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1.
Chaos ; 34(4)2024 Apr 01.
Article in English | MEDLINE | ID: mdl-38625080

ABSTRACT

Built upon the shoulders of graph theory, the field of complex networks has become a central tool for studying real systems across various fields of research. Represented as graphs, different systems can be studied using the same analysis methods, which allows for their comparison. Here, we challenge the widespread idea that graph theory is a universal analysis tool, uniformly applicable to any kind of network data. Instead, we show that many classical graph metrics-including degree, clustering coefficient, and geodesic distance-arise from a common hidden propagation model: the discrete cascade. From this perspective, graph metrics are no longer regarded as combinatorial measures of the graph but as spatiotemporal properties of the network dynamics unfolded at different temporal scales. Once graph theory is seen as a model-based (and not a purely data-driven) analysis tool, we can freely or intentionally replace the discrete cascade by other canonical propagation models and define new network metrics. This opens the opportunity to design-explicitly and transparently-dedicated analyses for different types of real networks by choosing a propagation model that matches their individual constraints. In this way, we take stand that network topology cannot always be abstracted independently from network dynamics but shall be jointly studied, which is key for the interpretability of the analyses. The model-based perspective here proposed serves to integrate into a common context both the classical graph analysis and the more recent network metrics defined in the literature which were, directly or indirectly, inspired by propagation phenomena on networks.

2.
Hum Brain Mapp ; 44(11): 4352-4371, 2023 08 01.
Article in English | MEDLINE | ID: mdl-37254960

ABSTRACT

The study of the brain's dynamical activity is opening a window to help the clinical assessment of patients with disorders of consciousness. For example, glucose uptake and the dysfunctional spread of naturalistic and synthetic stimuli has proven useful to characterize hampered consciousness. However, understanding of the mechanisms behind loss of consciousness following brain injury is still missing. Here, we study the propagation of endogenous and in-silico exogenous perturbations in patients with disorders of consciousness, based upon directed and causal interactions estimated from resting-state fMRI data, fitted to a linear model of activity propagation. We found that patients with disorders of consciousness suffer decreased capacity for neural propagation and responsiveness to events, and that this can be related to severe reduction of glucose metabolism as measured with [18 F]FDG-PET. In particular, we show that loss of consciousness is related to the malfunctioning of two neural circuits: the posterior cortical regions failing to convey information, in conjunction with reduced broadcasting of information from subcortical, temporal, parietal and frontal regions. These results shed light on the mechanisms behind disorders of consciousness, triangulating network function with basic measures of brain integrity and behavior.


Subject(s)
Consciousness Disorders , Consciousness , Humans , Consciousness Disorders/diagnostic imaging , Brain/diagnostic imaging , Brain Mapping/methods , Magnetic Resonance Imaging/methods , Fluorodeoxyglucose F18 , Unconsciousness
3.
Phys Rev E ; 107(2-1): 024121, 2023 Feb.
Article in English | MEDLINE | ID: mdl-36932548

ABSTRACT

Consciousness is supported by complex patterns of brain activity which are indicative of irreversible nonequilibrium dynamics. While the framework of stochastic thermodynamics has facilitated the understanding of physical systems of this kind, its application to infer the level of consciousness from empirical data remains elusive. We faced this challenge by calculating entropy production in a multivariate Ornstein-Uhlenbeck process fitted to Functional magnetic resonance imaging brain activity recordings. To test this approach, we focused on the transition from wakefulness to deep sleep, revealing a monotonous relationship between entropy production and the level of consciousness. Our results constitute robust signatures of consciousness while also advancing our understanding of the link between consciousness and complexity from the fundamental perspective of statistical physics.


