Cortical anatomy in human X monosomy

Abstract

Turner syndrome (TS) is a model for X-chromosome influences on neurodevelopment because it is most commonly caused by absence of one X-chromosome, and associated with altered brain structure and function. However, all prior in vivo magnetic resonance imaging studies of the brain in TS have either used manual approaches or voxel-based-morphometry (VBM) to measure cortical volume (CV). These methods, unlike surface-based-morphometry (SBM), cannot measure the two neurobiologically distinct determinants of CV– cortical thickness (CT) and surface area (SA) – which have differing genetic determinants, and may be independently altered. Therefore, in 24 adults with X-monosomy and 19 healthy female controls, we used SBM to compare (i) lobar CV, CT and SA, (ii) an index of hemispheric gyrification (iii) CT throughout the cortical sheet, and (iv) CT correlation between cortical regions. Compared to controls, females with TS had (i) significantly increased CT and decreased SA in parietal and occipital lobes (resulting in no significant difference in lobar CV), (ii) reduced hemispheric gyrification bilaterally, (iii) foci of significantly increased CT involving inferior-temporal, lateral-occipital, intraparietal sulcus (IPS), cingulate, and orbito-frontal cortices, (iv) significantly reduced CT correlation between the left IPS and cortical regions including supramarginal and lateral-occipital gyri. Our findings suggest that females with TS have complex, sometimes ‘opposing’, abnormalities in SA/gyrification (decreased) and CT (increased); which can result in no overall detectable differences in CV. Thus haploinsufficiency of X-chromosome genes, may differentially impact the distinct mechanisms shaping SA (e.g. cortical folding) and CT (e.g. dendritic arborization/pruning). CT disruptions are maximal within and between cortical regions previously implicated in the TS cognitive phenotype.

High resolution whole brain imaging of anatomical variation in XO, XX, and XY mice

“…Specifically, a recent systematic review (Raznahan et al, 2010) and subsequent MRI studies in TS (Lepage et al, 2012; Marzelli et al, 2011) have identified replicated foci of anatomical difference between XO and XX humans, which we now show to be significantly altered in XO mice relative to their XX littermates, including the parietal cortex and striatum. Since these shared anatomical alterations in human and murine X-monosomy occur despite the lack of overt ovarian dysgenesis in murine X-monosomy, they potentially point towards a regionally-specific and evolutionarily preserved role for X chromosome genes on brain development.…”

“…The potential for X chromosome dosage to directly influence the mammalian brain is clearly demonstrated by recent experimental work in genetically modified mice allow sex chromosome effects to be dissociated from those of circulating sex steroids (Hughes et al, 2012). A complementary, naturally occurring model for X chromosome influences on mammalian brain development is Turner Syndrome (TS): this sex chromosome aneuploidy syndrome arises due to X chromosome monosomy in females and has been linked to alterations of both sub-cortical and cortical brain anatomy (Lepage et al, 2012; Raznahan et al, 2010). …”

Imaging structural co-variance between human brain regions

“…Carriers of a 5-HTTLPR polymorphism that has been associated with increased risk of depression have decreased correlations between the amygdala and anterior cingulate cortex 77 . In addition, there is preliminary evidence for structural co-variance alterations in bipolar disorder 174 , Turner syndrome (usually associated with chromosome X monosomy) 175 , cancer survivors with chemotherapy-related cognitive impairment 176 , adolescents who had severely pre-term births 177 and grapheme–colour synaesthesia 178 .…”

Neuronal correlates of the five factor model (FFM) of human personality: Multimodal imaging in a large healthy sample

“…Morphometric measures of the cortical GM include cortical thickness and surface area, which together constitute the common index of GM volume. Cortical thickness and surface area carry distinct biological information (Chenn and Walsh, 2002;Panizzon et al, 2009;Rakic, 1995;Raznahan et al, 2010Raznahan et al, , 2011Winkler et al, 2010), are genetically unrelated (Panizzon et al, 2009;Winkler et al, 2010), show distinct developmental trajectories (Hogstrom et al, in press;Østby et al, 2009;Raznahan et al, 2011), and are differentially altered by environmental manipulation (Park et al, 2009) and allelic variations within established risk genes for developmental disorders (Joyner et al, 2009), emphasizing the importance of dissociating the two sources of GM volume when aiming to link personality to brain structure. Associations between GM structure and personality have only been investigated using GM volume or cortical thickness, and knowledge of how surface arealization relates to personality is lacking.…”