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Network-level analysis of cortical thickness of the epileptic brain.

ABSTRACT: Temporal lobe epilepsy (TLE) characterized by an epileptogenic focus in the medial temporal lobe is the most common form of focal epilepsy. However, the seizures are not confined to the temporal lobe but can spread to other, anatomically connected brain regions where they can cause similar structural abnormalities as observed in the focus. The aim of this study was to derive whole-brain networks from volumetric data and obtain network-centric measures, which can capture cortical thinning characteristic of TLE and can be used for classifying a given MRI into TLE or normal, and to obtain additional summary statistics that relate to the extent and spread of the disease. T1-weighted whole-brain images were acquired on a 4-T magnet in 13 patients with TLE with mesial temporal lobe sclerosis (TLE-MTS), 14 patients with TLE with normal MRI (TLE-no), and 30 controls. Mean cortical thickness and curvature measurements were obtained using the FreeSurfer software. These values were used to derive a graph, or network, for each subject. The nodes of the graph are brain regions, and edges represent disease progression paths. We show how to obtain summary statistics like mean, median, and variance defined for these networks and to perform exploratory analyses like correlation and classification. Our results indicate that the proposed network approach can improve accuracy of classifying subjects into two groups (control and TLE) from 78% for non-network classifiers to 93% using the proposed approach. We also obtain network "peakiness" values using statistical measures like entropy and complexity-this appears to be a good characterizer of the disease and may have utility in surgical planning.

SUBMITTER: Raj A

PROVIDER: S-EPMC2910126 | biostudies-literature | 2010 Oct

REPOSITORIES: biostudies-literature

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Network-level analysis of cortical thickness of the epileptic brain.

Raj A A Mueller S G SG Young K K Laxer K D KD Weiner M M

NeuroImage 20100527 4

Temporal lobe epilepsy (TLE) characterized by an epileptogenic focus in the medial temporal lobe is the most common form of focal epilepsy. However, the seizures are not confined to the temporal lobe but can spread to other, anatomically connected brain regions where they can cause similar structural abnormalities as observed in the focus. The aim of this study was to derive whole-brain networks from volumetric data and obtain network-centric measures, which can capture cortical thinning charact ...[more]

PMID: 20553893

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Project description:ObjectiveThe current study examined gender-related differences in hemispheric asymmetries of graph metrics, calculated from a cortical thickness-based brain structural covariance network named hemispheric morphological network.MethodsUsing the T1-weighted magnetic resonance imaging scans of 285 participants (150 females, 135 males) retrieved from the Human Connectome Project (HCP), hemispheric morphological networks were constructed per participant. In these hemispheric morphologic networks, the degree of similarity between two different brain regions in terms of the distributed patterns of cortical thickness values (the Jensen-Shannon divergence) was defined as weight of network edge that connects two different brain regions. After the calculation and summation of global and local graph metrics (across the network sparsity levels K = 0.10-0.36), asymmetry indexes of these graph metrics were derived.ResultsHemispheric morphological networks satisfied small-worldness and global efficiency for the network sparsity ranges of K = 0.10-0.36. Between-group comparisons (female versus male) of asymmetry indexes revealed opposite directionality of asymmetries (leftward versus rightward) for global metrics of normalized clustering coefficient, normalized characteristic path length, and global efficiency (all p < 0.05). For the local graph metrics, larger rightward asymmetries of cingulate-superior parietal gyri for nodal efficiency in male compared to female, larger leftward asymmetry of temporal pole for degree centrality in female compared to male, and opposite directionality of interhemispheric asymmetry of rectal gyrus for degree centrality between female (rightward) and male (leftward) were shown (all p < 0.05).ConclusionPatterns of interhemispheric asymmetries for cingulate, superior parietal gyrus, temporal pole, and rectal gyrus are different between male and female for the similarities of the cortical thickness distribution with other brain regions. Accordingly, possible effect of gender-by-hemispheric interaction has to be considered in future studies of brain morphology and brain structural covariance networks.

