Global sensitivity of EEG source analysis to tissue conductivity uncertainties.

Introduction: To reliably solve the EEG inverse problem, accurate EEG forward solutions based on a detailed, individual volume conductor model of the head are essential. A crucial-but often neglected-aspect in generating a volume conductor model is the choice of the tissue conductivities, as these may vary from subject to subject. In this study, we investigate the sensitivity of EEG forward and inverse solutions to tissue conductivity uncertainties for sources distributed over the whole cortex surface. Methods: We employ a detailed five-compartment head model distinguishing skin, skull, cerebrospinal fluid, gray matter, and white matter, where we consider uncertainties of skin, skull, gray matter, and white matter conductivities. We use the finite element method (FEM) to calculate EEG forward solutions and goal function scans (GFS) as inverse approach. To be able to generate the large number of EEG forward solutions, we employ generalized polynomial chaos (gPC) expansions. Results: For sources up to a depth of 4 cm, we find the strongest influence on the signal topography of EEG forward solutions for the skull conductivity and a notable effect for the skin conductivity. For even deeper sources, e.g., located deep in the longitudinal fissure, we find an increasing influence of the white matter conductivity. The conductivity variations translate to varying source localizations particularly for quasi-tangential sources on sulcal walls, whereas source localizations of quasi-radial sources on the top of gyri are less affected. We find a strong correlation between skull conductivity and the variation of source localizations and especially the depth of the reconstructed source for quasi-tangential sources. We furthermore find a clear but weaker correlation between depth of the reconstructed source and the skin conductivity. Discussion: Our results clearly show the influence of tissue conductivity uncertainties on EEG source analysis. We find a particularly strong influence of skull and skin conductivity uncertainties.

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.

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.

Interleaved deep brain stimulation for dyskinesia management in Parkinson's disease.

BACKGROUND: In patients with Parkinson's disease, stimulation above the subthalamic nucleus (STN) may engage the pallidofugal fibers and directly suppress dyskinesia. OBJECTIVES: The objective of this study was to evaluate the effect of interleaving stimulation through a dorsal deep brain stimulation contact above the STN in a cohort of PD patients and to define the volume of tissue activated with antidyskinesia effects. METHODS: We analyzed the Core Assessment Program for Surgical Interventional Therapies dyskinesia scale, Unified Parkinson's Disease Rating Scale parts III and IV, and other endpoints in 20 patients with interleaving stimulation for management of dyskinesia. Individual models of volume of tissue activated and heat maps were used to identify stimulation sites with antidyskinesia effects. RESULTS: The Core Assessment Program for Surgical Interventional Therapies dyskinesia score in the on medication phase improved 70.9 ± 20.6% from baseline with noninterleaved settings (P < 0.003). With interleaved settings, dyskinesia improved 82.0 ± 27.3% from baseline (P < 0.001) and 61.6 ± 39.3% from the noninterleaved phase (P = 0.006). The heat map showed a concentration of volume of tissue activated dorsally to the STN during the interleaved setting with an antidyskinesia effect. CONCLUSION: Interleaved deep brain stimulation using the dorsal contacts can directly suppress dyskinesia, probably because of the involvement of the pallidofugal tract, allowing more conservative medication reduction. © 2019 International Parkinson and Movement Disorder Society.

Evaluation of methodologies for computing the deep brain stimulation volume of tissue activated.

