Unified Framework for Robust Estimation of Brain Networks From fMRI Using Temporal and Spatial Correlation Analyses

There is a rapidly growing interest in the neuroimaging field to use functional magnetic resonance imaging (fMRI) to explore brain networks, i.e., how regions of the brain communicate with one another. This paper presents a general and novel statistical framework for robust and more complete estimation of brain functional connectivity from fMRI based on correlation analyses and hypothesis testing. In addition to the ability of examining the correlations with each individual seed as in the standard and existing methods, the proposed framework can detect functional interactions by simultaneously examining multiseed correlations via multiple correlation coefficients. Spatially structured noise in fMRI is also taken into account during the identification of functional interconnection networks through noncentral $F$ hypothesis tests. The associated issues for the multiple testing and the effective degrees-of-freedom are considered as well. Furthermore, partial multiple correlations are introduced and formulated to measure any additional task-induced but not stimulus-locked relation over brain regions so that we can take the analysis of functional connectivity closer to the characterization of direct functional interactions of the brain. Evaluation for accuracy and advantages, and comparisons of the new approaches in the presented general framework are performed using both realistic synthetic data and in vivo fMRI data.      

Group replicator dynamics: a novel group-wise evolutionary approach for sparse brain network detection

Functional magnetic resonance imaging (fMRI) is increasingly used for studying functional integration of the brain. However, large inter-subject variability in functional connectivity, particularly in disease populations, renders detection of representative group networks challenging. In this paper, we propose a novel technique, "group replicator dynamics" (GRD), for detecting sparse functional brain networks that are common across a group of subjects. We extend the replicator dynamics (RD) approach, which we show to be a solution of the nonnegative sparse principal component analysis problem, by integrating group information into each subject's RD process. Our proposed strategy effectively coaxes all subjects' networks to evolve towards the common network of the group. This results in sparse networks comprising the same brain regions across subjects yet with subject-specific weightings of the identified brain regions. Thus, in contrast to traditional averaging approaches, GRD enables inter-subject variability to be modeled, which facilitates statistical group inference. Quantitative validation of GRD on synthetic data demonstrated superior network detection performance over standard methods. When applied to real fMRI data, GRD detected task-specific networks that conform well to prior neuroscience knowledge.     

融合先验信息的脑功能图像分割

基于静息态功能磁共振图像(fMRI)的脑功能区分割广泛采用K均值聚类和谱聚类等无监督聚类算法。但这些算法对图像噪声较为敏感,可能会产生不可靠的脑区分割结果。文中提出了一种融合先验信息的半监督聚类算法,可以可靠地确定各子区间的边界,从而得到稳定的分割结果。提出的方法对人类右侧大脑的Broca区(BA44/45区)进行分割验证,实验结果表明,文中的方法不仅得到了可靠的功能子区边界,而且获得了较高的个体间一致性。     

Automatic identification of functional clusters in FMRI data using spatial dependence

In independent component analysis (ICA) of functional magnetic resonance imaging (fMRI) data, extracting a large number of maximally independent components provides a detailed functional segmentation of brain. However, such high-order segmentation does not establish the relationships among different brain networks, and also studying and classifying components can be challenging. In this study, we present a multidimensional ICA (MICA) scheme to achieve automatic component clustering. In our MICA framework, stable components are hierarchically grouped into clusters based on higher order statistical dependence--mutual information--among spatial components, instead of the typically used temporal correlation among time courses. The final cluster membership is determined using a statistical hypothesis testing method. Since ICA decomposition takes into account the modulation of the spatial maps, i.e., temporal information, our ICA-based approach incorporates both spatial and temporal information effectively. Our experimental results from both simulated and real fMRI datasets show that the use of spatial dependence leads to physiologically meaningful connectivity structure of brain networks, which is consistently identified across various ICA model orders and algorithms. In addition, we observe that components related to artifacts, including cerebrospinal fluid, arteries, and large draining veins, are grouped together and encouragingly distinguished from other components of interest.     

