Biology subjects

Cendes, F.

Publications and source records attributed to Cendes, F..

17 recordsLinked to original sources

bioRxiv2026

Sex-related structural alterations across common epilepsies: a worldwide ENIGMA study

Epilepsy is characterized by widespread structural brain alterations extending beyond the epileptic zone, involving both cortical and subcortical regions. Importantly, the clinical manifestation of epilepsy, including seizure types, psychiatric comorbidities, and treatment responses, has been shown to differ between sexes. However, sex differences in structural alterations in epilepsy have been seldomly reported in neuroimaging studies, partly due to limited sample sizes and single-center designs. Here, we systematically investigated sex differences in common epilepsies and their related clinical variables using structural neuroimaging biomarkers in an international multi-center cohort of 1,253 epilepsy patients and 1,077 healthy controls. We studied cortical thickness and subcortical volume in two types of epilepsy: temporal lobe epilepsy (TLE) and genetic generalized epilepsy (GGE). Both male and female patients with TLE showed widespread cortical and subcortical thinning compared with controls. In GGE, when compared separately to controls, male patients showed only subtle structural alterations, whereas female patients exhibited more widespread structural alterations. Sex-stratified analyses revealed some variation in the extent and distribution of cortical thickness and subcortical volume alterations between male and female patients in both epilepsy cohorts. Yet, we did not find significant sex-by-diagnosis interaction effects in TLE and GGE. Similarly, no significant interaction effects were observed between sex and age of onset or disease duration in either patient group. Overall, although we observed some differences in regional cortical thickness and subcortical volume between male and female patients with epilepsy, we did not find significant sex-by-diagnosis interactions. Our findings indicate that sex differences in behavioral and clinical outcomes of epilepsy may involve biological or functional processes that require further investigation.

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bioRxiv2026

A multimodal single-cell atlas of the adolescent brain reveals gene regulatory networks linking development to disease risk

Adolescence represents a critical window of brain maturation when many neuropsychiatric disorders first emerge, yet the molecular mechanisms driving this developmental period remain incompletely understood. To address this gap, we generated a high-resolution multimodal cell atlas of the developing adolescent brain using paired single-nucleus RNA and ATAC sequencing (snRNA-seq + snATAC-seq) from cortex, hippocampus, and amygdala tissue of six donors aged 6-15 years, profiling 88,658 high-quality nuclei. Integrative analyses identified 36 enhancer-driven gene regulatory networks (eGRNs) with significant age-dependent dynamics in the transition from childhood to adolescence. The majority of adolescence-associated eGRNs were active in oligodendrocytes and their precursors, reflecting active oligodendrogenesis and myelin remodeling during this developmental period. Notably, age-associated cis-regulatory elements were enriched for expression quantitative trait loci (eQTLs) and colocalized with genetic variants linked to both neurodevelopmental and neurodegenerative disorders, suggesting that regulatory networks may be shared across normal adolescent brain development and disease vulnerability. This multimodal cell atlas provides a valuable resource for understanding the human adolescent brain and offers new insights into the molecular origins of neuropsychiatric disorders.

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bioRxiv2025

A Core Pattern of Cerebellar and Brainstem Degeneration and Reduced Cerebrocerebellar Structural Covariance in Spinocerebellar Ataxia Type 3 (SCA3): MRI Volumetrics from ENIGMA-Ataxia

ObjectiveSpinocerebellar ataxia type 3 (SCA3) is a rare, inherited neurodegenerative disease. Here, we profile the spatial spread of atrophy across the whole brain, determine whether brain degeneration preferentially maps onto specific functional networks, and investigate the relationship between cerebellar and cerebral anatomical changes. MethodsWhole-brain grey and white matter (GM and WM) voxel-based morphometry was performed on 408 individuals with SCA3 (82 pre-ataxic) and 293 controls. The SCA3 cohort was stratified by ataxia severity to investigate disease progression, with cerebellar GM atrophy mapped onto a task-based functional atlas. Volume was correlated with disease duration and intensity. Cerebrocerebellar volumetric covariance was assessed to determine whether atrophy was coupled between infra- and supratentorial regions. ResultsThe pattern of atrophy is spatially consistent but progressive in magnitude across the disease course. The greatest atrophy was found in the pons, cerebellar WM, and cerebellar peduncles; correlations with disease severity and duration were also strongest in these regions. Cerebellar GM atrophy was greatest in functional regions associated with motor execution and planning, attention, and emotional processing. Sparse cerebral cortical atrophy appears only in the most severe disease subgroup, while striatal atrophy begins in the earliest stages. Reduced cerebrocerebellar structural covariance is observed in SCA3 participants versus controls. InterpretationWhile cerebellar and brainstem atrophy become more severe, the pattern of atrophy remains largely consistent as SCA3 progresses. Cerebellar GM degeneration occurs in regions associated with motor, cognitive, and affective control, in line with clinical presentation. Cerebellar atrophy is not directly mirrored by cerebral changes.

