The impact of CSF-filled cavities on scalp EEG and its implications.

Previous studies have found electroencephalogram (EEG) amplitude and scalp topography differences between neurotypical and neurological/neurosurgical groups, being interpreted at the cognitive level. However, these comparisons are invariably accompanied by anatomical changes. Critical to EEG are the so-called volume currents, which are affected by the spatial distribution of the different tissues in the head. We investigated the effect of cerebrospinal fluid (CSF)-filled cavities on simulated EEG scalp data. We simulated EEG scalp potentials for known sources using different volume conduction models: a reference model (i.e., unlesioned brain) and models with realistic CSF-filled cavities gradually increasing in size. We used this approach for a single source close or far from the CSF-lesion cavity, and for a scenario with a distributed configuration of sources (i.e., a "cognitive event-related potential effect"). The magnitude and topography errors between the reference and lesion models were quantified. For the single-source simulation close to the lesion, the CSF-filled lesion modulated signal amplitude with more than 17% magnitude error and topography with more than 9% topographical error. Negligible modulation was found for the single source far from the lesion. For the multisource simulations of the cognitive effect, the CSF-filled lesion modulated signal amplitude with more than 6% magnitude error and topography with more than 16% topography error in a nonmonotonic fashion. In conclusion, the impact of a CSF-filled cavity cannot be neglected for scalp-level EEG data. Especially when group-level comparisons are made, any scalp-level attenuated, aberrant, or absent effects are difficult to interpret without considering the confounding effect of CSF.

Automatic quality control of the numerical accuracy of EEG lead fields.

Precise individualized EEG source localization is predicated on having accurate subject-specific Lead Fields (LFs) obtained from their Magnetic Resonance Images (MRI). LF calculation is a complex process involving several error-prone steps that start with obtaining a realistic head model from the MRI and finalizing with computationally expensive solvers such as the Boundary Element Method (BEM) or Finite Element Method (FEM). Current Big-Data applications require the calculation of batches of hundreds or thousands of LFs. LF. Quality Control is conventionally checked subjectively by experts, a procedure not feasible in practice for larger batches. To facilitate this step, we introduce the Lead Field Automatic-Quality Control Index (LF-AQI) that flags LF with potential errors. We base our LF-AQI on the assumption that LFs obtained from simpler head models, i.e., the homogeneous head model LF (HHM-LF) or spherical head model LF (SHM-LF), deviate only moderately from a "good" realistic test LF. Since these simpler LFs are easier to compute and check for errors, they may serve as "reference LF" to detect anomalous realistic test LF. We investigated this assumption by comparing correlation-based channel ρmin(ref,test)and source τmin(ref,test) similarity indices (SI) between "gold standards," i.e., very accurate FEM and BEM LFs, and the proposed references (HHM-LF and SHM-LF). Surprisingly we found that the most uncomplicated possible reference, HHM-LF had high SI values with the gold standards-leading us to explore further use of the channel ρmin(HHM-LF,test)and source τmin(HHM-LF,test)SI as a basis for our LF-AQI. Indeed, these SI successfully detected five simulated scenarios of LFs artifacts. This result encouraged us to evaluate the SI on a large dataset and thus define our LF-AQI. We thus computed the SI of 1251 LFs obtained from the Child Mind Institute (CMI) MRI dataset. When ρmin(HHM-LF,test)and source τmin(HHM-LF,test) were plotted for all test subjects on a 2D space, most were tightly clustered around the median of a high similarity centroid (HSC), except for a smaller proportion of outliers. We define the LF-AQI for a given LF as the log Euclidean distance between its SI and the HSC median. To automatically detect outliers, the threshold is at the 90th percentile of the CMI LF-AQIs (-0.9755). LF-AQI greater than this threshold flag individual LF to be checked. The robustness of this LF-AQI screening was checked by repeated out-of-sample validation. Strikingly, minor corrections in re-processing the flagged cases eliminated their status as outliers. Furthermore, the "doubtful" labels assigned by LF-AQI were validated by neuroscience students using a Likert scale questionnaire designed to manually check the LF's quality. Item Response Theory (IRT) analysis was applied to the questionnaire results to compute an optimized model and a latent variable θ for that model. A linear mixed model (LMM) between the θ and LF-AQI resulted in an effect with a Cohen's d value of 1.3 and a p-value <0.001, thus validating the correspondence of LF-AQI with the visual quality control. We provide an open-source pipeline to implement both LF calculation and its quality control to allow further evaluation of our index.

