908 research outputs found

    The generalized shrinkage estimator for the analysis of functional connectivity of brain signals

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    We develop a new statistical method for estimating functional connectivity between neurophysiological signals represented by a multivariate time series. We use partial coherence as the measure of functional connectivity. Partial coherence identifies the frequency bands that drive the direct linear association between any pair of channels. To estimate partial coherence, one would first need an estimate of the spectral density matrix of the multivariate time series. Parametric estimators of the spectral density matrix provide good frequency resolution but could be sensitive when the parametric model is misspecified. Smoothing-based nonparametric estimators are robust to model misspecification and are consistent but may have poor frequency resolution. In this work, we develop the generalized shrinkage estimator, which is a weighted average of a parametric estimator and a nonparametric estimator. The optimal weights are frequency-specific and derived under the quadratic risk criterion so that the estimator, either the parametric estimator or the nonparametric estimator, that performs better at a particular frequency receives heavier weight. We validate the proposed estimator in a simulation study and apply it on electroencephalogram recordings from a visual-motor experiment.Comment: Published in at http://dx.doi.org/10.1214/10-AOAS396 the Annals of Applied Statistics (http://www.imstat.org/aoas/) by the Institute of Mathematical Statistics (http://www.imstat.org

    Markov models for fMRI correlation structure: is brain functional connectivity small world, or decomposable into networks?

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    Correlations in the signal observed via functional Magnetic Resonance Imaging (fMRI), are expected to reveal the interactions in the underlying neural populations through hemodynamic response. In particular, they highlight distributed set of mutually correlated regions that correspond to brain networks related to different cognitive functions. Yet graph-theoretical studies of neural connections give a different picture: that of a highly integrated system with small-world properties: local clustering but with short pathways across the complete structure. We examine the conditional independence properties of the fMRI signal, i.e. its Markov structure, to find realistic assumptions on the connectivity structure that are required to explain the observed functional connectivity. In particular we seek a decomposition of the Markov structure into segregated functional networks using decomposable graphs: a set of strongly-connected and partially overlapping cliques. We introduce a new method to efficiently extract such cliques on a large, strongly-connected graph. We compare methods learning different graph structures from functional connectivity by testing the goodness of fit of the model they learn on new data. We find that summarizing the structure as strongly-connected networks can give a good description only for very large and overlapping networks. These results highlight that Markov models are good tools to identify the structure of brain connectivity from fMRI signals, but for this purpose they must reflect the small-world properties of the underlying neural systems

    Small-Sample Analysis and Inference of Networked Dependency Structures from Complex Genomic Data

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    Die vorliegende Arbeit beschäftigt sich mit der statistischen Modellierung und Inferenz genetischer Netzwerke. Assoziationsstrukturen und wechselseitige Einflüsse sind ein wichtiges Thema in der Systembiologie. Genexpressionsdaten weisen eine hohe Dimensionalität auf, die geringen Stichprobenumfängen gegenübersteht ("small n, large p"). Die Analyse von Interaktionsstrukturen mit Hilfe graphischer Modelle ist demnach ein schlecht gestelltes (inverses) Problem, dessen Lösung Methoden zur Regularisierung erfordert. Ich schlage neuartige Schätzfunktionen für Kovarianzstrukturen und (partielle) Korrelationen vor. Diese basieren entweder auf Resampling-Verfahren oder auf Shrinkage zur Varianzreduktion. In der letzteren Methode wird die optimale Shrinkage Intensität analytisch berechnet. Im Vergleich zur klassischen Stichprobenkovarianzmatrix besitzt speziell diese Schätzfunktion wünschenswerte Eigenschaften im Sinne von gesteigerter Effizienz und von kleinerem mittleren quadratischen Fehler. Außerdem ergeben sich stets positiv definite und gut konditionierte Parameterschätzungen. Zur Bestimmung der Netzwerktopologie wird auf das Konzept graphischer Gaußscher Modelle zurückgegriffen, mit deren Hilfe sich sowohl marginale als auch bedingte Unabhängigkeiten darstellen lassen. Es wird eine Methode zur Modellselektion vorgestellt, die auf einer multiplen Testprozedur mit Kontrolle der False Discovery Rate beruht. Dabei wird die zugrunde liegende Nullverteilung adaptiv geschätzt. Das vorgeschlagene Framework ist rechentechnisch effizient und schneidet im Vergleich mit konkurrierenden Verfahren sowohl in Simulationen als auch in der Anwendung auf molekulare Daten sehr gut ab

