Spatio-temporal coupling of the electric and hemodynamic brain responses in humans

Our comprehension of human brain functions and their dynamics has been dramatically improved by recent developments in non-invasive imaging techniques. These methods can be divided into two different categories, according to the nature of the measured signal: hemodynamic techniques, such as functional magnetic resonance imaging (fMRI) and positiron emission tomography (PET), and electromagnetic techniques, such as electroencephalography (EEG) and magnetoencephalography (MEG). These two categories are have complementary characteristics: hemodynamic techniques have a good spatial resolution (on a millimeter spatial scale) but have a poor temporal resolution, which is inherently limited by the rate changes in blood flow and oxygenation. Electromagnetic techniques have sub-millisecond temporal resolution but have a poor spatial resolution, since the analysis of intracranial generators requires the solution of an underdetermined inverse problem (i.e. there are infinite solutions that can explain equally well the same scalp-recorded distribution). The complementarity of the characteristics of these two families of methods allowed researchers to suppose that the understanding of spatio-temporal brain dynamics can be drastically improved by their combination (so-called multimodal imaging). Unfortunately some caveats hinder such combination. First, the nature of neurovascular coupling is still poorly understood. Second, analytical methods for multimodal imaging are largely in their infancy. The first part of this thesis focuses on the analysis of the temporal characteristics of the blood oxygenation level dependent (BOLD) signal and on how they are modulated by stimulus conditions. To analyze the BOLD dynamics, a novel method for synchronizing stimulus delivery and volume acquisition was developed. This method allows for estimating the BOLD signal with a high temporal resolution (in this thesis up to 125 ms) and for studying how the temporal characteristics (in this thesis mainly the BOLD peak latency and slope) are modulated by stimulus conditions (with an approach similar to that used in the analysis of the EEG evoked potentials). We applied this novel technique to a simple reaction time task to lateralized visual stimuli (the so-called Poffenberger paradigm) as well as to a multisensory auditory-visual reaction time task. In the first study (the Poffenberger paradigm) the analysis of BOLD dynamics supported the theory of a bilateral visuo-motor pathway even in the case of a visual stimulus ipsilateral to the responding hand. In the second study, (the auditory-visual multisensory reaction-time task), the analysis showed auditory-visual interactions within both primary auditory and visual cortices that could not be otherwise revealed by traditional fMRI analysis methods since it does not involve changes in signal amplitude. The second part of this thesis focuses on the comparison of the statistical results obtained by the analyses of fMRI and of the intracranial local field potentials (LFPs), estimated by the ELECTRA inverse solution. We first developed a new method for the analysis of EEG data. This method is based on the statistical comparison of the spectral characteristics of the estimated intracranial LFPs of the pre- and post- stimulus onset periods. Each single trial is analyzed independently, without including an averaging step, so that the information carried by high frequencies is preserved. We also propose a new metric, called resemblance, to investigate the relationship between fMRI and the estimated intracranial LFPs. Single-trial analysis and the resemblance metric were applied in an experiment involving separate EEG and fMRI acquisitions during the same passive visual stimulation protocol. This experiment revealed that only a limited set of LFP frequencies shows a spatial correlation with fMRI. This set of frequencies changes across brain areas, such that progression from lower to higher cortical levels of visual processing incorporates at each step new frequencies. In conclusion, in this thesis we show that the estimation and the analysis of the BOLD time course can give an important contribution to better understanding brain functions and brain organization. To fully understand the meaning of changes in BOLD dynamics, we need a better knowledge of the neuro-vascular coupling. To do that, we introduced a new method for evaluating the relationship between EEG and fMRI across frequencies and anatomical regions.

EEG-fMRI integration for the study of human brain function

Patricia Figueiredo, João Pedro Forjaco Jorge, Wietske Van der Zwaag

Electroencephalography (EEG) and functional magnetic resonance imaging (fMRI) have proved to be extremely valuable tools for the non-invasive study of human brain function. Moreover, due to a notable degree of complementarity between the two modalities, the combination of EEG and fMRI data has been actively sought in the last two decades. Although initially focused on epilepsy, EEG-fMRI applications were rapidly extended to the study of healthy brain function, yielding new insights into its underlying mechanisms and pathways. Nevertheless, EEG and fMRI have markedly different spatial and temporal resolutions, and probe neuronal activity through distinct biophysical processes, many aspects of which are still poorly understood. The remarkable conceptual and methodological challenges associated with EEG-fMRI integration have motivated the development of a wide range of analysis approaches over the years, each relying on more or less restrictive assumptions, and aiming to shed further light on the mechanisms of brain function along with those of the EEG-fMRI coupling itself. Here, we present a review of the most relevant EEG-fMRI integration approaches yet proposed for the study of brain function, supported by a general overview of our current understanding of the biophysical mechanisms coupling the signals obtained from the two modalities.

