Event-based modelling in temporal lobe epilepsy demonstrates progressive atrophy from cross-sectional data

OBJECTIVE: Recent work has shown that people with common epilepsies have characteristic patterns of cortical thinning, and that these changes may be progressive over time. Leveraging a large multi-centre cross-sectional cohort, we investigated whether regional morphometric changes occur in a sequential manner, and whether these changes in people with mesial temporal lobe epilepsy and hippocampal sclerosis (MTLE-HS) correlate with clinical features. METHODS: We extracted regional measures of cortical thickness, surface area and subcortical brain volumes from T1-weighted (T1W) MRI scans collected by the ENIGMA-Epilepsy consortium, comprising 804 people with MTLE-HS and 1,625 healthy controls from 25 centres. Features with a moderate case-control effect size (Cohen's d≥0.5) were used to train an Event-Based Model (EBM), which estimates a sequence of disease-specific biomarker changes from cross-sectional data and assigns a biomarker-based fine-grained disease stage to individual patients. We tested for associations between EBM disease stage and duration of epilepsy, age of onset and anti-seizure medicine (ASM) resistance. RESULTS: In MTLE-HS, decrease in ipsilateral hippocampal volume along with increased asymmetry in hippocampal volume was followed by reduced thickness in neocortical regions, reduction in ipsilateral thalamus volume and, finally, increase in ipsilateral lateral ventricle volume. EBM stage was correlated to duration of illness (Spearman's ρ=0.293, p=7.03x10-16 ), age of onset (ρ=-0.18, p=9.82x10-7 ) and ASM resistance (AUC=0.59, p=0.043, Mann-Whitney U test). However, associations were driven by cases assigned to EBM stage zero, which represents MTLE-HS with mild or non-detectable abnormality on T1W MRI. SIGNIFICANCE: From cross-sectional MRI, we reconstructed a disease progression model that highlights a sequence of MRI changes that aligns with previous longitudinal studies. This model could be used to stage MTLE-HS subjects in other cohorts and help establish connections between imaging-based progression staging and clinical features

White matter abnormalities across different epilepsy syndromes in adults: an ENIGMA-Epilepsy study

The epilepsies are commonly accompanied by widespread abnormalities in cerebral white matter. ENIGMA-Epilepsy is a large quantitative brain imaging consortium, aggregating data to investigate patterns of neuroimaging abnormalities in common epilepsy syndromes, including temporal lobe epilepsy, extratemporal epilepsy, and genetic generalized epilepsy. Our goal was to rank the most robust white matter microstructural differences across and within syndromes in a multicentre sample of adult epilepsy patients. Diffusion-weighted MRI data were analysed from 1069 healthy controls and 1249 patients: temporal lobe epilepsy with hippocampal sclerosis (n = 599), temporal lobe epilepsy with normal MRI (n = 275), genetic generalized epilepsy (n = 182) and non-lesional extratemporal epilepsy (n = 193). A harmonized protocol using tract-based spatial statistics was used to derive skeletonized maps of fractional anisotropy and mean diffusivity for each participant, and fibre tracts were segmented using a diffusion MRI atlas. Data were harmonized to correct for scanner-specific variations in diffusion measures using a batch-effect correction tool (ComBat). Analyses of covariance, adjusting for age and sex, examined differences between each epilepsy syndrome and controls for each white matter tract (Bonferroni corrected at P < 0.001). Across ‘all epilepsies’ lower fractional anisotropy was observed in most fibre tracts with small to medium effect sizes, especially in the corpus callosum, cingulum and external capsule. There were also less robust increases in mean diffusivity. Syndrome-specific fractional anisotropy and mean diffusivity differences were most pronounced in patients with hippocampal sclerosis in the ipsilateral parahippocampal cingulum and external capsule, with smaller effects across most other tracts. Individuals with temporal lobe epilepsy and normal MRI showed a similar pattern of greater ipsilateral than contralateral abnormalities, but less marked than those in patients with hippocampal sclerosis. Patients with generalized and extratemporal epilepsies had pronounced reductions in fractional anisotropy in the corpus callosum, corona radiata and external capsule, and increased mean diffusivity of the anterior corona radiata. Earlier age of seizure onset and longer disease duration were associated with a greater extent of diffusion abnormalities in patients with hippocampal sclerosis. We demonstrate microstructural abnormalities across major association, commissural, and projection fibres in a large multicentre study of epilepsy. Overall, patients with epilepsy showed white matter abnormalities in the corpus callosum, cingulum and external capsule, with differing severity across epilepsy syndromes. These data further define the spectrum of white matter abnormalities in common epilepsy syndromes, yielding more detailed insights into pathological substrates that may explain cognitive and psychiatric co-morbidities and be used to guide biomarker studies of treatment outcomes and/or genetic research

