Dataset Information

Genetics of microstructure of the corpus callosum in older adults.

ABSTRACT: The current study sought to examine the relative influence of genetic and environmental factors on corpus callosum (CC) microstructure in a community sample of older adult twins. Analyses were undertaken in 284 healthy older twins (66% female; 79 MZ and 63 DZ pairs) from the Older Australian Twins Study. The average age of the sample was 69.82 (SD?=?4.76) years. Brain imaging scans were collected and DTI measures were estimated for the whole CC as well as its five subregions. Parcellation of the CC was performed using Analyze. In addition, white matter lesion (WMLs) burden was estimated. Heritability and genetic correlation analyses were undertaken using the SOLAR software package. Age, sex, scanner, handedness and blood pressure were considered as covariates. Heritability (h(2)) analysis for the DTI metrics of whole CC, indicated significant h(2) for fractional anisotropy (FA) (h(2)?=?0.56; p?=?2.89×10(-10)), mean diffusivity (MD) (h(2)?=?0.52; p?=?0.30×10(-6)), radial diffusivity (RD) (h(2)?=?0.49; p?=?0.2×10(-6)) and axial diffusivity (AD) (h(2)?=?0.37; p?=?8.15×10(-5)). We also performed bivariate genetic correlation analyses between (i) whole CC DTI measures and (ii) whole CC DTI measures with total brain WML burden. Across the DTI measures for the whole CC, MD and RD shared 84% of the common genetic variance, followed by MD-AD (77%), FA-RD (52%), RD-AD (37%) and FA-MD (11%). For total WMLs, significant genetic correlations indicated that there was 19% shared common genetic variance with whole CC MD, followed by CC RD (17%), CC AD (16%) and CC FA (5%). Our findings suggest that the CC microstructure is under moderate genetic control. There was also evidence of shared genetic factors between the CC DTI measures. In contrast, there was less shared genetic variance between WMLs and the CC DTI metrics, suggesting fewer common genetic variants.

SUBMITTER: Kanchibhotla SC

PROVIDER: S-EPMC4267776 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

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Genetics of microstructure of the corpus callosum in older adults.

Kanchibhotla Sri C SC Mather Karen A KA Thalamuthu Anbupalam A Zhuang Lin L Schofield Peter R PR Kwok John B J JB Ames David D Wright Margaret J MJ Trollor Julian N JN Wen Wei W Sachdev Perminder S PS

PloS one 20141216 12

The current study sought to examine the relative influence of genetic and environmental factors on corpus callosum (CC) microstructure in a community sample of older adult twins. Analyses were undertaken in 284 healthy older twins (66% female; 79 MZ and 63 DZ pairs) from the Older Australian Twins Study. The average age of the sample was 69.82 (SD = 4.76) years. Brain imaging scans were collected and DTI measures were estimated for the whole CC as well as its five subregions. Parcellation of the ...[more]

PMID: 25514436

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Project description:BackgroundAccumulating evidence indicates maladaptive neural information interactions between different brain regions underlie bulimia nervosa (BN). However, little is known about the alterations in interhemispheric communication of BN, which is facilitated by the corpus callosum (CC), the major commissural fiber connecting the two hemispheres. To shed light on the interhemispheric communications in BN, the present study aims to explore alterations of interhemispheric homotopic functional connectivity and the CC microstructure in BN.MethodsBased on magnetic resonance imaging (MRI) data collected from 42 BN patients and 38 healthy controls (HCs), the group differences of voxel-mirrored homotopic connectivity (VMHC) index and CC white matter microstructure were compared. Then brain regions with significant group differences in VMHC were selected as seeds for subsequent functional connectivity (FC) analysis. Seed-based fiber tracking and correlation analysis were used to analyze the relationship between VMHC and CC changes. And correlation analysis was used to reveal the correlation between abnormal imaging variables and the clinical features of BN.ResultsCompared with HCs, the BN group showed decreased fractional anisotropy (FA) in middle part of CC (CCMid) and increased VMHC in bilateral orbitofrontal cortex (OFC) and middle temporal gyrus (MTG) [false discovery rate (FDR) correction with a corrected threshold of P<0.05]. Subsequent FC analyses indicated increased FC between left OFC and right OFC, bilateral MTG, left middle occipital gyrus and right precuneus (PCUN); between right OFC and left cerebellum crus II and right PCUN; and between left MTG and right inferior temporal gyrus, right cerebellum lobule VI and right medial superior frontal gyrus (FDR correction with a corrected threshold of P<0.05). The VMHC values of OFC and MTG showed no correlations with FA values of the CCMid and the white fibers between the bilateral OFC and MTG were not through the CCMid. In addition, several regions with abnormal FC had a potential correlation trend with abnormal eating behaviors in BN patients (P<0.05, uncorrected).ConclusionsAberrant interhemispheric homotopic functional connectivity and CC microstructure were observed in BN, and they may be independent of each other. Regions with aberrant interhemispheric homotopic functional connectivity showed hyperconnectivity with regions related to reward processing, body shape perception, and self-reference.