Analysis of FMRI data using an integrated principal component analysis and supervised affinity propagation clustering approach

Clustering analysis is a promising data-driven method for analyzing functional magnetic resonance imaging (fMRI) time series data. The huge computational load, however, creates practical difficulties for this technique. We present a novel approach, integrating principal component analysis (PCA) and supervised affinity propagation clustering (SAPC). In this method, fMRI data are initially processed by PCA to obtain a preliminary image of brain activation. SAPC is then used to detect different brain functional activation patterns. We used a supervised Silhouette index to optimize clustering quality and automatically search for the optimal parameter p in SAPC, so that the basic affinity propagation clustering is improved by applying SAPC. Four simulation studies and tests with three in vivo fMRI datasets containing data from both block-design and event-related experiments revealed that functional brain activation was effectively detected and different response patterns were distinguished using our integrated method. In addition, the improved SAPC method was superior to the k -centers clustering and hierarchical clustering methods in both block-design and event-related fMRI data, as measured by the average squared error. These results suggest that our proposed novel integrated approach will be useful for detecting brain functional activation in both block-design and event-related experimental fMRI data.     

非线性脑区相关性分析及动态脑网络构建方法

针对静息态脑功能磁共振的血氧依赖水平信号中的非线性特征,在基于滑动窗口的动态数据分析技术的基础上,本文重点对构建全脑动态特征矩阵过程中的不同非线性相关分析方法展开了对比研究,并给出了构建脑网络中的阈值确定方法。脑网络降维和状态聚类实验结果显示,在阈值参数选择合理的前提下,采用三种非线性分析方法对BOLD信号进行的相关分析均可得到结构规模相似的脑网络,并且其状态转换结果均显现出相似的规律性,从而为下一步展开脑网络的动态特性分析和演化过程研究奠定了基础。      

Automatic classification of brain resting states using fMRI temporal signals

A novel technique is presented for the automatic discrimination between networks of `resting states? of the human brain and physiological fluctuations in functional magnetic resonance imaging (fMRI). The method is based on features identified via a statistical approach to group independent component analysis time courses, which may be extracted from fMRI data. This technique is entirely automatic and, unlike other approaches, uses temporal rather than spatial information. The method achieves 83% accuracy in the identification of resting state networks.     

A sparse and spatially constrained generative regression model for fMRI data analysis

In this study, we present an advanced Bayesian framework for the analysis of functional magnetic resonance imaging (fMRI) data that simultaneously employs both spatial and sparse properties. The basic building block of our method is the general linear regression model that constitutes a well-known probabilistic approach. By treating regression coefficients as random variables, we can apply an enhanced Gibbs distribution function that captures spatial constrains and at the same time allows sparse representation of fMRI time series. The proposed scheme is described as a maximum a posteriori approach, where the known expectation maximization algorithm is applied offering closed-form update equations for the model parameters. We have demonstrated that our method produces improved performance and functional activation detection capabilities in both simulated data and real applications.     

Independent Component Analysis Applied to fMRI Data: A Generative Model for Validating Results

Methods for testing and validating independent component analysis (ICA) results in fMRI are growing in importance as the popularity of this model for studying brain function increases. We introduce and apply a synthesis/analysis model for analyzing functional Magnetic Resonance Imaging (fMRI) data using ICA. Classes of signal types relevant to fMRI are described and a statistical approach for validation of simulation results is developed. Additionally, we propose an empirical version of our validation approach to test the performance of various ICA approaches in “hybrid” fMRI data, a mixture of real fMRI data and known (validatable) sources. The synthesis portion of the model assumes statistically independent spatial sources in the brain. We also assume that the fMRI scanner acquires overdetermined data such that there are more time points than hemodynamic brain sources. We propose several signal classes relevant to fMRI and discuss the properties of each. The analysis portion of the model includes several candidates for spatial smoothing, ICA algorithm, and data reduction. We use the Kullback-Leibler divergence between the estimated source distributions and the “true” distributions as a measure of the optimality of the final ICA decomposition. Using this model, we generate fMRI-like data and optimize the analysis stage as a function of ICA algorithm, data reduction scheme, and spatial smoothing. An example of how our synthesis/analysis model can be used in validating an fMRI experiment is demonstrated using simulations and “hybrid” fMRI data.     