Subject(s)
Brain , Consciousness , Humans , Entropy , Wakefulness , Thermodynamics
4.
Neuroimage Clin ; 36: 103262, 2022.
Article in English | MEDLINE | ID: mdl-36451365

ABSTRACT

Functional magnetic resonance imaging (fMRI) captures information on brain function beyond the anatomical alterations that are traditionally visually examined by neuroradiologists. However, the fMRI signals are complex in addition to being noisy, so fMRI still faces limitations for clinical applications. Here we review methods that have been proposed as potential solutions so far, namely statistical, biophysical and decoding models, with their strengths and weaknesses. We especially evaluate the ability of these models to directly predict clinical variables from their parameters (predictability) and to extract clinically relevant information regarding biological mechanisms and relevant features for classification and prediction (interpretability). We then provide guidelines for useful applications and pitfalls of such fMRI-based models in a clinical research context, looking beyond the current state of the art. In particular, we argue that the clinical relevance of fMRI calls for a new generation of models for fMRI data, which combine the strengths of both biophysical and decoding models. This leads to reliable and biologically meaningful model parameters, which thus fulfills the need for simultaneous interpretability and predictability. In our view, this synergy is fundamental for the discovery of new pharmacological and interventional targets, as well as the use of models as biomarkers in neurology and psychiatry.


Subject(s)
Brain Mapping , Brain , Humans , Brain Mapping/methods , Brain/diagnostic imaging , Magnetic Resonance Imaging/methods , Functional Neuroimaging , Neuroimaging
5.
Cereb Cortex Commun ; 3(3): tgac027, 2022.
Article in English | MEDLINE | ID: mdl-36072710

ABSTRACT

In the past decade, several studies have shown that Neurofeedback (NFB) by functional magnetic resonance imaging can alter the functional coupling of targeted and non-targeted areas. However, the causal mechanisms underlying these changes remain uncertain. Here, we applied a whole-brain dynamical model to estimate Effective Connectivity (EC) profiles of resting-state data acquired before and immediately after a single-session NFB training for 17 participants who underwent motor imagery NFB training and 16 healthy controls who received sham feedback. Within-group and between-group classification analyses revealed that only for the NFB group it was possible to accurately discriminate between the 2 resting-state sessions. NFB training-related signatures were reflected in a support network of direct connections between areas involved in reward processing and implicit learning, together with regions belonging to the somatomotor, control, attention, and default mode networks, identified through a recursive-feature elimination procedure. By applying a data-driven approach to explore NFB-induced changes in spatiotemporal dynamics, we demonstrated that these regions also showed decreased switching between different brain states (i.e. metastability) only following real NFB training. Overall, our findings contribute to the understanding of NFB impact on the whole brain's structure and function by shedding light on the direct connections between brain areas affected by NFB training.

6.
Brain Struct Funct ; 227(6): 2087-2102, 2022 Jul.
Article in English | MEDLINE | ID: mdl-35524072

ABSTRACT

In the past decades, there has been a growing scientific interest in characterizing neural correlates of meditation training. Nonetheless, the mechanisms underlying meditation remain elusive. In the present work, we investigated meditation-related changes in functional dynamics and structural connectivity (SC). For this purpose, we scanned experienced meditators and control (naive) subjects using magnetic resonance imaging (MRI) to acquire structural and functional data during two conditions, resting-state and meditation (focused attention on breathing). In this way, we aimed to characterize and distinguish both short-term and long-term modifications in the brain's structure and function. First, to analyze the fMRI data, we calculated whole-brain effective connectivity (EC) estimates, relying on a dynamical network model to replicate BOLD signals' spatio-temporal structure, akin to functional connectivity (FC) with lagged correlations. We compared the estimated EC, FC, and SC links as features to train classifiers to predict behavioral conditions and group identity. Then, we performed a network-based analysis of anatomical connectivity. We demonstrated through a machine-learning approach that EC features were more informative than FC and SC solely. We showed that the most informative EC links that discriminated between meditators and controls involved several large-scale networks mainly within the left hemisphere. Moreover, we found that differences in the functional domain were reflected to a smaller extent in changes at the anatomical level as well. The network-based analysis of anatomical pathways revealed strengthened connectivity for meditators compared to controls between four areas in the left hemisphere belonging to the somatomotor, dorsal attention, subcortical and visual networks. Overall, the results of our whole-brain model-based approach revealed a mechanism underlying meditation by providing causal relationships at the structure-function level.


