Men's and women's brains, though quite similar in gross anatomy, are different in specific areas. − Rakyat Biologi

Men's and women's brains, though quite similar in gross anatomy, are different in specific areas. It might come as no surprise that those areas of the brain which are known to play a role in reproductive functions, or which are located very close to those areas, have been found to be sexually dimorphic. This is the case of several hypothalamic nuclei, the preoptic, ventromedial and suprachiasmatic nuclei for example, and certain interstitial nuclei of the anterior hypothalamus such as INAH3 (INAH3, whose neurons may overlap those of the preoptic nucleus, is about 40% larger in men than women, roughly confirming prior studies. Bill Byne also recently found corresponding dimorphism in the INAH3 analog in the rhesus monkey, and suggestive evidence for a hormone dependence of this dimorphism, from two hormonally manipulated females), the bed nucleus of the stria terminalis (BNSTc) which is a medial (midline) limbic nucleus of the forebrain located in front of the hypothalamus, and an area near the cerebral aqueduct (containing cerebrospinal fluid) in the periaqueductal grey area of the midbrain. Nearly all of these nuclei are larger in men than in women. However, the INAH3 nucleus seems to be outstandingly larger in the human male (Byne et al, 2000). The ventromedial hypothalamic nucleus is the only brain nucleus presently known to be more voluminous in women than in men. The sex-specific periaqueductal gray matter area of the midbrain is not known to be larger in females, but it is involved in female-specific sexual behavior. For example, in rats, when stimulated it provokes lordosis, and when destroyed, it inhibits lordosis. Furthermore, several of these nuclei have been found to be specifically involved in sexual behavior and even sexual “orientation” in rats, and in some cases also in humans. One experiment consisted of implanting male neurons of the preoptic nucleus into the preoptic nucleus area of female rats. These females manifested more male-like behaviors. The ventromedial nucleus of the hypothalamus is believed to be particularly involved in female behavior: it controls certain hormonal cycles not observed in males. Certain anterior nuclei of the hypothalamus have also been linked to propensity toward lordosis in rats.

There exists a fascinating male/female dialectic -implemented in two hypothalamic nuclei. Though what I am about to say may be a bit too much of a simplification, I wish to draw out the full distinction between the best known «male» hypothalamic nucleus, and the best known «female» hypothalamic nucleus. The first part of this story has been told by the psychophysiologist Jean-Didier Vincent in his wonderful 1994 book The biology of passions: First, the preoptic nucleus is larger in male mammals in general, and the ventromedial is larger in female mammals in general. Castrated rats become sexually inactive over time. However, this can be reversed by an injection of either testosterone or estradiol into either of these two «gender-specific» nuclei. When the injection is into the preoptic nucleus, the castrated rat, whether female or male, becomes sexually active, -in a male-typical manner (i.e., mounting). When the injection is into the ventromedial area, the castrated rat, whether male or female, becomes sexually active, -but in the female-typical manner (i.e., lordosis). Now here is whats really interesting about these two nuclei. The preoptic nucleus is a pleasure center and the ventromedial nucleus is a center of aversion. How do we know this ? By the intracranial self-stimulation technique. The technique consists of allowing a rat with a stimulating electrode implanted in his brain to self-stimulate himself by pressing a lever (this proves that the brain area implanted is a pleasure center), or allowing the rat to stop the brain stimulation by pressing a lever (when the rat does this it proves the electrode is implanted in an aversion center). As if this were not enough, direct electrical stimulation of these two hypothalamic nuclei has shown that they are both involved in sexual behavior, indeed, but that in addition, the preoptic nucleus is generally involved in appetitive (approach) behavior whereas the ventromedial nucleus is generally involved in avoidance (flight) behavior, relating to non-sexual stimuli and conditions (ex: food, same-sex relations, introduction of a new object, etc...). Now, here is the part of our little story not contributed by Jean-Didier Vincent. These two opposed sets of properties of the hypothalamic sub-areas are a reflection of the psychopathologies for which the two genders are differentially at risk in humans ! Men are more at risk for disorders of approach systems involving pleasure (drug dependence, alcoholism, sexual promiscuity and paraphylia, gambling, etc), whereas women are more at risk for disorders of avoidance systems involving aversion (depression, frigidity, anorgasmia, phobia, anorexia, etc). For details about these psychopathologies, see chapter 4.