Estimating the influence of stroke lesions on MEG source reconstruction.

Source reconstruction of magnetoencephalography (MEG) has been used to assess brain reorganization after brain damage, such as stroke. Lesions result in parts of the brain having an electrical conductivity that differs from the normal values. The effect this has on the forward solutions (i.e., the propagation of electric currents and magnetic fields generated by cortical activity) is well predictable. However, their influence on source localization results is not well characterized and understood. This is specifically a concern for patient studies with asymmetric (i.e., within one hemisphere) lesions focusing on asymmetric and lateralized brain activity, such as language. In particular, it is good practice to consider the level of geometrical detail that is necessary to compute and interpret reliable source reconstruction results. To understand the effect of lesions on source estimates and propose recommendations to researchers working with clinical data, in this study we consider the trade off between improved accuracy and the additional effort to compute more realistic head models, with the aim to answer the question whether the additional effort is worth it. We simulated and analyzed the effects of a stroke lesion (i.e., an asymmetrically distributed CSF-filled cavity) in the head model with three different sizes and locations when performing MEG source reconstruction using a finite element method (FEM). We compared the effect of the lesion with a homogeneous head model that neglects the lesion. We computed displacement and attenuation/amplification maps to quantify the localization errors and signal magnitude modulation. We conclude that brain lesions leading to asymmetrically distributed CSF-filled cavities should be modeled when performing MEG source reconstruction, especially when investigating deep sources or post-stroke hemispheric lateralization of functions. The strongest effects are not only visible in perilesional areas, but can extend up to 20 mm from the lesion. Bigger lesions lead to stronger effects impacting larger areas, independently from the lesion location. Lastly, we conclude that more priority should be given to usability and accessibility of the required computational tools, to allow researchers with less technical expertise to use the improved methods that are available but currently not widely adopted yet.

Time course of right-hemisphere recruitment during word production following left-hemisphere damage: A single case of young stroke.

Our understanding of post-stroke language function is largely based on older age groups, who show increasing age-related brain pathology and neural reorganisation. To illustrate language outcomes in the young-adult brain, we present the case of J., a 23-year-old woman with chronic aphasia from a left-hemisphere stroke affecting the temporal lobe. Diffusion MRI-based tractography indicated that J.'s language-relevant white-matter structures were severely damaged. Employing magnetoencephalography (MEG), we explored J.'s conceptual preparation and word planning abilities using context-driven and bare picture-naming tasks. These revealed naming deficits, manifesting as word-finding difficulties and semantic paraphasias about half of the time. Naming was however facilitated by semantically constraining lead-in sentences. Altogether, this pattern indicates disrupted lexical-semantic and phonological retrieval abilities. MEG revealed that J.'s conceptual and naming-related neural responses were supported by the right hemisphere, compared to the typical left-lateralised brain response of a matched control. Differential recruitment of right-hemisphere structures (330-440 ms post-picture onset) was found concurrently during successful naming (right mid-to-posterior temporal lobe) and word-finding attempts (right inferior frontal gyrus). Disconnection of the temporal lobes via corpus callosum was not critical for recruitment of the right hemisphere in visually guided naming, possibly due to neural activity right lateralising from the outset. Although J.'s right hemisphere responded in a timely manner during word planning, its lexical and phonological retrieval abilities remained modest.

Reconstructing subcortical and cortical somatosensory activity via the RAMUS inverse source analysis technique using median nerve SEP data.

