ORCID Profile
0000-0003-2345-7938
Current Organisation
Inselspital
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Publisher: Oxford University Press (OUP)
Date: 18-03-2017
DOI: 10.1093/BRAIN/AWX067
Publisher: Oxford University Press (OUP)
Date: 30-01-2018
DOI: 10.1093/BRAIN/AWX341
Publisher: Cold Spring Harbor Laboratory
Date: 05-05-2020
DOI: 10.1101/2020.05.04.076836
Abstract: 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 in idual 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.
Publisher: Elsevier BV
Date: 2018
DOI: 10.1016/J.EARLHUMDEV.2017.11.003
Abstract: Very preterm birth influences brain development and may result in alterations of cortical morphometry. These structural alterations may interact with cognitive development. The aim of the present study was to investigate the structure-function relationship in school-aged very preterm and term-born control children. A comprehensive neuropsychological test battery was administered to 41 very preterm ( controls). No group differences occurred for cortical surface area. The relationship between cortical morphometry and cognition differed between very preterm and control children. In very preterm children, some cognitive domains correlated positively and others negatively with regional cortical thickness and cortical surface area. Our findings contribute to the understanding of the structure-function relationship in very preterm children and their term-born peers. They add to the notion that this relationship varies depending on the brain region and the cognitive function in question and suggest developmental differences between very preterm and term-born children.
Publisher: Cold Spring Harbor Laboratory
Date: 23-10-2023
Publisher: Wiley
Date: 05-09-2021
DOI: 10.1111/NAN.12758
Abstract: The causes of distinct patterns of reduced cortical thickness in the common human epilepsies, detectable on neuroimaging and with important clinical consequences, are unknown. We investigated the underlying mechanisms of cortical thinning using a systems‐level analysis. Imaging‐based cortical structural maps from a large‐scale epilepsy neuroimaging study were overlaid with highly spatially resolved human brain gene expression data from the Allen Human Brain Atlas. Cell‐type deconvolution, differential expression analysis and cell‐type enrichment analyses were used to identify differences in cell‐type distribution. These differences were followed up in post‐mortem brain tissue from humans with epilepsy using Iba1 immunolabelling. Furthermore, to investigate a causal effect in cortical thinning, cell‐type‐specific depletion was used in a murine model of acquired epilepsy. We identified elevated fractions of microglia and endothelial cells in regions of reduced cortical thickness. Differentially expressed genes showed enrichment for microglial markers and, in particular, activated microglial states. Analysis of post‐mortem brain tissue from humans with epilepsy confirmed excess activated microglia. In the murine model, transient depletion of activated microglia during the early phase of the disease development prevented cortical thinning and neuronal cell loss in the temporal cortex. Although the development of chronic seizures was unaffected, the epileptic mice with early depletion of activated microglia did not develop deficits in a non‐spatial memory test seen in epileptic mice not depleted of microglia. 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.
Publisher: Frontiers Media SA
Date: 03-2018
Publisher: American Association for the Advancement of Science (AAAS)
Date: 20-11-2020
Abstract: Brain atrophy in human epilepsy syndromes is explainable by network architecture and strongest in hub regions.
Publisher: Elsevier BV
Date: 09-2014
DOI: 10.1016/J.EARLHUMDEV.2014.05.013
Abstract: Cortical gray matter thinning occurs during childhood due to pruning of inefficient synaptic connections and an increase in myelination. Preterms show alterations in brain structure, with prolonged maturation of the frontal lobes, smaller cortical volumes and reduced white matter volume. These findings give rise to the question if there is a differential influence of age on cortical thinning in preterms compared to controls. To investigate the relationship between age and cortical thinning in school-aged preterms compared to controls. The automated surface reconstruction software FreeSurfer was applied to obtain measurements of cortical thickness based on T1-weighted MRI images. Forty-one preterms (<32weeks gestational age and/or <1500g birth weight) and 30 controls were included in the study (7-12years). In preterms, age correlated negatively with cortical thickness in right frontal, parietal and inferior temporal regions. Furthermore, young preterms showed a thicker cortex compared to old preterms in bilateral frontal, parietal and temporal regions. In controls, age was not associated with cortical thickness. In preterms, cortical thinning still seems to occur between the age of 7 and 12years, mainly in frontal and parietal areas whereas in controls, a substantial part of cortical thinning appears to be completed before they reach the age of 7years. These data indicate slower cortical thinning in preterms than in controls.