OBJECTIVE: Computational models are a popular tool for predicting the effects of deep brain stimulation (DBS) on neural tissue. One commonly used model, the volume of tissue activated (VTA), is computed using multiple methodologies. We quantified differences in the VTAs generated by five methodologies: the traditional axon model method, the electric field norm, and three activating function based approaches-the activating function at each grid point in the tangential direction (AF-Tan) or in the maximally activating direction (AF-3D), and the maximum activating function along the entire length of a tangential fiber (AF-Max). APPROACH: We computed the VTA using each method across multiple stimulation settings. The resulting volumes were compared for similarity, and the methodologies were analyzed for their differences in behavior. MAIN RESULTS: Activation threshold values for both the electric field norm and the activating function varied with regards to electrode configuration, pulse width, and frequency. All methods produced highly similar volumes for monopolar stimulation. For bipolar electrode configurations, only the maximum activating function along the tangential axon method, AF-Max, produced similar volumes to those produced by the axon model method. Further analysis revealed that both of these methods are biased by their exclusive use of tangential fiber orientations. In contrast, the activating function in the maximally activating direction method, AF-3D, produces a VTA that is free of axon orientation and projection bias. SIGNIFICANCE: Simulating tangentially oriented axons, the standard approach of computing the VTA, is too computationally expensive for widespread implementation and yields results biased by the assumption of tangential fiber orientation. In this work, we show that a computationally efficient method based on the activating function, AF-Max, reliably reproduces the VTAs generated by direct axon modeling. Further, we propose another method, AF-3D as a potentially superior model for representing generic neural tissue activation.

The multipole approach for EEG forward modeling using the finite element method.

For accurate EEG forward solutions, it is necessary to apply numerical methods that allow to take into account the realistic geometry of the subject's head. A commonly used method to solve this task is the finite element method (FEM). Different approaches have been developed to obtain EEG forward solutions for dipolar sources with the FEM. The St. Venant approach is frequently applied, since its high numerical accuracy and stability as well as its computational efficiency was demonstrated in multiple comparison studies. In this manuscript, we propose a variation of the St. Venant approach, the multipole approach, to improve the numerical accuracy of the St. Venant approach even further and to allow for the simulation of additional source scenarios, such as quadrupolar sources. Exploiting the multipole expansion of electric fields, we demonstrate that the newly proposed multipole approach achieves even higher numerical accuracies than the St. Venant approach in both multi-layer sphere and realistic head models. Additionally, we exemplarily show that the multipole approach allows to not only simulate dipolar but also quadrupolar sources.

A retrospective evaluation of automated optimization of deep brain stimulation parameters.

OBJECTIVE: We performed a retrospective analysis of an optimization algorithm for the computation of patient-specific multipolar stimulation configurations employing multiple independent current/voltage sources. We evaluated whether the obtained stimulation configurations align with clinical data and whether the optimized stimulation configurations have the potential to lead to an equal or better stimulation of the target region as manual programming, while reducing the time required for programming sessions. APPROACH: For three patients (five electrodes) diagnosed with essential tremor, we derived optimized multipolar stimulation configurations using an approach that is suitable for the application in clinical practice. To evaluate the automatically derived stimulation settings, we compared them to the results of the monopolar review. MAIN RESULTS: We observe a good agreement between the findings of the monopolar review and the optimized stimulation configurations, with the algorithm assigning the maximal voltage in the optimized multipolar pattern to the contact that was found to lead to the best therapeutic effect in the clinical monopolar review in all cases. Additionally, our simulation results predict that the optimized stimulation settings lead to the activation of an equal or larger volume fraction of the target compared to the manually determined settings in all cases. SIGNIFICANCE: Our results demonstrate the feasibility of an automatic determination of optimal DBS configurations and motivate a further evaluation of the applied optimization algorithm.

Influence of Head Tissue Conductivity Uncertainties on EEG Dipole Reconstruction.

Reliable EEG source analysis depends on sufficiently detailed and accurate head models. In this study, we investigate how uncertainties inherent to the experimentally determined conductivity values of the different conductive compartments influence the results of EEG source analysis. In a single source scenario, the superficial and focal somatosensory P20/N20 component, we analyze the influence of varying conductivities on dipole reconstructions using a generalized polynomial chaos (gPC) approach. We find that in particular the conductivity uncertainties for skin and skull have a significant influence on the EEG inverse solution, leading to variations in source localization by several centimeters. The conductivity uncertainties for gray and white matter were found to have little influence on the source localization, but a strong influence on the strength and orientation of the reconstructed source, respectively. As the CSF conductivity is most accurately determined of all conductivities in a realistic head model, CSF conductivity uncertainties had a negligible influence on the source reconstruction. This small uncertainty is a further benefit of distinguishing the CSF in realistic volume conductor models.

