SEX DIFFERENCES IN LEARNING

Findings in the field of neuroendocrinology, which explores the functional relationships between hormones and the brain, have indicated that the release of testicular (androgens) and ovarian (estrogens) hormones during critical periods of brain development exert a profound effect on the genesis and survival of neurons in specific brain areas, resulting in sex differences in reproductive behaviors. Sex differences are not restricted to the reproductive sphere, however. They are found in a broad range of nonreproductive behaviors such as aggression, locomotor activity, play behavior, and learning abilities. While the debate on whether sex differences in cognition are determined by biological or sociocultural factors is long lasting, increasing experimental evidence indicates that sex differences could be determined by genetic or hormonal factors. Support for this conclusion is of four kinds. First, sex differences have been reported in various learning abilities that depend on neural structures other than those involved in reproductive functions. Second, there are sex differences in the morphology of neural structures mediating learning abilities. Third, lesions of neural structures underlying learning abilities can affect males and females differently. Finally, sex differences in learning abilities, brain morphology, and/or in the effects of brain lesions can be reversed by manipulations of gonadal steroid hormones in animals or by normal fluctuation of sex hormones across the life span in humans.

Sexual Dimorphism in Learning Abilities

Although the majority of data pertaining to the effects of gonadal steroid hormones on learning abilities have been gathered in rodents, there is growing evidence for similar effects in primates, including humans. In rodents (Beatty, 1979), mature male rats make fewer errors than females in learning complex mazes, and are faster learners in appetitive learning. Conversely, female rats outperform males in discrimination reversal learning and in the acquisition of active avoidance. This pattern of male and female performance in avoidance learning can be reversed by treating ovariectomized female rats with androgens (testosterone) and male rats with antiandrogens from birth to adulthood. Finally, lesions of brain areas known to be functionally involved in avoidance learning, such as the basal ganglia, do not impair performance of males and females equally. For example, small lesions of the globus pallidus impair acquisition of active avoidance in males but not in females. This sex difference in the effects of pallidal lesions can be reversed by androgenization of female rats and feminization of male rats. These data in rodents suggest that androgens are, at least in part, responsible for the sex differences in learning abilities.

In nonhuman primates (Mitchell, 1977), adult female rhesus monkeys outperform males in spatial memory, as measured by the delayed-response task. Similarly, adult female chimpanzees exhibit significantly superior short-term stimulus memory, as measured by the delayed matching-to-sample task. Finally, although male and female rhesus monkeys perform similarly on tasks of object memory and executive function, young males outperform young females on a spatial memory task (Lacreuse et al., 1999). This superior level of spatial ability in young males declined sharply with age, and, at older age, males do not perform significantly better than females. These studies in adult primates did not examine whether the sex differences in learning abilities could be reversed by perinatal gonadal steroid hormone treatments, but such evidence has been obtained in studies of infant primates.

Acquisition of an object discrimination reversal task, known to depend on the integrity of the orbital prefrontal cortex in the adult monkey, is significantly more rapid in male infant monkeys than in females (Clark and Goldman-Rakic, 1989). Postnatal injections of testosterone propionate in the females enhances their performance to the level of the normal infant males. When orbital prefrontal cortex is removed in infancy, intact male monkeys and androgenized female monkeys are as impaired as adult monkeys with the same lesions, whereas untreated infant females do not differ from untreated age-matched females. The data suggest that the orbital prefrontal cortex matures earlier in male than in female monkeys. Conversely, acquisition of a concurrent visual discrimination learning task, known to depend on the integrity of the inferior temporal cortex, is significantly more rapid in female infant monkeys than in males (Bachevalier and Hagger, 1991) and this sex difference is positively correlated in three-month-old male animals with circulating levels of testosterone (the higher the level of testosterone, the poorer the score), but not with estradiol levels. Neonatal orchiectomy, which reduced plasma testosterone levels, hastens performance on visual discrimination learning in male infant monkeys, whereas treatment of androgens (dihydrotestosterone) in neonatally ovariectomized female infant monkeys delays their performance. Finally, early postnatal inferior temporal cortex lesions affect performance of female but not of male infant monkeys, though male and female adults with the same lesions are impaired equally. The data suggest that this temporal cortical area is functionally more mature in female infant monkeys than in males. Thus, gonadal steroid hormones appear to play an inductive role in the postnatal differentiation of cortical mechanisms.

