Influence of the head model on EEG and MEG source connectivity analysis

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 problem. 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 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

Automated modeling of brain bioelectric activity within the 3D Slicer environment

Electrocorticography (ECoG) or intracranial electroencephalography (iEEG) monitors electric potential directly on the surface of the brain and can be used to inform treatment planning for epilepsy surgery when paired with numerical modeling. For solving the inverse problem in epilepsy seizure onset localization, accurate solution of the iEEG forward problem is critical which requires accurate representation of the patient's brain geometry and tissue electrical conductivity. In this study, we present an automatic framework for constructing the brain volume conductor model for solving the iEEG forward problem and visualizing the brain bioelectric field on a deformed patient-specific brain model within the 3D Slicer environment. We solve the iEEG forward problem on the predicted postoperative geometry using the finite element method (FEM) which accounts for patient-specific inhomogeneity and anisotropy of tissue conductivity. We use an epilepsy case study to illustrate the workflow of our framework developed and integrated within 3D Slicer

Multimodal image analysis of the human brain

Gedurende de laatste decennia heeft de snelle ontwikkeling van multi-modale en niet-invasieve hersenbeeldvorming technologieën een revolutie teweeg gebracht in de mogelijkheid om de structuur en functionaliteit van de hersens te bestuderen. Er is grote vooruitgang geboekt in het beoordelen van hersenschade door gebruik te maken van Magnetic Reconance Imaging (MRI), terwijl Elektroencefalografie (EEG) beschouwd wordt als de gouden standaard voor diagnose van neurologische afwijkingen. In deze thesis focussen we op de ontwikkeling van nieuwe technieken voor multi-modale beeldanalyse van het menselijke brein, waaronder MRI segmentatie en EEG bronlokalisatie. Hierdoor voegen we theorie en praktijk samen waarbij we focussen op twee medische applicaties: (1) automatische 3D MRI segmentatie van de volwassen hersens en (2) multi-modale EEG-MRI data analyse van de hersens van een pasgeborene met perinatale hersenschade. We besteden veel aandacht aan de verbetering en ontwikkeling van nieuwe methoden voor accurate en ruisrobuuste beeldsegmentatie, dewelke daarna succesvol gebruikt worden voor de segmentatie van hersens in MRI van zowel volwassen als pasgeborenen. Daarenboven ontwikkelden we een geïntegreerd multi-modaal methode voor de EEG bronlokalisatie in de hersenen van een pasgeborene. Deze lokalisatie wordt gebruikt voor de vergelijkende studie tussen een EEG aanval bij pasgeborenen en acute perinatale hersenletsels zichtbaar in MRI