Elsevier2014

Methods for Single Trial Analysis of Asynchronous EEG Patterns

Nicolas Bourdaud

Processing of electroencephalographic (EEG) signals has mostly focused on analysing correlates that are time-locked to an observable event. However, when the signal is acquired in less controlled environment, like in the context of a brain-computer interface operating in the real-world, this synchronous nature does not hold any longer. The analysis of such signal requires the design of methods that rely less on time-locked nature. These methods are also the requirements for study endogenous processes for which the ground truth of when the process take place in time is not available. In this thesis, we present methods to analyse brain signals, EEG in particular, that are not time-locked to observable events. This thesis documents three major contributions : (i) it proposes a Bayesian formalism to the problem of asynchronous EEG pattern classification, (ii) it shows the importance of generative models to achieve this task and (iii) it shows that such methods can be used to gather information and classify the EEG correlates of decision-making process while classical methods fail at it. First, we propose methods to handle non-time-locked EEG patterns by making the hypothesis that, in each trial, only a part of the signal contains the relevant pattern of interest. This relevant part can appear at any time in the analysis window and differently for each trial. The rest of the trial corresponds to a non-informative part irrelevant to the targeted cognitive task. Starting from a discriminant asynchronous approach handling independently the time-samples in the trial, we extend this method to a generative Bayesian model where each part is formally modelled. This is a main difference compared to the classical approach which usually try to avoid to model the non-informative part. Then, making the assumption that the informative part can be modelled by a time sequence, we adapt the previous method to a Bayesian model of asynchronous template matching which allows the recognition of the time onset of the pattern of interest in each trial. Second, we show the importance of the generative model which, thanks to the Bayesian approach allows us to alleviate the problem of choosing of the hyperparameters of the initial discriminative approach. Compared to the initial discriminant model, us- ing a generative approach leads to use more parameters into the model but whose estimation is helped by the prior we provide. By doing so, we provide a more intuitive way for the experimenter to adapt the method to other problems. Using a generative model and a Bayesian estimation also enables us to improve the generalisation of the model of asynchronous template matching. This model has indeed been tested as benchmark on jittered evoked potential data and has shown to successfully improve the signal-to-noise ratio, recover the evoked response and classify better than classical methods. Finally, we see the importance of asynchronous methods for classification of the EEG correlates of decision-making process. We test this in the context of the study of the exploration/exploitation contrast. Exploration is related to decision making in an uncertain environment. This situation arises a conflict between two opposing needs : gathering information about the environment and exploiting this knowledge in order to optimise the decision. Using an experimental setup that forces the subjects to switch between exploratory or exploitative actions, we show for the first time that it is possible to classify the EEG correlates of the exploratory behaviour. Moreover, we show that synchronous methods fail at classify this contrast thus requiring advanced asynchronous ones. The results also confirm that the brain areas relevant to this switch are mainly the left parietal and medial frontal cortex which is consistent with the neurophysiological findings based on functional magnetic resonance imagery. In addition we have been able to show the importance of alpha rhythm for this contrast. In summary, this thesis provides a formal framework for classification of asynchronous EEG patterns using a generative Bayesian approach. It also provides a methodology to approach the study of EEG correlates of cognitive tasks when little is known about them and when the targeted pattern is reasonably assumed to be non time-locked.

EPFL2012

Tonotopic mapping of human auditory cortex

Melissa Saenz

Since the early days of functional magnetic resonance imaging (fMRI), retinotopic mapping emerged as a powerful and widely-accepted tool, allowing the identification of individual visual cortical fields and furthering the study of visual processing. In contrast, tonotopic mapping in auditory cortex proved more challenging primarily because of the smaller size of auditory cortical fields. The spatial resolution capabilities of fMRI have since advanced, and recent reports from our labs and several others demonstrate the reliability of tonotopic mapping in human auditory cortex. Here we review the wide range of stimulus procedures and analysis methods that have been used to successfully map tonotopy in human auditory cortex. We point out that recent studies provide a remarkably consistent view of human tonotopic organisation, although the interpretation of the maps continues to vary. In particular, there remains controversy over the exact orientation of the primary gradients with respect to Heschl's gyrus, which leads to different predictions about the location of human A1, R, and surrounding fields. We discuss the development of this debate and argue that literature is converging towards an interpretation that core fields A1 and R fold across the rostral and caudal banks of Heschl's gyrus, with tonotopic gradients laid out in a distinctive V-shaped manner. This suggests an organisation that is largely homologous with non-human primates. This article is part of a Special Issue entitled . (C) 2013 Elsevier B.V. All rights reserved.

Elsevier2014

Methods for Single Trial Analysis of Asynchronous EEG Patterns

Nicolas Bourdaud

EPFL2012