Reconstruction de l'activité corticale à partir de données MEG à l'aide de réseaux cérébraux et de délais de transmission estimés à partir d'IRMd

White matter fibers transfer information between brain regions with delays that are observable with magnetoencephalography and electroencephalography (M/EEG) due to their millisecond temporal resolution. We can represent the brain as a graph where nodes are the cortical sources or areas and edges are the physical connections between them: either local (between adjacent vertices on the cortical mesh) or non-local (long-range white matter fibers). Long-range anatomical connections can be obtained with diffusion MRI (dMRI) tractography which yields a set of streamlines representing white matter fiber bundles. Given the streamlines’ lengths and the information conduction speed, transmission delays can be estimated for each connection. dMRI can thus give an insight into interaction delays of the macroscopicbrain network.Localizing and recovering electrical activity of the brain from M/EEG measurements is known as the M/EEG inverse problem. Generally, there are more unknowns (brain sources) than the number of sensors, so the solution is non-unique and the problem ill-posed. To obtain a unique solution, prior constraints on the characteristics of source distributions are needed. Traditional linear inverse methods deploy different constraints which can favour solutions with minimum norm, impose smoothness constraints in space and/or time along the cortical surface, etc. Yet, structural connectivity is rarely considered and transmission delays almost always neglected.The first contribution of this thesis consists of a multimodal preprocessing pipeline used to integrate structural MRI, dMRI and MEG data into a same framework, and of a simulation procedure of source-level brain activity that was used as a synthetic dataset to validate the proposed reconstruction approaches.In the second contribution, we proposed a new framework to solve the M/EEG inverse problem called Connectivity-Informed M/EEG Inverse Problem (CIMIP), where prior transmission delays supported by dMRI were included to enforce temporal smoothness between time courses of connected sources. This was done by incorporating a Laplacian operator into the regularization, that operates on a time-dependent connectivity graph. Nonetheless, some limitations of the CIMIP approach arised, mainly due to the nature of the Laplacian, which acts on the whole graph, favours smooth solutions across all connections, for all delays, and it is agnostic to directionality.In this thesis, we aimed to investigate patterns of brain activity during visuomotor tasks, during which only a few regions typically get significantly activated, as shown by previous studies. This led us to our third contribution, an extension of the CIMIP approach that addresses the aforementioned limitations, named CIMIP_OML (“Optimal Masked Laplacian”). We restricted the full source space network (the whole cortical mesh) to a network of regions of interest and tried to find how the information is transferred between its nodes. To describe the interactions between nodes in a directed graph, we used the concept of network motifs. We proposed an algorithm that (1) searches for an optimal network motif – an optimal pattern of interaction between different regions and (2) reconstructs source activity given the found motif. Promising results are shown for both simulated and real MEG data for a visuomotor task and compared with 3 different state-of-the-art reconstruction methods.To conclude, we tackled a difficult problem of exploiting delays supported by dMRI for the reconstruction of brain activity, while also considering the directionality in the information transfer, and provided new insights into the complex patterns of brain activity.Les fibres de la matière blanche permettent le transfert d’information dans le cerveau avec des délais observables en Magnétoencéphalographie et Électroencéphalographie (M/EEG) grâce à leur haute résolution temporelle. Le cerveau peut être représenté comme un graphe où les nœuds sont les régions corticales et les liens sont les connexions physiques entre celles-ci: soit locales (entre sommets adjacents sur le maillage cortical), soit non locales (fibres de la matière blanche). Les connexions non-locales peuvent être reconstruites avec la tractographie de l’IRM de diffusion (IRMd) qui génère un ensemble de courbes («streamlines») représentant des fibres de la matière blanche. Sachant les longueurs des fibres et la vitesse de conduction de l’information, les délais de transmission peuvent être estimés. L’IRMd peut donc donner un aperçu des délais d’interaction du réseau cérébral macroscopique.La localisation et la reconstruction de l’activité électrique cérébrale à partir des mesures M/EEG est un problème inverse. En général, il y a plus d’inconnues (sources cérébrales) que de capteurs. La solution n’est donc pas unique et le problème est dit mal posé. Pour obtenir une solution unique, des hypothèses sur les caractéristiques des distributions de sources sont requises. Les méthodes inverses linéaires traditionnelles utilisent différentes hypothèses qui peuvent favoriser des solutions de norme minimale, imposer des contraintes de lissage dans l’espace et/ou dans le temps, etc. Pourtant, la connectivité structurelle est rarement prise en compte et les délais de transmission sont presque toujours négligés.La première contribution de cette thèse est un pipeline de prétraitement multimodal utilisé pour l’intégration des données d’IRM, IRMd et MEG dans un même cadre, et d’une méthode de simulation de l’activité corticale qui a été utilisée comme jeu de données synthétiques pour valider les approches de reconstruction proposées. Nous proposons également une nouvelle approche pour résoudre le problème inverse M/EEG appelée «Problème Inverse M/EEG Informé par la Connectivité» (CIMIP pour Connectivity-Informed M/EEG Inverse Problem), où des délais de transmission provenant de l’IRMd sont inclus pour renforcer le lissage temporel entre les décours des sources connectées. Pour cela, un opérateur Laplacien, basé sur un graphe de connectivité en fonction du temps, a été intégré dans la régularisation. Cependant, certaines limites de l’approche CIMIP sont apparues en raison de la nature du Laplacien qui agit sur le graphe entier et favorise les solutions lisses sur toutes les connexions, pour tous les délais, et indépendamment de la directionnalité.Lors de tâches visuo-motrices, seules quelques régions sont généralement activées significativement. Notre troisième contribution est une extension de CIMIP pour ce type de tâches qui répond aux limitations susmentionnées, nommée CIMIP_OML («Optimal Masked Laplacian») ou Laplacien Masqué Optimal. Nous essayons de trouver comment l’information est transférée entre les nœuds d’un sous-réseau de régions d’intérêt du réseau complet de l’espace des sources. Pour décrire les interactions entre nœuds dans un graphe orienté, nous utilisons le concept de motifs de réseau. Nous proposons un algorithme qui 1) cherche un motif de réseau optimal- un modèle optimal d’interaction entre régions et 2) reconstruit l’activité corticale avec le motif trouvé. Des résultats prometteurs sont présentés pour des données MEG simulées et réelles (tâche visuo-motrice) et comparés avec 3 méthodes de l’état de l’art. Pour conclure, nous avons abordé un problème difficile d’exploitation des délais de l’IRMd lors l’estimation de l’activité corticale en tenant compte de la directionalité du transfert d’information, fournissant ainsi de nouvelles perspectives sur les patterns complexes de l’activité cérébrale