    Learning Graphical Models of Multivariate Functional Data with Applications to Neuroimaging

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    This dissertation investigates the functional graphical models that infer the functional connectivity based on neuroimaging data, which is noisy, high dimensional and has limited samples. The dissertation provides two recipes to infer the functional graphical model: 1) a fully Bayesian framework 2) an end-to-end deep model. We first propose a fully Bayesian regularization scheme to estimate functional graphical models. We consider a direct Bayesian analog of the functional graphical lasso proposed by Qiao et al. (2019).. We then propose a regularization strategy via the graphical horseshoe. We compare both Bayesian approaches to the frequentist functional graphical lasso, and compare the Bayesian functional graphical lasso to the functional graphical horseshoe. We applied the proposed methods with electroencephalography (EEG) data and diffusion tensor imaging (DTI) data. We find that the Bayesian methods tend to outperform the standard functional graphical lasso, and that the functional graphical horseshoe performs best overall, a procedure for which there is no direct frequentist analog. Then we consider a deep neural network architecture to estimate functional graphical models, by combining two simple off-the-shelf algorithms: adaptive functional principal components analysis (FPCA) Yao et al., 2021a) and convolutional graph estimator (Belilovsky et al., 2016). We train our proposed model with synthetic data which emulate the real world observations and prior knowledge. Based on synthetic data generation process, our model convert an inference problem as a supervised learning problem. Compared with other framework, our proposed deep model which offers a general recipe to infer the functional graphical model based on data-driven approach, take the raw functional dataset as input and avoid deriving sophisticated closed-form. Through simulation studies, we find that our deep functional graph model trained on synthetic data generalizes well and outperform other popular baselines marginally. In addition, we apply deep functional graphical model in the real world EEG data, and our proposed model discover meaningful brain connectivity. Finally, we are interested in estimating casual graph with functional input. In order to process functional covariates in causal estimation, we leverage the similar strategy as our deep functional graphical model. We extend popular deep causal models to infer causal effects with functional confoundings within the potential outcomes framework. Our method is simple yet effective, where we validate our proposed architecture in variety of simulation settings. Our work offers an alternative way to do causal inference with functional data

    Disentangling causal webs in the brain using functional Magnetic Resonance Imaging: A review of current approaches

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    In the past two decades, functional Magnetic Resonance Imaging has been used to relate neuronal network activity to cognitive processing and behaviour. Recently this approach has been augmented by algorithms that allow us to infer causal links between component populations of neuronal networks. Multiple inference procedures have been proposed to approach this research question but so far, each method has limitations when it comes to establishing whole-brain connectivity patterns. In this work, we discuss eight ways to infer causality in fMRI research: Bayesian Nets, Dynamical Causal Modelling, Granger Causality, Likelihood Ratios, LiNGAM, Patel's Tau, Structural Equation Modelling, and Transfer Entropy. We finish with formulating some recommendations for the future directions in this area

    Statistical Methods for Functional Magnetic Resonance Imaging Data

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    Understanding how the brain functions is one of the most important goals in science and medicine today. Functional magnetic resonance imaging (fMRI) is a noninvasive, widely used technology for studying brain function in humans. While fMRI has great potential to shed light on cognitive development, decline and disorders, it also presents statistical and computational challenges due to a myriad of sources of noise and the large size of the data. In this thesis, I propose several methods to improve the analysis of resting-state fMRI, which is used to understand connectivity between different regions of the brain. Specifically, this thesis addresses two primary themes. First, I propose shrinkage estimators for functional connectivity, which improve reliability of subject-level estimates by "borrowing strength" across subjects. Second, I propose a method of identifying artifacts in fMRI data through a novel high-dimensional outlier detection method. The proposed methods can be used together and have the potential to significantly improve our understanding of brain connectivity at the subject level using resting-state fMRI