Lead-DBS v2: Towards a comprehensive pipeline for deep brain stimulation imaging.

Deep brain stimulation (DBS) is a highly efficacious treatment option for movement disorders and a growing number of other indications are investigated in clinical trials. To ensure optimal treatment outcome, exact electrode placement is required. Moreover, to analyze the relationship between electrode location and clinical results, a precise reconstruction of electrode placement is required, posing specific challenges to the field of neuroimaging. Since 2014 the open source toolbox Lead-DBS is available, which aims at facilitating this process. The tool has since become a popular platform for DBS imaging. With support of a broad community of researchers worldwide, methods have been continuously updated and complemented by new tools for tasks such as multispectral nonlinear registration, structural/functional connectivity analyses, brain shift correction, reconstruction of microelectrode recordings and orientation detection of segmented DBS leads. The rapid development and emergence of these methods in DBS data analysis require us to revisit and revise the pipelines introduced in the original methods publication. Here we demonstrate the updated DBS and connectome pipelines of Lead-DBS using a single patient example with state-of-the-art high-field imaging as well as a retrospective cohort of patients scanned in a typical clinical setting at 1.5T. Imaging data of the 3T example patient is co-registered using five algorithms and nonlinearly warped into template space using ten approaches for comparative purposes. After reconstruction of DBS electrodes (which is possible using three methods and a specific refinement tool), the volume of tissue activated is calculated for two DBS settings using four distinct models and various parameters. Finally, four whole-brain tractography algorithms are applied to the patient's preoperative diffusion MRI data and structural as well as functional connectivity between the stimulation volume and other brain areas are estimated using a total of eight approaches and datasets. In addition, we demonstrate impact of selected preprocessing strategies on the retrospective sample of 51 PD patients. We compare the amount of variance in clinical improvement that can be explained by the computer model depending on the preprocessing method of choice. This work represents a multi-institutional collaborative effort to develop a comprehensive, open source pipeline for DBS imaging and connectomics, which has already empowered several studies, and may facilitate a variety of future studies in the field.

Anodic stimulation misunderstood: preferential activation of fiber orientations with anodic waveforms in deep brain stimulation.

OBJECTIVE: During deep brain stimulation (DBS), it is well understood that extracellular cathodic stimulation can cause activation of passing axons. Activation can be predicted from the second derivative of the electric potential along an axon, which depends on axonal orientation with respect to the stimulation source. We hypothesize that fiber orientation influences activation thresholds and that fiber orientations can be selectively targeted with DBS waveforms. APPROACH: We used bioelectric field and multicompartment NEURON models to explore preferential activation based on fiber orientation during monopolar or bipolar stimulation. Preferential fiber orientation was extracted from the principal eigenvectors and eigenvalues of the Hessian matrix of the electric potential. We tested cathodic, anodic, and charge-balanced pulses to target neurons based on fiber orientation in general and clinical scenarios. MAIN RESULTS: Axons passing the DBS lead have positive second derivatives around a cathode, whereas orthogonal axons have positive second derivatives around an anode, as indicated by the Hessian. Multicompartment NEURON models confirm that passing fibers are activated by cathodic stimulation, and orthogonal fibers are activated by anodic stimulation. Additionally, orthogonal axons have lower thresholds compared to passing axons. In a clinical scenario, fiber pathways associated with therapeutic benefit can be targeted with anodic stimulation at 50% lower stimulation amplitudes. SIGNIFICANCE: Fiber orientations can be selectively targeted with simple changes to the stimulus waveform. Anodic stimulation preferentially activates orthogonal fibers, approaching or leaving the electrode, at lower thresholds for similar therapeutic benefit in DBS with decreased power consumption.

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.

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.

Optimized programming algorithm for cylindrical and directional deep brain stimulation electrodes.