This study concerns reconstructing brain activity at various depths based on non-invasive EEG (electroencephalography) scalp measurements. We aimed at demonstrating the potential of the RAMUS (randomized multiresolution scanning) technique in localizing weakly distinguishable far-field sources in combination with coinciding cortical activity. As we have shown earlier theoretically and through simulations, RAMUS is a novel mathematical method that by employing the multigrid concept, allows marginalizing noise and depth bias effects and thus enables the recovery of both cortical and subcortical brain activity. To show this capability with experimental data, we examined the 14-30 ms post-stimulus somatosensory evoked potential (SEP) responses of human median nerve stimulation in three healthy adult subjects. We aim at reconstructing the different response components by evaluating a RAMUS-based estimate for the primary current density in the nervous tissue. We present source reconstructions obtained with RAMUS and compare them with the literature knowledge of the SEP components and the outcome of the unit-noise gain beamformer (UGNB) and standardized low-resolution brain electromagnetic tomography (sLORETA). We also analyzed the effect of the iterative alternating sequential technique, the optimization technique of RAMUS, compared to the classical minimum norm estimation (MNE) technique. Matching with our previous numerical studies, the current results suggest that RAMUS could have the potential to enhance the detection of simultaneous deep and cortical components and the distinction between the evoked sulcal and gyral activity.

A comprehensive study on electroencephalography and magnetoencephalography sensitivity to cortical and subcortical sources.

Signal-to-noise ratio (SNR) maps are a good way to visualize electroencephalography (EEG) and magnetoencephalography (MEG) sensitivity. SNR maps extend the knowledge about the modulation of EEG and MEG signals by source locations and orientations and can therefore help to better understand and interpret measured signals as well as source reconstruction results thereof. Our work has two main objectives. First, we investigated the accuracy and reliability of EEG and MEG finite element method (FEM)-based sensitivity maps for three different head models, namely an isotropic three and four-compartment and an anisotropic six-compartment head model. As a result, we found that ignoring the cerebrospinal fluid leads to an overestimation of EEG SNR values. Second, we examined and compared EEG and MEG SNR mappings for both cortical and subcortical sources and their modulation by source location and orientation. Our results for cortical sources show that EEG sensitivity is higher for radial and deep sources and MEG for tangential ones, which are the majority of sources. As to the subcortical sources, we found that deep sources with sufficient tangential source orientation are recordable by the MEG. Our work, which represents the first comprehensive study where cortical and subcortical sources are considered in highly detailed FEM-based EEG and MEG SNR mappings, sheds a new light on the sensitivity of EEG and MEG and might influence the decision of brain researchers or clinicians in their choice of the best modality for their experiment or diagnostics, respectively.

The FieldTrip-SimBio pipeline for EEG forward solutions.

BACKGROUND: Accurately solving the electroencephalography (EEG) forward problem is crucial for precise EEG source analysis. Previous studies have shown that the use of multicompartment head models in combination with the finite element method (FEM) can yield high accuracies both numerically and with regard to the geometrical approximation of the human head. However, the workload for the generation of multicompartment head models has often been too high and the use of publicly available FEM implementations too complicated for a wider application of FEM in research studies. In this paper, we present a MATLAB-based pipeline that aims to resolve this lack of easy-to-use integrated software solutions. The presented pipeline allows for the easy application of five-compartment head models with the FEM within the FieldTrip toolbox for EEG source analysis. METHODS: The FEM from the SimBio toolbox, more specifically the St. Venant approach, was integrated into the FieldTrip toolbox. We give a short sketch of the implementation and its application, and we perform a source localization of somatosensory evoked potentials (SEPs) using this pipeline. We then evaluate the accuracy that can be achieved using the automatically generated five-compartment hexahedral head model [skin, skull, cerebrospinal fluid (CSF), gray matter, white matter] in comparison to a highly accurate tetrahedral head model that was generated on the basis of a semiautomatic segmentation with very careful and time-consuming manual corrections. RESULTS: The source analysis of the SEP data correctly localizes the P20 component and achieves a high goodness of fit. The subsequent comparison to the highly detailed tetrahedral head model shows that the automatically generated five-compartment head model performs about as well as a highly detailed four-compartment head model (skin, skull, CSF, brain). This is a significant improvement in comparison to a three-compartment head model, which is frequently used in praxis, since the importance of modeling the CSF compartment has been shown in a variety of studies. CONCLUSION: The presented pipeline facilitates the use of five-compartment head models with the FEM for EEG source analysis. The accuracy with which the EEG forward problem can thereby be solved is increased compared to the commonly used three-compartment head models, and more reliable EEG source reconstruction results can be obtained.