Neurohistologists (specialists of brain tissue) are continuously developing new techniques for mapping various naturally synthesized molecules in the brain. One of these techniques enables a researcher to detect which neurons of the brain “drink up” testosterone. The researcher injects testosterone into the blood stream with a marker that will show up in color in slices of the brain after death. Then they anesthetize the animal, sacrifice it, and slice the brain. In one study, such “autoradiograms” were prepared from the brains of male rats injected with a fluorescent retrograde tracer (the neuron “drinks” the marker from its axon terminals) and with a sort of testosterone (namely, dihydrotestosterone or DHT) into the midbrain. Results showed an abundance of neurons that bind DHT and project to the midbrain in the medial preoptic area and bed nucleus of the stria terminalis. These neurons were also observed in the ventromedial section of the hypothalamus. It is now known that in rats, pigs and humans, the preoptic nucleus of the hypothalamus is larger in males than in females. Furthermore, one investigation has demonstrated that in rats, this sex difference is due to neuron loss in developing females rather than neuronal multiplication in developing males. In addition, these sex differences can be reversed in rats and pigs by post-natal castration (orchidectomy or ovariectomy). One study has recently reported a substantial sex difference in the localization of estrogen receptors within SRIF neurons (neurons which use somatostatin as their neurotransmitter) of the bed nucleus of the stria terminalis. It has now been demonstrated that gonadal hormones are critical in the implementation of anatomical sex differences these nuclei. For example, one investigation studied the effects of postnatal male orchidectomy (ablation of the testes) and female androgenization (injection of testosterone) on the bed nucleus of the stria terminalis (BNST), using 10 male and 10 female Wistar rat pups. The volume of the medial posterior region of the BNST was greater in 5 control males than in 5 control females. Sex differences occurred in the medial anterior region where females always showed a greater volume. Orchidectomy increased significantly the volume of the medial anterior region, but there was no effect from androgenization. Bill Byne has recently found from peptide and in situ markers, as well as cytoarchitectonic analysis, that INAH3 and Gorski's SDN in rat may be homologous. In fact these nuclei are all intimately and richly neuronally connected to each other in the several mammals studied so far, including humans. We will see in chapter 7 that several of these nuclei are also different in human homosexuals as compared to heterosexuals. However, before we come to too simplistic conclusions, I must say that the brain nuclei I have just mentioned are not involved only in sexual behavior, they are involved in many types of behavior such as aggressiveness, feeding, the stress response, etc.

Furthermore, several brain areas not known to play a key role in reproductive functions are also sexually dimorphic in mammals. The globus pallidus, a large nucleus deep in the hemisphere, is sexually dimorphic in humans, with boys and men having a larger one than girls and women. This particular nucleus has classically been considered to have a primitive motor role in humans. However, recent research has shown that the globus pallidus is very intimitaley linked not only with the emotional part of the brain called the limbic system, but also with the intelligent part of the brain called the cortex, particularly the part that controls action -namely the frontal lobes. In fact, it is now well established that the globus pallidus contributes to the emergence of appetitive behavior because it injects « reward » into the neural stream. Furthermore, this nucleus is also involved in psychomotor baseline, a property that is inferred from the effects of its destruction in humans in both hemispheres: indeed one of the effects of such a lesion (which occurs in hepatic encephalopathy, in Hallervorden-Spatz disease or carbon monoxide poisoning), is severe apathy. In addition, agitated schizophrenics have enlarged globus pallidi. In the case of hyperactive children, it has been found that the larger the right globus pallidus is, the more hyperactive the child is. Since we know that the human male is more turbulent and is more of a hedonistic pleasure seeker (drugs, alcohol, sex, gambling, sports), in a sense, one could consider that the globus pallidus might be a «masculine» brain center. Since there is no such thing as a brain nucleus which exists only in one sex, what we mean by a masculine or feminine brain center is one which grows bigger (the masculine center) or shrinks (the feminine center) under the influence of prenatal or postnatal testosterone.