Topographic divergence of atypical cortical asymmetry and atrophy patterns in temporal lobe epilepsy

Temporal lobe epilepsy, a common drug-resistant epilepsy in adults, is primarily a limbic network disorder associated with predominant unilateral hippocampal pathology. Structural MRI has provided an in vivo window into whole-brain grey matter structural alterations in temporal lobe epilepsy relative to controls, by either mapping (i) atypical inter-hemispheric asymmetry; or (ii) regional atrophy. However, similarities and differences of both atypical asymmetry and regional atrophy measures have not been systematically investigated. Here, we addressed this gap using the multisite ENIGMA-Epilepsy dataset comprising MRI brain morphological measures in 732 temporal lobe epilepsy patients and 1418 healthy controls. We compared spatial distributions of grey matter asymmetry and atrophy in temporal lobe epilepsy, contextualized their topographies relative to spatial gradients in cortical microstructure and functional connectivity calculated using 207 healthy controls obtained from Human Connectome Project and an independent dataset containing 23 temporal lobe epilepsy patients and 53 healthy controls and examined clinical associations using machine learning. We identified a marked divergence in the spatial distribution of atypical inter-hemispheric asymmetry and regional atrophy mapping. The former revealed a temporo-limbic disease signature while the latter showed diffuse and bilateral patterns. Our findings were robust across individual sites and patients. Cortical atrophy was significantly correlated with disease duration and age at seizure onset, while degrees of asymmetry did not show a significant relationship to these clinical variables. Our findings highlight that the mapping of atypical inter-hemispheric asymmetry and regional atrophy tap into two complementary aspects of temporal lobe epilepsy-related pathology, with the former revealing primary substrates in ipsilateral limbic circuits and the latter capturing bilateral disease effects. These findings refine our notion of the neuropathology of temporal lobe epilepsy and may inform future discovery and validation of complementary MRI biomarkers in temporal lobe epilepsy.11Nsciescopu

Selección con ayuda de ordenador en programas de mejora genética utilizando el algoritmo del programa MATLAB

In plant and animal breeding, the best individuals are selected for the next breeding cycle based on the selection index computed from observed phenotypic values of several traits. However, in calculating the selection index, large amounts of data must be analyzed which is still performed by a calculator. This can cause imperfections in the breeding procedures. In this paper an automatic method for simulating a population under natural selection is proposed based on the selection operator of the genetic algorithms. The fitness function of the algorithm is a linear combination of the individual traits imported by the user. The algorithm generates both general and detailed scores of each trait for each labeled individual. The individuals are sorted with respect to their general scores and it is possible to extract individuals whose general scores are greater than a threshold defined by the user. The outlier individuals can also be eliminated. Moreover, for improved illustration and comparison, the individuals are displayed in a graph based on their index values. The proposed algorithm was applied to two distinct dataset and shown that results of the two methods coincide. The proposed method is automatic, fast, and free of human mistakes. Therefore, it is expected to improve the breeding procedures, especially when the numbers of individuals and traits are huge.Tanto en mejora vegetal como animal, se seleccionan los mejores individuos para el próximo ciclo de reproducción basándose en el índice de selección de varios caracteres calculado a partir de valores fenotípicos observados. Sin embargo, al calcular el índice de selección, se deben analizar gran cantidad de datos, lo que aún se realiza con una calculadora. Esto puede causar imperfecciones en los procedimientos de mejora. En este trabajo se propone un método automático para la simulación de una población sometida a selección natural basado en el operador de selección de los algoritmos genéticos. La función de aptitud del algoritmo es una combinación lineal de los caracteres individuales importados por el usuario. El algoritmo genera tanto puntuaciones generales como detalladas de cada carácter para cada individuo etiquetado. Los individuos son ordenados de acuerdo a su puntuación general y es posible extraer aquellos cuyos resultados generales son mayores que un umbral definido por el usuario. Los individuos anómalos también pueden ser eliminados. Para una mayor ilustración y comparación, se muestran los individuos en un gráfico según sus valores. Se aplicó el algoritmo propuesto a dos conjuntos de datos distintos y los resultados de los dos métodos coincidieron. El método propuesto es automático, rápido y libre de errores humanos. Por lo tanto, se espera que mejore los procedimientos de cultivo, sobre todo cuando el número de individuos es grande y los caracteres numerosos