How to assess the accuracy of volume conduction models? A validation study with stereotactic EEG data.

Introduction: Volume conduction models of the human head are used in various neuroscience fields, such as for source reconstruction in EEG and MEG, and for modeling the effects of brain stimulation. Numerous studies have quantified the accuracy and sensitivity of volume conduction models by analyzing the effects of the geometrical and electrical features of the head model, the sensor model, the source model, and the numerical method. Most studies are based on simulations as it is hard to obtain sufficiently detailed measurements to compare to models. The recording of stereotactic EEG during electric stimulation mapping provides an opportunity for such empirical validation. Methods: In the study presented here, we used the potential distribution of volume-conducted artifacts that are due to cortical stimulation to evaluate the accuracy of finite element method (FEM) volume conduction models. We adopted a widely used strategy for numerical comparison, i.e., we fixed the geometrical description of the head model and the mathematical method to perform simulations, and we gradually altered the head models, by increasing the level of detail of the conductivity profile. We compared the simulated potentials at different levels of refinement with the measured potentials in three epilepsy patients. Results: Our results show that increasing the level of detail of the volume conduction head model only marginally improves the accuracy of the simulated potentials when compared to in-vivo sEEG measurements. The mismatch between measured and simulated potentials is, throughout all patients and models, maximally 40 microvolts (i.e., 10% relative error) in 80% of the stimulation-recording combination pairs and it is modulated by the distance between recording and stimulating electrodes. Discussion: Our study suggests that commonly used strategies used to validate volume conduction models based solely on simulations might give an overly optimistic idea about volume conduction model accuracy. We recommend more empirical validations to be performed to identify those factors in volume conduction models that have the highest impact on the accuracy of simulated potentials. We share the dataset to allow researchers to further investigate the mismatch between measurements and FEM models and to contribute to improving volume conduction models.

Neurophysiological signatures reflect differences in visual attention during absence seizures.

OBJECTIVE: Absences affect visual attention and eye movements variably. Here, we explore whether the dissimilarity of these symptoms during absences is reflected in differences in electroencephalographic (EEG) features, functional connectivity, and activation of the frontal eye field. METHODS: Pediatric patients with absences performed a computerized choice reaction time task, with simultaneous recording of EEG and eye-tracking. We quantified visual attention and eye movements with reaction times, response correctness, and EEG features. Finally, we studied brain networks involved in the generation and propagation of seizures. RESULTS: Ten pediatric patients had absences during the measurement. Five patients had preserved eye movements (preserved group) and five patients showed disrupted eye movements (unpreserved group) during seizures. Source reconstruction showed a stronger involvement of the right frontal eye field during absences in the unpreserved group than in the preserved group (dipole fraction 1.02% and 0.34%, respectively, p < 0.05). Graph analysis revealed different connection fractions of specific channels. CONCLUSIONS: The impairment of visual attention varies among patients with absences and is associated with differences in EEG features, network activation, and involvement of the right frontal eye field. SIGNIFICANCE: Assessing the visual attention of patients with absences can be usefully employed in clinical practice for tailored advice to the individual patient.

A Method to Experimentally Estimate the Conductivity of Chronic Stroke Lesions: A Tool to Individualize Transcranial Electric Stimulation.

