trial to test progesterone in treating brain injury in humans. As Stein and others point out, this type of research, which may have begun with a seeming anomaly in female study animals, now shows potential benefit for both sexes. Says Stein: "My research applies equally well to men as it does to women." Karen Young Kreeger (kykreeger@aol.com) is a contributing editor. References 1. G. Gron et al., "Brain activation during human navigation: gender-different neural networks as substrate of performance," Nature Neuroscience, 3:404-8, 2000. 2. H. Black, "Amygdala's inner workings," The Scientist, 15[19]:20, Oct. 1, 2001. 3. K.Y. Kreeger, " Yes, biologically speaking, sex does matter," The Scientist, 16[1]:35-6, Jan. 7, 2002. 4. S.A. Berenbaum, "Psychological outcome in congenital adrenal hyperplasia," In: Therapeutic Outcome of Endocrine Disorders: Efficacy, Innovation, and Quality of Life, B. Stabler and B.B. Bercy, eds. New York: Springer, 2000, pp. 186-99. 5. D.E. Everhart, et al., "Sex-related differences in event-related potentials, face recognition, and facial affect processing in prepubertal children," Neuropsychology, 15:329-41, July 2001. 6. B.A. Shaywitz, et al., "Sex differences in the functional organization of the brain for language, Nature, 373:607-9, 1995. 7. R.C. Gur et al., "Sex differences in brain gray and white matter in healthy young adults: Correlations with cognitive performance," Journal of Neuroscience, 19:4065-72, 1999. 8. R.C. Gur et al., "An fMRI study of sex differences in regional activation to a verbal and a spatial task," Brain and Language, 74:157-70, 2000. 9. D.G. Stein, "Brain damage, sex hormones and recovery: A new role for progesterone and estrogen?" Trends in Neuroscience, 24:386-91, July 2001.

Deciphering How the Sexes Think

Interested in reading more?

Become a Member of