Incorporation of anisotropic conductivities in EEG source analysis

The electroencephalogram (EEG) is a measurement of brain activity over a period of time by placing electrodes at the scalp (surface EEG) or in the brain (depth EEG) and is used extensively in the clinical practice. In the past 20 years, EEG source analysis has been increasingly used as a tool in the diagnosis of neurological disorders (like epilepsy) and in the research of brain functionality. EEG source analysis estimates the origin of brain activity given the electrode potentials measured at the scalp. This involves solving an inverse problem where a forward solution, which depends on the source parameters, is fitted to the given set of electrode potentials. The forward solution are the electrode potentials caused by a source in a given head model. The head model is dependent on the geometry and the conductivity. Often an isotropic conductivity (i.e. the conductivity is equal in all directions) is used, although the skull and white matter have an anisotropic conductivity (i.e. the conductivity can differ depending on the direction the current flows). In this dissertation a way to incorporate the anisotropic conductivities is presented and the effect of not incorporating these anisotropic conductivities is investigated. Spherical head models are simple head models where an analytical solution to the forward problem exists. A small simulation study in a 5 shell spherical head model was performed to investigate the estimation error due to neglecting the anisotropic properties of skull and white matter. The results show that the errors in the dipole location can be larger than 15 mm, which is unacceptable for an accurate dipole estimation in the clinical practice. Therefore, anisotropic conductivities have to be included in the head model. However, these spherical head models are not representative for the human head. Realistic head models are usually made from magnetic resonance scans through segmentation and are a better approximation to the geometry of the human head. To solve the forward problem in these head models numerical methods are needed. In this dissertation we proposed a finite difference technique that can incorporate anisotropic conductivities. Moreover, by using the reciprocity theorem the forward calculation time during an dipole source estimation procedure can be significantly reduced. By comparing the analytical solution for the dipole estimation problem with the one using the numerical method, the anisotropic finite difference with reciprocity method (AFDRM) is validated. Therefore, a cubic grid is made on the 5 shell spherical head model. The electrode potentials are obtained in the spherical head model with anisotropic conductivities by solving the forward problem using the analytical solution. Using these electrode potentials the inverse problem was solved in the spherical head model using the AFDRM. In this way we can determine the location error due to using the numerical technique. We found that the incorporation of anisotropic conductivities results in a larger location error when the head models are fully isotropical conducting. Furthermore, the location error due to the numerical technique is smaller if the cubic grid is made finer. To minimize the errors due to the numerical technique, the cubic grid should be smaller than or equal to 1 mm. Once the numerical technique is validated, a realistic head model can now be constructed. As a cubic grid should be used of at most 1 mm, the use of segmented T1 magnetic resonance images is best suited the construction. The anisotropic conductivities of skull and white matter are added as follows: The anisotropic conductivity of the skull is derived by calculating the normal and tangential direction to the skull at each voxel. The conductivity in the tangential direction was set 10 times larger than the normal direction. The conductivity of the white matter was derived using diffusion weighted magnetic resonance imaging (DW-MRI), a technique that measures the diffusion of water in several directions. As diffusion is larger along the nerve fibers, it is assumed that the conductivity along the nerve fibers is larger than the perpendicular directions to the nerve bundle. From the diffusion along each direction, the conductivity can be derived using two approaches. A simplified approach takes the direction with the largest diffusion and sets the conductivity along that direction 9 times larger than the orthogonal direction. However, by calculating the fractional anisotropy, a well-known measure indicating the degree of anisotropy, we can appreciate that a fractional anisotropy of 0.8715 is an overestimation. In reality, the fractional anisotorpy is mostly smaller and variable throughout the white matter. A realistic approach was therefore presented, which states that the conductivity tensor is a scaling of the diffusion tensor. The volume constraint is used to determine the scaling factor. A comparison between the realistic approach and the simplified approach was made. The results showed that the location error was on average 4.0 mm with a maximum of 10 mm. The orientation error was found that the orientation could range up to 60 degrees. The large orientation error was located at regions where the anisotropic ratio was low using the realistic approach but was 9 using the simplified approach. Furthermore, as the DW-MRI can also be used to measure the anisotropic diffusion in a gray matter voxel, we can derive a conductivity tensor. After investigating the errors due to neglecting these anisotropic conductivities of the gray matter, we found that the location error was very small (average dipole location error: 2.8 mm). The orientation error was ranged up to 40 degrees, although the mean was 5.0 degrees. The large errors were mostly found at the regions that had a high anisotropic ratio in the anisotropic conducting gray matter. Mostly these effects were due to missegmentation or to partial volume effects near the boundary interfaces of the gray and white matter compartment. After the incorporation of the anisotropic conductivities in the realistic head model, simulation studies can be performed to investigate the dipole estimation errors when these anisotropic conductivities of the skull and brain tissues are not taken into account. This can be done by comparing the solution to the dipole estimation problem in a head model with anisotropic conductivities with the one in a head model, where all compartments are isotropic conducting. This way we determine the error when a simplified head model is used instead of a more realistic one. When the anisotropic conductivity of both the skull and white matter or the skull only was neglected, it was found that the location error between the original and the estimated dipole was on average, 10 mm (maximum: 25 mm). When the anisotropic conductivity of the brain tissue was neglected, the location error was much smaller (an average location error of 1.1 mm). It was found that the anisotropy of the skull acts as an extra shielding of the electrical activity as opposed to an isotropic skull. Moreover, we saw that if the dipole is close to a highly anisotropic region, the potential field is changed reasonable in the near vicinity of the location of the dipole. In reality EEG contains noise contributions. These noise contribution will interact with the systematical error by neglecting anisotropic conductivities. The question we wanted to solve was “Is it worthwhile to incorporate anisotropic conductivities, even if the EEG contains noise?” and “How much noise should the EEG contain so that incorporating anisotropic conductivities improves the accuracy of EEG source analysis?”. When considering the anisotropic conductivities of the skull and brain tissues and the skull only, the location error due to the noise and neglecting the anisotropic conductivities is larger then the location error due to noise only. When only neglecting the anisotropic conductivities of the brain tissues only, the location error due to noise is similar to the location error due to noise and neglecting the anisotropic conductivities. When more advanced MR techniques can be used a better model to construct the anisotropic conductivities of the soft brain tissues can be used, which could result in larger errors even in the presence of noise. However, this is subject to further investigation. This suggests that the anisotropic conductivities of the skull should be incorporated. The technique presented in the dissertation can be used to epileptic patients in the presurgical evaluation. In this procedure patients are evaluated by means of medical investigations to determine the cause of the epileptic seizures. Afterwards, a surgical procedure can be performed to render the patient seizure free. A data set from a patiënt was obtained from a database of the Reference Center of Refractory Epilepsy of the Department of Neurology and the Department of Radiology of the Ghent University Hospital (Ghent, Belgium). The patient was monitored with a video/EEG monitoring with scalp and with implanted depth electrodes. An MR image was taken from the patient with the implanted depth electrodes, therefore, we could pinpoint the hippocampus as the onset zone of the epileptic seizures. The patient underwent a resective surgery removing the hippocampus, which rendered the patient seizure free. As DW-MRI images were not available, the head model constructed in chapter 4 and 5 was used. A neuroradiologist aligned the hippocampus in the MR image from which the head model was constructed. A spike was picked from a dataset and was used to estimate the source in a head model where all compartments were isotropic conducting, on one hand, and where the skull and brain tissues were anisotropic conducting, on the other. It was found that using the anisotropic head model, the source was estimated closer to the segmented hippocampus than the isotropic head model. This example shows the possibilities of this technique and allows us to apply it in the clinical practice. Moreover, a thorough validation of the technique has yet to be performed. There is a lot of discussion in the clinical community whether the spikes and epileptical seizures originate from the same origin in the brain. This question can be solved by applying our technique in patient studies

