MEG Source Localization via Deep Learning

We present a deep learning solution to the problem of localization of magnetoencephalography (MEG) brain signals. The proposed deep model architectures are tuned for single and multiple time point MEG data, and can estimate varying numbers of dipole sources. Results from simulated MEG data on the cortical surface of a real human subject demonstrated improvements against the popular RAP-MUSIC localization algorithm in specific scenarios with varying SNR levels, inter-source correlation values, and number of sources. Importantly, the deep learning models had robust performance to forward model errors and a significant reduction in computation time, to a fraction of 1 ms, paving the way to real-time MEG source localization

Transcranial magnetic stimulation and EEG in studies of brain function

Transcranial magnetic stimulation (TMS) combined with electroencephalography (EEG) is a multimodal technique, with a temporal resolution of submilliseconds, for studying cortical excitability and connectivity. When TMS is combined with neuronavigation, resulting in so-called navigated TMS (nTMS), the technique becomes very powerful. However, despite the potential of TMS–EEG, its use for studying lateral areas has been restricted because the TMS pulse induces strong muscle artifacts, making the EEG data useless for further analyses. In this Thesis, methods for analyzing TMS-evoked EEG data from lateral areas are introduced. First, TMS–EEG is used to study Broca's area and dorsal premotor cortex. Due to the fact that those areas are close to cranial muscles, their stimulation evokes large muscle artifacts in EEG recordings. The behavior of the artifacts is described in detail. Two approaches to deal with large artifacts are presented. In the first approach, independent component analysis (ICA) is used. Here, FastICA algorithm is modified to make the search of the components more robust and easier, allowing one to get more stable results. The second approach presents methods for suppressing the artifacts rather than removing them. These methods were combined with source localization showing that the artifact suppression is efficient. The methods were tested with both real and simulated data, suggesting they are useful for artifact correction. For a better understanding of the effects of repetitive nTMS during naming tasks and the cortical organization of speech in general, here another study is introduced to understand the sensitivity of object and action naming tasks to repetitive nTMS. The distributions of cortical sites, where repetitive nTMS produced naming errors during both tasks, are compared. Thus, it is shown how this study can impact on both cognitive neuroscience and clinical practice. In the last part, the beamformer method is improved to study source localization, which makes it a robust method to study time-correlated sources. In this Thesis, I discuss how all these methods together can contribute to study brain connectivity of language and lateral areas with TMS–EEG, opening new possibilities for basic research and clinical applications

Open Database of Epileptic EEG with MRI and Postoperational Assessment of Foci—a Real World Verification for the EEG Inverse Solutions

This paper introduces a freely accessible database http://eeg.pl/epi, containing 23 datasets from patients diagnosed with and operated on for drug-resistant epilepsy. This was collected as part of the clinical routine at the Warsaw Memorial Child Hospital. Each record contains (1) pre-surgical electroencephalography (EEG) recording (10–20 system) with inter-ictal discharges marked separately by an expert, (2) a full set of magnetic resonance imaging (MRI) scans for calculations of the realistic forward models, (3) structural placement of the epileptogenic zone, recognized by electrocorticography (ECoG) and post-surgical results, plotted on pre-surgical MRI scans in transverse, sagittal and coronal projections, (4) brief clinical description of each case. The main goal of this project is evaluation of possible improvements of localization of epileptic foci from the surface EEG recordings. These datasets offer a unique possibility for evaluating different EEG inverse solutions. We present preliminary results from a subset of these cases, including comparison of different schemes for the EEG inverse solution and preprocessing. We report also a finding which relates to the selective parametrization of single waveforms by multivariate matching pursuit, which is used in the preprocessing for the inverse solutions. It seems to offer a possibility of tracing the spatial evolution of seizures in time

Review on solving the inverse problem in EEG source analysis

In this primer, we give a review of the inverse problem for EEG source localization. This is intended for the researchers new in the field to get insight in the state-of-the-art techniques used to find approximate solutions of the brain sources giving rise to a scalp potential recording. Furthermore, a review of the performance results of the different techniques is provided to compare these different inverse solutions. The authors also include the results of a Monte-Carlo analysis which they performed to compare four non parametric algorithms and hence contribute to what is presently recorded in the literature. An extensive list of references to the work of other researchers is also provided

Sparse algorithms for EEG source localization

Source localization using EEG is important in diagnosing various physiological and psychiatric diseases related to the brain. The high temporal resolution of EEG helps medical professionals assess the internal physiology of the brain in a more informative way. The internal sources are obtained from EEG by an inversion process. The number of sources in the brain outnumbers the number of measurements. In this article, a comprehensive review of the state of the art sparse source localization methods in this field is presented. A recently developed method, certainty based reduced sparse solution (CARSS), is implemented and is examined. A vast comparative study is performed using a sixty four channel setup involving two source spaces. The first source space has 5004 sources and the other has 2004 sources. Four test cases with one, three, five, and seven simulated active sources are considered. Two noise levels are also being added to the noiseless data. The CARSS is also evaluated. The results are examined. A real EEG study is also attempted.Comment: Published in Medical & Biological Engineering & Computing, Springer on Oct 02, 202