The inconsistent response to transcranial electric stimulation in the stroke population is attributed to, among other factors, unknown effects of stroke lesion conductivity on stimulation strength at the targeted brain areas. Volume conduction models are promising tools to determine optimal stimulation settings. However, stroke lesion conductivity is often not considered in these models as a source of inter-subject variability. The goal of this study is to propose a method that combines MRI, EEG, and transcranial stimulation to estimate the conductivity of cortical stroke lesions experimentally. In this simulation study, lesion conductivity was estimated from scalp potentials during transcranial electric stimulation in 12 chronic stroke patients. To do so, first, we determined the stimulation configuration where scalp potentials are maximally affected by the lesion. Then, we calculated scalp potentials in a model with a fixed lesion conductivity and a model with a randomly assigned conductivity. To estimate the lesion conductivity, we minimized the error between the two models by varying the conductivity in the second model. Finally, to reflect realistic experimental conditions, we test the effect rotation of measurement electrode orientation and the effect of the number of electrodes used. We found that the algorithm converged to the correct lesion conductivity value when noise on the electrode positions was absent for all lesions. Conductivity estimation error was below 5% with realistic electrode coregistration errors of 0.1° for lesions larger than 50 ml. Higher lesion conductivities and lesion volumes were associated with smaller estimation errors. In conclusion, this method can experimentally estimate stroke lesion conductivity, improving the accuracy of volume conductor models of stroke patients and potentially leading to more effective transcranial electric stimulation configurations for this population.

DUNEuro-A software toolbox for forward modeling in bioelectromagnetism.

Accurate and efficient source analysis in electro- and magnetoencephalography using sophisticated realistic head geometries requires advanced numerical approaches. This paper presents DUNEuro, a free and open-source C++ software toolbox for the numerical computation of forward solutions in bioelectromagnetism. Building upon the DUNE framework, it provides implementations of modern fitted and unfitted finite element methods to efficiently solve the forward problems of electro- and magnetoencephalography. The user can choose between a variety of different source models that are implemented. The software's aim is to provide interfaces that are extendable and easy-to-use. In order to enable a closer integration into existing analysis pipelines, interfaces to Python and MATLAB are provided. The practical use is demonstrated by a source analysis example of somatosensory evoked potentials using a realistic six-compartment head model. Detailed installation instructions and example scripts using spherical and realistic head models are appended.

The Discontinuous Galerkin Finite Element Method for Solving the MEG and the Combined MEG/EEG Forward Problem.

In Electro- (EEG) and Magnetoencephalography (MEG), one important requirement of source reconstruction is the forward model. The continuous Galerkin finite element method (CG-FEM) has become one of the dominant approaches for solving the forward problem over the last decades. Recently, a discontinuous Galerkin FEM (DG-FEM) EEG forward approach has been proposed as an alternative to CG-FEM (Engwer et al., 2017). It was shown that DG-FEM preserves the property of conservation of charge and that it can, in certain situations such as the so-called skull leakages, be superior to the standard CG-FEM approach. In this paper, we developed, implemented, and evaluated two DG-FEM approaches for the MEG forward problem, namely a conservative and a non-conservative one. The subtraction approach was used as source model. The validation and evaluation work was done in statistical investigations in multi-layer homogeneous sphere models, where an analytic solution exists, and in a six-compartment realistically shaped head volume conductor model. In agreement with the theory, the conservative DG-FEM approach was found to be superior to the non-conservative DG-FEM implementation. This approach also showed convergence with increasing resolution of the hexahedral meshes. While in the EEG case, in presence of skull leakages, DG-FEM outperformed CG-FEM, in MEG, DG-FEM achieved similar numerical errors as the CG-FEM approach, i.e., skull leakages do not play a role for the MEG modality. In particular, for the finest mesh resolution of 1 mm sources with a distance of 1.59 mm from the brain-CSF surface, DG-FEM yielded mean topographical errors (relative difference measure, RDM%) of 1.5% and mean magnitude errors (MAG%) of 0.1% for the magnetic field. However, if the goal is a combined source analysis of EEG and MEG data, then it is highly desirable to employ the same forward model for both EEG and MEG data. Based on these results, we conclude that the newly presented conservative DG-FEM can at least complement and in some scenarios even outperform the established CG-FEM approaches in EEG or combined MEG/EEG source analysis scenarios, which motivates a further evaluation of DG-FEM for applications in bioelectromagnetism.