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Gilson, M.

Publications and source records attributed to Gilson, M..

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Analysis of brain network dynamics estimated from fMRI data: A new framework based on communicability and flow

Neuroimaging techniques such as MRI have been widely used to explore the associations between brain areas. Structural connectivity (SC) captures the anatomical pathways across the brain and functional connectivity (FC) measures the correlation between the activity of brain regions. These connectivity measures have been much studied using network theory in order to uncover the distributed organization of brain structures, in particular FC for task-specific brain communication. However, the application of network theory to study FC matrices is often "static" despite the dynamic nature of time series obtained from fMRI. The present study aims to overcome this limitation by introducing a network-oriented analysis applied to whole-brain effective connectivity (EC) useful to interpret the brain dynamics. Technically, we tune a multivariate Ornstein-Uhlenbeck (MOU) process to reproduce the statistics of the whole-brain resting-state fMRI signals, which provides estimates for MOU-EC as well as input properties (similar to local excitabilities). The network analysis is then based on the Green function (or network impulse response) that describes the interactions between nodes across time for the estimated dynamics. This model-based approach provides time-dependent graph-like descriptor, named communicability, that characterize the roles that either nodes or connections play in the propagation of activity within the network. They can be used at both global and local levels, and also enables the comparison of estimates from real data with surrogates (e.g. random network or ring lattice). In contrast to classical graph approaches to study SC or FC, our framework stresses the importance of taking the temporal aspect of fMRI signals into account. Our results show a merging of functional communities over time (in which input properties play a role), moving from segregated to global integration of the network activity. Our formalism sets a solid ground for the analysis and interpretation of fMRI data, including task-evoked activity.

neuroscience

Distinct Functional Connectivity Mode during Viewing Natural Scenes Revealed by Principal Component Analysis

A fundamental question in systems neuroscience is how spontaneous activity at rest is reorganized during task performance. Recent studies suggest a strong relationship between resting and task FC. Furthermore, the relationship between resting and task FC has been shown to reflect individual differences. Particularly, various studies have demonstrated that the FC has higher reliability and provides enhanced detection of individual differences while viewing natural scenes. Although the large-scale organization of FC during rest and movie-viewing conditions have been well studied in relation to individual variations, the re-organization of FC during viewing natural scenes have not been studied in depth. In this study, we used principal component analysis on FC during rest and movie-viewing condition to characterize the dimensionality of FC patterns across conditions and subjects. We found that the variations in FC patterns related to viewing natural scenes can be explained by a single component, which enables identification of the task over subjects with 100% accuracy. We showed that the FC mode associated to viewing natural scenes better reflects individual variations. Furthermore, we investigated the signatures of movie-viewing-specific functional modes in dynamic FC based on phase-locking values between brain regions. We found that the movie-specific functional mode is persistent across time; suggesting the emergence of a stable processing mode. To explain the reorganization of whole-brain FC through the changes in local dynamics, we appeal to a large-scale computational model. This modelling suggested that the reorganization of whole-brain FC is associated to the interaction between frontal-parietal and frontal-temporal activation patterns.

neuroscience

Analysis of fMRI data using noise-diffusion network models: a new covariance-coding perspective

Since the middle of the 1990s, studies of resting-state fMRI/BOLD data have explored the correlation patterns of activity across the whole brain, which is referred to as functional connectivity (FC). Among the many methods that have been developed to interpret FC, a recently proposed model-based approach describes the propagation of fluctuating BOLD activity within the recurrently connected brain network by inferring the effective connectivity (EC). In this model, EC quantifies the strengths of directional interactions between brain regions, viewed from the proxy of BOLD activity. In addition, the tuning procedure for the model provides estimates for the local variability (input variances) to explain how the observed FC is generated. Generalizing, the network dynamics can be studied in the context of an input-output mapping - determined by EC - for the second-order statistics of fluctuating nodal activities. The present paper focuses on the following detection paradigm: observing output covariances, how discriminative is the (estimated) network model with respect to various input covariance patterns? An application with the model fitted to experimental fMRI data - movie viewing versus resting state - illustrates that changes in excitability and changes in brain coordination go hand in hand.