Project description:Background: Preterm birth is associated with increased risk of neuromotor impairment. Rates of major neuromotor impairment (cerebral palsy) have decreased; however, in a large proportion of those who do not develop cerebral palsy impaired neuromotor function is observed and this often has implications for everyday life. The aim of this study was to investigate motor performance in preterm born adolescents without cerebral palsy, and to examine associations with alterations of motor system pathway structure. Design/Methods: Thirty-two adolescents (12 males) without cerebral palsy, born before 33 weeks of gestation (mean 27.4 weeks, SD 2.4; birth weight mean 1,084.5 g; SD 387.2), treated at a single tertiary unit, were assessed (median age 16 years; min 14, max 18). Timed performance and quality of movements were assessed with the Zürich Neuromotor Assessment. Neuroimaging included Diffusion Magnetic Resonance Imaging for tractography of the major motor tracts and measurement of fractional anisotropy as a measure of microstructure of the tracts along the major motor pathways. Separate analyses were conducted for areas with predominantly single and predominantly crossing fiber regions. Results: Motor performance in both tasks assessing timed performance and quality of movements, was poorer than expected in the preterm group in relation to norm population. The strongest significant correlations were seen between performance in tasks assessing movement quality and fractional anisotropy in corpus callosum fibers connecting primary motor, primary somatosensory and premotor areas. In addition, timed motor performance was significantly related to fractional anisotropy in the cortico-spinal and thalamo-cortical to premotor area fibers, and the corpus callosum. Conclusions: Impairments in motor abilities are present in preterm born adolescents without major neuromotor impairment and in the absence of focal brain injury. Altered microstructure of the corpus callosum microstructure appears a crucial factor, in particular for movement quality.

Project description:Cerebral white matter exhibits age-related degenerative changes during the course of normal aging, including decreases in axon density and alterations in axonal structure. Noninvasive approaches to measure these microstructural alterations throughout the lifespan would be invaluable for understanding the substrate and regional variability of age-related white matter degeneration. Recent advances in diffusion magnetic resonance imaging (MRI) have leveraged high gradient strengths to increase sensitivity toward axonal size and density in the living human brain. Here, we examined the relationship between age and indices of axon diameter and packing density using high-gradient strength diffusion MRI in 36 healthy adults (aged 22-72) in well-defined central white matter tracts in the brain. A recently validated method for inferring the effective axonal compartment size and packing density from diffusion MRI measurements acquired with 300 mT/m maximum gradient strength was applied to the in vivo human brain to obtain indices of axon diameter and density in the corpus callosum, its sub-regions, and adjacent anterior and posterior fibers in the forceps minor and forceps major. The relationships between the axonal metrics, corpus callosum area and regional gray matter volume were also explored. Results revealed a significant increase in axon diameter index with advancing age in the whole corpus callosum. Similar analyses in sub-regions of the corpus callosum showed that age-related alterations in axon diameter index and axon density were most pronounced in the genu of the corpus callosum and relatively absent in the splenium, in keeping with findings from previous histological studies. The significance of these correlations was mirrored in the forceps minor and forceps major, consistent with previously reported decreases in FA in the forceps minor but not in the forceps major with age. Alterations in the axonal imaging metrics paralleled decreases in corpus callosum area and regional gray matter volume with age. Among older adults, results from cognitive testing suggested an association between larger effective compartment size in the corpus callosum, particularly within the genu of the corpus callosum, and lower scores on the Montreal Cognitive Assessment, largely driven by deficits in short-term memory. The current study suggests that high-gradient diffusion MRI may be sensitive to the axonal substrate of age-related white matter degeneration reflected in traditional DTI metrics and provides further evidence for regionally selective alterations in white matter microstructure with advancing age.

Dataset Information

Genetics of microstructure of the corpus callosum in older adults.

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Genetics of microstructure of the corpus callosum in older adults.

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