Computer aided selection in breeding programs using genetic algorithm in MATLAB program

In plant and animal breeding, the best individuals are selected for the next breeding cycle based on the selection index computed from observed phenotypic values of several traits. However, in calculating the selection index, large amounts of data must be analyzed which is still performed by a calculator. This can cause imperfections in the breeding procedures. In this paper an automatic method for simulating a population under natural selection is proposed based on the selection operator of the genetic algorithms. The fitness function of the algorithm is a linear combination of the individual traits imported by the user. The algorithm generates both general and detailed scores of each trait for each labeled individual. The individuals are sorted with respect to their general scores and it is possible to extract individuals whose general scores are greater than a threshold defined by the user. The outlier individuals can also be eliminated. Moreover, for improved illustration and comparison, the individuals are displayed in a graph based on their index values. The proposed algorithm was applied to two distinct dataset and shown that results of the two methods coincide. The proposed method is automatic, fast, and free of human mistakes. Therefore, it is expected to improve the breeding procedures, especially when the numbers of individuals and traits are huge.Tanto en mejora vegetal como animal, se seleccionan los mejores individuos para el próximo ciclo de reproducción basándose en el índice de selección de varios caracteres calculado a partir de valores fenotípicos observados. Sin embargo, al calcular el índice de selección, se deben analizar gran cantidad de datos, lo que aún se realiza con una calculadora. Esto puede causar imperfecciones en los procedimientos de mejora. En este trabajo se propone un método automático para la simulación de una población sometida a selección natural basado en el operador de selección de los algoritmos genéticos. La función de aptitud del algoritmo es una combinación lineal de los caracteres individuales importados por el usuario. El algoritmo genera tanto puntuaciones generales como detalladas de cada carácter para cada individuo etiquetado. Los individuos son ordenados de acuerdo a su puntuación general y es posible extraer aquellos cuyos resultados generales son mayores que un umbral definido por el usuario. Los individuos anómalos también pueden ser eliminados. Para una mayor ilustración y comparación, se muestran los individuos en un gráfico según sus valores. Se aplicó el algoritmo propuesto a dos conjuntos de datos distintos y los resultados de los dos métodos coincidieron. El método propuesto es automático, rápido y libre de errores humanos. Por lo tanto, se espera que mejore los procedimientos de cultivo, sobre todo cuando el número de individuos es grande y los caracteres numerosos

The connectivity domain: Analyzing resting state fMRI data using feature-based data-driven and model-based methods

