Guillaume Marrelec

Partial correlation for functional brain interactivity investigation in functional MRI.

Examination of functional interactions through effective connectivity requires the determination of three distinct levels of information: (1) the regions involved in the process and forming the spatial support of the network, (2) the presence or absence of interactions between each pair of regions, and (3) the directionality of the existing interactions. While many methods exist to select regions (Step 1), very little is available to complete Step 2. The two main methods developed so far, structural equation modeling (SEM) and dynamical causal modeling (DCM), usually require precise prior information to be used, while such information is sometimes lacking. Assuming that Step 1 was successfully completed, we here propose a data-driven method to deal with Step 2 and extract functional interactions from fMRI datasets through partial correlations. Partial correlation is more closely related to effective connectivity than marginal correlation and provides a convenient graphical representation for functional interactions. As an instance of brain interactivity investigation, we consider how simple hand movements are processed by the bihemispheric cortical motor network. In the proposed framework, Bayesian analysis makes it possible to estimate and test the partial statistical dependencies between regions without any prior model on the underlying functional interactions. We demonstrate the interest of this approach on real data.

Brain functional integration decreases during propofol-induced loss of consciousness

Consciousness has been related to the amount of integrated information that the brain is able to generate. In this paper, we tested the hypothesis that the loss of consciousness caused by propofol anesthesia is associated with a significant reduction in the capacity of the brain to integrate information. To assess the functional structure of the whole brain, functional integration and partial correlations were computed from fMRI data acquired from 18 healthy volunteers during resting wakefulness and propofol-induced deep sedation. Total integration was significantly reduced from wakefulness to deep sedation in the whole brain as well as within and between its constituent networks (or systems). Integration was systematically reduced within each system (i.e., brain or networks), as well as between networks. However, the ventral attentional network maintained interactions with most other networks during deep sedation. Partial correlations further suggested that functional connectivity was particularly affected between parietal areas and frontal or temporal regions during deep sedation. Our findings suggest that the breakdown in brain integration is the neural correlate of the loss of consciousness induced by propofol. They stress the important role played by parietal and frontal areas in the generation of consciousness.

Symmetrical event-related EEG/fMRI information fusion in a variational Bayesian framework.

In this work, we propose a symmetrical multimodal EEG/fMRI information fusion approach dedicated to the identification of event-related bioelectric and hemodynamic responses. Unlike existing, asymmetrical EEG/fMRI data fusion algorithms, we build a joint EEG/fMRI generative model that explicitly accounts for local coupling/uncoupling of bioelectric and hemodynamic activities, which are supposed to share a common substrate. Under a dedicated assumption of spatio-temporal separability, the spatial profile of the common EEG/fMRI sources is introduced as an unknown hierarchical prior on both markers of cerebral activity. Thereby, a devoted Variational Bayesian (VB) learning scheme is derived to infer common EEG/fMRI sources from a joint EEG/fMRI dataset. This yields an estimate of the common spatial profile, which is built as a trade-off between information extracted from EEG and fMRI datasets. Furthermore, the spatial structure of the EEG/fMRI coupling/uncoupling is learned exclusively from the data. The proposed data generative model and devoted VBEM learning scheme thus provide an un-supervised well-balanced approach for the fusion of EEG/fMRI information. We first demonstrate our approach on synthetic data. Results show that, in contrast to classical EEG/fMRI fusion approach, the method proved efficient and robust regardless of the EEG/fMRI discordance level. We apply the method on EEG/fMRI recordings from a patient with epilepsy, in order to identify brain areas involved during the generation of epileptic spikes. The results are validated using intracranial EEG measurements.

Robust Bayesian estimation of the hemodynamic response function in event-related BOLD fMRI using basic physiological information

In BOLD fMRI data analysis, robust and accurate estimation of the Hemodynamic Response Function (HRF) is still under investigation. Parametric methods assume the shape of the HRF to be known and constant throughout the brain, whereas non‐parametric methods mostly rely on artificially increasing the signal‐to‐noise ratio. We extend and develop a previously proposed method that makes use of basic yet relevant temporal information about the underlying physiological process of the brain BOLD response in order to infer the HRF in a Bayesian framework. A general hypothesis test is also proposed, allowing to take advantage of the knowledge gained regarding the HRF to perform activation detection. The performances of the method are then evaluated by simulation. Great improvement is shown compared to the Maximum‐Likelihood estimate in terms of estimation error, variance, and bias. Robustness of the estimators with regard to the actual noise structure or level, as well as the stimulus sequence, is also proven. Lastly, fMRI data with an event‐related paradigm are analyzed. As suspected, the regions selected from highly discriminating activation maps resulting from the method exhibit a certain inter‐regional homogeneity in term of HRF shape, as well as noticeable inter‐regional differences. Hum. Brain Mapping 19:1–17, 2003.

Unsupervised robust nonparametric estimation of the hemodynamic response function for any fMRI experiment

This paper deals with the estimation of the blood oxygen level-dependent response to a stimulus, as measured in functional magnetic resonance imaging (fMRI) data. A precise estimation is essential for a better understanding of cerebral activations. The most recent works have used a nonparametric framework for this estimation, considering each brain region as a system characterized by its impulse response, the so-called hemodynamic response function (HRF). However, the use of these techniques has remained limited since they are not well-adapted to real fMRI data. Here, we develop a threefold extension to previous works. We consider asynchronous event-related paradigms account for different trial types and integrate several fMRI sessions into the estimation. These generalizations are simultaneously addressed through a badly conditioned observation model. Bayesian formalism is used to model temporal prior information of the underlying physiological process of the brain hemodynamic response. By this way, the HRF estimate results from a tradeoff between information brought by the data and by our prior knowledge. This tradeoff is modeled with hyperparameters that are set to the maximum-likelihood estimate using an expectation conditional maximization algorithm. The proposed unsupervised approach is validated on both synthetic and real fMRI data, the latter originating from a speech perception experiment.