neuroscience

Subject- and behavior-specific signatures extracted from fMRI data using whole-brain effective connectivity

The study of brain communication based on fMRI data is often limited because such measurements are a mixture of session-to-session variability with subject- and condition-related information. Disentangling these contributions is crucial for real-life applications, in particular when only a few recording sessions are available. The present study aims to define a reliable standard for the extraction of multiple signatures from fMRI data, while verifying that they do not mix information about the different modalities. In particular, condition-specific signature should not be contaminated by subject-related information. Practically, signatures correspond to subnetworks of directed interactions between brain regions (typically 100 covering the whole brain) supporting the subject and condition identification for single fMRI sessions. The key for robust prediction is using effective connectivity instead of functional connectivity. Our method demonstrates excellent generalization capabilities for subject identification in two datasets, using only a few sessions per subject as reference. Using another dataset with resting state and movie viewing, we show that the two signatures related to subjects and tasks correspond to distinct subnetworks, which are thus topologically orthogonal. Our results set solid foundations for applications tailored to individual subjects, such as clinical diagnostic.

neuroscience

Propagation of BOLD activity reveals directed interactions across human visual cortex

It has recently been shown that large-scale propagation of blood-oxygen level dependent (BOLD) activity is constrained by anatomical connections and reflects transitions between behavioral states. It remains to be seen, however, if the propagation of BOLD activity can also relate to the brain anatomical structure at a more local scale. Here, we hypothesized that BOLD propagation reflects structured neuronal activity across early visual field maps. To explore this hypothesis, we characterize the propagation of BOLD activity across V1, V2 and V3 using a modeling approach that aims to disentangle the contributions of local activity and directed interactions in shaping BOLD propagation. It does so by estimating the effective connectivity (EC) and the excitability of a noise-diffusion network to reproduce the spatiotemporal covariance structure of the data. We apply our approach to 7T fMRI recordings acquired during resting state (RS) and visual field mapping (VFM). Our results reveal different EC interactions and changes in cortical excitability in RS and VFM, and point to a reconfiguration of feedforward and feedback interactions across the visual system. We conclude that the propagation of BOLD activity has functional relevance, as it reveals directed interactions and changes in cortical excitability in a task-dependent manner.

neuroscience

Task-related effective connectivity reveals that the cortical rich club gates cortex-wide communication

Higher cognition may require the globally coordinated integration of specialized brain regions into functional networks. A collection of structural cortical hubs - referred to as the rich club - has been hypothesized to support task-specific functional integration. In the present paper, we use a whole-cortex model to estimate directed interactions between 68 cortical regions from fMRI activity for four different tasks (reflecting different cognitive domains) and resting state. We analyze the state-dependent input and output effective connectivity of the structural rich club and relate these to whole-cortex dynamics and network reconfigurations. We find that the cortical rich club exhibits an increase in outgoing effective connectivity during task performance as compared to rest while incoming connectivity remains constant. Increased outgoing connectivity targets a sparse set of peripheral regions with specific regions strongly overlapping between tasks. At the same time, community detection analyses reveal massive reorganizations of interactions among peripheral regions, including those serving as target of increased rich club output. This suggests that while peripheral regions may play a role in several tasks, their concrete interplay might nonetheless be task-specific. Furthermore, we observe that whole-cortex dynamics are faster during task as compared to rest. The decoupling effects usually accompanying faster dynamics appear to be counteracted by the increased rich club outgoing effective connectivity. Together our findings speak to a gating mechanism of the rich club that supports fast-paced information exchange among relevant peripheral regions in a task-specific and goal-directed fashion, while constantly listening to the whole network.

neuroscience

Limited contribution of rare, noncoding variation to autism spectrum disorder from sequencing of 2,076 genomes in quartet families