Subject(s)
Meditation , Brain , Brain Mapping/methods , Humans , Magnetic Resonance Imaging/methods , Meditation/methods , Nerve Net/diagnostic imaging
7.
Brain Commun ; 3(4): fcab233, 2021.
Article in English | MEDLINE | ID: mdl-34729479

ABSTRACT

Recent resting-state functional MRI studies in stroke patients have identified two robust biomarkers of acute brain dysfunction: a reduction of inter-hemispheric functional connectivity between homotopic regions of the same network, and an abnormal increase of ipsi-lesional functional connectivity between task-negative and task-positive resting-state networks. Whole-brain computational modelling studies, at the individual subject level, using undirected effective connectivity derived from empirically measured functional connectivity, have shown a reduction of measures of integration and segregation in stroke as compared to healthy brains. Here we employ a novel method, first, to infer whole-brain directional effective connectivity from zero-lagged and lagged covariance matrices, then, to compare it to empirically measured functional connectivity for predicting stroke versus healthy status, and patient performance (zero, one, multiple deficits) across neuropsychological tests. We also investigated the accuracy of functional connectivity versus model effective connectivity in predicting the long-term outcome from acute measures. Both functional and effective connectivity predicted healthy from stroke individuals significantly better than the chance-level; however, accuracy for the effective connectivity was significantly higher than for functional connectivity at 1- to 2-week, 3-month and 1-year post-stroke. Predictive functional connections mainly included those reported in previous studies (within-network inter-hemispheric and between task-positive and -negative networks intra-hemispherically). Predictive effective connections included additional between-network links. Effective connectivity was a better predictor than functional connectivity of the number of behavioural domains in which patients suffered deficits, both at 2-week and 1-year post-onset of stroke. Interestingly, patient deficits at 1-year time-point were better predicted by effective connectivity values at 2 weeks rather than at 1-year time-point. Our results thus demonstrate that the second-order statistics of functional MRI resting-state activity at an early stage of stroke, derived from a whole-brain effective connectivity, estimated in a model fitted to reproduce the propagation of neuronal activity, has pertinent information for clinical prognosis.

8.
PLoS Comput Biol ; 16(10): e1008127, 2020 10.
Article in English | MEDLINE | ID: mdl-33044953

ABSTRACT

Learning in neuronal networks has developed in many directions, in particular to reproduce cognitive tasks like image recognition and speech processing. Implementations have been inspired by stereotypical neuronal responses like tuning curves in the visual system, where, for example, ON/OFF cells fire or not depending on the contrast in their receptive fields. Classical models of neuronal networks therefore map a set of input signals to a set of activity levels in the output of the network. Each category of inputs is thereby predominantly characterized by its mean. In the case of time series, fluctuations around this mean constitute noise in this view. For this paradigm, the high variability exhibited by the cortical activity may thus imply limitations or constraints, which have been discussed for many years. For example, the need for averaging neuronal activity over long periods or large groups of cells to assess a robust mean and to diminish the effect of noise correlations. To reconcile robust computations with variable neuronal activity, we here propose a conceptual change of perspective by employing variability of activity as the basis for stimulus-related information to be learned by neurons, rather than merely being the noise that corrupts the mean signal. In this new paradigm both afferent and recurrent weights in a network are tuned to shape the input-output mapping for covariances, the second-order statistics of the fluctuating activity. When including time lags, covariance patterns define a natural metric for time series that capture their propagating nature. We develop the theory for classification of time series based on their spatio-temporal covariances, which reflect dynamical properties. We demonstrate that recurrent connectivity is able to transform information contained in the temporal structure of the signal into spatial covariances. Finally, we use the MNIST database to show how the covariance perceptron can capture specific second-order statistical patterns generated by moving digits.


Subject(s)
Models, Neurological , Neural Networks, Computer , Algorithms , Animals , Computational Biology , Computer Simulation , Databases, Factual , Humans , Image Processing, Computer-Assisted , Learning/physiology , Neurons/cytology
9.
Cereb Cortex ; 30(11): 5899-5914, 2020 10 01.
Article in English | MEDLINE | ID: mdl-32577717

ABSTRACT

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's 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.


