Inter-hemispheric functional connectivity changes with corpus callosum morphology in multiple sclerosis.

Multiple sclerosis (MS) affects myelin sheaths within the central nervous system, concurring to cause brain atrophy and neurodegeneration as well as gradual functional disconnections. To explore early signs of altered connectivity in MS from a structural and functional perspective, the morphology of corpus callosum (CC) was correlated with a dynamic inter-hemispheric connectivity index. Twenty mildly disabled patients affected by a relapsing-remitting (RR) form of MS (EDSS⩽3.5) and 15 healthy subjects underwent structural MRI to measure CC thickness over 100 sections and electroencephalography to assess a spectral coherence index between primary regions devoted to hand control, at rest and during an isometric handgrip. In patients, an overall CC atrophy was associated with increased lesion load. A less efficacious inter-hemispheric coherence (IHCoh) during movement was associated with CC atrophy in sections interconnecting homologous primary motor areas (anterior mid-body). In healthy controls, less efficacious IHCoh at rest was associated with a thinner CC splenium. Our data suggest that in mildly disabled RR-MS patients a covert impairment may be detected in the correlation between the structural (CC thickness) and functional (IHCoh) measures of homologous networks, whereas these two counterparts do not yet differ individually from controls.

Puberty in the corpus callosum.

Adolescence is an important period for brain development. White matter growth is influenced by sex hormones such as testosterone, and the corpus callosum-the largest white matter structure in the human brain-may change structurally during the hormone-laden period of adolescence. Little is known about puberty's relationship to structural brain development, even though pubertal stage may better predict cognitive and behavioral maturity than chronological age. We therefore aimed to establish the presence and direction of pubertal effects on callosal anatomy. For this purpose, we applied advanced surface-based mesh-modeling to map correlations between callosal thickness and pubertal stage in a large and well-matched sample of 124 children and adolescents (62 female and 62 male) aged 5-18years from a normative database. When linking callosal anatomy to pubertal status, only positive correlations reached statistical significance, indicating that callosal growth advances with puberty. In tests of differences in callosal anatomy at different stages of puberty, callosal growth was concentrated in different locations depending on the pubertal stage. Changing levels of circulating sex hormones during different phases of puberty likely contributed to the observed effects, and further research is clearly needed. Direct quantification of sex hormone levels and regional fiber connectivity-ideally using fiber tractography-will reveal whether hormones are the main drivers of callosal change during puberty. These callosal findings may lead to hypotheses regarding cortical changes during puberty, which may promote or result from changes in inter-hemispheric connectivity.

The structure of the corpus callosum in obsessive compulsive disorder.

Abnormal brain connectivity has recently been reported in obsessive compulsive disorder (OCD). However, structural differences in the corpus callosum (CC), the primary structure connecting the two hemispheres, have not been extensively studied. In this case-control study, we recruited 30 patients with OCD and 30 healthy control subjects carefully matched for age, sex and handedness. Combining surface-based mesh-modeling and voxel-based morphometry (VBM), we compared callosal thickness and white matter (WM) density in patients and controls. We investigated associations between callosal structure and cortical gray matter (GM) density, and we related CC measures to neuropsychological performance in OCD. OCD patients showed small anterior and posterior callosal regions compared to healthy control subjects. In the OCD group, anterior callosal thickness was positively correlated with GM density of the right mid-dorso-lateral prefrontal (BA 9/46) area, while posterior callosal thickness was positively correlated with GM density in the left supramarginal gyrus (BA 40). Moreover, posterior callosal WM density was positively correlated with verbal memory, visuo-spatial memory, verbal fluency, and visuo-spatial reasoning performances. Callosal attributes were related to GM density in cortical areas innervated by the CC, and were also related to performance in cognitive domains impaired in the disorder. The CC may therefore be integrally involved in OCD.

WITHDRAWN: The structure of the corpus callosum in obsessive compulsive disorder.

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Multimodal MRI analysis of the corpus callosum reveals white matter differences in presymptomatic and early Huntington's disease.

Recent magnetic resonance imaging (MRI) studies suggest that abnormalities in Huntington's disease (HD) extend to white matter (WM) tracts in early HD and even in presymptomatic stages. Thus, changes of the corpus callosum (CC) may reflect various aspects of HD pathogenesis. We recruited 17 HD patients, 17 pre-HD subjects, and 34 healthy age-matched controls. Three-dimensional anatomical MRI and diffusion tensor images of the brain were acquired on a 3T scanner. Combining region-of-interest analyses, voxel-based morphometry, and tract-based spatial statistics, we investigated callosal thickness, WM density, fractional anisotropy, and radial and axial diffusivities. Compared with controls, pre-HD subjects showed reductions of the isthmus, likely due to myelin damage. Compared with pre-HD subjects, HD patients showed reductions of isthmus and body, with axonal damage confined to the body. Compared with controls, HD patients had significantly decreased callosal measures in extended regions across almost the entire CC. At this disease stage, both myelin and axonal damage are detectable. Supplementary multiple regression analyses revealed that WM reduction density in the isthmus as well as Disease Burden scores allowed to predict the "HD development" index. While callosal changes seem to proceed in a posterior-to-anterior direction as the diseases progresses, this observation requires validation in future longitudinal investigations.

