Differences between females and males have been reported for several cortical structures. A postmortem study of the language-associated corti- cal areas of the brains of 11 females and 10 males has reported that the vol- ume of the superior temporal cortex was 18 percent larger in females than in males. The overall difference in volume was accounted for primarily by differences in the planum temporale (mostly the auditory association cortex), which was 30 percent larger in females (Harasty et al. 1997).
A cytoarchitectural study of the planum temporale in females and males has reported particularly interesting results (Witelson et al. 1995). This study offers some especially useful information because although it used tissue obtained postmortem, not only was the cause of death well understood but the subjects were also known to have had normal cog- nitive function in life. The subjects for the study were five females and four males suffering from metastatic cancer. At the time the subjects were recruited for the study they were free from obvious symptoms of their disease. The subjects gave their consent for their brains to be examined at autopsy. At the time of recruitment, they underwent extensive medi- cal and neuropsychological testing. In addition, they developed no neuro- logical or psychiatric complications as the disease progressed. All subjects were predominantly right-handed. The mean age at death was 49 years for the males and 54 years for the females.
Following death, the brains were removed and fixed for histologi- cal analysis. The time between death and tissue fixation was on average 3.5 hours for the males and 7.2 hours for the females. The variables mea- sured were the total cortical depth, the number of neurons per 1 mm2 of
cortical surface and the number of neurons per unit volume (the density of cell packing). Neither the cortical depth nor the number of cells dif- fered between females and males. The number of neurons per unit vol- ume, however, was significantly greater in females (by 11 percent) than in males. The authors point out that this is almost the same difference as the difference in total brain volume generally reported between females and males. They suggest that reported overall differences in brain volume may simply be because cells are packed more densely in the female brain than in the male brain. A similar suggestion has been made by Gur et al.
Chapter 3: Brain structure 47
(1999), who have reported, using MRI, that females have a higher percent- age of cortical gray matter while males have a higher percentage of corti- cal white matter. They suggest that the increased density of gray matter in females could compensate for the smaller overall volume. By contrast, Rabinowicz et al. (1999) have reported significantly higher neuronal den- sity and higher estimated neuronal numbers in males than in females.
Despite superficial appearances, the brain is not symmetrical around its longitudinal axis. This asymmetry has been shown to apply to both structure, discussed in this chapter, and function (Chapter 4). Many stud- ies have demonstrated that the brains of normal individuals are asym- metrical, with the right hemisphere larger than the left, and that this asymmetry is evident in the newborn child. This normal asymmetry is so well documented, in fact, that individual variations in asymmetry may be indicative of brain pathology such as schizophrenia (Chapter 7). It is also reported that the female brain is more symmetrical than the male brain. The asymmetry is reported to differ most between females and males in areas related to language function and to handedness (Chapter 6).
A number of recent studies have demonstrated that, in people who are right-handed, the frontal areas of the brain tend to be larger on the right side. Paus et al. (1996) have reported frontal lobe differences in an MRI study of 105 right-handed individuals (Table 3.3). In their study, these authors reported that the volume of gray matter in the anterior cin- gulate sulcus and in the superior-rostral sulcus was larger in the right hemisphere than the left hemisphere, while the volume of gray matter in the posterior cingulate sulcus and paracingulate sulcus was greater on the left. The cingulate sulcus was significantly larger in females than in males, and the paracingulate sulcus was significantly larger in males. However, an imaging study by Bullmore et al. (1995) has demonstrated that these differences are not nearly so clear-cut when you consider hand- edness as a variable. In their study, the only consistent pattern of asym- metry was for right-handed males. As the authors point out, their result is consistent with the idea that the female brain is more symmetrical
Table 3.3 Estimated frontal lobe asymmetry using MRI.
Region Asymmetry
Volume of gray matter, anterior cingulate sulcus R > L, f and m Volume of gray matter, posterior cingulate sulcus L > R, f and m Volume of gray matter, paracingulate sulcus L > R, f and m Sex differences in asymmetry:
cingulate sulcus f > m
paracingulate sulcus m > f
Source: From Paus et al. (1996).
48 The Female Brain, Second Edition
than the male brain. On the other hand, Reiss et al. (1996), in a study of children, reported that the brain asymmetry, greater volume in the right cortical areas, was the same for boys and girls. Although the proportion of left-handed to right-handed children was balanced between the two groups (15 percent were left-handed), the results were not analyzed for differences in handedness.
One area where clear size and shape differences have been noted is in the fiber tracts that connect the cerebral hemispheres. These fiber crossings are known as commissures or decussations, depending upon their loca- tion. The largest of the commissures is the corpus callosum (Figure 3.3), which relays information between the two cerebral hemispheres. Most fiber tracts in the human brain and spinal cord are bilaterally crossed and symmetrical (Figure 3.4). Sensory information from one side crosses to the opposite side and is relayed to the cerebral cortices for processing. The corpus callosum has generally been reported to be larger in females, and some authors have attributed sex differences in the lateralization of cognitive and language functions to this size difference (Chapter 6). Some studies, both histological (de Lacoste-Utamsing and Holloway 1982) and MRI (Allen et al. 1991), have suggested that the previously reported sex differences may be due to a different shape in females rather than a differ- ence in the overall size of the corpus callosum. The anterior commissure, which crosses the deep diencephalon, near the hypothalamus, contains axons that primarily connect the two temporal lobes. In a study of autopsy
corpus callosum
Chapter 3: Brain structure 49
material from 100 human females and males it has been reported that the anterior commissure is approximately 12 percent larger in females than in males (Allen and Gorski 1991).
The hypothalamus is known to play a role in sexual behavior and reproduction. Not surprisingly, it was one of the first regions to be sys- tematically examined for sexual dimorphism. The hypothalamus may be divided into a number of distinct regions, based upon the function of the neurons located in each different area. Some authors classify the preoptic area as a part of the hypothalamus and others classify it as a separate nucleus. The two areas are so intimately linked, however, that to consider them together is probably the logical option, at least for our purposes (Figure 3.5).
Sexual dimorphism in the human preoptic nucleus was first reported in 1985 by Swaab and Fliers. In that study both the size and the
thalamus
sensory signal on left side of body
sensory signal on right side of brain
spinal cord
Figure 3.4 Sensory information, for example, touch, from one side of the body is relayed, via the thalamus, to the opposite side of the brain. The information is then “shared” via the corpus callosum with the other side of the brain.
50 The Female Brain, Second Edition
total number of neurons in particular regions of the preoptic nucleus were reported to be significantly larger in males than in females. The volume of the bed nucleus of the stria terminalis in males has also been reported to be approximately twice the volume in females (Allen et al. 1990; Zhou et al. 1995). The evidence for sexual dimorphism in the hypothalamus was reviewed by Swaab and Hofman (1995). In their article, the authors noted that the nucleus is the same size in females and males at birth, but is smaller in adult females relative to adult males because the size decreases with maturity in females. Another area where the female/male size relationship changes with develop- ment is the amygdala. At birth, it is the same size in females and males, but by the age of around 8 years it has grown to a larger overall size in males. At around 10 years, however, the volume has begun to decrease in males, but continues to increase in females so that from about the age of 20 onward, the volume of the amygdala is greater in females than in males (Goldstein et al. 1999).
lateral hypothalamic areas
fornix
lateral tuberal nucleus ventromedial hypothalamic nucleus arcuate nucleus dorsomedial hypothalamic nucleus peviventricular nucleus hypothalamus
Figure 3.5 Schematic representation of the subregions of the human hypothala- mus. Shaded region represents approximate location of enlarged area; i.e., inter- nal capsule.
Chapter 3: Brain structure 51