Subject(s)
Brain Mapping/methods , Models, Neurological , Visual Cortex/physiology , Visual Pathways/physiology , Adult , Female , Humans , Magnetic Resonance Imaging , Male
10.
Netw Neurosci ; 4(2): 338-373, 2020.
Article in English | MEDLINE | ID: mdl-32537531

ABSTRACT

Neuroimaging techniques are now widely used to study human cognition. The functional associations between brain areas have become a standard proxy to describe how cognitive processes are distributed across the brain network. Among the many analysis tools available, dynamic models of brain activity have been developed to overcome the limitations of original connectivity measures such as functional connectivity. This goes in line with the many efforts devoted to the assessment of directional interactions between brain areas from the observed neuroimaging activity. This opinion article provides an overview of our model-based whole-brain effective connectivity to analyze fMRI data, while discussing the pros and cons of our approach with respect to other established approaches. Our framework relies on the multivariate Ornstein-Uhlenbeck (MOU) process and is thus referred to as MOU-EC. Once tuned, the model provides a directed connectivity estimate that reflects the dynamical state of BOLD activity, which can be used to explore cognition. We illustrate this approach using two applications on task-evoked fMRI data. First, as a connectivity measure, MOU-EC can be used to extract biomarkers for task-specific brain coordination, understood as the patterns of areas exchanging information. The multivariate nature of connectivity measures raises several challenges for whole-brain analysis, for which machine-learning tools present some advantages over statistical testing. Second, we show how to interpret changes in MOU-EC connections in a collective and model-based manner, bridging with network analysis. Our framework provides a comprehensive set of tools that open exciting perspectives to study distributed cognition, as well as neuropathologies.

11.
Cereb Cortex ; 30(3): 1213-1233, 2020 03 14.
Article in English | MEDLINE | ID: mdl-31381086

ABSTRACT

To go beyond the disconnectivity hypothesis of schizophrenia, directed (effective) connectivity was measured between 94 brain regions, to provide evidence on the source of the changes in schizophrenia and a mechanistic model. Effective connectivity (EC) was measured in 180 participants with schizophrenia and 208 controls. For the significantly different effective connectivities in schizophrenia, on average the forward (stronger) effective connectivities were smaller, whereas the backward connectivities tended to be larger. Further, higher EC in schizophrenia was found from the precuneus and posterior cingulate cortex (PCC) to areas such as the parahippocampal, hippocampal, temporal, fusiform, and occipital cortices. These are backward effective connectivities and were positively correlated with the positive symptoms of schizophrenia. Lower effective connectivities were found from temporal and other regions and were negatively correlated with the symptoms, especially the negative and general symptoms. Further, a signal variance parameter was increased for areas that included the parahippocampal gyrus and hippocampus, consistent with the hypothesis that hippocampal overactivity is involved in schizophrenia. This investigation goes beyond the disconnectivity hypothesis by drawing attention to differences in schizophrenia between backprojections and forward connections, with the backward connections from the precuneus and PCC implicated in memory stronger in schizophrenia.


Subject(s)
Brain/physiopathology , Schizophrenia/physiopathology , Brain Mapping , Gyrus Cinguli/physiopathology , Humans , Magnetic Resonance Imaging , Models, Neurological , Neural Pathways/physiopathology , Parietal Lobe/physiopathology
12.
Autism Res ; 13(1): 32-44, 2020 01.
Article in English | MEDLINE | ID: mdl-31657138

ABSTRACT

The aim was to go beyond functional connectivity, by measuring in the first large-scale study differences in effective, that is directed, connectivity between brain areas in autism compared to controls. Resting-state functional magnetic resonance imaging was analyzed from the Autism Brain Imaging Data Exchange (ABIDE) data set in 394 people with autism spectrum disorder and 473 controls, and effective connectivity (EC) was measured between 94 brain areas. First, in autism, the middle temporal gyrus and other temporal areas had lower effective connectivities to the precuneus and cuneus, and these were correlated with the Autism Diagnostic Observational Schedule total, communication, and social scores. This lower EC from areas implicated in face expression analysis and theory of mind to the precuneus and cuneus implicated in the sense of self may relate to the poor understanding of the implications of face expression inputs for oneself in autism, and to the reduced theory of mind. Second, the hippocampus and amygdala had higher EC to the middle temporal gyrus in autism, and these are thought to be back projections based on anatomical evidence and are weaker than in the other direction. This may be related to increased retrieval of recent and emotional memories in autism. Third, some prefrontal cortex areas had higher EC with each other and with the precuneus and cuneus. Fourth, there was decreased EC from the temporal pole to the ventromedial prefrontal cortex, and there was evidence for lower activity in the ventromedial prefrontal cortex, a brain area implicated in emotion-related decision-making. Autism Res 2020, 13: 32-44. © 2019 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY: To understand autism spectrum disorders better, it may be helpful to understand whether brain systems cause effects on each other differently in people with autism. In this first large-scale neuroimaging investigation of effective connectivity in people with autism, it is shown that parts of the temporal lobe involved in facial expression identification and theory of mind have weaker effects on the precuneus and cuneus implicated in the sense of self. This may relate to the poor understanding of the implications of face expression inputs for oneself in autism, and to the reduced theory of mind.


