The majority of animal studies on sexual dimorphism in the brain have come from studies in the laboratory rat, although monkeys, ferrets, gerbils, and squirrels have also had their day. In general, the results of the experi- mental studies are consistent with the results obtained in humans. For this reason, this section will give only a brief overview of the animal literature.
Sexual dimorphism has, not surprisingly, been clearly demonstrated in the hypothalamus. One particular region of the preoptic area has been reported to be five to six times greater in volume in male rats than in female rats (Gorski et al. 1978). This region was named the “sexually dimorphic nucleus of the preoptic area” by Gorski et al., who first reported the size difference. Another part of the preoptic area, the anteroventral periven- tricular nucleus of the preoptic area, shows the opposite pattern of sexual dimorphism: the area is substantially larger and more densely packed with neurons in the female than in the male.
Brain regions where anatomical dimorphism has been observed are summarized in Table 3.4. This table is not meant to be a comprehensive listing of the literature. It is meant only as a list of examples. In most cases, the difference reported seems to be a larger area in the male. One area that has been deliberately omitted from the list is that of the song-related nuclei that show distinct differences in a number of bird species. The song- related nuclei play an important role in the sexual behavior of many birds. The song of the male is part of an elaborate courtship display necessary to seduce the female. While human males may indeed use song as part of their courtship display (have a look at a rock star in action), anything even close to the song-related nuclei is yet to be discovered in the brain of the human male.
In the cerebral cortex, differences have been reported in regions related to vision, motor control, sense of smell, and emotion. In the visual cortex, there are more neurons in males than in females and the dendrites of some neurons are larger in males. Sex-based differences have been reported in the hippocampus and amygdala. In the hippocampus, which is clearly divided into layers composed of different types of neurons, the granule cell layer is larger in males than in females. The amygdala is also larger in males and receives a greater number of axons from neurons in the hypothalamus carrying the hormone vasopressin. In the brain stem, differences have been noted in the striatum and the locus coeruleus. In both of these regions, neurons containing the major neurotransmitter of the region (noradrenaline in the case of the locus coeruleus, and GABA in the case of the striatum) are more numerous in females than in males. In addition to areas containing neuronal cell bodies, a number of animal studies have also reported size differences in the corpus callosum and the anterior commissure, similar to those already discussed in humans.
52 The Female Brain, Second Edition
Table 3.4 Examples of studies reporting regional brain differences in rat.
Region Difference Reference
amygdala volume, Mizukami et al. 1983
m > f
bed nucleus olfactory tract volume, m > f Collado et al. cell count, m > f
corpus callosum unmyelinated axons,
f > m Mack et al. 1995.
myelinated axons, m > f
hippocampus granule cell number,
m > f Roof 1993
CA3 pyramidal cells, proximal dendrite volume, f > m; distal dendrite volume, m > f
Juraska et al. 1989
hypothalamus:
anterior ventral volume, f > m Simerly et al. 1985 periventricular preoptic
area cell count, f > m Leal et al. 1998
arcuate nucleus volume, m > f, density denditric branching and spines, f > m
medial preoptic area volume, m > f Gorski et al. 1978 locus coeruleus noradrenaline neurons Guillamon et al. 1988
number, f > m volume, f > m
neocortex volume, m > f Reid & Juraska 1992b
bed nucleus stria terminalis volume, m > f De Vries et al. 1994
striatum GABA neurons Ovtscharoff et al. 1992
number, f > m
suprachiasmatic nucleus spine synapses, Guldner 1982 m > f
visual cortex volume, number of
neurons,
Reid & Juraska 1992a m > f
The CT scan is a multiple X-ray method that provides a snapshot of brain structure at a given point in time. The machinery is rotated around the head of the subject, taking X-rays at every degree of rotation. By sum- ming the density of the image, for each individual exposure, for individ- ual coordinates throughout the brain, a three-dimensional representation of the brain structures can be created that distinguishes gray matter and
Chapter 3: Brain structure 53
white matter, as well as CSF and blood. The advent of CT was a major step forward in providing anatomical analysis of the human brain. It allowed visualization of individual brain structures without the distortion associ- ated with anatomical studies of fixed tissue. It was also a breakthrough as a diagnostic tool, providing accurate localization (about 1 mm resolution) of tumors and lesions.
An early CT study of 75 males and 41 females reported a significantly greater ratio of ventricles to brain volume in males than in females, with larger sulci and fissures in the males (Jacobson 1986). An MRI study in 1999 presented similar results. The study, which measured volume of gray matter, white matter, and CSF, found a higher percentage of gray matter in females than males. The males, on the other hand, had a higher per- centage of white matter and CSF. There were no hemispheric asymme- tries in females. However, gray matter percentage was higher in the left hemisphere of males, while CSF was higher in the right (Gur et al. 1999). Im et al. (2008) also concluded that reported sex differences in brain size between females and males required differences in connectivity, as sug- gested by the differences in gray and white matter.
MRI, like CT, also uses computerized analysis of sequential brain images to produce a three-dimensional image of the brain. “Magnetic res- onance” refers to the oscillations observed in the nuclei of elements with odd atomic numbers (e.g., hydrogen, H) when they are exposed to a mag- netic field. The oscillating nuclei align themselves with the magnetic field. Once the nuclei are aligned, a burst of radio waves will disrupt the align- ment. When the radio waves stop, the nuclei will “snap back” into their alignment with the magnetic field, and in doing so will emit a radio signal of their own. This radio signal may be recorded, using the same multiple exposure, rotating-image protocol, to build up a three-dimensional image of the object. The human body is ideal for this kind of imaging, because the different structures have quite different chemical compositions and different water (H 2O) content. Bone, for example, contains little water so
there are few H nuclei to oscillate, producing a very weak signal. White matter, on the other hand, has a higher water content and produces stron- ger signals. The result is a high-resolution image (about 0.1 mm). Because changes in water content accompany neuropathologies such as tumors or multiple sclerosis, MRI is a much better diagnostic tool than CT.
MRI has proved to be a valuable tool in studying the effects of aging on the living brain. The corpus callosum (CC), because of its importance to the transfer of information between the hemispheres, has received a good deal of attention. Probably the most interesting result to come out of these studies is the demonstration that while the CC has a tubular shape in males, in females it has a clearly bulbous shape at the posterior end (Allen et al. 1991). The volume of the CC has also been demonstrated to decrease with age in females. Cowell et al. (1994) have reported that the frontal and
54 The Female Brain, Second Edition
temporal lobes have a greater volume in males than in females, with the right volume being the greatest. The study of 130 subjects, 70 males and 60 females, included an age range from 18 to 80 years. The frontal and temporal lobes have also been reported to decrease with age, with greater age-related reductions in females than males (Cowell et al. 1992). A recent study of the putamen, an area related to motor function, has demonstrated that compared with females, males show a greater age-related loss in gray matter (Nunneman et al., in press).