OBJECTIVE: Deep brain stimulation (DBS) is a growing treatment option for movement and psychiatric disorders. As DBS technology moves toward directional leads with increased numbers of smaller electrode contacts, trial-and-error methods of manual DBS programming are becoming too time-consuming for clinical feasibility. We propose an algorithm to automate DBS programming in near real-time for a wide range of DBS lead designs. APPROACH: Magnetic resonance imaging and diffusion tensor imaging are used to build finite element models that include anisotropic conductivity. The algorithm maximizes activation of target tissue and utilizes the Hessian matrix of the electric potential to approximate activation of neurons in all directions. We demonstrate our algorithm's ability in an example programming case that targets the subthalamic nucleus (STN) for the treatment of Parkinson's disease for three lead designs: the Medtronic 3389 (four cylindrical contacts), the direct STNAcute (two cylindrical contacts, six directional contacts), and the Medtronic-Sapiens lead (40 directional contacts). MAIN RESULTS: The optimization algorithm returns patient-specific contact configurations in near real-time-less than 10 s for even the most complex leads. When the lead was placed centrally in the target STN, the directional leads were able to activate over 50% of the region, whereas the Medtronic 3389 could activate only 40%. When the lead was placed 2 mm lateral to the target, the directional leads performed as well as they did in the central position, but the Medtronic 3389 activated only 2.9% of the STN. SIGNIFICANCE: This DBS programming algorithm can be applied to cylindrical electrodes as well as novel directional leads that are too complex with modern technology to be manually programmed. This algorithm may reduce clinical programming time and encourage the use of directional leads, since they activate a larger volume of the target area than cylindrical electrodes in central and off-target lead placements.

Connectivity Predicts deep brain stimulation outcome in Parkinson disease.

OBJECTIVE: The benefit of deep brain stimulation (DBS) for Parkinson disease (PD) may depend on connectivity between the stimulation site and other brain regions, but which regions and whether connectivity can predict outcome in patients remain unknown. Here, we identify the structural and functional connectivity profile of effective DBS to the subthalamic nucleus (STN) and test its ability to predict outcome in an independent cohort. METHODS: A training dataset of 51 PD patients with STN DBS was combined with publicly available human connectome data (diffusion tractography and resting state functional connectivity) to identify connections reliably associated with clinical improvement (motor score of the Unified Parkinson Disease Rating Scale [UPDRS]). This connectivity profile was then used to predict outcome in an independent cohort of 44 patients from a different center. RESULTS: In the training dataset, connectivity between the DBS electrode and a distributed network of brain regions correlated with clinical response including structural connectivity to supplementary motor area and functional anticorrelation to primary motor cortex (p < 0.001). This same connectivity profile predicted response in an independent patient cohort (p < 0.01). Structural and functional connectivity were independent predictors of clinical improvement (p < 0.001) and estimated response in individual patients with an average error of 15% UPDRS improvement. Results were similar using connectome data from normal subjects or a connectome age, sex, and disease matched to our DBS patients. INTERPRETATION: Effective STN DBS for PD is associated with a specific connectivity profile that can predict clinical outcome across independent cohorts. This prediction does not require specialized imaging in PD patients themselves. Ann Neurol 2017;82:67-78.

Electrical Stimulation of the Human Cerebral Cortex by Extracranial Muscle Activity: Effect Quantification With Intracranial EEG and FEM Simulations.

OBJECTIVE: Electric fields (EF) of approx. 0.2 V/m have been shown to be sufficiently strong to both modulate neuronal activity in the cerebral cortex and have measurable effects on cognitive performance. We hypothesized that the EF caused by the electrical activity of extracranial muscles during natural chewing may reach similar strength in the cerebral cortex and hence might act as an endogenous modality of brain stimulation. Here, we present first steps toward validating this hypothesis. METHODS: Using a realistic volume conductor head model of an epilepsy patient having undergone intracranial electrode placement and utilizing simultaneous intracranial and extracranial electrical recordings during chewing, we derive predictions about the chewing-related cortical EF strength to be expected in healthy individuals. RESULTS: We find that in the region of the temporal poles, the expected EF strength may reach amplitudes in the order of 0.1-1 V/m. CONCLUSION: The cortical EF caused by natural chewing could be large enough to modulate ongoing neural activity in the cerebral cortex and influence cognitive performance. SIGNIFICANCE: The present study lends first support for the assumption that extracranial muscle activity might represent an endogenous source of electrical brain stimulation. This offers a new potential explanation for the puzzling effects of gum chewing on cognition, which have been repeatedly reported in the literature.