AbstractSpontaneous fluctuations of resting state functional MRI (rsfMRI) have been widely used to understand the macro-connectome of the human brain. However, these fluctuations are not synchronized among subjects, which leads to limitations and makes utilization of first-level model-based methods challenging. Considering this limitation of rsfMRI data in the time domain, we propose to transfer the spatiotemporal information of the rsfMRI data to another domain, the connectivity domain, in which each value represents the same effect across subjects. Using a set of seed networks and a connectivity index to calculate the functional connectivity for each seed network, we transform data into the connectivity domain by generating connectivity weights for each subject. Comparison of the two domains using a data-driven method suggests several advantages in analyzing data using data-driven methods in the connectivity domain over the time domain. We also demonstrate the feasibility of applying model-based methods in the connectivity domain, which offers a new pathway for the use of first-level model-based methods on rsfMRI data. The connectivity domain, furthermore, demonstrates a unique opportunity to perform first-level feature-based data-driven and model-based analyses. The connectivity domain can be constructed from any technique that identifies sets of features that are similar across subjects and can greatly help researchers in the study of macro-connectome brain function by enabling us to perform a wide range of model-based and data-driven approaches on rsfMRI data, decreasing susceptibility of analysis techniques to parameters that are not related to brain connectivity information, and evaluating both static and dynamic functional connectivity of the brain from a new perspective

MEG Coherence and DTI Connectivity in mTLE

Magnetoencephalography (MEG) is a noninvasive imaging method for localization of focal epileptiform activity in patients with epilepsy. Diffusion tensor imaging (DTI) is a noninvasive imaging method for measuring the diffusion properties of the underlying white matter tracts through which epileptiform activity is propagated. This study investigates the relationship between the cerebral functional abnormalities quantified by MEG coherence and structural abnormalities quantified by DTI in mesial temporal lobe epilepsy (mTLE). Resting state MEG data was analyzed using MEG coherence source imaging (MEG-CSI) method to determine the coherence in 54 anatomical sites in 17 adult mTLE patients with surgical resection and Engel class I outcome, and 17 age- and gender- matched controls. DTI tractography identified the fiber tracts passing through these same anatomical sites of the same subjects. Then, DTI nodal degree and laterality index were calculated and compared with the corresponding MEG coherence and laterality index. MEG coherence laterality, after Bonferroni adjustment, showed significant differences for right versus left mTLE in insular cortex and both lateral orbitofrontal and superior temporal gyri (p \u3c 0.017). Likewise, DTI nodal degree laterality, after Bonferroni adjustment, showed significant differences for right versus left mTLE in gyrus rectus, insular cortex, precuneus and superior temporal gyrus (p \u3c 0.017). In insular cortex, MEG coherence laterality correlated with DTI nodal degree laterality ([Formula: see text] in the cases of mTLE. None of these anatomical sites showed statistically significant differences in coherence laterality between right and left sides of the controls. Coherence laterality was in agreement with the declared side of epileptogenicity in insular cortex (in 82 % of patients) and both lateral orbitofrontal (88 %) and superior temporal gyri (88 %). Nodal degree laterality was also in agreement with the declared side of epileptogenicity in gyrus rectus (in 88 % of patients), insular cortex (71 %), precuneus (82 %) and superior temporal gyrus (94 %). Combining all significant laterality indices improved the lateralization accuracy to 94 % and 100 % for the coherence and nodal degree laterality indices, respectively. The associated variations in diffusion properties of fiber tracts quantified by DTI and coherence measures quantified by MEG with respect to epileptogenicity possibly reflect the chronic microstructural cerebral changes associated with functional interictal activity. The proposed methodology for using MEG and DTI to investigate diffusion abnormalities related to focal epileptogenicity and propagation may provide a further means of noninvasive lateralization