The functional anatomy of semantic retrieval is influenced by gender, menstrual cycle, and sex hormones.

This study examines the neurobiology of semantic retrieval and describes the influence of gender, menstrual cycle, and sex hormones on semantic networks. Healthy right-handed subjects (12 men, 12 women) were investigated with 3T-fMRI during synonym generation. Behavioral performance and sex hormone levels were assessed. Women were examined during the early follicular and midluteal cycle phase. The activation pattern in all groups involved left frontal and temporal as well as bilateral medial frontal, cingulate, occipital, basal ganglia, and cerebellar regions. Men showed greater left frontal activation than women in both menstrual cycle phases. Women yielded high correlations of left prefrontal activation with estradiol in the midluteal phase and with progesterone in both phases. Testosterone levels correlated highly with left prefrontal activation in all three groups. In all, we describe a cerebral network involved in semantic processing and demonstrate that it is significantly affected by gender and sex steroid hormones.

Generalized tensor-based morphometry of HIV/AIDS using multivariate statistics on deformation tensors.

This paper investigates the performance of a new multivariate method for tensor-based morphometry (TBM). Statistics on Riemannian manifolds are developed that exploit the full information in deformation tensor fields. In TBM, multiple brain images are warped to a common neuroanatomical template via 3-D nonlinear registration; the resulting deformation fields are analyzed statistically to identify group differences in anatomy. Rather than study the Jacobian determinant (volume expansion factor) of these deformations, as is common, we retain the full deformation tensors and apply a manifold version of Hotelling's $T(2) test to them, in a Log-Euclidean domain. In 2-D and 3-D magnetic resonance imaging (MRI) data from 26 HIV/AIDS patients and 14 matched healthy subjects, we compared multivariate tensor analysis versus univariate tests of simpler tensor-derived indices: the Jacobian determinant, the trace, geodesic anisotropy, and eigenvalues of the deformation tensor, and the angle of rotation of its eigenvectors. We detected consistent, but more extensive patterns of structural abnormalities, with multivariate tests on the full tensor manifold. Their improved power was established by analyzing cumulative p-value plots using false discovery rate (FDR) methods, appropriately controlling for false positives. This increased detection sensitivity may empower drug trials and large-scale studies of disease that use tensor-based morphometry.

Parasagittal asymmetries of the corpus callosum.

Significant relationships have been reported between midsagittal areas of the corpus callosum and the degree of interhemispheric transfer, functional lateralization and structural brain asymmetries. No study, however, has examined whether parasagittal callosal asymmetries (i.e. those close to the midline of the brain), which may be of specific functional consequence, are present in the human brain. Thus, we applied magnetic resonance imaging and novel computational surface-based methods to encode hemispheric differences in callosal thickness at a very high resolution. Discrete callosal areas were also compared between the hemispheres. Furthermore, acknowledging the frequently reported sex differences in callosal morphology, parasagittal callosal asymmetries were examined within each gender. Results showed significant rightward asymmetries of callosal thickness predominantly in the anterior body and anterior third of the callosum, suggesting a more diffuse functional organization of callosal projections in the right hemisphere. Asymmetries were increased in men, supporting the assumption of a sexually dimorphic organization of male and female brains that involves hemispheric relations and is reflected in the organization and distribution of callosal fibers.

Gender effects on cortical thickness and the influence of scaling.

Using magnetic resonance imaging and well-validated computational cortical pattern matching methods in a large and well-matched sample of healthy subjects (n = 60), we analyzed the regional specificity of gender-related cortical thickness differences across the lateral and medial cortices at submillimeter resolution. To establish the influences of brain size correction on gender effects, comparisons were performed with and without applying affine transformations to scale each image volume to a template. We revealed significantly greater cortical thickness in women compared to men, after correcting for individual differences in brain size, while no significant regional thickness increases were observed in males. The pattern and direction of the results were similar without brain size correction, although effects were less pronounced and a small cortical region in the lateral temporal lobes showed greater thickness in males. Our gender-specific findings support a dimorphic organization in male and female brains that appears to involve the architecture of the cortical mantle and that manifests as increased thickness in female brains. This sexual dimorphism favoring women, even without correcting for brain size, may have functional significance and possibly account for gender-specific abilities and/or behavioral differences between sexes.

A curvature-based approach to estimate local gyrification on the cortical surface.

Using magnetic resonance imaging and a new method to analyze local surface shape, we examined the effects of gender on gyrification in a large and well-matched sample of healthy subjects. Unlike traditional 2D methods that produce whole-brain measurements of cortical complexity or more sophisticated 3D parametric mesh-based techniques that allow only different sections (lobes) of the cortex to be investigated, we employed a novel approach with increased spatial resolution. Although our method is sensitive to similar cortical features like the classic whole-brain gyrification index (depths of sulci and heights of gyri), we are now able to provide detailed and regionally specific estimates of cortical convolution at thousands of points across the cortical surface without introducing any bias through the rater or the selected orientation of the slices. We revealed pronounced gender differences, showing increased gyrification in frontal and parietal regions in females compared to males that agree with recent regions-of-interest findings. In addition, we detected higher female gyrification in temporal and occipital cortices that was not previously identified in studies using more global measures. No cortical area was significantly more convoluted in males compared to females. Our results demonstrate the sensitivity of this automated approach for identifying very local changes in gyrification. This technique may serve to isolate regionally specific changes in fissuration/gyrification in neurodevelopmental or neuropsychiatric disorders.