For humans, many studies have reported that women excel in verbal abilities, perceptual speed, articulation, and fine motor skills, whereas men generally excel in tasks measuring visuospatial abilities, particularly those requiring mental rotation of objects and imagining what an object would look like from a different vantage point (Halpern, 1992). Although direct manipulation of gonadal hormones is not possible in humans, the organizational and activational effects of the hormones on cognitive functions have usually been inferred from the studies of different populations of individuals. They include boys and girls suffering from long-standing prenatal hormonal anomalies or that have been exposed to exogenous hormones in utero, women during regular fluctuations of estrogen and progesterone throughout the menstrual cycle or postmenopausal women receiving hormone replacement therapy, and elderly individuals showing a decline in cognitive functions. Thus, girls with congenital adrenal hyperplasia (CAH) who are genetically masculinized and prenatally exposed to excessive androgens show significant enhancement of visuospatial ability as compared to unaffected females. Also, boys exposed prenatally with DES (a synthetic estrogen) show poorer performance on several spatial tasks than males who suffer from low testosterone due to post puberty pathology (Reisnich et al., 1991). In addition, when performance on several visuospatial tasks is compared at different phases of the menstrual cycle, women perform significantly more poorly during the estrogen surge just prior to ovulation than at other points in the cycle. Conversely, higher levels of estrogen during the cycle are associated with better performance on many tasks in which women typically excel. When postmenopausal women are tested either when receiving their estrogen therapy or when they are off their medication for at least four days, performance on fine motor and spatial tasks tends to be faster and more accurate during the testosterone treatment compared with the off-treatment phase (Hampson and Kimura, 1992). Finally, estrogen deficiency in menopausal women is associated with memory impairments that are reversible by estrogen replacement therapy, whereas testosterone replacement therapy in elderly men enhances spatial performance (Janowsky et al., 1994).

The double dissociation found in infant monkeys with the object discrimination reversal and concurrent discrimination tasks have been replicated in very young children using almost identical cognitive tasks and nonverbal procedures (Overman et al., 1997). Boys under the age of twenty-nine months significantly outperform girls on the object reversal task, but girls outperform boys on the concurrent discrimination task. Given the close parallel in learning behavior in human infants and infant monkeys, it is reasonable to propose that the gender differences are mediated by similar biological mechanisms in both species. Therefore, in children, as in infant monkeys, there may be a more rapid maturation of orbital prefrontal circuits in boys and a more rapid maturation of inferior temporal circuits in girls.

Sex Differences in Brain Areas Related to Learning Abilities

Although no direct correlation has been established between sex differences in learning abilities and morphology of brain areas, sex differences in numerous neural structures related to learning abilities are well documented in rodents (Beatty, 1979; Juraska, 1991). In the limbic system (bed nucleus of the stria terminalis and hippocampus), the number and volume of neurons differ in male and female rats. These morphological differences are reversed after postnatal treatment with gonadal steroid hormones. The rate of neonatal cell proliferation has been shown to be slower in male than in female rats, indicating a delayed maturation of the neocortex in males compared with that of females. Similarly, the neurons in the somatosensory cortex of young male rats are larger than those of females, reflecting a cortical immaturity and, possibly, a less developed synaptic network in males than in females. In research conducted in the 1990s, sex differences in humans have also been found for functional asymmetry (Voyer, 1996), brain morphology, metabolism, weigh, volume, and neocortical neuron number (Gur et al., 1995; Pakkenberg and Gundersen, 1997; Hampson and Kimura, 1992).

Mechanisms of Action

The question of precisely how gonadal hormones exert their organizational and activational influence on brain areas related to learning abilities remains to be answered. There is, however, indirect evidence regarding the mechanism of their action on brain areas mediating learning abilities (Luine and McEwen, 1985). For example, gonadal steroid hormones are known to act via intracellular receptors located in limbic structures and some parts of the neocortex. In the developing rhesus monkey, androgen metabolism has been observed in all cortical areas; this activity declines from prenatal to early postnatal life. Also, the presence of sex differences in neurochemical concentrations and regulatory processes suggests an influence of gonadal steroid hormones on the differentiation of neurochemical features of neurons. Finally, gonadal steroid hormones stimulate neurite outgrowth during the sensitive period of brain differentiation, presumably by increasing the competitive advantage of neurons to make connections with other neurons. The perinatal androgen surge seen in infant males could therefore affect the rate of brain maturation by influencing neuronal connectivity at the cortical level.

There are also several possible mechanisms by which gonadal steroids may exert more transient, or activational, effects on central nervous system during adulthood. Estradiol as well as other gonadal hormones can regulate the concentrations of specific enzymes involved in neurotransmitter synthesis and breakdown (McEwen et al., 1984). This action may offer a way by which a single hormone can simultaneously exert different effects on different behavioral systems.

Conclusion

Although sex differences in cognitive and learning abilities are presently widely acknowledged, the basis for these differences remains controversial. The data reviewed in this entry suggest that androgens organize the brain pre- and perinatally for all sexually dimorphic behaviors, including problem-solving behaviors, and this appears to be true in mammals, non-human primates, and humans. Moreover, the pattern of variation in learning abilities documented over the menstrual cycle and during aging processes raises the possibility that sex differences in cognitive abilities in humans may also at least be partly due to an activational influence of sex hormones on the brain throughout life. Thus, it is becoming clear that sex differences in structure and function are likely to be a pervasive characteristic of brain organization and mediated by gonadal steroid hormones. Nevertheless, the challenge is to precisely specify biological mechanisms by which these differences occur and to take into consideration the circular interactions between biological factors and socioenvironmental factors. Ultimately, the understanding of cognitive sex differences will necessarily depend upon converging evidence from many different disciplines, including endocrinology, animal and human behavior, neurobiology, electrophysiology, and brain imaging.

See also:DISCRIMINATION AND GENERALIZATION; NEURAL SUBSTRATES OF AVOIDANCE LEARNING

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Jocelyne B.Bachevalier