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bioRxiv2025

Associations between epilepsy-related polygenic risk and brain morphology in childhood

AO_SCPLOWBSTRACTC_SCPLOWTemporal lobe epilepsy with hippocampal sclerosis (TLE-HS) is associated with a complex genetic architecture, but the translation from genetic risk factors to brain vulnerability remains unclear. Here, we examined associations between epilepsy-related polygenic risk scores for HS (PRS-HS) and brain structure in a large sample of neurotypical children, and correlated these signatures with case-control findings in in multicentric cohorts of patients with TLE-HS. Imaging-genetic analyses revealed PRS-related cortical thinning in temporo-parietal and fronto-central regions, strongly anchored to distinct functional and structural network epicentres. Compared to disease-related effects derived from epilepsy case-control cohorts, structural correlates of PRS-HS mirrored atrophy and epicentre patterns in patients with TLE-HS. By identifying a potential pathway between genetic vulnerability and disease mechanisms, our findings provide new insights into the genetic underpinnings of structural alterations in TLE-HS and highlight potential imaging-genetic biomarkers for early risk stratification and personalized interventions.

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bioRxiv2024

Cell type mapping of mild malformations of cortical development with oligodendroglial hyperplasia in epilepsy using single-nucleus multiomics

ObjectiveMild malformations of cortical development with oligodendroglial hyperplasia in epilepsy (MOGHE) are brain lesions associated with focal epilepsy and characterized by increased oligodendroglial density, heterotopic neurons, and hypomyelination in the white matter. While previous studies have implicated somatic mutations in the SLC35A2 gene, the cellular and molecular mechanisms underlying MOGHE pathogenesis remain elusive. To address this gap, this study aimed to systematically characterize the cell type composition and molecular alterations of MOGHE lesions at cellular resolution using single-nucleus multiomics profiling. MethodsWe performed single-nucleus multiomics sequencing to obtain paired gene expression and chromatin accessibility profiles of > 31,000 nuclei from gray matter and white matter regions of MOGHE lesions, and compared the results with publicly available neurotypical control datasets. ResultsThe analysis of gray and white matter regions from two MOGHE patients revealed significant cellular composition alterations, including the presence of heterotopic neurons and disease-specific oligodendrocytes populations within the subcortical white matter. MOGHE-specific oligodendrocytes were characterized by the upregulation of synaptic functions and enhanced neuron communication, denoting a possible role in synaptic support and the mediation of glial-neuron interactions in the disease. On the other hand, MOGHE heterotopic neurons were characterized by the upregulation of genes associated with neuronal migration and the Wnt signaling pathway, suggesting a mechanism underlying their atypical localization. SignificanceThis high-resolution cell type mapping of MOGHE lesions in clinical samples unveils neuronal and glial populations affected by the disease, and provides novel insights into the pathophysiological mechanisms of MOGHE. Key PointsO_LIWe provide a multimodal cellular atlas of the human cortical and subcortical regions affected in MOGHE C_LIO_LIMOGHE-associated oligodendrocytes showed upregulation of synaptic functions and enhanced neuron communication C_LIO_LINeuronal migration and Wnt signaling are upregulated in MOGHE heterotopic neurons C_LI

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bioRxiv2024

EPILEPTOGENESIS INHIBITS THE CIRCADIAN CLOCK AND RESHAPES THE DIURNAL TRANSCRIPTOMIC RHYTHMICITY IN THE MOUSE HIPPOCAMPUS