Hemispheric asymmetries in cortical thickness.

Using magnetic resonance imaging and computational cortical pattern matching methods, we analyzed hemispheric differences in regional gray matter thickness across the lateral and medial cortices in young, healthy adults (n = 60). In addition, we investigated the influence of gender on the degree of thickness asymmetry. Results revealed global and regionally specific differences between the two hemispheres, with generally thicker cortex in the left hemisphere. Regions with significant leftward asymmetry were identified in the precentral gyrus, middle frontal, anterior temporal and superior parietal lobes, while rightward asymmetry was prominent in the inferior posterior temporal lobe and inferior frontal lobe. On the medial surface, significant rightward asymmetries were observed in posterior regions, while significant leftward asymmetries were evident from the vicinity of the paracentral gyrus extending anteriorly. Asymmetry profiles were similar in both sexes, but hemispheric differences appeared slightly pronounced in males compared with females, albeit a few regions also indicated greater asymmetry in females compared with males. Hemispheric differences in the thickness of the cortex might be related to hemisphere-specific functional specializations that are possibly related to behavioral asymmetries.

Mapping cortical gray matter in the young adult brain: effects of gender.

Using magnetic resonance imaging and well-validated computational cortical pattern matching methods in a large and well-matched sample of healthy subjects, we analyzed the effects of gender on regional gray matter (GM) concentration across the cortex. To clarify discrepancies in previous reports, we also examined sexual dimorphisms for whole-brain tissue volumes with and without controlling for brain size differences. In addition, we generated spatially detailed maps of average GM distributions and variability across the entire cortex given that these descriptors are not well characterized in the normative literature. After brain size correction, we detected numerous cortical regions showing significantly increased GM concentration in females compared to males, but no regionally increased GM concentration in males. Permutation testing confirmed the statistical significance of these findings. Locally increased concentration of cortical GM in females corroborates findings of larger global GM volumes in females after correcting for individual brain sizes. Larger global volumes of GM, white matter and CSF, however, are observed in males when individual brain volumes are not taken into account. Our results show that gender is a major contributor to regional and global GM differences between individuals, although the nature of these effects depend on whether brain size is taken into account.

A voxel-based approach to gray matter asymmetries.

Voxel-based morphometry (VBM) was used to analyze gray matter (GM) asymmetries in a large sample (n = 60) of male and female professional musicians with and without absolute pitch (AP). We chose to examine these particular groups because previous studies using traditional region-of-interest (ROI) analyses have shown differences in hemispheric asymmetry related to AP and gender. Voxel-based methods may have advantages over traditional ROI-based methods since the analysis can be performed across the whole brain with minimal user bias. After determining that the VBM method was sufficiently sensitive for the detection of differences in GM asymmetries between groups, we found that male AP musicians were more leftward lateralized in the anterior region of the planum temporale (PT) than male non-AP musicians. This confirmed the results of previous studies using ROI-based methods that showed an association between PT asymmetry and the AP phenotype. We further observed that male non-AP musicians revealed an increased leftward GM asymmetry in the postcentral gyrus compared to female non-AP musicians, again corroborating results of a previously published study using ROI-based methods. By analyzing hemispheric GM differences across our entire sample, we were able to partially confirm findings of previous studies using traditional morphometric techniques, as well as more recent, voxel-based analyses. In addition, we found some unusually pronounced GM asymmetries in our musician sample not previously detected in subjects unselected for musical training. Since we were able to validate gender- and AP-related brain asymmetries previously described using traditional ROI-based morphometric techniques, the results of our analyses support the use of VBM for examinations of GM asymmetries.

Relationships between sulcal asymmetries and corpus callosum size: gender and handedness effects.

Magnetic resonance imaging was used to establish the presence and nature of relationships between sulcal asymmetries and mid-sagittal callosal size in neurologically intact subjects, and to determine the influences of sex and handedness. Against a background of long-standing disputes, effects of gender and handedness on callosal size, shape, and variability were additionally examined. Both positive and negative correlations between sulcal asymmetry and callosal size were observed, with effects influenced by sex and handedness. The direction of relationships, however, were dependent on the regional asymmetry measured and on whether real or absolute values were used to quantify sulcal asymmetries. Callosal measurements showed no significant effects of sex or handedness, although subtle differences in callosal shape were observed in anterior and posterior regions between males and females and surface variability was increased in males. Individual variations in callosal size appear to outrange any detectable divergences in size between groups. Relationships between sulcal asymmetries and callosal size, however, are influenced by both sex and handedness. Whether magnitudes of asymmetry are related to increases or decreases in callosal size appears dependent on the chosen indicators of asymmetry. It is an oversimplification, therefore, to assume a single relationship exists between cerebral asymmetries and callosal connections.