Hierarchical clustering of brain activity during human nonrapid eye movement sleep

Consciousness is reduced during nonrapid eye movement (NREM) sleep due to changes in brain function that are still poorly understood. Here, we tested the hypothesis that impaired consciousness during NREM sleep is associated with an increased modularity of brain activity. Cerebral connectivity was quantified in resting-state functional magnetic resonance imaging times series acquired in 13 healthy volunteers during wakefulness and NREM sleep. The analysis revealed a modification of the hierarchical organization of large-scale networks into smaller independent modules during NREM sleep, independently from EEG markers of the slow oscillation. Such modifications in brain connectivity, possibly driven by sleep ultraslow oscillations, could hinder the brains ability to integrate information and account for decreased consciousness during NREM sleep.

Relating Structure and Function in the Human Brain: Relative Contributions of Anatomy, Stationary Dynamics, and Non-stationarities

Investigating the relationship between brain structure and function is a central endeavor for neuroscience research. Yet, the mechanisms shaping this relationship largely remain to be elucidated and are highly debated. In particular, the existence and relative contributions of anatomical constraints and dynamical physiological mechanisms of different types remain to be established. We addressed this issue by systematically comparing functional connectivity (FC) from resting-state functional magnetic resonance imaging data with simulations from increasingly complex computational models, and by manipulating anatomical connectivity obtained from fiber tractography based on diffusion-weighted imaging. We hypothesized that FC reflects the interplay of at least three types of components: (i) a backbone of anatomical connectivity, (ii) a stationary dynamical regime directly driven by the underlying anatomy, and (iii) other stationary and non-stationary dynamics not directly related to the anatomy. We showed that anatomical connectivity alone accounts for up to 15% of FC variance; that there is a stationary regime accounting for up to an additional 20% of variance and that this regime can be associated to a stationary FC; that a simple stationary model of FC better explains FC than more complex models; and that there is a large remaining variance (around 65%), which must contain the non-stationarities of FC evidenced in the literature. We also show that homotopic connections across cerebral hemispheres, which are typically improperly estimated, play a strong role in shaping all aspects of FC, notably indirect connections and the topographic organization of brain networks.

Dynamics of motor-related functional integration during motor sequence learning.

Motor skill learning is associated with profound changes in brain activation patterns over time. Associative and rostral premotor cortical and subcortical regions are mostly recruited during the early phase of explicit motor learning, while sensorimotor regions may increase their activity during the late learning phases. Distinct brain networks are therefore engaged during the early and late phases of motor skill learning. How these regions interact with one another and how information is transferred from one circuit to the other has been less extensively studied. In this study, we used functional MRI (fMRI) at 3T to follow the changes in functional connectivity in the associative/premotor and the sensorimotor networks, during extended practice (4 weeks) of an explicitly known sequence of finger movements. Evolution of functional connectivity was assessed using integration, a measure that quantifies the total amount of interaction within a network. When comparing the integration associated with a complex finger movement sequence to that associated with a simple sequence, we observed two patterns of decrease during the 4 weeks of practice. One was not specific as it was observed for all sequences, whereas a specific decrease was observed only for the execution of the learned sequence. This second decrease was a consequence of a relative decrease in associative/premotor network integration, together with a relative increase in between-network integration. These findings are in line with the hypothesis that information is transferred from the associative/premotor circuit to the sensorimotor circuit during the course of motor learning.

Regions, systems, and the brain: Hierarchical measures of functional integration in fMRI

In neuroscience, the notion has emerged that the brain abides by two principles: segregation and integration. Segregation into functionally specialized systems and integration of information flow across systems are basic principles that are thought to shape the functional architecture of the brain. A measure called integration, originating from information theory and derived from mutual information, has been proposed to characterize the global integrative state of a network. In this paper, we show that integration can be applied in a hierarchical fashion to quantify functional interactions between compound systems, each system being composed of several regions. We apply this method to fMRI datasets from patients with low-grade glioma and show how it can efficiently extract information related to both intra- and interhemispheric reorganization induced by lesional brain plasticity.

Large-scale neural model validation of partial correlation analysis for effective connectivity investigation in functional MRI

Recent studies of functional connectivity based upon blood oxygen level dependent functional magnetic resonance imaging have shown that this technique allows one to investigate large‐scale functional brain networks. In a previous study, we advocated that data‐driven measures of effective connectivity should be developed to bridge the gap between functional and effective connectivity. To attain this goal, we proposed a novel approach based on the partial correlation matrix. In this study, we further validate the use of partial correlation analysis by employing a large‐scale, neurobiologically realistic neural network model to generate simulated data that we analyze with both structural equation modeling (SEM) and the partial correlation approach. Unlike real experimental data, where the interregional anatomical links are not necessarily known, the links between the nodes of the network model are fully specified, and thus provide a standard against which to judge the results of SEM and partial correlation analyses. Our results show that partial correlation analysis from the data alone exhibits patterns of effective connectivity that are similar to those found using SEM, and both are in agreement with respect to the underlying neuroarchitecture. Our findings thus provide a strong validation for the partial correlation method. Hum Brain Mapp, 2009.