Male and Female Brains

Summary of Lecture for Women's Forum West Annual Meeting,
San Francisco, California 2003

Sex differences and the brain. What does it matter, you say? I think it does. Through such knowledge we will eventually be better able to understand the basis for behaviors that many now perceive as entirely rooted in social custom or familial history. From that understanding, we will gain the acceptance, patience, and respect so vital to all human endeavor.

Interestingly, people who see a human brain for the first time often ask, "Is it male or female?" Yet, for many millennia no one, even scientists, thought about sex-related differences and similarities in the human brain. A brain was just a brain. Now hardly a year goes by that we don't read authoritative studies showing these differences. I was taken aback just a few months ago when, at a Ph.D. examination dealing with Magnetic Resonance Imaging of human brains, the student reported having pooled the data from both sexes. Even if the intent was not to explore male-female differences, one can hardly expect to make accurate interpretations from such mixed data.

Obviously, no single factor accounts for the gender-related differences we are finding. We are slowly, one by one, unraveling the various integrative factors involved in this mystery. A basic question being asked is whether the differences between male and female brains outweigh the similarities or vice versa. Some researchers report finding more differences within the sexes than between the sexes. Please understand that the objective of my talk is not to discuss whether the brain of one sex is superior to the brain of the other but to explore the significance of the differences we are discovering in the brains of males and females. As you might imagine, to conduct these studies, we need brain samples so that we can make our comparisons. So far, no live human beings, males or females, have been willing to give us their brain tissue to use in our experiments. But all is not lost: The rat brain, oddly enough, has the basic components and major structures in its little pecan-size brain that we humans have in our large cantaloupe-size brain. In general terms, what we have learned about the anatomy of the rat brain has later been replicated by studies in higher mammals including humans. What is particularly important, of course, is that using the laboratory rat allows us to control many variables--the sex, the age, the living conditions, the diet, the water intake, the environment, and so forth, thus assuring clear comparisons.

To appreciate the work we do, let me take a moment to give you some fundamentals of the brain's anatomy. In the embryo our nervous system starts as a simple tube, the head end forming the brain and the remainder forming the spinal cord. The brain is divided into three parts: the hind brain, midbrain and forebrain. Our interest is primarily in the forebrain, which expands tremendously over the course of its development to form about 85% of our total brain, called the cerebral hemispheres. These two large hemispheres are familiar to anyone who has seen a picture of the brain The outer layers of the cerebral hemispheres are called the cerebral cortex. (Cortex means bark.) With the use of a light microscope we can easily measure the thickness of this cortex in the rat because it is smooth and does not have folds as do more highly evolved brains.

Factors affecting cortical thickness are the main interest in our gender studies because the cerebral cortex is the most highly evolved part of the brain and deals with higher cognitive processing. The cerebral cortex, like other parts of the brain, consists of nerve cells with branches and functional connections called synapses; glial cells, the metabolic and structural support cells for the nerve cells; and blood vessels. Cortical thickness is a key factor; it gives us an overall indication of what is happening collectively to these structures within the cortex.

Table 1

Statistical significance of differences between right and left cerebral cortical thickness in male and female rats ( S=statistically significant; NS=nonstatistically significant)

					Cortical Areas
	Age (days)	N	Frontal		Parietal			Occipital
			10	4	3	2	18	17	18A
	6	13	S	S	S	NS	S	S	S
	14	17	S	S	S	NS	S	S	S
Males	20	15	S	S	S	NS	S	S	NS
	90	15	NS	S	S	NS	NS	S	NS
	185	15	S	NS	S	S	S	S	S
	400	15	S	NS	S	S	S	S	NS
	900	8	NS	NS	NS	NS	NS	NS	NS
All Ss R>L
	7	15	NS	NS	NS	NS	NS	NS	NS
	14	15	NS	NS	NS	NS	NS	NS	NS
Females	21	15	NS	NS	S#	NS	NS	NS	NS
	90	19	NS	NS	NS	NS	NS	NS	NS
	180	11	NS	NS	NS	NS	NS	NS	NS
	390	17	NS	NS	S#	NS	NS	NS	NS
S#=L>R

The cortical areas sampled are seen in Figure 1. As the name implies, the frontal area is in the front of the brain, the parietal is in the middle and the occipital is at the back of the hemisphere. In very simple terms, the frontal area deals with motor behavior and planning for action, the parietal area with general sensory functions, and the occipital cortex with visual functions.

By measuring the thickness in the frontal, parietal and occipital cortex in our experimental rats, we can begin to assemble important information and to ask such questions as:

1. Are there sex-related differences in the growth of the cerebral cortex at birth? The female cortex shows some areas are more highly developed than others at birth compared to the male. Her motor cortex (frontal) shows the highest development with her sensory cortex (parietal) next and visual cortex (occipital) least developed. In the male brain, the motor, sensory and visual cortical all show a similar degree of development at birth; differences in growth rates appear soon after birth.

