京都大学 / 0048 / 新制・課程博士 / 博士(医学) / 甲第21680号 / 医博第4486号 / 新制||医||1036(附属図書館) / 京都大学大学院医学研究科医学専攻 / (主査)教授 伊佐 正, 教授 村井 俊哉, 教授 松原 和夫 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM

The analysis of Human brain activity in magnetoencephalography (MEG) can be generally conducted in two ways: either by focusing on the average response evoked by a stimulus repeated over time, more commonly known as an ''event-related field'' (ERF), or by decomposing the signal into functionally relevant oscillatory or frequency bands (such as alpha, beta or gamma). However, the major part of brain activity is arrhythmic and these approaches fail in describing its complexity, particularly in resting-state. As an alternative, the analysis of the 1/f-type power spectrum observed in the very low frequencies, a hallmark of scale-free dynamics, can overcome these issues. Yet it remains unclear whether this scale-free property is functionally relevant and whether its fluctuations matter for behavior. To address this question, our first concern was to establish a visual learning paradigm that would entail functional plasticity during an MEG session. In order to optimize the training effects, we developed new audiovisual (AV) stimuli (an acoustic texture paired with a colored visual motion) that induced multisensory integration and indeed improved learning compared to visual training solely (V) or accompanied with acoustic noise (AVn). This led us to investigate the neural correlates of these three types of training using first a classical method such as the ERF analysis. After source reconstruction on each individual cortical surface using MNE-dSPM, the network involved in the task was identified at the group-level. The selective plasticity observed in the human motion area (hMT+) correlated across all individuals with the behavioral improvement and was supported by a larger network in AV comprising multisensory areas. On the basis of these findings, we further explored the links between the behavior and scale-free properties of these same source-reconstructed MEG signals. Although most studies restricted their analysis to the global measure of self-similarity (i.e. long-range fluctuations), we also considered local fluctuations (i.e. multifractality) by using the Wavelet Leader Based Multifractal Formalism (WLBMF). We found intertwined modulations of self-similarity and multifractality in the same cortical regions as those revealed by the ERF analysis. Most astonishing, the degree of multifractality observed in each individual converged during the training towards a single attractor that reflected the asymptotic behavioral performance in hMT+. Finally, these findings and their associated methodological issues are compared with the ones that came out from the ERF analysis.