Comparison Study for Whitney (Raviart-Thomas)-Type Source Models in Finite-Element-Method-Based EEG Forward Modeling.

This study concentrates on finite-element-method (FEM)-based electroencephalography (EEG) forward simulation in which the electric potential evoked by neural activity in the brain is to be calculated at the surface of the head. The main advantage of the FEM is that it allows realistic modeling of tissue conductivity inhomogeneity. However, it is not straightforward to apply the classical model of a dipolar source with the FEM, due to its strong singularity and the resulting irregularity. The focus of this study is on comparing different methods to cope with this problem. In particular, we evaluate the accuracy of Whitney (Raviart-Thomas)-type dipole-like source currents compared to two reference dipole modeling methods: the St. Venant and partial integration approach. Common to all these methods is that they enable direct approximation of the potential field utilizing linear basis functions. In the present context, Whitney elements are particularly interesting, as they provide a simple means to model a divergence-conforming primary current vector field satisfying the square integrability condition. Our results show that a Whitney-type source model can provide simulation accuracy comparable to the present reference methods. It can lead to superior accuracy under optimized conditions with respect to both source location and orientation in a tetrahedral mesh. For random source orientations, the St. Venant approach turns out to be the method of choice over the interpolated version of the Whitney model. The overall moderate differences obtained suggest that practical aspects, such as the focality, should be prioritized when choosing a source model.

Combined EEG/MEG can outperform single modality EEG or MEG source reconstruction in presurgical epilepsy diagnosis.

We investigated two important means for improving source reconstruction in presurgical epilepsy diagnosis. The first investigation is about the optimal choice of the number of epileptic spikes in averaging to (1) sufficiently reduce the noise bias for an accurate determination of the center of gravity of the epileptic activity and (2) still get an estimation of the extent of the irritative zone. The second study focuses on the differences in single modality EEG (80-electrodes) or MEG (275-gradiometers) and especially on the benefits of combined EEG/MEG (EMEG) source analysis. Both investigations were validated with simultaneous stereo-EEG (sEEG) (167-contacts) and low-density EEG (ldEEG) (21-electrodes). To account for the different sensitivity profiles of EEG and MEG, we constructed a six-compartment finite element head model with anisotropic white matter conductivity, and calibrated the skull conductivity via somatosensory evoked responses. Our results show that, unlike single modality EEG or MEG, combined EMEG uses the complementary information of both modalities and thereby allows accurate source reconstructions also at early instants in time (epileptic spike onset), i.e., time points with low SNR, which are not yet subject to propagation and thus supposed to be closer to the origin of the epileptic activity. EMEG is furthermore able to reveal the propagation pathway at later time points in agreement with sEEG, while EEG or MEG alone reconstructed only parts of it. Subaveraging provides important and accurate information about both the center of gravity and the extent of the epileptogenic tissue that neither single nor grand-averaged spike localizations can supply.

Influence of the head model on EEG and MEG source connectivity analyses.

The results of brain connectivity analysis using reconstructed source time courses derived from EEG and MEG data depend on a number of algorithmic choices. While previous studies have investigated the influence of the choice of source estimation method or connectivity measure, the effects of the head modeling errors or simplifications have not been studied sufficiently. In the present simulation study, we investigated the influence of particular properties of the head model on the reconstructed source time courses as well as on source connectivity analysis in EEG and MEG. Therefore, we constructed a realistic head model and applied the finite element method to solve the EEG and MEG forward problems. We considered the distinction between white and gray matter, the distinction between compact and spongy bone, the inclusion of a cerebrospinal fluid (CSF) compartment, and the reduction to a simple 3-layer model comprising only the skin, skull, and brain. Source time courses were reconstructed using a beamforming approach and the source connectivity was estimated by the imaginary coherence (ICoh) and the generalized partial directed coherence (GPDC). Our results show that in both EEG and MEG, neglecting the white and gray matter distinction or the CSF causes considerable errors in reconstructed source time courses and connectivity analysis, while the distinction between spongy and compact bone is just of minor relevance, provided that an adequate skull conductivity value is used. Large inverse and connectivity errors are found in the same regions that show large topography errors in the forward solution. Moreover, we demonstrate that the very conservative ICoh is relatively safe from the crosstalk effects caused by imperfect head models, as opposed to the GPDC.