The corpus callosum (a structure containing approximately 700 million neurons linking the neocortices of each hemisphere to each other) is larger in male rats, and this sex dimorphism can be reversed either by perinatal injections of testosterone into female rats or of female hormones into male rats.

The medial amygdala (a limbic structure located in front of the ear involved in emotion and memory, and to some extent with sexual behavior) is larger in males of several species, and its ultrastructure is also sexually dimorphic: males have larger cell bodies and more synapses. These sex differences can be reversed by perinatal injection of testosterone into the infant female.

Nuclear and cytosolic androgen receptors in the limbic brain increase gradually over the first 10 days of life. In general, nuclear receptor levels are higher in males than in females; however, this sex difference is most consistently seen in the amygdala. The reader is cautioned that a recent attempt has been made to extend the finding of larger medial amygdala in males to the human species, and failed. The volume of the medial nucleus of the amygdala was determined in the right and in the left hemispheres in 17 human brains ranging in age from 35 weeks of gestation to 94 years of age. An analysis of covariance which adjusted for differing age and brain size distributions in the male and female samples showed no significant sexual dimorphism in medial nucleus volume.

There are several indirect indications of sex differences in brain noradrenalin in mammals. One important sex difference in one of the main sites of noradrenalin synthesis of the brain, the locus coeruleus, has been reported in rats. The dorsal locus coeruleus was found to be larger in males.

Other sexually dimorphic brain structures include the anterior commissure (a structure similar to, but much smaller than the corpus callosum, linking the anterior neocortices) and the habenula (a structure connecting the two sides of the brain within the thalamus, which is itself situated right in the very center of the brain). In several submammalian species, the habenula is known to contain receptors for sex hormones, and also shows a sex difference with regard to concentrations of various neurotransmitters.

Several studies have found subtle metabolic (gonadal hormone binding, neurotransmitter) sex differences in the arcuate nucleus (another hypothalamic nucleus) of several species, including in rats and African green monkeys. Finally, several studies have found sex differences in brain nuclei involved in vasopressin physiology. Vasopressin is a hormone which plays a role in blood pressure. Men are more at risk for high blood pressure, so a sex difference in the neural control of blood pressure has long been expected, was sought, and has been found. The vasopressinergic innervation of the lateral septum (a limbic nucleus) is much denser in male than in female rats. One study demonstrated that, under physiological conditions, the development of this sex difference is dependent on the presence of androgens around the seventh postnatal day. It has been possible to induce in female or neonatally castrated male rats a fiber density as high as in control males by high doses of testosterone, given in the first, second or even third week of life.

The hippocampus is one of the major structures in the temporal lobe. A sub-population of neurons in the hippocampus, which use gamma-aminobutyric acid as their neurotransmitter, is sexually dimorphic in prenatal rats. Males have more of these particular neurons. Apparently, a sub-population of hippocampal neurons which use noradrenalin as their neurotransmitter is also sexually dimorphic, also in rats, an effect which has been found to be reversable by prenatal maculinization of females. In voles (a sort of mouse), kangaroo rats, gerbils and laboratory mice the hippocampus is larger in adult males than females and in the first four of these species hippocampal size is correlated with (related to) spatial ability. In chapter 3, I explain that spatial ability is greater in males in most mammalian species studied to date. Evolution of traits is driven by adaptational advantages which allow species to settle into a specific ecological niche. It seems that the hippocampus is important for spatial orientation and spatial learning. But there are many types of spatial orientation and spatial learning, and the specific contribution of the hippocampus to each of these has not yet been exhaustively explored by scientists. Females of the brood-parasitic brown-headed cowbird (Molothrus ater) search for host nests in which to lay their eggs. Females normally return to lay a single egg from one to several days after first locating a potential host nest and lay up to 40 eggs in a breeding season. Male brown-headed cowbirds do not assist females in locating nests. One group of researchers predicted that the spatial abilities required to locate and return accurately to host nests may have produced a sex difference in the size of the hippocampal complex in cowbirds, in favor of females. The size of the hippocampal complex, relative to size of the telencephalon, was indeed found to be greater in female than in male cowbirds. No sex difference was found in two closely related nonparasitic icterines, the red-winged blackbird (Agelaius phoeniceus) and the common grackle (Quiscalus quiscula). These authors believe that differences among these species in parental care, migration, foraging, and diet are unlikely to have produced the sex difference attributed to search for host nests by female cowbirds. This is one of few indications, in any species, of greater specialization for spatial ability in females and confirms that use of space, rather than sex, breeding system, or foraging behavior per se, can influence the relative size of the hippocampus. Another study compared male and female hippocampi and spatial ability in wild-caught black-capped chickadees (Parus atricapillus). There were no sex differences in hippocampal size or spatial ability. This suggests that the sex difference in spatial ability could be a specifically mammalian trait and could be heavily dependent upon the hippocampus. However, in birds, it seems possible that only certain spatially demanding adaptations might present with such a sex difference, which could be opposite to that observed in mammals. One investigation found that hippocampal neurons sensitive to mineralocorticoids (a hormone secreted by the adrenal gland) known to be involved in the brain’s response to stress recover (return to baseline activity levels) more quickly after stress in adult male than in adult female rats. One recent study analyzed hippocampal tissue of the right and left hemispheres excised from men and women with epilepsy. The findings were reported to suggest greater hippocampal lateralization in men than in women with higher hippocampal neuronal connectivity on the left in males than on the right. Prenatal androgens and estrogen influence sex differences in adult spatial navigation and exert differential effects on hippocampal CA1 and CA3 pyramidal neuron morphology in rats (Sengelaub, 1998).