2. Is the thickness of the right and left cerebral cortex different between male and female animals? The answer is decidedly "yes" as revealed by a glance at Table 1. "N" shows the number of brains sampled in each age group from shortly after birth to well into adulthood and for males into very old age. "S" means there is a statistically significant difference between the cortical thickness in the right and left hemispheres. "NS" means there is no statistically significant difference between the thickness in the hemispheres.

In the female brain,we observe no statistically significant differences in cortical thickness between the right and left hemispheres from birth well into adulthood. We found nonsignificant differences in 41 of the 43 regions measured; in other words, in 95% of the cases she displays a symmetrical cortex

It has been commonly stated that the female cortex is symmetrical and the male cortex is asymmetrical. Turning again to Table 1, this time to assess the development of the male cortex, we find that the hemispheric thickness differences from birth to old age are definitely not as consistent as in the female brain. In fact, in the male cortex the right hemisphere is significantly thicker than the left in 31 of the 49 regions measured. In other words, in 60% of the cases, the cortex of the male rat brain is significantly asymmetric.

With the data in Table 1, we now need to state more accurately that parts of the male cortex are asymmetrical and parts are not. Two consistent findings in the male rat brain were the following: (1) area 2 in the parietal cortex showed nonsignificant findings or symmetry from birth to 90 days of age; differences in cortical thickness were seen only after 90 days of age. (2) In the 900-day-old male rats, all areas of the cortex showed nonsignificant differences between the hemispheres. At this very old age, the male cortex appeared similar to that of the female cortex in terms of its symmetry.

One obvious question to ask when we assess our findings in the female brain is: What role do the sex steroid play in establishing cortical thickness ? As we would expect, in those animals with ovaries, there is no significant difference in the thickness of the hemispheres, but in those without ovaries, two areas of the occipital cortex show significant differences in thickness between the right and left hemispheres. It seems that the visual cortex in female animals without ovarian hormones is more like that of the normal male cortex. (Though not shown, in our 800 day old females, we also found this pattern was similar in the occipital cortex.)

In summary, the female animal, with or without ovaries, shows no significant difference in the thickness of her right and left cerebral cortices except in part of the visual cortex where those without ovaries develop right dominance. Other researchers have reported that two major connecting fiber tracts between the two hemispheres are larger in females than in males, a finding that supports the notion that the female exhibits symmetrical cortical patterns. What might be the advantage of such symmetry in cortical morphology?

For the female animal, the main functions in life are to bear, protect and raise her offspring. These roles challenge her to go in many directions, both geographical and conceptual, something that may be more accessible and readily achieved with a symmetrical brain. We might conjecture that the trend to right dominance in the older brain of the female without ovarian hormones suggests a shift to the more visual focus demanded of the male.

Now we need to ask the same question we asked of the female brain: What role do sex steroid hormones play in determining cortical thickness patterns in the male? In rats without testes some cerebral cortical areas show significant differences and some do not. Of interest to me is that areas 17 and 18a dealing with visual processing in both males and females devoid of sex steroid hormones showed statistically significant differences between the right and left hemispheres. Area 17 in the male also showed statistically significant differences in the cortical thickness of the right and left hemispheres among animals with circulating sex hormones, but area 18 a did not

In summary, the male cerebral cortex displays both symmetrical and nonsymmetrical right/left patterns in cortical thickness with the nonsymmetrical pattern being slightly more anatomically frequent (60%). and in turn suggesting functionally more frequent. What might be the advantage of having some cortical areas asymmetrical in the male? In general, male behavior involves finding and defending his territory and finding his female, all rather focused functions, possibly benefiting from an asymmetrical cortex.

Another consideration is the similarity between male and female; in these studies, the question is in what areas do males and females have the same right/left pattern, whether symmetrical or nonsymmetrical? In area 10 (motor behavior and planning for action) at 90 days of age both are nonsymmetrical; in area 2 (general sensory functions) from birth to 90 days of age both are nonsymmetrical; in area 18A (visual functions) from 20-21 to 90 days of age both are nonsymmetrical. In area 3 (general sensory functions) at 2-21 days of age both are symmetrical and at 400-390 days of age both are symmetrical.

Needless to say, these data further emphasize the necessity of considering the numerous variables that contribute to anatomical and in turn physiological development generally and specifically to the growth of the cerebral cortex. Furthermore, wresting meaning from the multiplicity of similarities and differences between male and female brains presents a considerable challenge in the decades ahead, but a challenge that those of us who dedicate our professional lives to such research anticipate with relish.