Publications by authors named "Focke N"

Article Synopsis
  • This study investigates white matter (WM) changes in newly diagnosed epilepsy patients who had a first seizure, focusing on differences in WM integrity compared to healthy controls using diffusion imaging.
  • Results showed that first-seizure patients exhibited decreased fractional anisotropy (FA) in specific brain areas, including the corpus callosum, indicating microstructural abnormalities even before a formal epilepsy diagnosis.
  • The findings suggest that patients who go on to develop epilepsy show distinct WM alterations compared to those who do not, highlighting the significance of early brain changes in the epileptogenic process.
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Generalized epilepsy (GE) encompasses a heterogeneous group of hyperexcitability disorders that clinically manifest as seizures. At the whole-brain level, distinct seizure patterns as well as interictal epileptic discharges (IEDs) reflect key signatures of hyperexcitability in magneto- and electroencephalographic (M/EEG) recordings. Moreover, it had been suggested that aperiodic activity, specifically the slope of the 1/ decay function of the power spectrum, might index neural excitability.

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Objectives: Temporal 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.

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For the one third of people with epilepsy whose seizures are not controlled with medications, targeting the seizure focus with neurostimulation can be an effective therapeutic strategy. In this focused review, we summarize a discussion of targeted neurostimulation modalities during a workshop held in Frankfurt, Germany in September 2023. Topics covered include: available devices for seizure focus stimulation; alternating current (AC) and direct current (DC) stimulation to reduce focal cortical excitability; modeling approaches to simulate DC stimulation; reconciling the efficacy of focal stimulation with the network theory of epilepsy; and the emerging concept of 'neurostimulation zones,' which are defined as cortical regions where focal stimulation is most effective for reducing seizures and which may or may not directly involve the seizure onset zone.

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This paper presents a fully automated pipeline using a sparse convolutional autoencoder for quality control (QC) of affine registrations in large-scale T1-weighted (T1w) and T2-weighted (T2w) magnetic resonance imaging (MRI) studies. Here, a customized 3D convolutional encoder-decoder (autoencoder) framework is proposed and the network is trained in a fully unsupervised manner. For cross-validating the proposed model, we used 1000 correctly aligned MRI images of the human connectome project young adult (HCP-YA) dataset.

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In drug-resistant focal epilepsy, detecting epileptogenic lesions using MRI poses a critical diagnostic challenge. Here, we assessed the utility of MP2RAGE-a T1-weighted sequence with self-bias correcting properties commonly utilized in ultra-high field MRI-for the detection of epileptogenic lesions using a surface-based morphometry pipeline based on FreeSurfer, and compared it to the common approach using T1w MPRAGE, both at 3T. We included data from 32 patients with focal epilepsy (5 MRI-positive, 27 MRI-negative with lobar seizure onset hypotheses) and 94 healthy controls from two epilepsy centres.

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Objective: To determine the effect of inverse methods and timepoints of interictal epileptic discharges (IEDs) used for high-density electric source imaging (hd-ESI) in pharmacoresistant focal epilepsies.

Methods: We retrospectively evaluated the hd-ESI and [18F]fluorodeoxyglucose positron emission tomography (FDG-PET) of 21 operated patients with pharmacoresistant focal epilepsy (Engel I). Volumetric hd-ESI was performed with three different inverse methods such as the inverse solution linearly constrained minimum variance (LCMV, a beamformer method), standardized low resolution electromagnetic tomography (sLORETA) and weighted minimum-norm estimation (wMNE) and at different IED phases.

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Oscillatory power and phase synchronization map neuronal dynamics and are commonly studied to differentiate the healthy and diseased brain. Yet, little is known about the course and spatial variability of these features from early adulthood into old age. Leveraging magnetoencephalography (MEG) resting-state data in a cross-sectional adult sample (n = 350), we probed lifespan differences (18-88 years) in connectivity and power and interaction effects with sex.

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Background And Objectives: Genetic generalized epilepsy (GGE) is the most common form of generalized epilepsy. Although individual patients with GGE typically present without structural alterations, group differences have been demonstrated in GGE and some GGE subtypes like juvenile myoclonic epilepsy (GGE-JME). Previous studies usually involved only small cohorts from single centers and therefore could not assess imaging markers of multiple GGE subtypes.

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Article Synopsis
  • Genetic generalized epilepsy (GGE) is a brain disorder characterized by widespread connectivity issues, which can be studied using simultaneous EEG and fMRI, but there are challenges due to MRI-related artifacts affecting the EEG data.
  • This study explored the effects of these artifacts on group comparisons of EEG power and functional connectivity between GGE patients and healthy controls, finding that while some power differences were reduced in significance, measures of functional connectivity (ImCoh) remained consistent across conditions.
  • Notably, increased functional connectivity was observed in GGE patients, particularly from the thalamus to the precuneus cortex, suggesting that using ImCoh for EEG analysis within the MRI is valid and that group differences can be effectively maintained despite the measurement conditions
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Image templates are a common tool for neuroscience research. Often, they are used for spatial normalization of magnetic resonance imaging (MRI) data, which is a necessary procedure for analyzing brain morphology and function via voxel-based analysis. This allows the researcher to reduce individual shape differences across images and make inferences across multiple subjects.