MEG Coherence and DTI Connectivity in mTLE

Magnetoencephalography (MEG) is a noninvasive imaging method for localization of focal epileptiform activity in patients with epilepsy. Diffusion tensor imaging (DTI) is a noninvasive imaging method for measuring the diffusion properties of the underlying white matter tracts through which epileptiform activity is propagated. This study investigates the relationship between the cerebral functional abnormalities quantified by MEG coherence and structural abnormalities quantified by DTI in mesial temporal lobe epilepsy (mTLE). Resting state MEG data was analyzed using MEG coherence source imaging (MEG-CSI) method to determine the coherence in 54 anatomical sites in 17 adult mTLE patients with surgical resection and Engel class I outcome, and 17 age- and gender- matched controls. DTI tractography identified the fiber tracts passing through these same anatomical sites of the same subjects. Then, DTI nodal degree and laterality index were calculated and compared with the corresponding MEG coherence and laterality index. MEG coherence laterality, after Bonferroni adjustment, showed significant differences for right versus left mTLE in insular cortex and both lateral orbitofrontal and superior temporal gyri (p \u3c 0.017). Likewise, DTI nodal degree laterality, after Bonferroni adjustment, showed significant differences for right versus left mTLE in gyrus rectus, insular cortex, precuneus and superior temporal gyrus (p \u3c 0.017). In insular cortex, MEG coherence laterality correlated with DTI nodal degree laterality ([Formula: see text] in the cases of mTLE. None of these anatomical sites showed statistically significant differences in coherence laterality between right and left sides of the controls. Coherence laterality was in agreement with the declared side of epileptogenicity in insular cortex (in 82 % of patients) and both lateral orbitofrontal (88 %) and superior temporal gyri (88 %). Nodal degree laterality was also in agreement with the declared side of epileptogenicity in gyrus rectus (in 88 % of patients), insular cortex (71 %), precuneus (82 %) and superior temporal gyrus (94 %). Combining all significant laterality indices improved the lateralization accuracy to 94 % and 100 % for the coherence and nodal degree laterality indices, respectively. The associated variations in diffusion properties of fiber tracts quantified by DTI and coherence measures quantified by MEG with respect to epileptogenicity possibly reflect the chronic microstructural cerebral changes associated with functional interictal activity. The proposed methodology for using MEG and DTI to investigate diffusion abnormalities related to focal epileptogenicity and propagation may provide a further means of noninvasive lateralization

MEG Coherence and DTI Connectivity in mTLE

Magnetoencephalography (MEG) is a noninvasive imaging method for localization of focal epileptiform activity in patients with epilepsy. Diffusion tensor imaging (DTI) is a noninvasive imaging method for measuring the diffusion properties of the underlying white matter tracts through which epileptiform activity is propagated. This study investigates the relationship between the cerebral functional abnormalities quantified by MEG coherence and structural abnormalities quantified by DTI in mesial temporal lobe epilepsy (mTLE). Resting state MEG data was analyzed using MEG coherence source imaging (MEG-CSI) method to determine the coherence in 54 anatomical sites in 17 adult mTLE patients with surgical resection and Engel class I outcome, and 17 age- and gender- matched controls. DTI tractography identified the fiber tracts passing through these same anatomical sites of the same subjects. Then, DTI nodal degree and laterality index were calculated and compared with the corresponding MEG coherence and laterality index. MEG coherence laterality, after Bonferroni adjustment, showed significant differences for right versus left mTLE in insular cortex and both lateral orbitofrontal and superior temporal gyri (p \u3c 0.017). Likewise, DTI nodal degree laterality, after Bonferroni adjustment, showed significant differences for right versus left mTLE in gyrus rectus, insular cortex, precuneus and superior temporal gyrus (p \u3c 0.017). In insular cortex, MEG coherence laterality correlated with DTI nodal degree laterality ([Formula: see text] in the cases of mTLE. None of these anatomical sites showed statistically significant differences in coherence laterality between right and left sides of the controls. Coherence laterality was in agreement with the declared side of epileptogenicity in insular cortex (in 82 % of patients) and both lateral orbitofrontal (88 %) and superior temporal gyri (88 %). Nodal degree laterality was also in agreement with the declared side of epileptogenicity in gyrus rectus (in 88 % of patients), insular cortex (71 %), precuneus (82 %) and superior temporal gyrus (94 %). Combining all significant laterality indices improved the lateralization accuracy to 94 % and 100 % for the coherence and nodal degree laterality indices, respectively. The associated variations in diffusion properties of fiber tracts quantified by DTI and coherence measures quantified by MEG with respect to epileptogenicity possibly reflect the chronic microstructural cerebral changes associated with functional interictal activity. The proposed methodology for using MEG and DTI to investigate diffusion abnormalities related to focal epileptogenicity and propagation may provide a further means of noninvasive lateralization