Epileptogenesis is the process that leads the brain into epileptic activity. Clinical evidence shows that [~]90% of people with epilepsy present rhythmicity in the timing of their seizures presentation. However, whether the circadian clock is a key player during epileptogenesis remains unknown. Here, we triggered epileptogenesis in mice by the intra-amygdala injection of kainic acid and profiled by RNA sequencing their hippocampal diurnal mRNA rhythmicity. We show that epileptogenesis largely reshapes the hippocampal transcriptomic rhythmicity and that the molecular clock machinery is inhibited due to the disruption of the core clock gene Bmal1. We identified relevant dysregulated pathways and their dynamics in epileptogenesis, predicting a key role for microglial-driven neuroinflammation. We predicted the genes that Bmal1 is directly controlling over time. Finally, we sought for translational relevance evidence by performing RNA sequencing in hippocampal samples resected from patients with mesial temporal lobe epilepsy with hippocampal sclerosis (mTLE-HS) and cross-analyzing datasets.

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bioRxiv2024

Multimodal single-cell sequencing of the human cortex reveals neuronal vulnerability and activated glial cell states in focal cortical dysplasia

Focal Cortical Dysplasia (FCD) is a neurodevelopmental condition characterized by malformations of the cerebral cortex that often cause drug-resistant epilepsy. In this study, we performed multi-omics single-cell profiling to map the chromatin accessibility and transcriptome landscapes of FCD type II, generating a comprehensive multimodal single-cell dataset comprising 61,525 cells from 11 clinical samples of lesions and controls. Our findings revealed profound chromatin, transcriptomic, and cellular alterations affecting neuronal and glial cells in FCD lesions, including the selective loss of upper-layer excitatory neurons, significant expansion of oligodendrocytes and immature astrocytic populations, and a unique neuronal subpopulation harboring dysmorphic neurons. Furthermore, we uncovered activated microglia subsets, particularly in FCD IIb cases. This comprehensive study unveils neuronal and glial cell states driving FCD development and epileptogenicity, enhancing our understanding of FCD and offering new directions for targeted therapy development.

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bioRxiv2024

A worldwide ENIGMA study on epilepsy-related gray and white matter compromise across the adult lifespan

ObjectivesTemporal lobe epilepsy (TLE) is commonly associated with mesiotemporal pathology and widespread alterations of grey and white matter structures. Evidence supports a progressive condition although the temporal evolution of TLE is poorly defined. This ENIGMA-Epilepsy study utilized multimodal magnetic resonance imaging (MRI) data to investigate structural alterations in TLE patients across the adult lifespan. We charted both grey and white matter changes and explored the covariance of age-related alterations in both compartments. MethodsWe studied 769 TLE patients and 885 healthy controls across an age range of 17-73 years, from multiple international sites. To assess potentially non-linear lifespan changes in TLE, we harmonized data and combined median split assessments with cross-sectional sliding window analyses of grey and white matter age-related changes. Covariance analyses examined the coupling of grey and white matter lifespan curves. ResultsIn TLE, age was associated with a robust grey matter thickness/volume decline across a broad cortico-subcortical territory, extending beyond the mesiotemporal disease epicentre. White matter changes were also widespread across multiple tracts with peak effects in temporo-limbic fibers. While changes spanned the adult time window, changes accelerated in cortical thickness, subcortical volume, and fractional anisotropy (all decreased), and mean diffusivity (increased) after age 55 years. Covariance analyses revealed strong limbic associations between white matter tracts and subcortical structures with cortical regions. ConclusionsThis study highlights the profound impact of TLE on lifespan changes in grey and white matter structures, with an acceleration of aging-related processes in later decades of life. Our findings motivate future longitudinal studies across the lifespan and emphasize the importance of prompt diagnosis as well as intervention in patients.

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bioRxiv2023

Patterns of subregional cerebellar atrophy across epilepsy syndromes: An ENIGMA-Epilepsy study

