Neural sexual mosaicism: Sexual differentiation of the human temporo-parietal region for functional asymmetry

Sex differences in human brain organization and behavior are documented by several converging lines of evidence based on patterns of functional asymmetry and cognitive abilities in normal adults and children, in patients with unilateral brain damage, and in clinical groups having atypical levels of sex hormones. Sex differences also exist in the structure of the human brain, and these are reviewed in detail herein. In addition, dichotomous differences, rather than just differences along a continuum, are noted in anatomical-functional correlations between men and women. Many of the anatomical differences cluster in the temporo-parietal regions of the brain, which subserve the asymmetric representation of some linguistic, motoric and spatial functions. The hypothesis is presented that development of the temporo-parietal region of the human brain is an anatomic network dependent on the organizing effects of sex hormones during embryonic or perinatal sexual differentiation, and that in each sex the pattern of functional asymmetries and cognitive attributes is differentially influenced by early sex hormone exposure. It is further suggested that the naturally occurring regressive events of cell death and axon elimination in early brain development contribute to the variation in the structure of the temporo-parietal region, and that this mechanism is differentially influenced by sex hormones in each sex. The specific, directional hypothesis put forward is that in early development of the male brain, lower levels of androgenic hormones or receptors lead to less regressive events in some brain regions, such as the temporo-parietal region, resulting in a larger isthmus of the corpus callosum, less cerebral functional asymmetry, and some cognitive correlates. Some supporting evidence for this hypothesis from neuropsychological studies of clinical groups and homosexual individuals is presented. The neuroanatomical correlate of functional asymmetry in posterior brain regions in women is not evident. The neural regressive events which occur in each sex may be related differently to lateralization. The concept of sexual mosaicism in the human brain is discussed.