Subject(s)
Autism Spectrum Disorder/diagnostic imaging , Autism Spectrum Disorder/physiopathology , Brain Mapping/methods , Brain/diagnostic imaging , Brain/physiopathology , Magnetic Resonance Imaging/methods , Female , Humans , Male
13.
Adv Exp Med Biol ; 1192: 139-158, 2019.
Article in English | MEDLINE | ID: mdl-31705494

ABSTRACT

Neuroimaging-based personalized medicine is emerging to characterize brain disorders and their evolution at the patient level. In this chapter, we present the most classic methods used to infer large-scale brain connectivity based on functional MRI. We adopt a modeling perspective where every connectivity measure is linked to a specific model that allows to interpret the connectivity estimate. This perspective allows to analyze the quality of retrieved connectivity profiles in terms of modeling error and estimation error. In the first part of the chapter, we present undirected functional connectivity (Pearson's correlation and MI) and effective connectivity (partial correlation), as well as directed effective connectivity (VAR, MOU, Granger causality, DCM). In addition, some of these measures correspond to fully connected graphs (Pearson's correlation) while others to sparse ones (MOU, DCM), where the sparsity can come from the integration of functional and structural data. In the second part, we claim that machine learning tools are better suited than null-hypothesis testing to link the estimated connectomes with diagnosis and prognosis of neuropsychiatric diseases. Finally, we propose that linear models and features selection are preferable to more complex and nonlinear tools (when prediction performance is on a par) for building interpretable algorithms to predict clinical variables.


Subject(s)
Brain Diseases , Connectome , Neural Networks, Computer , Brain , Humans , Linear Models , Magnetic Resonance Imaging
14.
Neuroimage ; 201: 116007, 2019 11 01.
Article in English | MEDLINE | ID: mdl-31306771

ABSTRACT

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, 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.


Subject(s)
Brain/physiology , Connectome/methods , Models, Neurological , Humans , Magnetic Resonance Imaging , Nerve Net/physiology , Neural Pathways/physiology
15.
Neuroimage ; 184: 335-348, 2019 01 01.
Article in English | MEDLINE | ID: mdl-30237036

ABSTRACT

A fundamental question in systems neuroscience is how endogenous neuronal activity self-organizes during particular brain states. Recent neuroimaging studies have demonstrated systematic relationships between resting-state and task-induced functional connectivity (FC). In particular, continuous task studies, such as movie watching, speak to alterations in coupling among cortical regions and enhanced fluctuations in FC compared to the resting-state. This suggests that FC may reflect systematic and large-scale reorganization of functionally integrated responses while subjects are watching movies. In this study, we characterized fluctuations in FC during resting-state and movie-watching conditions. We found that the FC patterns induced systematically by movie-watching can be explained with a single principal component. These condition-specific FC fluctuations overlapped with inter-subject synchronization patterns in occipital and temporal brain regions. However, unlike inter-subject synchronization, condition-specific FC patterns were characterized by increased correlations within frontal brain regions and reduced correlations between frontal-parietal brain regions. We investigated these condition-specific functional variations as a shorter time scale, using time-resolved FC. The time-resolved FC showed condition-specificity over time; notably when subjects watched both the same and different movies. To explain self-organisation of global FC through the alterations in local dynamics, we used a large-scale computational model. We found that condition-specific reorganization of FC could be explained by local changes that engendered changes in FC among higher-order association regions, mainly in frontal and parietal cortices.


