Asymmetry of cerebral gray and white matter and structural volumes in relation to sex hormones and chromosomes

Abstract

Whilst many studies show sex differences in cerebral asymmetry, their mechanisms are still unknown. This report describes the potential impact of sex hormones and sex chromosomes by comparing MR data from 39 male and 47 female controls and 33 men with an extra X-chromosome (47,XXY).Methods: Regional asymmetry in gray and white matter volumes (GMV and WMV) was calculated using voxel based moprhometry (SPM5), by contrasting the unflipped and flipped individual GMV and WMV images. In addition, structural volumes were calculated for the thalamus, caudate, putamen, amygdala, and hippocampus, using the FreeSurfer software. Effects of plasma testosterone and estrogen on the GMV and WMV, as well on the right/left ratios of the subcortical volumes were tested by multi-regression analysis.Results: All three groups showed a leftward asymmetry in the motor cortex and the planum temporale, and a rightward asymmetry of the middle occipital cortex. Both asymmetries were more pronounced in 46,XY males than 46,XX females and 47,XXY males, and were positively correlated with testosterone levels. There was also a rightward asymmetry of the vermis and leftward GMV asymmetry in the cerebellar hemispheres in all groups. Notably, cerebellar asymmetries were larger in 46,XX females and 47,XXY males, but were not related to sex hormone levels. No asymmetry differences between 46,XX females and 47,XXY males, and no overall effects of brain size were detected.Conclusion: The asymmetry in the planum temporale area and the occipital cortex seem related to processes associated with testosterone, whereas the observed cerebellar asymmetries suggest a link with X-chromosome escapee genes. Sex differences in cerebral asymmetry are moderated by sex hormones and X-chromosome genes, in a regionally differentiated manner.

Sexual dimorphism of Broca's region: More gray matter in female brains in Brodmann areas 44 and 45

“…Our results indicate a lack of sexual dimorphism with respect to gray matter asymmetry in BA 44/45 and as such are in line with prior findings that do not support a sex difference in region-specific asymmetry (Good et al 2001a; Luders et al 2004; Savic 2014; Takao et al 2011; Watkins et al 2001). Furthermore, they seem to agree with conclusions drawn based on a meta-analysis (Frost et al 1999; Sommer et al 2004) negating that women are having more bilateral language representation (and thus presumably less asymmetry) than men, as also critically reviewed elsewhere (Wallentin 2009).…”

A 3 tesla magnetic resonance imaging volumetric analysis of the hippocampal formation: dependence on handedness and age

“…According to some others [11,25], the brain size is more important than sex in explaining interindividual differences in volume of its parts. In any case, the eventual presence of the HF asymmetry in general population, as was noticed in our study, can be explained by the influence of corresponding X chromosome genes and the sex hormones [15,39].…”

“…Nevertheless, such right-left differences mostly develop in utero under the influence of certain genes [39]. In general, the right-left asymmetry of the HF, related to the handedness, is only part of the global hemispheric asymmetry, which is based on the various structural and functional features of the corresponding right and left regions of the brain [12,21,23,40].…”

Asymmetry of the Brain: Development and Implications

“…This candidate gene is interesting given the association between handedness and gender, with males tending to be more represented among LHs (reviewed in 133). Moreover, structural asymmetries in the PT area and the occipital cortex are more pronounced in XY males than in XX females or XXY males, further suggesting that the development of cerebral structural asymmetries is influenced by testosterone levels (147). These genetic associations need to be further confirmed in independent studies with larger sample of individuals.…”