There are several indications that cerebral neocortex (the more evolutionarily recent part of the cortex -comprising six layers of neuronal types) is somewhat sexually dimorphic in humans. The Sylvian fissure is a cleft between convolutions of the brain so big that it is recognized as a border between the frontal and temporal lobes of the brain, and the end point of its rear extension is one of the markers used to define the beginning of another lobe, the occipital lobe. It has long been known that the Sylvian fissure does not have the same length in human males and females, suggesting that the cortex surrounding it may be organized differently. Only recently have researchers investigated the possibility that cortical language areas of the left hemisphere might be relatively more voluminous in women than in men. This hypothesis makes obvious sense on the basis of what we know about sex differences in cognitive ability (see the next chapter). A team of Dutch researchers analyzed human fetal brains in 1991. They found that striate and extrastriate cortices (parts of the the occipital lobe cortex dealing with vision) were far more asymmetrical in male brains than in their female counterparts (M = 33%; F = 13%). Overall indexes of asymmetry indicated that, on the average, volumetric asymmetries in the male brain favored the right hemisphere. In contrast, the human fetal female was likely to have two hemispheres of the same size or a left hemisphere that was slightly larger than its right counterpart. The authors believed, at the time of their publication, that these results supported the hypothesis that testosterone in utero may lead to a more rapid growth of the right hemisphere or, alternatively, retard the growth of the left hemisphere. This finding is all the more interesting in light of the fact that the structure of individual neurons in this part of the cortex has been found to be sexually dimorphic in rats. One study found specific sex differences in the development of dendritic spines (tiny studs on the receiving end of neurons) in the apical shaft (the main trunk of the arborization of dendrites) of visual cortex pyramidal cells (their cell bodies are prism-shaped). An Australian research team recently looked at 11 brains of women and 10 brains of men with this hypothesis in mind. The results were astounding. Overall hemispheric asymmetry was similar for the two sexes, and asymmetry of the anterior pole of the two frontal lobes was identical. However, the volume of the left planum temporale (the top surface of the temporal lobe) and of the left Broca's area (a cortical area at the foot of the frontal lobe) relative to whole brain volume, was very sex-dimorphic. First, I must explain that these are the main language areas of the brain. The left planum temporale is the area most important for understanding spoken language. The left Broca's area is the most important area for the expression of intelligent speech. Women had a relatively larger planum temporale by a whopping factor of 29.8% and a larger Broca's area by a factor of 20.4%, and both of these sex differences were statistically significant! It is amazing that this sex difference had not been observed before 1997. Of course, the samples used in this particular recent investigation were small. So it is with trepidation that we await replication. Replication is all the more important since one older study actually found that the planum temporale, was more asymmetric (larger on the left) in men than in women. However, recall that the Australian study was not looking at zone-by-zone asymmetry per se...