Connectivity-informed M/EEG inverse problem

International audienceInformation between brain regions is transferred through white matter fibers with delays that are measurable with magnetoencephalography and electroencephalography (M/EEG) due to its millisecond temporal resolution. Therefore, a useful representation of the brain is that of a graph where its nodes are the cortical areas and edges are the physical connections between them: either local (between adjacent vertices on the cortical mesh) or non-local (long-range white matter fibers). These long-range anatomical connections can be obtained by diffusion MRI (dMRI) tractography, thus giving us an insight on interaction delays of the macroscopic brain network. A fundamental role in shaping the rich temporal structure of functional connectivity is played by the structural connectivity [6] that places constraints on which functional interactions occur in the network. In the context of regularizing the dynamics of M/EEG and recovering electrical activity of the brain from M/EEG measurements, traditional linear inverse methods deploy different constraints such as minimum norm, maximum-smoothness in space and/or time along the cortical surface. However, they usually do not take into account the structural connectivity and very few include delays supported by dMRI as a prior information [1]. The goal of this work is to include these delays into the MEG source reconstruction process by imposing temporal smoothness in structurally connected sources, with the corresponding delays. We propose to encapsulate delays provided by dMRI in a graph representation and show their potential in improving the MEG source reconstruction when compared to a state-of-the-art approach [4]

Connectivity-informed solution for spatio-temporal M/EEG source reconstruction

National audienceRecovering brain activity from M/EEG measurements is an ill–posed problem and prior constraints need to be introduced in order to obtain unique solution [1]. The majority of the methods use spatial and/or temporal constraints, without taking account of long–range connectivity. In this work, we propose a new connectivity–informed spatio–temporal approach to constrain the inverse problem using supplementary information coming from difusion MRI. We present results based on simulated brain activity obtained with realistic subject anatomy from Human Connectome Project [4] dataset

Incorporating transmission delays supported by diffusion MRI in MEG source reconstruction

International audienceWhite matter fibers transfer the information between brain regions with delays that are measurable with magnetoencephalography and electroencephalography (M/EEG). In the context of regularizing the dynamics of M/EEG and recovering electrical activity of the brain from M/EEG measurements, this article proposes a graph representation-based framework to solve the M/EEG inverse problem, where prior information about transmission delays supported by diffusion MRI (dMRI) are included to enforce temporal smoothness. Results of the reconstruction of brain activity from simulated MEG measurements are compared to MNE, LORETA and CGS methods and we show that our approach improves MEG source localization when compared to these three state-of-theart approaches. In addition, we show preliminary qualitative results of the proposed reconstruction method on real MEG data for a sensory-motor task

Connectivity–informed spatio–temporal MEG source reconstruction: Simulation results using a MAR model

National audienceRecovering brain activity from M/EEG measurements is an ill–posed problem and prior constraints need to be introduced in order to obtain unique solution [1]. The majority of the methods use spatial and/or temporal constraints, without taking account of long–range connectivity. In this work, we propose a new connectivity–informed spatio–temporal approach to constrain the inverse problem using supplementary information coming from difusion MRI. We present results based on simulated brain activity using a Multivariate Autoregressive Model, with realistic subject anatomy obtained from Human Connectome Project [4] dataset

Connectivity-informed solution for spatio-temporal M/EEG source reconstruction

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