A sparse Bayesian method for determination of flexible design matrix for fMRI data analysis

The construction of a design matrix is critical to the accurate detection of activation regions of the brain in functional magnetic resonance imaging (fMRI). The design matrix should be flexible to capture the unknown slowly varying drifts as well as robust enough to avoid overfitting. In this paper, a sparse Bayesian learning method is proposed to determine a suitable design matrix for fMRI data analysis. Based on a generalized linear model, this learning method lets the data itself determine the form of the regressors in the design matrix. It automatically finds those regressors that are relevant to the generation of the fMRI data and discards the others that are irrelevant. The proposed approach integrates the advantages of currently employed methods of fMRI data analysis (the model-driven and the data-driven methods). Results from the simulation studies clearly reveal the superiority of the proposed scheme to the conventional t-test method of fMRI data analysis.     

Kernel Granger Causality Mapping Effective Connectivity on fMRI Data

Although it is accepted that linear Granger causality can reveal effective connectivity in functional magnetic resonance imaging (fMRI), the issue of detecting nonlinear connectivity has hitherto not been considered. In this paper, we address kernel Granger causality (KGC) to describe effective connectivity in simulation studies and real fMRI data of a motor imagery task. Based on the theory of reproducing kernel Hilbert spaces, KGC performs linear Granger causality in the feature space of suitable kernel functions, assuming an arbitrary degree of nonlinearity. Our results demonstrate that KGC captures effective couplings not revealed by the linear case. In addition, effective connectivity networks between the supplementary motor area (SMA) as the seed and other brain areas are obtained from KGC.      

Joint Detection-Estimation of Brain Activity in Functional MRI: A Multichannel Deconvolution Solution

Analysis of functional magnetic resonance imaging (fMRI) data focuses essentially on two questions: first, a detection problem that studies which parts of the brain are activated by a given stimulus and, second, an estimation problem that investigates the temporal dynamic of the brain response during activations. Up to now, these questions have been addressed independently. However, the activated areas need to be known prior to the analysis of the temporal dynamic of the response. Similarly, a typical shape of the response has to be assumed a priori for detection purpose. This situation motivates the need for new methods in neuroimaging data analysis that are able to go beyond this unsatisfactory tradeoff. The present paper raises a novel detection-estimation approach to perform these two tasks simultaneously in region-based analysis. In the Bayesian framework, the detection of brain activity is achieved using a mixture of two Gaussian distributions as a prior model on the “neural” response levels, whereas the hemodynamic impulse response is constrained to be smooth enough in the time domain with a Gaussian prior. All parameters of interest, as well as hyperparameters, are estimated from the posterior distribution using Gibbs sampling and posterior mean estimates. Results obtained both on simulated and real fMRI data demonstrate first that our approach can segregate activated and nonactivated voxels in a given region of interest (ROI) and, second, that it can provide spatial activation maps without any assumption on the exact shape of the Hemodynamic Response Function (HRF), in contrast to standard model-based analysis.     

Group Study of Simulated Driving fMRI Data by Multiset Canonical Correlation Analysis

In this work, we apply a novel statistical method, multiset canonical correlation analysis (M-CCA), to study a group of functional magnetic resonance imaging (fMRI) datasets acquired during simulated driving task. The M-CCA method jointly decomposes fMRI datasets from different subjects/sessions into brain activation maps and their associated time courses, such that the correlation in each group of estimated activation maps across datasets is maximized. Therefore, the functional activations across all datasets are extracted in the order of consistency across different dataset. On the other hand, M-CCA preserves the uniqueness of the functional maps estimated from each dataset by avoiding concatenation of different datasets in the analysis. Hence, the cross-dataset variation of the functional activations can be used to test the hypothesis of functional-behavioral association. In this work, we study 120 simulated driving fMRI datasets and identify parietal-occipital regions and frontal lobe as the most consistently engaged areas across all the subjects and sessions during simulated driving. The functional-behavioral association study indicates that all the estimated brain activations are significantly correlated with the steering operation during the driving task. M-CCA thus provides a new approach to investigate the complex relationship between the brain functions and multiple behavioral variables, especially in naturalistic tasks as demonstrated by the simulated driving study.     

An integrated neighborhood correlation and hierarchical clustering approach of functional MRI

Clustering analysis is a promising data-driven method for the analysis of functional magnetic resonance imaging (fMRI) time series, however, the huge computation load makes it difficult for practical use. In this paper, neighborhood correlation (NC) and hierarchical clustering (HC) methods are integrated as a new approach where fMRI data are processed first by NC to get a preliminary image of brain activations, and then by HC to remove some noises. In HC, to better use spatial and temporal information in fMRI data, a new spatio-temporal measure is introduced. A simulation study and an application to visual fMRI data show that the brain activations can be effectively detected and that different response patterns can be discriminated. These results suggest that the proposed new integrated approach could be useful in detecting weak fMRI signals.     