A guideline for head volume conductor modeling in EEG and MEG.

For accurate EEG/MEG source analysis it is necessary to model the head volume conductor as realistic as possible. This includes the distinction of the different conductive compartments in the human head. In this study, we investigated the influence of modeling/not modeling the conductive compartments skull spongiosa, skull compacta, cerebrospinal fluid (CSF), gray matter, and white matter and of the inclusion of white matter anisotropy on the EEG/MEG forward solution. Therefore, we created a highly realistic 6-compartment head model with white matter anisotropy and used a state-of-the-art finite element approach. Starting from a 3-compartment scenario (skin, skull, and brain), we subsequently refined our head model by distinguishing one further of the above-mentioned compartments. For each of the generated five head models, we measured the effect on the signal topography and signal magnitude both in relation to a highly resolved reference model and to the model generated in the previous refinement step. We evaluated the results of these simulations using a variety of visualization methods, allowing us to gain a general overview of effect strength, of the most important source parameters triggering these effects, and of the most affected brain regions. Thereby, starting from the 3-compartment approach, we identified the most important additional refinement steps in head volume conductor modeling. We were able to show that the inclusion of the highly conductive CSF compartment, whose conductivity value is well known, has the strongest influence on both signal topography and magnitude in both modalities. We found the effect of gray/white matter distinction to be nearly as big as that of the CSF inclusion, and for both of these steps we identified a clear pattern in the spatial distribution of effects. In comparison to these two steps, the introduction of white matter anisotropy led to a clearly weaker, but still strong, effect. Finally, the distinction between skull spongiosa and compacta caused the weakest effects in both modalities when using an optimized conductivity value for the homogenized compartment. We conclude that it is highly recommendable to include the CSF and distinguish between gray and white matter in head volume conductor modeling. Especially for the MEG, the modeling of skull spongiosa and compacta might be neglected due to the weak effects; the simplification of not modeling white matter anisotropy is admissible considering the complexity and current limitations of the underlying modeling approach.

Combining EEG and MEG for the reconstruction of epileptic activity using a calibrated realistic volume conductor model.

To increase the reliability for the non-invasive determination of the irritative zone in presurgical epilepsy diagnosis, we introduce here a new experimental and methodological source analysis pipeline that combines the complementary information in EEG and MEG, and apply it to data from a patient, suffering from refractory focal epilepsy. Skull conductivity parameters in a six compartment finite element head model with brain anisotropy, constructed from individual MRI data, are estimated in a calibration procedure using somatosensory evoked potential (SEP) and field (SEF) data. These data are measured in a single run before acquisition of further runs of spontaneous epileptic activity. Our results show that even for single interictal spikes, volume conduction effects dominate over noise and need to be taken into account for accurate source analysis. While cerebrospinal fluid and brain anisotropy influence both modalities, only EEG is sensitive to skull conductivity and conductivity calibration significantly reduces the difference in especially depth localization of both modalities, emphasizing its importance for combining EEG and MEG source analysis. On the other hand, localization differences which are due to the distinct sensitivity profiles of EEG and MEG persist. In case of a moderate error in skull conductivity, combined source analysis results can still profit from the different sensitivity profiles of EEG and MEG to accurately determine location, orientation and strength of the underlying sources. On the other side, significant errors in skull modeling are reflected in EEG reconstruction errors and could reduce the goodness of fit to combined datasets. For combined EEG and MEG source analysis, we therefore recommend calibrating skull conductivity using additionally acquired SEP/SEF data.