Subject(s)
Brain Mapping/methods , Brain/physiology , Image Processing, Computer-Assisted/methods , Motion Pictures , Nerve Net/physiology , Adult , Female , Humans , Magnetic Resonance Imaging , Male , Principal Component Analysis , Young Adult
16.
Neuroimage ; 178: 238-254, 2018 09.
Article in English | MEDLINE | ID: mdl-29753842

ABSTRACT

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 (e.g., subjects and conditions such as tasks performed by them). In particular, condition-specific signatures should not be contaminated by subject-related information, since they aim to generalize over subjects. 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.


Subject(s)
Brain/diagnostic imaging , Brain/physiology , Connectome/methods , Image Processing, Computer-Assisted/methods , Individuality , Magnetic Resonance Imaging/methods , Models, Theoretical , Adult , Humans , Rest
17.
Article in English | MEDLINE | ID: mdl-29529414

ABSTRACT

BACKGROUND: Resting-state functional connectivity reflects correlations in the activity between brain areas, whereas effective connectivity between different brain areas measures directed influences of brain regions on each other. Using the latter approach, we compare effective connectivity results in patients with major depressive disorder (MDD) and control subjects. METHODS: We used a new approach to the measurement of effective connectivity, in which each brain area has a simple dynamical model, and known anatomical connectivity is used to provide constraints. This helps the approach to measure the effective connectivity between the 94 brain areas parceled in the automated anatomical labeling (AAL2) atlas, using resting-state functional magnetic resonance imaging. Moreover, we show how the approach can be used to measure the differences in effective connectivity between different groups of individuals, using as an example effective connectivity in the healthy brain and in individuals with depression. The first brainwide resting-state effective-connectivity neuroimaging analysis of depression, with 350 healthy individuals and 336 patients with major depressive disorder, is described. RESULTS: Key findings are that the medial orbitofrontal cortex, implicated in reward and subjective pleasure, has reduced effective connectivity from temporal lobe input areas in depression; that the lateral orbitofrontal cortex, implicated in nonreward, has increased activity (variance) in depression, with decreased effective connectivity to and from cortical areas contralateral to language-related areas; and that the hippocampus, implicated in memory, has increased activity (variance) in depression and increased effective connectivity from the temporal pole. CONCLUSIONS: Measurements of effective connectivity made using the new method provide a new approach to causal mechanisms in the brain in depression.


Subject(s)
Depressive Disorder, Major/physiopathology , Neural Pathways/physiopathology , Prefrontal Cortex/physiopathology , Temporal Lobe/physiopathology , Cerebral Cortex/physiopathology , Female , Hippocampus/physiopathology , Humans , Magnetic Resonance Imaging/methods , Male , Nerve Net/physiopathology , Reward
18.
Neuroimage ; 171: 40-54, 2018 05 01.
Article in English | MEDLINE | ID: mdl-29294385

ABSTRACT

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 nonstationary process which could be described as state switching. In 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. We 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 report some interesting characteristics that clearly support nonstationary features in the data. In particular, we find that the brain spends more time in the troughs of modulations than can be expected from stationary dynamics.


Subject(s)
Brain Mapping/methods , Brain/physiology , Image Processing, Computer-Assisted/methods , Neural Pathways/physiology , Rest/physiology , Adolescent , Adult , Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged , Young Adult
19.
Neuroimage ; 180(Pt B): 534-546, 2018 10 15.
Article in English | MEDLINE | ID: mdl-29024792

ABSTRACT

Our behavior entails a flexible and context-sensitive interplay between brain areas to integrate information according to goal-directed requirements. However, 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.


Subject(s)
Auditory Perception/physiology , Brain/physiology , Models, Neurological , Nerve Net/physiology , Visual Perception/physiology , Acoustic Stimulation , Adult , Brain Mapping/methods , Female , Humans , Image Processing, Computer-Assisted/methods , Magnetic Resonance Imaging/methods , Male , Motion Pictures , Neural Pathways/physiology , Photic Stimulation , Rest/physiology , Young Adult
20.
Biol Cybern ; 112(1-2): 153-161, 2018 04.
Article in English | MEDLINE | ID: mdl-29204807

ABSTRACT

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 local variability and changes in brain coordination go hand in hand.


Subject(s)
Brain/diagnostic imaging , Brain/physiology , Magnetic Resonance Imaging , Models, Neurological , Neural Pathways/diagnostic imaging , Neural Pathways/physiology , Brain Mapping , Humans , Image Processing, Computer-Assisted , Oxygen/blood
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