Multivariate reconstruction of functional networks from cortical sources dynamics in MEG/EEG

In this paper, we present a simple method to find networks of time-correlated brain sources, using a singular value decomposition (SVD) analysis of the source matrix estimated after any linear distributed inverse problem in magnetoencephalography (MEG) and electroencephalography (EEG). Despite the high dimension of the source space, our method allows for the rapid computation of the source matrix. In order to do this, we use the linear relationship between sensors and sources, and show that the SVD can be calculated through a simple and fast computation. We show that this method allows the estimation of one or several global networks of correlated sources without calculating a coupling coefficient between all pairs of sources. A series of simulations studies were performed to estimate the efficiency of the method. In order to illustrate the validity of this approach in experimental conditions, we used real MEG data from a visual stimulation task on one test subject and estimated, in different time windows of interest, functional networks of correlated sources.     

A model selection method for nonlinear system identification based FMRI effective connectivity analysis

In this paper a model selection algorithm for a nonlinear system identification method is proposed to study functional magnetic resonance imaging (fMRI) effective connectivity. Unlike most other methods, this method does not need a pre-defined structure/model for effective connectivity analysis. Instead, it relies on selecting significant nonlinear or linear covariates for the differential equations to describe the mapping relationship between brain output (fMRI response) and input (experiment design). These covariates, as well as their coefficients, are estimated based on a least angle regression (LARS) method. In the implementation of the LARS method, Akaike's information criterion corrected (AICc) algorithm and the leave-one-out (LOO) cross-validation method were employed and compared for model selection. Simulation comparison between the dynamic causal model (DCM), nonlinear identification method, and model selection method for modelling the single-input-single-output (SISO) and multiple-input multiple-output (MIMO) systems were conducted. Results show that the LARS model selection method is faster than DCM and achieves a compact and economic nonlinear model simultaneously. To verify the efficacy of the proposed approach, an analysis of the dorsal and ventral visual pathway networks was carried out based on three real datasets. The results show that LARS can be used for model selection in an fMRI effective connectivity study with phase-encoded, standard block, and random block designs. It is also shown that the LOO cross-validation method for nonlinear model selection has less residual sum squares than the AICc algorithm for the study.     

A Connectivity-Based Method for Defining Regions-of-Interest in fMRI Data

In this paper, we describe a new methodology for defining brain regions-of-interset (ROIs) in functional magnetic resonance imaging (fMRI) data. The ROIs are defined based on their functional connectivity to other ROIs, i.e., ROIs are defined as sets of voxels with similar connectivity patterns to other ROIs. The method relies on 1) a spatially regularized canonical correlation analysis for identifying maximally correlated signals, which are not due to correlated noise; 2) a test for merging ROIs which have similar connectivity patterns to the other ROIs; and 3) a graph-cuts optimization for assigning voxels to ROIs. Since our method is fully connectivity-based, the extracted ROIs and their corresponding time signals are ideally suited for a subsequent brain connectivity analysis.      

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.     

基于fMRI功能网络和贝叶斯矩阵分解的脑电源成像方法

脑电(EEG)是一种重要的脑功能成像技术,根据头皮记录的EEG信号重构皮层脑活动称为EEG源成像。然而脑源活动位置和尺寸的准确重构依然是一个挑战。为充分利用EEG和功能磁共振(fMRI)信号在时空分辨率上的互补信息,该文提出一个新的源成像方法——基于fMRI脑网络和时空约束的EEG源重构算法(FN-STCSI)。该方法在参数贝叶斯框架下,基于矩阵分解思想将源信号分解为若干时间基函数的线性组合。此外,为融合fMRI的高空间分辨率信息,FN-STCSI利用独立成分分析提取fMRI信号的功能网络,构建EEG源成像的空间协方差基,通过变分贝叶斯推断技术确定每个空间协方差基的相对贡献,实现EEG-fMRI融合。通过蒙特卡罗数值仿真和实验数据分析比较了FN-STCSI与现有算法在不同信噪比和不同先验条件下的性能,结果表明FN-STCSI能有效融合EEG-fMRI在时空上的互补信息,提高EEG弥散源成像的性能。