Il existe deux façons d'analyser l'activité cérébrale acquise en magnétoencéphalographie (MEG) : soit en moyennant les réponses suscitées par la répétition d'un stimulus afin d'observer le « champ évoqué »; soit en décomposant le signal en bandes oscillatoires (tel que l'alpha, le bêta ou le gamma), chacune étant associée à différents rôles fonctionnels. Ces méthodes ne prennent cependant pas compte de la complexité de l'activité cérébrale dont l'essentiel est arythmique, notamment au repos. Pour pallier à cela, une autre approche consiste à analyser le spectre de puissance en 1/f observable dans les très basses fréquences, une caractéristique des systèmes dont la dynamique est invariante d'échelle. Pour savoir si cette propriété joue un quelconque rôle dans le fonctionnement cérébral et si elle a des conséquences sur le comportement, nous avons établit un paradigme d'apprentissage visuel permettant d'observer de la plasticité fonctionnelle au cours d'une session MEG. Pour avoir un entraînement optimal, nous avons développé de nouveaux stimuli audiovisuels (AV) (une texture acoustique associée à un nuage de points colorés en mouvement) permettant une intégration multisensorielle et de ce fait un meilleur apprentissage que celui apporté par un entraînement visuel seul (V) ou accompagné d'un bruit acoustique (AVn). Nous avons ensuite étudié les corrélats neuronaux de ces trois types d'apprentissage par l'analyse classique des champs évoqués. Une fois l'activité reconstruite sur la surface corticale de chaque individu à l'aide de MNE-dSPM, nous avons identifié le réseau impliqué dans la tâche au sein de chaque groupe. En particulier, la plasticité sélective observée dans l'aire hMT+ associée au traitement du mouvement visuel corrélait avec les progressions comportementales des individus et était soutenue en AV par un plus vaste réseau comprenant notamment des aires multisensorielles. Parallèlement, nous avons exploré les liens reliant le comportement et les propriétés d'invariance d'échelle de ces mêmes signaux MEG reconstruits sur le cortex. Tandis que la plupart des études se limitent à analyser l'auto-similarité (une caractéristique globale synonyme de longue mémoire), nous avons aussi considéré les fluctuations locales (c-à-d la multifractalité) au moyen de l'analyse WLBMF. Nous avons trouvé des modulations couplées de l'auto-similarité et de la multifractalité dans des régions similaires à celles révélées par l'analyse des champs évoqués. Plus surprenant, Le degré de multifractalité relevé dans chaque individu convergeait durant l'entraînement vers un même attracteur reflétant la performance comportementale asymptotique. / The analysis of Human brain activity in magnetoencephalography (MEG) can be generally conducted in two ways: either by focusing on the average response evoked by a stimulus repeated over time, more commonly known as an ``event-related field'' (ERF), or by decomposing the signal into functionally relevant oscillatory or frequency bands (such as alpha, beta or gamma). However, the major part of brain activity is arrhythmic and these approaches fail in describing its complexity, particularly in resting-state. As an alternative, the analysis of the 1/f-type power spectrum observed in the very low frequencies, a hallmark of scale-free dynamics, can overcome these issues. Yet it remains unclear whether this scale-free property is functionally relevant and whether its fluctuations matter for behavior. To address this question, our first concern was to establish a visual learning paradigm that would entail functional plasticity during an MEG session. In order to optimize the training effects, we developed new audiovisual (AV) stimuli (an acoustic texture paired with a colored visual motion) that induced multisensory integration and indeed improved learning compared to visual training solely (V) or accompanied with acoustic noise (AVn). This led us to investigate the neural correlates of these three types of training using first a classical method such as the ERF analysis. After source reconstruction on each individual cortical surface using MNE-dSPM, the network involved in the task was identified at the group-level. The selective plasticity observed in the human motion area (hMT+) correlated across all individuals with the behavioral improvement and was supported by a larger network in AV comprising multisensory areas. On the basis of these findings, we further explored the links between the behavior and scale-free properties of these same source-reconstructed MEG signals. Although most studies restricted their analysis to the global measure of self-similarity (i.e. long-range fluctuations), we also considered local fluctuations (i.e. multifractality) by using the Wavelet Leader Based Multifractal Formalism (WLBMF). We found intertwined modulations of self-similarity and multifractality in the same cortical regions as those revealed by the ERF analysis. Most astonishing, the degree of multifractality observed in each individual converged during the training towards a single attractor that reflected the asymptotic behavioral performance in hMT+. Finally, these findings and their associated methodological issues are compared with the ones that came out from the ERF analysis.

Resting state functional magnetic resonance imaging (fMRI) is currently at the forefront of research on cognition and the brain’s large-scale organization. Patterns of hemodynamic activity that it records have been strongly linked to certain behaviors and cognitive pathologies. These signals are widely assumed to reflect local neuronal activity but our understanding of the exact relationship between them remains incomplete. Researchers often address this using multimodal approaches, pairing fMRI signals with known measures of neuronal activity such as electroencephalography (EEG). It has long been thought that infraslow (< 0.1 Hz) fMRI signals, which have become so important to the study of brain function, might have a direct electrophysiological counterpart. If true, EEG could be positioned as a low-cost alternative to fMRI when fMRI is impractical and therefore could also become much more influential in the study of functional brain networks. Previous works have produced indirect support for the fMRI-EEG relationship, but until recently the hypothesized link between them had not been tested in resting humans. The objective of this study was to investigate and characterize their relationship by simultaneously recording infraslow fMRI and EEG signals in resting human adults. We present evidence strongly supporting their link by demonstrating significant stationary and dynamic correlations between the two signal types. Moreover, functional brain networks appear to be a fundamental unit of this coupling. We conclude that infraslow electrophysiology is likely playing an important role in the dynamic configuration of the resting state brain networks that are well-known to fMRI research. Our results provide new insights into the neuronal underpinnings of hemodynamic activity and a foundational point on which the use of infraslow EEG in functional connectivity studies can be based.