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Objective: Presurgical high-density electric source imaging (hdESI) of interictal epileptic discharges (IEDs) is only used by few epilepsy centers. One obstacle is the time-consuming workflow both for recording as well as for visual review. Therefore, we analyzed the effect of (a) an automated IED detection and (b) the number of IEDs on the accuracy of hdESI and time-effectiveness.

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The objective of the study was to characterize the pattern of cognitive dysfunction in patients with multiple system atrophy (MSA) applying a standardized neuropsychological assessment. A total of 20 patients with the diagnosis of probable or possible MSA were enrolled for neuropsychological assessment applying the CERAD plus battery. All patients were tested at baseline and 14/20 patients received additional follow-up assessments (median follow-up of 24 months).

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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 epilepsy risk gene expression patterns. Brain network analysis included 578 adults with temporal lobe epilepsy (TLE), 288 adults with idiopathic generalized epilepsy (IGE), and 1328 healthy controls from 18 centres worldwide.

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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 multicenter 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) magnetic resonance imaging (MRI) scans collected by the ENIGMA-Epilepsy consortium, comprising 804 people with MTLE-HS and 1625 healthy controls from 25 centers.

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Objective: Genetic generalized epilepsy (GGE) is characterized by aberrant neuronal dynamics and subtle structural alterations. We evaluated whether a combination of magnetic and electrical neuronal signals and cortical thickness would provide complementary information about network pathology in GGE. We also investigated whether these imaging phenotypes were present in healthy siblings of the patients to test for genetic influence.

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Article Synopsis
  • Temporal lobe epilepsy (TLE) is mainly a limbic network disorder characterized by unilateral hippocampal issues and has been studied using structural MRI for brain grey matter changes.
  • The study utilized the ENIGMA-Epilepsy dataset to compare grey matter asymmetry and atrophy in TLE patients versus healthy controls, finding distinct patterns: atypical asymmetry showed a temporo-limbic signature, while atrophy appeared diffuse and bilateral.
  • Results indicated that cortical atrophy correlates with factors like disease duration and age at seizure onset, while asymmetry levels did not, suggesting that these two measures capture different but complementary aspects of TLE pathology.
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Interindividual anatomical differences in the human cortex can lead to suboptimal current directions and may result in response variability of transcranial electrical stimulation methods. These differences in brain anatomy require individualized electrode stimulation montages to induce an optimal current density in the targeted area of each individual subject. We aimed to explore the possible modulatory effects of 140 Hz transcranial alternating current stimulation (tACS) on the somatosensory cortex using personalized multi-electrode stimulation montages.

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Background: Magnetic resonance imaging (MRI)-based morphometry and relaxometry are proven methods for the structural assessment of the human brain in several neurological disorders. These procedures are generally based on T1-weighted (T1w) and/or T2-weighted (T2w) MRI scans, and rigid and affine registrations to a standard template(s) are essential steps in such studies. Therefore, a fully automatic quality control (QC) of these registrations is necessary in big data scenarios to ensure that they are suitable for subsequent processing.

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Article Synopsis
  • The study investigates the causes of reduced cortical thickness in human epilepsies using brain imaging and gene expression data to understand underlying mechanisms.* -
  • Researchers found higher levels of activated microglia and endothelial cells in areas of reduced cortical thickness, both in imaging studies and post-mortem brain tissue from epilepsy patients.* -
  • Targeted depletion of activated microglia in a mouse model prevented cortical thinning and neuronal loss, suggesting microglia play a crucial role in these changes, potentially offering new approaches for epilepsy treatment beyond seizure control.*
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Artificial intelligence has recently gained popularity across different medical fields to aid in the detection of diseases based on pathology samples or medical imaging findings. Brain magnetic resonance imaging (MRI) is a key assessment tool for patients with temporal lobe epilepsy (TLE). The role of machine learning and artificial intelligence to increase detection of brain abnormalities in TLE remains inconclusive.

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Pathogenic variants in HECW2 are extremely rare. So far, only 19 cases have been reported. They were associated with epilepsy, intellectual disability, absent language, hypotonia, and autism.

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Restructuring of healthcare services during the COVID-19 pandemic has led to lockdown of Epilepsy Monitoring Units (EMUs) in many hospitals. The ad-hoc taskforce of the International League Against Epilepsy (ILAE) and the International Federation of Clinical Neurophysiology (IFCN) highlights the detrimental effect of postponing video-EEG monitoring of patients with epilepsy and other paroxysmal events. The taskforce calls for action to continue functioning of Epilepsy Monitoring Units during emergency situations, such as the COVID-19 pandemic.

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Restructuring of healthcare services during the COVID-19 pandemic has led to lockdown of epilepsy monitoring units (EMUs) in many hospitals. The ad-hoc taskforce of the International League Against Epilepsy (ILAE) and the International Federation of Clinical Neurophysiology (IFCN) highlights the detrimental effect of postponing video-EEG monitoring of patients with epilepsy and other paroxysmal events. The taskforce calls for action for continued functioning of EMUs during emergency situations, such as the COVID-19 pandemic.

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Objective: To assess whether neuronal signals in patients with genetic generalized epilepsy (GGE) are heritable, we examined magnetoencephalography resting-state recordings in patients and their healthy siblings.

Methods: In a prospective, cross-sectional design, we investigated source-reconstructed power and functional connectivity in patients, siblings, and controls. We analyzed 5 minutes of cleaned and awake data without epileptiform discharges in 6 frequency bands (1-40 Hz).

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