Project description:OBJECTIVES:The thickness of the brain's cortical gray matter (GM) and the fractional anisotropy (FA) of the cerebral white matter (WM) each follow an inverted U-shape trajectory with age. The two measures are positively correlated and may be modulated by common biological mechanisms. We employed four types of genetic analyses to localize individual genes acting pleiotropically upon these phenotypes. METHODS:Whole-brain and regional GM thickness and FA values were measured from high-resolution anatomical and diffusion tensor MR images collected from 712, Mexican American participants (438 females, age?=?47.9?±?13.2?years) recruited from 73 (9.7?±?9.3 individuals/family) large families. The significance of the correlation between two traits was estimated using a bivariate genetic correlation analysis. Localization of chromosomal regions that jointly influenced both traits was performed using whole-genome quantitative trait loci (QTL) analysis. Gene localization was performed using SNP genotyping on Illumina 1M chip and correlation with leukocyte-based gene-expression analyses. The gene-expressions were measured using the Illumina BeadChip. These data were available for 371 subjects. RESULTS:Significant genetic correlation was observed among GM thickness and FA values. Significant logarithm of odds (LOD???3.0) QTLs were localized within chromosome 15q22-23. More detailed localization reported no significant association (p?<?5·10(-5)) for 1565 SNPs located within the QTLs. Post hoc analysis indicated that 40% of the potentially significant (p???10(-3)) SNPs were localized to the related orphan receptor alpha (RORA) and NARG2 genes. A potentially significant association was observed for the rs2456930 polymorphism reported as a significant GWAS finding in Alzheimer's disease neuroimaging initiative subjects. The expression levels for RORA and ADAM10 genes were significantly (p?<?0.05) correlated with both FA and GM thickness. NARG2 expressions were significantly correlated with GM thickness (p?<?0.05) but failed to show a significant correlation (p?=?0.09) with FA. DISCUSSION:This study identified a novel, significant QTL at 15q22-23. SNP correlation with gene-expression analyses indicated that RORA, NARG2, and ADAM10 jointly influence GM thickness and WM-FA values.

Project description:ImportanceSchizophrenia is a complex heritable disorder associated with many genetic variants, each with a small effect. While cortical differences between patients with schizophrenia and healthy controls are consistently reported, the underlying molecular mechanisms remain elusive.ObjectiveTo investigate the extent of shared genetic architecture between schizophrenia and brain cortical surface area (SA) and thickness (TH) and to identify shared genomic loci.Design, setting, and participantsIndependent genome-wide association study data on schizophrenia (Psychiatric Genomics Consortium and CLOZUK: n = 105 318) and SA and TH (UK Biobank: n = 33 735) were obtained. The extent of polygenic overlap was investigated using MiXeR. The specific shared genomic loci were identified by conditional/conjunctional false discovery rate analysis and were further examined in 3 independent cohorts. Data were collected from December 2019 to February 2021, and data analysis was performed from May 2020 to February 2021.Main outcomes and measuresThe primary outcomes were estimated fractions of polygenic overlap between schizophrenia, total SA, and average TH and a list of functionally characterized shared genomic loci.ResultsBased on genome-wide association study data from 139 053 participants, MiXeR estimated schizophrenia to be more polygenic (9703 single-nucleotide variants [SNVs]) than total SA (2101 SNVs) and average TH (1363 SNVs). Most SNVs associated with total SA (1966 of 2101 [93.6%]) and average TH (1322 of 1363 [97.0%]) may be associated with the development of schizophrenia. Subsequent conjunctional false discovery rate analysis identified 44 and 23 schizophrenia risk loci shared with total SA and average TH, respectively. The SNV associations of shared loci between schizophrenia and total SA revealed en masse concordant association between the discovery and independent cohorts. After removing high linkage disequilibrium regions, such as the major histocompatibility complex region, the shared loci were enriched in immunologic signature gene sets. Polygenic overlap and shared loci between schizophrenia and schizophrenia-associated regions of interest for SA (superior frontal and middle temporal gyri) and for TH (superior temporal, inferior temporal, and superior frontal gyri) were also identified.Conclusions and relevanceThis study demonstrated shared genetic loci between cortical morphometry and schizophrenia, among which a subset are associated with immunity. These findings provide an insight into the complex genetic architecture and associated with schizophrenia.

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Network-level analysis of cortical thickness of the epileptic brain.

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Network-level analysis of cortical thickness of the epileptic brain.

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