ObjectiveThe intricate neuroanatomical structure of the cerebellum is of longstanding interest in epilepsy, but has been poorly characterized within the current cortico-centric models of this disease. We quantified cross-sectional regional cerebellar lobule volumes using structural MRI in 1,602 adults with epilepsy and 1,022 healthy controls across twenty-two sites from the global ENIGMA-Epilepsy working group. MethodsA state-of-the-art deep learning-based approach was employed that parcellates the cerebellum into 28 neuroanatomical subregions. Linear mixed models compared total and regional cerebellar volume in i) all epilepsies; ii) temporal lobe epilepsy with hippocampal sclerosis (TLE-HS); iii) non-lesional temporal lobe epilepsy (TLE-NL); iv) genetic generalised epilepsy; and (v) extra-temporal focal epilepsy (ETLE). Relationships were examined for cerebellar volume versus age at seizure onset, duration of epilepsy, phenytoin treatment, and cerebral cortical thickness. ResultsAcross all epilepsies, reduced total cerebellar volume was observed (d=0.42). Maximum volume loss was observed in the corpus medullare (dmax=0.49) and posterior lobe grey matter regions, including bilateral lobules VIIB (dmax= 0.47), Crus I/II (dmax= 0.39), VIIIA (dmax=0.45) and VIIIB (dmax=0.40). Earlier age at seizure onset ({eta}{rho}2max=0.05) and longer epilepsy duration ({eta}{rho}2max=0.06) correlated with reduced volume in these regions. Findings were most pronounced in TLE-HS and ETLE with distinct neuroanatomical profiles observed in the posterior lobe. Phenytoin treatment was associated with reduced posterior lobe volume. Cerebellum volume correlated with cerebral cortical thinning more strongly in the epilepsy cohort than in controls. SignificanceWe provide robust evidence of deep cerebellar and posterior lobe subregional grey matter volume loss in patients with chronic epilepsy. Volume loss was maximal for posterior subregions implicated in non-motor functions, relative to motor regions of both the anterior and posterior lobe. Associations between cerebral and cerebellar changes, and variability of neuroanatomical profiles across epilepsy syndromes argue for more precise incorporation of cerebellum subregions into neurobiological models of epilepsy. Key pointsO_LICerebellar involvement in epilepsy is poorly understood within current cortico-centric models of this disease C_LIO_LIWe used a novel, deep learning segmentation tool to parcellate the cerebellum into 28 anatomical subunits using an international MRI dataset of 1,602 individuals with epilepsy (aged between 18 and 65 years old) including temporal lobe epilepsy with hippocampal sclerosis (TLE-HS, n=562), TLE non-lesional (TLE-NL, n=284), generalised genetic epilepsy (GGE, n=186) and extra temporal focal epilepsy (ETLE, n=251) and 1,022 controls. C_LIO_LIAcross all epilepsies (vs. controls) robust changes in the corpus medullare and posterior lobe "non-motor" regions were observed, with maximal differences in bilateral VIIB and Crus II lobules. Lower volume of these regions correlated with longer disease duration. Anterior "motor lobe" regions were relatively spared. C_LIO_LIFindings were most pronounced in TLE-HS and ETLE groups, with distinct neuroanatomical profiles observed. C_LIO_LICortical thinning was associated with pronounced cerebellar volume loss in TLE-HS epilepsy, relative to controls. C_LI ETHICAL PUBLICATION STATEMENTWe confirm that we have read the Journals position on issues involved in ethical publication and affirm that this report is consistent with those guidelines.

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bioRxiv2023

Identifying cellular markers of focal cortical dysplasia type II with cell-type deconvolution and single-cell signatures

Focal cortical dysplasia (FCD) is a brain malformation that causes medically refractory epilepsy. FCD is classified into three categories based on structural and cellular abnormalities, with FCD type II being the most common and characterized by disrupted organization of the cortex and abnormal neuronal development. In this study, we employed cell-type deconvolution and single-cell signatures to analyze bulk RNA-seq from multiple transcriptomic studies, aiming to characterize the cellular composition of brain lesions in patients with FCD IIa and IIb subtypes. Our deconvolution analyses revealed specific cellular changes in FCD IIb, including neuronal loss and an increase in reactive astrocytes (astrogliosis) when compared to FCD IIa. Astrogliosis in FCD IIb was further supported by a gene signature analysis and histologically confirmed by glia fibrilla acidic protein (GAP) immunostaining. Overall, our findings demonstrate that FCD II subtypes exhibit differential neuronal and glial compositions, with astrogliosis emerging as a hallmark of FCD IIb. These observations, validated in independent patient cohorts and confirmed using immunohistochemistry, offer novel insights into the involvement of glial cells in FCD type II pathophysiology and may contribute to the development of targeted therapies for this condition.