Dynamic imaging of coherent sources reveals different network connectivity underlying the generation and perpetuation of epileptic seizures

The concept of focal epilepsies includes a seizure origin in brain regions with hyper synchronous activity (epileptogenic zone and seizure onset zone) and a complex epileptic network of different brain areas involved in the generation, propagation, and modulation of seizures. The purpose of this work was to study functional and effective connectivity between regions involved in networks of epileptic seizures. The beginning and middle part of focal seizures from ictal surface EEG data were analyzed using dynamic imaging of coherent sources (DICS), an inverse solution in the frequency domain which describes neuronal networks and coherences of oscillatory brain activities. The information flow (effective connectivity) between coherent sources was investigated using the renormalized partial directed coherence (RPDC) method. In 8/11 patients, the first and second source of epileptic activity as found by DICS were concordant with the operative resection site; these patients became seizure free after epilepsy surgery. In the remaining 3 patients, the results of DICS / RPDC calculations and the resection site were discordant; these patients had a poorer post-operative outcome. The first sources as found by DICS were located predominantly in cortical structures; subsequent sources included some subcortical structures: thalamus, Nucl. Subthalamicus and cerebellum. DICS seems to be a powerful tool to define the seizure onset zone and the epileptic networks involved. Seizure generation seems to be related to the propagation of epileptic activity from the primary source in the seizure onset zone, and maintenance of seizures is attributed to the perpetuation of epileptic activity between nodes in the epileptic network. Despite of these promising results, this proof of principle study needs further confirmation prior to the use of the described methods in the clinical praxis