EpiGauss : caracterização espacio-temporal da actividade cerebral em epilepsia

Doutoramento em Engenharia ElectrotécnicaA epilepsia é uma patologia cerebral que afecta cerca de 0,5% da população mundial. Nas epilepsias focais, o principal objectivo clínico é a localização da zona epileptogénica (área responsável pelas crises), uma informação crucial para uma terapêutica adequada. Esta tese é centrada na caracterização da actividade cerebral electromagnética do cérebro epiléptico. As contribuições nesta área, entre a engenharia e neurologia clínica, são em duas direcções. Primeiro, mostramos que os conceitos associados às pontas podem ser imprecisos e não ter uma definição objectiva, tornando necessária uma reformulação de forma a definir uma referência fiável em estudos relacionados com a análise de pontas. Mostramos que as características das pontas em EEG são estatisticamente diferentes das pontas em MEG. Esta constatação leva a concluir que a falta de objectividade na definição de ponta na literatura pode induzir utilizações erradas de conceitos associados ao EEG na análise de MEG. Também verificamos que o uso de conjuntos de detecções de pontas efectuadas por especialistas (MESS) como referência pode fornecer resultados enganadores quando apenas baseado em critérios de consenso clínico, nomeadamente na avaliação da sensibilidade e especificidade de métodos computorizados de detecção de pontas Em segundo lugar, propomos o uso de métodos estatísticos para ultrapassar a falta de precisão e objectividade das definições relacionadas com pontas. Propomos um novo método de neuroimagem suportado na caracterização de geradores electromagnéticos – EpiGauss – baseado na análise individual dos geradores de eventos do EEG que explora as suas estruturas espacio-temporais através da análise de “clusters”. A aplicação de análise de “clusters” à análise geradores de eventos do EEG tem como objectivo usar um método não supervisionado, para encontrar estruturas espacio-temporais dps geradores relevantes. Este método, como processo não supervisionado, é orientado a utilizadores clínicos e apresenta os resultados sob forma de imagens médicas com interpretação similar a outras técnicas de imagiologia cerebral. Com o EpiGauss, o utilizador pode determinar a localização estatisticamente mais provável de geradores, a sua estabilidade espacial e possíveis propagações entre diferente áreas do cérebro. O método foi testado em dois estudos clínicos envolvendo doentes com epilepsia associada aos hamartomas hipotalâmicos e o outro com doentes com diagnóstico de epilepsia occipital. Em ambos os estudos, o EpiGauss foi capaz de identificar a zona epileptogénica clínica, de forma consistente com a história e avaliação clínica dos neurofisiologistas, fornecendo mais informação relativa à estabilidade dos geradores e possíveis percursos de propagação da actividade epileptogénica contribuindo para uma melhor caracterização clínica dos doentes. A conclusão principal desta tese é que o uso de técnicas não supervisionadas, como a análise de “clusters”, associadas as técnicas não-invasivas de EMSI, pode contribuir com um valor acrescido no processo de diagnóstico clínico ao fornecer uma caracterização objectiva e representação visual de padrões complexos espaciotemporais da actividade eléctrica epileptogénica.Epilepsy is a brain pathology that affects 0.5% of the world population. In focal epilepsies, the main clinical objective is the localization of the epileptogenic zone (brain area responsible for the epileptic seizures – EZ), a key information to decide an adequate therapeutic approach. This thesis is centred on electromagnetic activity characterization of the epileptic brain. Our contribution to this boundary area between engineering and clinical neurology is two-folded. First we show that spike related clinical concepts can be unprecise and some do not have objective definitions making necessary a reformulation in order to have a reliable reference in spike related studies. We show that EEG spike wave quantitative features are statistically different from their MEG counterparts. This finding leads to the conclusion that the lack of objective spike feature definitions in the literature can induce the wrong usage of EEG feature definition in MEG analysis. We also show that the use of multi-expert spike selections sets (MESS) as gold standard, although clinically useful, may be misleading whenever defined solely in terms of clinical agreement criteria, namely as references for automatic spike detection algorithms in sensitivity and specificity method analysis. Second, we propose the use of statistical methods to overcome some lack of precision and objectivity in spike related definitions. In this context, we propose a new ElectroMagnetic Source Imaging (EMSI) method – EpiGauss – based on cluster analysis that explores both spatial and temporal information contained in individual events sources analysis characterisation. This automatic cluster method for the analysis of spike related electric generators based in EEG is used to provide an unsupervised tool to find their relevant spatio-temporal structures. This method enables a simple unsupervised procedure aimed for clinical users and presents its results in an intuitive representation similar to other brain imaging techniques. With EpiGauss, the user is able to determine statistically probable source locations, their spatial stability and propagation patterns between different brain areas. The method was tested in two different clinical neurophysiology studies, one with a group of Hypothalamic Hamartomas and another with a group of Occipital Epilepsy patients. In both studies EpiGauss identified the clinical epileptogenic zone, consistent with the clinical background and evaluation of neurophysiologists, providing further information on stability of source locations and their probable propagation pathways that enlarges their clinical interpretation. This thesis main conclusion is that the use of unsupervised techniques, such as clustering, associated with EMSI non-invasive techniques, can bring an added value in clinical diagnosis process by providing objective and visual representation of complex epileptic brain spatio-temporal activity patterns