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bioRxiv2021

Structural network alterations in focal and generalized epilepsy follow axes of epilepsy risk gene expression: An ENIGMA study

Epilepsy is associated with genetic risk factors and cortico-subcortical network alterations, but associations between neurobiological mechanisms and macroscale connectomics remain unclear. This multisite ENIGMA-Epilepsy study examined whole-brain structural covariance networks in patients with epilepsy and related findings to postmortem co-expression patterns of epilepsy risk genes. Brain network analysis included 578 adults with temporal lobe epilepsy (TLE), 288 adults with idiopathic generalized epilepsy (IGE), and 1,328 healthy controls from 18 centres worldwide. Graph theoretical analysis of structural covariance networks revealed increased clustering and path length in orbitofrontal and temporal regions in TLE, suggesting a shift towards network regularization. Conversely, people with IGE showed decreased clustering and path length in fronto-temporo-parietal cortices, indicating a random network configuration. Syndrome-specific topological alterations reflected expression patterns of risk genes for hippocampal sclerosis in TLE and for generalized epilepsy in IGE. These imaging-genetic signatures could guide diagnosis, and ultimately, tailor therapeutic approaches to specific epilepsy syndromes.

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bioRxiv2021

Topographic divergence of atypical cortical asymmetry and regional atrophy patterns in temporal lobe epilepsy: a worldwide enigma study

AO_SCPLOWBSTRACTC_SCPLOWTemporal lobe epilepsy (TLE), 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 pathology in TLE 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 multi-site ENIGMA-Epilepsy dataset comprising MRI brain morphological measures in 732 TLE patients and 1,418 healthy controls. We compared spatial distributions of grey matter asymmetry and atrophy in TLE, contextualized their topographies relative to spatial gradients in cortical microstructure and functional connectivity, 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 TLE-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 TLE and may inform future discovery and validation of complementary MRI biomarkers in TLE.

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bioRxiv2020

Network-based atrophy modelling in the common epilepsies: a worldwide ENIGMA study

Epilepsy is increasingly conceptualized as a network disorder. In this cross-sectional mega-analysis, we integrated neuroimaging and connectome analysis to identify network associations with atrophy patterns in 1,021 adults with epilepsy compared to 1,564 healthy controls from 19 international sites. In temporal lobe epilepsy, areas of atrophy co-localized with highly interconnected cortical hub regions, whereas idiopathic generalized epilepsy showed preferential subcortical hub involvement. These morphological abnormalities were anchored to the connectivity profiles of distinct disease epicenters, pointing to temporo-limbic cortices in temporal lobe epilepsy and fronto-central cortices in idiopathic generalized epilepsy. Indices of progressive atrophy further revealed a strong influence of connectome architecture on disease progression in temporal lobe, but not idiopathic generalized, epilepsy. Our findings were reproduced across individual sites and single patients, and were robust across different analytical methods. Through worldwide collaboration in ENIGMA-Epilepsy, we provided novel insights into the macroscale features that shape the pathophysiology of common epilepsies.

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bioRxiv2019

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 analyzed from 1,069 non-epileptic controls and 1,249 patients: temporal lobe epilepsy with hippocampal sclerosis (N=599), temporal lobe epilepsy with normal MRI (N=275), genetic generalized epilepsy (N=182) and nonlesional 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 fiber 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 fiber tracts with small to medium effect sizes, especially in the corpus callosum, cingulum and external capsule. Less robust effects were seen with 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. Those 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 differences in fractional anisotropy in the corpus callosum, corona radiata and external capsule, and in mean diffusivity of the anterior corona radiata. Earlier age of seizure onset and longer disease duration were associated with a greater extent of microstructural abnormalities in patients with hippocampal sclerosis. We demonstrate microstructural abnormalities across major association, commissural, and projection fibers in a large multicentre study of epilepsy. Overall, epilepsy patients 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 new insights into pathological substrates that may be used to guide future therapeutic and genetic studies.