Genomic studies to date in autism spectrum disorder (ASD) have largely focused on newly arising mutations that disrupt protein coding sequence and strongly influence risk. We evaluate the contribution of noncoding regulatory variation across the size and frequency spectrum through whole genome sequencing of 519 ASD cases, their unaffected sibling controls, and parents. Cases carry a small excess of de novo (1.02-fold) noncoding variants, which is not significant after correcting for paternal age. Assessing 51,801 regulatory classes, no category is significantly associated with ASD after correction for multiple testing. The strongest signals are observed in coding regions, including structural variation not detected by previous technologies and missense variation. While rare noncoding variation likely contributes to risk in neurodevelopmental disorders, no category of variation has impact equivalent to loss-of-function mutations. Average effect sizes are likely to be smaller than that for coding variation, requiring substantially larger samples to quantify this risk.

genomics

Stereotypical Modulations In Dynamic Functional Connectivity Explained By Changes In BOLD Variance

Spontaneous activity measured in human subject under the absence of any task exhibits complex patterns of correlation that largely correspond to large-scale functional topographies obtained with a wide variety of cognitive and perceptual tasks. These \"resting state networks\" (RSNs) fluctuate over time, forming and dissolving on the scale of seconds to minutes. While these fluctuations, most prominently those of the default mode network, have been linked to cognitive function, it remains unclear whether they result from random noise or whether they index a non-stationary process which could be described as state switching.\n\nIn this study, we use a sliding windows-approach to relate temporal dynamics of RSNs to global modulations in correlation and BOLD variance. We compare empirical data, phase-randomized surrogate data, and data simulated with a stationary model. We find that RSN time courses exhibit a large amount of coactivation in all three cases, and that the modulations in their activity are closely linked to global dynamics of the underlying BOLD signal.\n\nWe find that many properties of the observed fluctuations in FC and BOLD, including their ranges and their correlations amongst each other, are explained by fluctuations around the average FC structure. However, we also encounter interesting characteristics that are not explained in this way. In particular, we find that the brain spends more time in the troughs of modulations than can be expected from stationary dynamics.

neuroscience

Effective connectivity inferred from fMRI transition dynamics during movie viewing points to a balanced reconfiguration of cortical interactions

Our behavior entails a flexible and context-sensitive interplay between brain areas to integrate information according to goal-directed requirements. How-ever, the neural mechanisms governing the entrainment of functionally specialized brain areas remain poorly understood. In particular, the question arises whether observed changes in the regional activity for different cognitive conditions are explained by modifications of the inputs to the brain or its connectivity? We observe that transitions of fMRI activity between areas convey information about the tasks performed by 19 subjects, watching a movie versus a black screen (rest). We use a model-based framework that explains this spatiotemporal functional connectivity pattern by the local variability for 66 cortical regions and the network effective connectivity between them. We find that, among the estimated model parameters, movie viewing affects to a larger extent the local activity, which we interpret as extrinsic changes related to the increased stimulus load. However, detailed changes in the effective connectivity preserve a balance in the propagating activity and select specific pathways such that high-level brain regions integrate visual and auditory information, in particular boosting the communication between the two brain hemispheres. These findings speak to a dynamic coordination underlying the functional integration in the brain.

neuroscience

Non-parametric test for connectivity detection in multivariate autoregressive networks and application to multiunit activity data

Directed connectivity inference has become a cornerstone in neuroscience following the recent progress in neuroimaging and elctrophysiological techniques to characterize anatomical and functional networks. This paper focuses on the detection of existing connections from the observed activity in networks of 50 to 150 nodes with linear feedback in discrete time. Through the variation of multiple network parameters, our numerical results indicate that directed connections - in the time domain - are more accurately estimated based on the coefficients obtained from multivariate autoregressive (MVAR) than Granger causality analysis, which is based on the error residuals of the same MVAR linear regression. Based on these findings, we propose a non-parametric significance test for connectivity detection, which achieves a good control of false positives (type 1 error) and is robust to various network topologies. When generating surrogate distributions, we compare the effects of circular shifts, random permutations and phase randomization of the observed time series, each breaking down covariances in a specific manner: the MVAR estimates from those shuffled covariances build a null-hypothesis distribution for each connection, from which the original connectivity estimate can be compared. We apply our method to multiunit activity data recorded from Utah electrode arrays in monkey and examine the detected interactions between 25 channels for a proof of concept. The results unravel a non-trivial underlying connectivity structure, which differentiates the effect of incoming and outgoing connections.