Publisher: Springer International Publishing
Date: 2019
Publisher: Springer Science and Business Media LLC
Date: 13-02-2020
DOI: 10.1186/S13063-019-4022-Z
Abstract: The population of adult patients with early-treated phenylketonuria (PKU) following newborn screening is growing substantially. The ideal target range of blood phenylalanine (Phe) levels in adults outside pregnancy is a matter of debate. Therefore, prospective intervention studies are needed to evaluate the effects of an elevated Phe concentration on cognition and structural, functional, and neurometabolic parameters of the brain. The PICO (Phenylalanine and Its Impact on Cognition) Study evaluates the effect of a 4-week Phe load on cognition and cerebral parameters in adults with early-treated PKU in a double-blind, randomized, placebo-controlled, crossover, noninferiority trial. Thirty adult patients with early-treated PKU and 30 healthy controls comparable to patients with regard to age, sex, and educational level will be recruited from the University Hospitals Bern and Zurich, Switzerland. Patients are eligible for the study if they are 18 years of age or older and had PKU diagnosed after a positive newborn screening and were treated with a Phe-restricted diet starting within the first 30 days of life. Intervention: The cross-over intervention consists of 4-week oral Phe or placebo administration in patients with PKU. The study design mimics a Phe-restricted and a Phe-unrestricted diet using a double-blinded, placebo-controlled approach. The primary objective of the PICO Study is to prospectively assess whether a temporarily elevated Phe level influences cognitive performance (working memory assessed with a n-back task) in adults with early-treated PKU. As a secondary objective, the PICO Study will elucidate the cerebral (fMRI, neural activation during a n-back task rsfMRI, functional connectivity at rest DTI, white matter integrity and ASL, cerebral blood flow) and neurometabolic mechanisms (cerebral Phe level) that accompany changes in Phe concentration. Cognition, and structural and functional parameters of the brain of adult patients with early-treated PKU will be cross-sectionally compared to healthy controls. All assessments will take place at the University Hospital Bern, Switzerland. Central randomization will be used to assign participants to the different treatment arms with age, sex, and center serving as the stratification factors. Randomization lists will be generated by an independent statistician. Blinding: All trial personnel other than the statistician generating the randomization list and the personnel at the facility preparing the interventional product are blinded to the assigned treatment. Using a combination of neuropsychological and neuroimaging data, the PICO Study will considerably contribute to improve the currently insufficient level of evidence on how adult patients with early-treated PKU should be managed. The study is registered at clinicaltrials.gov ( NCT03788343 ) on the 27th of December 2018, at kofam.ch ( SNCTP000003117 ) on the 17th of December 2018, and on the International Clinical Trials Registry Platform of the WHO.
Publisher: Public Library of Science (PLoS)
Date: 17-08-2017
Publisher: Springer Science and Business Media LLC
Date: 07-07-2016
DOI: 10.1038/SREP29215
Abstract: Surgery is a valuable option for pharmacologically intractable epilepsy. However, significant post-operative improvements are not always attained. This is due in part to our incomplete understanding of the seizure generating (ictogenic) capabilities of brain networks. Here we introduce an in silico , model-based framework to study the effects of surgery within ictogenic brain networks. We find that factors conventionally determining the region of tissue to resect, such as the location of focal brain lesions or the presence of epileptiform rhythms, do not necessarily predict the best resection strategy. We validate our framework by analysing electrocorticogram (ECoG) recordings from patients who have undergone epilepsy surgery. We find that when post-operative outcome is good, model predictions for optimal strategies align better with the actual surgery undertaken than when post-operative outcome is poor. Crucially, this allows the prediction of optimal surgical strategies and the provision of quantitative prognoses for patients undergoing epilepsy surgery.
Publisher: Cold Spring Harbor Laboratory
Date: 14-11-2018
DOI: 10.1101/470518
Abstract: 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 ,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.
Publisher: Cold Spring Harbor Laboratory
Date: 19-10-2021
DOI: 10.1101/2021.10.18.464713
Abstract: 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 hippoc al 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.
Publisher: Wiley
Date: 29-05-2020
DOI: 10.1002/HBM.25037
Abstract: Epilepsy is a common and serious neurological disorder, with many different constituent conditions characterized by their electro clinical, imaging, and genetic features. MRI has been fundamental in advancing our understanding of brain processes in the epilepsies. Smaller‐scale studies have identified many interesting imaging phenomena, with implications both for understanding pathophysiology and improving clinical care. Through the infrastructure and concepts now well‐established by the ENIGMA Consortium, ENIGMA‐Epilepsy was established to strengthen epilepsy neuroscience by greatly increasing s le sizes, leveraging ideas and methods established in other ENIGMA projects, and generating a body of collaborating scientists and clinicians to drive forward robust research. Here we review published, current, and future projects, that include structural MRI, diffusion tensor imaging (DTI), and resting state functional MRI (rsfMRI), and that employ advanced methods including structural covariance, and event‐based modeling analysis. We explore age of onset‐ and duration‐related features, as well as phenomena‐specific work focusing on particular epilepsy syndromes or phenotypes, multimodal analyses focused on understanding the biology of disease progression, and deep learning approaches. We encourage groups who may be interested in participating to make contact to further grow and develop ENIGMA‐Epilepsy.
No related grants have been discovered for Christian Rummel.