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bioRxiv2018

A systems-level analysis highlights microglial activation as a modifying factor in common forms of human epilepsy

The common human epilepsies are associated with distinct patterns of reduced cortical thickness, detectable on neuroimaging, with important clinical consequences. To explore underlying mechanisms, we layered MRI-based cortical structural maps from a large-scale epilepsy neuroimaging study onto highly spatially-resolved human brain gene expression data, identifying >2,500 genes overexpressed in regions of reduced cortical thickness, compared to relatively-protected regions. The resulting set of differentially-expressed genes shows enrichment for microglial markers, and in particular, activated microglial states. Parallel analyses of cell-specific eQTLs show enrichment in human genetic signatures of epilepsy severity, but not epilepsy causation. Post mortem brain tissue from humans with epilepsy shows excess activated microglia. In an experimental model, depletion of activated microglia prevents cortical thinning, but not the development of chronic seizures. These convergent data strongly implicate activated microglia in cortical thinning, representing a new dimension for concern and disease modification in the epilepsies, potentially distinct from seizure control.

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bioRxiv2017

Default Mode Network patterns and its interactions with memory performance in patients with Temporal Lobe Epilepsy and controls

Objectiveto investigate abnormal functional connectivity in the resting-state default mode network (DMN) and its relation to memory impairments in patients with temporal lobe epilepsy with and without hippocampal sclerosis (HS)\n\nMethodwe enrolled 122 MTLE patients divided into right-HS (n=42), left-HS (n=49), MRI-negative MTLE (n=31) and controls (n=69). All underwent resting-state seed-based connectivity fMRI, with a seed placed at the posterior cingulate cortex, an essential node for the DMN. In addition, patients and 41 controls were tested for verbal and visual memory, estimated intelligence coefficient and delayed recall.\n\nResultsBoth right-HS and MRI-negative group presented the poorest visual memory scores, and right-HS and left-HS had a worse performance in verbal memory compared to controls and MRI-negative groups. As expected, hippocampus was less connected than controls in all groups of patients. Although EEGs indicated that 64.5% of MRI-negative patients were lateralized to the left, this group showed activations similar to the right-HS.\n\nConclusionOur data suggest that there is a disruption of the normal pattern of DMN in MTLE. Patients with left and right-HS presented similar, increased and decreased connectivity in the ipsilateral hemisphere; however, left-HS had abnormal decreased connectivity in the contralateral hemisphere. Per neuropsychological examination, the presence of HS in the left hemisphere had more impact on verbal memory, which was not found when the seizure focus is in the left hemisphere in the absence of HS. The absence of hippocampal atrophy seems to yield a less prominent disruption in both functional connectivity and neuropsychological performance.

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bioRxiv2017

Mapping Cortical Brain Asymmetry in 17,141 Healthy Individuals Worldwide via the ENIGMA Consortium

Hemispheric asymmetry is a cardinal feature of human brain organization. Altered brain asymmetry has also been linked to some cognitive and neuropsychiatric disorders. Here the ENIGMA consortium presents the largest ever analysis of cerebral cortical asymmetry and its variability across individuals. Cortical thickness and surface area were assessed in MRI scans of 17,141 healthy individuals from 99 datasets worldwide. Results revealed widespread asymmetries at both hemispheric and regional levels, with a generally thicker cortex but smaller surface area in the left hemisphere relative to the right. Regionally, asymmetries of cortical thickness and/or surface area were found in the inferior frontal gyrus, transverse temporal gyrus, parahippocampal gyrus, and entorhinal cortex. These regions are involved in lateralized functions, including language and visuospatial processing. In addition to population-level asymmetries, variability in brain asymmetry was related to sex, age, and brain size (indexed by intracranial volume). Interestingly, we did not find significant associations between asymmetries and handedness. Finally, with two independent pedigree datasets (N = 1,443 and 1,113, respectively), we found several asymmetries showing modest but highly reliable heritability. The structural asymmetries identified, and their variabilities and heritability provide a reference resource for future studies on the genetic basis of brain asymmetry and altered laterality in cognitive, neurological, and psychiatric disorders.\n\nSignificance StatementLeft-right asymmetry is a key feature of the human brain's structure and function. It remains unclear which cortical regions are asymmetrical on average in the population, and how biological factors such as age, sex and genetic variation affect these asymmetries. Here we describe by far the largest ever study of cerebral cortical brain asymmetry, based on data from 17,141 participants. We found a global anterior-posterior 'torque' pattern in cortical thickness, together with various regional asymmetries at the population level, which have not been previously described, as well as effects of age, sex, and heritability estimates. From these data, we have created an on-line resource that will serve future studies of human brain anatomy in health and disease.

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