Neurophysiological Aspects of Time Perception

In magneto- und electroencephalographic (MEG/EEG) experiments the source structure and the amplitudes of the evoked fields and potentials recorded during the fulfillment of an attentional task on discriminating durations were investigated. This was done for tones, tone pauses, pictures and picture pauses to investigate the dependence upon sensory input and modality. The attention-specific differences found include primary sensory responses and a parietal activation in particular. The tone and tone pause tasks were also examined using functional magnetic resonance imaging (fMRI) to gather model-independent evidence for the location and extension of the parietal network. Further, the relation between electrophysiological and psychometric data was explored, where the study on tones played a crucial role. Here the strength of the parietal activity was largest, the individual discriminative abilities were highest and the two variables were found to be significantly correlated. Finally, the discriminative ability for all tasks covaried with the individual rhythmic musical aptitude. The frame of this work is given by a sketch of neurophysiological and -psychological findings on the perception of time and music; findings which get embedded into philosophical considerations on time and on psychophysical correlations (mind-body-problem)

Magnetoencephalography

This is a practical book on MEG that covers a wide range of topics. The book begins with a series of reviews on the use of MEG for clinical applications, the study of cognitive functions in various diseases, and one chapter focusing specifically on studies of memory with MEG. There are sections with chapters that describe source localization issues, the use of beamformers and dipole source methods, as well as phase-based analyses, and a step-by-step guide to using dipoles for epilepsy spike analyses. The book ends with a section describing new innovations in MEG systems, namely an on-line real-time MEG data acquisition system, novel applications for MEG research, and a proposal for a helium re-circulation system. With such breadth of topics, there will be a chapter that is of interest to every MEG researcher or clinician

NON INVASIVE INVESTIGATION OF SENSORIMOTOR CONTROL FOR FUTURE DEVELOPMENT OF BRAIN-MACHINE-INTERFACE (BMI)

My thesis focuses on describing novel functional connectivity properties of the sensorimotor system that are of potential interest in the field of brain-machine interface. In particular, I have investigated how the connectivity changes as a consequence of either pathologic conditions or spontaneous fluctuations of the brain's internal state. An ad-hoc electronic device has been developed to implement the appropriate experimental settings. First, the functional communication among sensorimotor primary nodes was investigated in multiple sclerosis patients afflicted by persistent fatigue. I selected this condition, for which there is no effective pharmacological treatment, since existing literature links this type of fatigue to the motor control system. In this study, electroencephalographic (EEG) and electromyographic (EMG) traces were acquired together with the pressure exerted on a bulb during an isometric hand grip. The results showed a higher frequency connection between central and peripheral nervous systems (CMC) and an overcorrection of the exerted movement in fatigued multiple sclerosis patients. In fact, even though any fatigue-dependent brain and muscular oscillatory activity alterations were absent, their connectivity worked at higher frequencies as fatigue increased, explaining 67% of the fatigue scale (MFIS) variance (p=.002). In other terms, the functional communication within the central-peripheral nervous systems, namely involving primary sensorimotor areas, was sensitive to tiny alterations in neural connectivity leading to fatigue, well before the appearance of impairments in single nodes of the network. The second study was about connectivity intended as propagation of information and studied in dependence on spontaneous fluctuations of the sensorimotor system triggered by an external stimulus. Knowledge of the propagation mechanisms and of their changes is essential to extract significant information from single trials. The EEG traces were acquired during transcranial magnetic stimulation (TMS) to yield to a deeper knowledge about the response to an external stimulation while the cortico-spinal system passes through different states. The results showed that spontaneous increases of the excitation of the node originating the transmission within the hand control network gave rise to dynamic recruitment patterns with opposite behaviors, weaker in homotopic and parietal circuits, stronger in frontal ones. As probed by TMS, this behavior indicates that the effective connectivity within bilateral circuits orchestrating hand control are dynamically modulated in time even in resting state. The third investigation assessed the plastic changes in the sensorimotor system after stroke induced by 3 months of robotic rehabilitation in chronic phase. A functional source extraction procedure was applied on the acquired EEG data, enabling the investigation of the functional connectivity between homologous areas in the resting state. The most significant result was that the clinical ameliorations were associated to a ‘normalization’ of the functional connectivity between homologous areas. In fact, the brain connectivity did not necessarily increase or decrease, but it settled within a ‘physiological’ range of connectivity. These studies strengthen our knowledge about the behavioral role of the functional connectivity among neuronal networks’ nodes, which will be essential in future developments of enhanced rehabilitative interventions, including brain-machine interfaces. The presented research also moves the definition of new indices of clinical state evaluation relevant for compensating interventions, a step forward