neuroscience

Robust extraction of spatio-temporal patterns from resting state fMRI

It is well-established that patterns of functional connectivity (FC) - measures of correlated activity between pairs of voxels or regions observed in the human brain using neuroimaging - are robustly expressed in spontaneous activity during rest. These patterns are not static, but exhibit complex spatio-temporal dynamics. Over the last years, a multitude of methods have been proposed to reveal these dynamics on the level of the whole brain. One finding is that the brain transitions through different FC configurations over time, and substantial effort has been put into characterizing these configurations. However, the dynamics governing these transitions are more elusive, specifically, the contribution of stationary vs. non-stationary dynamics is an active field of inquiry. In this study, we use a whole-brain approach, considering FC dynamics between 66 ROIs covering the entire cortex. We combine an innovative dimensionality reduction technique, tensor decomposition, with a mean field model which possesses stationary dynamics. It has been shown to explain resting state FC averaged over time and multiple subjects, however, this average FC summarizes the spatial distribution of correlations while hiding their temporal dynamics. First, we apply tensor decomposition to resting state scans from 24 healthy controls in order to characterize spatio-temporal dynamics present in the data. We simultaneously utilize temporal and spatial information by creating tensors that are subsequently decomposed into sets of brain regions (\"communities\") that share similar temporal dynamics, and their associated time courses. The tensors contain pairwise FC computed inside of overlapping sliding windows. Communities are discovered by clustering features pooled from all subjects, thereby ensuring that they generalize. We find that, on the group level, the data give rise to four distinct communities that resemble known resting state networks (RSNs): default mode network, visual network, control networks, and somatomotor network. Second, we simulate data with our stationary mean field model whose nodes are connected according to results from DTI and fiber tracking. In this model, all spatio-temporal structure is due to noisy fluctuations around the average FC. We analyze the simulated data in the same way as the empirical data in order to determine whether stationary dynamics can explain the emergence of distinct FC patterns (RSNs) which have their own time courses. We find that this is the case for all four networks using the spatio-temporal information revealed by tensor decomposition if nodes in the simulation are connected according to model-based effective connectivity. Furthermore, we find that these results require only a small part of the FC values, namely the highest values that occur across time and ROI pair. Our findings show that stationary dynamics can account for the emergence of RSNs. We provide an innovative method that does not make strong assumptions about the underlying data and is generally applicable to resting state or task data from different subject populations.

neuroscience

Exploring Anti-correlated Resting State BOLD Signals Through Dynamic Functional Connectivity and Whole-brain Computational Modeling

Resting-state functional magnetic resonance imaging and diffusion weight imaging became a conventional tool to study brain connectivity in healthy and diseased individuals. However, both techniques provide indirect measures of brain connectivity leading to controversies on their interpretation. Among these controversies, interpretation of anti-correlated functional connections and global average signal is a major challenge for the field. In this paper, we used dynamic functional connectivity to calculate the probability of anti-correlations between brain regions. The brain regions forming task-positive and task-negative networks showed high anti-correlation probabilities. The fluctuations in anti-correlation probabilities were significantly correlated with those in global average signal and functional connectivity. We investigated the mechanisms behind these fluctuations using whole-brain computational modeling approach. We found that the underlying effective connectivity and intrinsic noise reflect the static spatiotemporal patterns, whereas the hemodynamic response function is the key factor defining the fluctuations in functional connectivity and anti-correlations. Furthermore, we illustrated the clinical implications of these findings on a group of bipolar disorder patients suffering a depressive relapse (BPD).

neuroscience