    Bayesian Mixed Effect Sparse Tensor Response Regression Model with Joint Estimation of Activation and Connectivity

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    Brain activation and connectivity analyses in task-based functional magnetic resonance imaging (fMRI) experiments with multiple subjects are currently at the forefront of data-driven neuroscience. In such experiments, interest often lies in understanding activation of brain voxels due to external stimuli and strong association or connectivity between the measurements on a set of pre-specified group of brain voxels, also known as regions of interest (ROI). This article proposes a joint Bayesian additive mixed modeling framework that simultaneously assesses brain activation and connectivity patterns from multiple subjects. In particular, fMRI measurements from each individual obtained in the form of a multi-dimensional array/tensor at each time are regressed on functions of the stimuli. We impose a low-rank PARAFAC decomposition on the tensor regression coefficients corresponding to the stimuli to achieve parsimony. Multiway stick breaking shrinkage priors are employed to infer activation patterns and associated uncertainties in each voxel. Further, the model introduces region specific random effects which are jointly modeled with a Bayesian Gaussian graphical prior to account for the connectivity among pairs of ROIs. Empirical investigations under various simulation studies demonstrate the effectiveness of the method as a tool to simultaneously assess brain activation and connectivity. The method is then applied to a multi-subject fMRI dataset from a balloon-analog risk-taking experiment in order to make inference about how the brain processes risk.Comment: 27 pages, 7 figure

    Contributions to the study of Austism Spectrum Brain conectivity

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    164 p.Autism Spectrum Disorder (ASD) is a largely prevalent neurodevelopmental condition with a big social and economical impact affecting the entire life of families. There is an intense search for biomarkers that can be assessed as early as possible in order to initiate treatment and preparation of the family to deal with the challenges imposed by the condition. Brain imaging biomarkers have special interest. Specifically, functional connectivity data extracted from resting state functional magnetic resonance imaging (rs-fMRI) should allow to detect brain connectivity alterations. Machine learning pipelines encompass the estimation of the functional connectivity matrix from brain parcellations, feature extraction and building classification models for ASD prediction. The works reported in the literature are very heterogeneous from the computational and methodological point of view. In this Thesis we carry out a comprehensive computational exploration of the impact of the choices involved while building these machine learning pipelines

    A Bayesian alternative to mutual information for the hierarchical clustering of dependent random variables

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    The use of mutual information as a similarity measure in agglomerative hierarchical clustering (AHC) raises an important issue: some correction needs to be applied for the dimensionality of variables. In this work, we formulate the decision of merging dependent multivariate normal variables in an AHC procedure as a Bayesian model comparison. We found that the Bayesian formulation naturally shrinks the empirical covariance matrix towards a matrix set a priori (e.g., the identity), provides an automated stopping rule, and corrects for dimensionality using a term that scales up the measure as a function of the dimensionality of the variables. Also, the resulting log Bayes factor is asymptotically proportional to the plug-in estimate of mutual information, with an additive correction for dimensionality in agreement with the Bayesian information criterion. We investigated the behavior of these Bayesian alternatives (in exact and asymptotic forms) to mutual information on simulated and real data. An encouraging result was first derived on simulations: the hierarchical clustering based on the log Bayes factor outperformed off-the-shelf clustering techniques as well as raw and normalized mutual information in terms of classification accuracy. On a toy example, we found that the Bayesian approaches led to results that were similar to those of mutual information clustering techniques, with the advantage of an automated thresholding. On real functional magnetic resonance imaging (fMRI) datasets measuring brain activity, it identified clusters consistent with the established outcome of standard procedures. On this application, normalized mutual information had a highly atypical behavior, in the sense that it systematically favored very large clusters. These initial experiments suggest that the proposed Bayesian alternatives to mutual information are a useful new tool for hierarchical clustering
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