Neuroanatomical spatial patterns in Turner syndrome

Abstract

Turner syndrome (TS) is a highly prevalent genetic condition caused by partial or complete absence of one X-chromosome in a female and is associated with a lack of endogenous estrogen during development secondary to gonadal dysgenesis. Prominent cognitive weaknesses in executive and visuospatial function in the context of normal overall IQ also occur in affected individuals. Previous neuroimaging studies of TS point to a profile of neuroanatomical variation relative to age and sex matched controls. However, there are no neuroimaging studies focusing on young girls with TS before they receive exogenous estrogen treatment to induce puberty. Information obtained from young girls with TS may help to establish an early neural correlate of the cognitive phenotype associated with the disorder. Further, univariate analysis has predominantly been the method of choice in prior neuroimaging studies of TS. Univariate approaches examine between-group differences on the basis of individual image elements (i.e., a single voxel's intensity or the volume of an a priori defined brain region). This is in contrast to multivariate methods that can elucidate complex neuroanatomical profiles in a clinical population by determining the pattern of between-group differences from many image elements evaluated simultaneously. In this case, individual image elements might not be significantly different between groups but can still contribute to a significantly different overall spatial pattern. In this study, voxel-based morphometry (VBM) of high-resolution magnetic resonance images was used to investigate differences in brain morphology between 13 pediatric, pre-estrogen girls with monosomic TS and 13 age-matched typically developing controls (3.0T imaging: mean age 9.1 ± 2.1). A similar analysis was performed with an older cohort of 13 girls with monosomic TS and 13 age-matched typically developing controls (1.5T imaging: mean age 15.8 ± 4.5). A multivariate, linear support vector machine analysis using leave-one-out cross-validation was then employed to discriminate girls with TS from typically developing controls based on differences in neuroanatomical spatial patterns and to assess how accurately such patterns translate across heterogeneous cohorts. VBM indicated that both TS cohorts had significantly reduced gray matter volume in the precentral, postcentral, and supramarginal gyri and enlargement of the left middle and superior temporal gyri. Support vector machine (SVM) classifiers achieved high accuracy for discriminating brain morphology patterns in TS from typically developing controls and also displayed spatial patterns consistent with VBM results. Furthermore, the SVM classifiers identified additional neuroanatomical variations in individuals with TS, localized in the hippocampus, orbitofrontal cortex, insula, caudate, and cuneus. Our results demonstrate robust spatial patterns of altered brain morphology in developmentally dynamic populations with TS,

Genomic Imprinting Effects of the X Chromosome on Brain Morphology

“…Overall, our results replicate most previous findings regarding structural abnormalities seen in adults and adolescent with TS, namely enlargement of the hippocampus and amygdala (Good et al, 2003; Kesler et al, 2004), reductions of GMV and WMV in the parieto-occipital and postcentral cortical regions (Brown et al, 2004; Cutter et al, 2006; Holzapfel et al, 2006; Marzelli et al, 2011), enlargement of the temporal gyri and insula (Kesler et al, 2003; Cutter et al, 2006; Marzelli et al, 2011), as well as increased cortical thickness in the temporal regions (Raznahan et al, 2010: Lepage et al, 2012). Our study also shows the existence of abnormal surface area in TS, as reduced surface area is observed in both TS groups in the postcentral, superior parietal, and entorhinal regions, coupled with an increase of surface area in the insular cortex visible in the X m group.…”

“…For structural data, whole brain characteristics including total cortical GMV, subcortical GMV, total WMV, total surface area, mean cortical thickness and cerebellar volume were investigated using ANCOVA with age and total brain volume as covariates. Total brain volume was defined as total gray and white matter tissue within the cerebrum in order to exclude the larger ventricles sometimes observed in the TS population (Marzelli et al, 2011). Results of the individual cortical regions pertaining to GMV, WMV, surface area and cortical thickness were investigated using ANCOVAs with group as a fixed factor, and age, total brain volume and FSIQ as covariates.…”

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 Brain Basis of the Phonological Deficit in Dyslexia Is Independent of IQ

“…We performed leave-one-out linear support vector machine (SVM) analyses (regularization parameter C=1) using in-house Matlab-based (Mathworks, Natick MA) tools which adopts LIBSVM (http://www.csie.ntu.edu.tw/~cjlin/libsvm/), and has been used successfully in several prior studies (Gothelf, et al, 2011; Hoeft, et al, 2008; Hoeft, McCandliss, et al, 2011; Hoeft, Walter, et al, 2011; Marzelli, Hoeft, Hong, & Reiss, 2011). First, we constructed a class vector constituting either ‘+1’s and ‘−1’s assigning each of the child from the three groups to either class label depending on the analysis.…”