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Zhengwu Zhang

Publications and source records attributed to Zhengwu Zhang.

At least 37 records · Page 2Linked to original sources

Outlier Detection for Multi-Network Data

It has become routine in neuroscience studies to measure brain networks for different individuals using neuroimaging. These networks are typically expressed as adjacency matrices, with each cell containing a summary of connectivity between a pair of brain regions. There is an emerging statistical literature describing methods for the analysis of such multi-network data in which nodes are common across networks but the edges vary. However, there has been essentially no consideration of the important problem of outlier detection. In particular, for certain subjects, the neuroimaging data are so poor quality that the network cannot be reliably reconstructed. For such subjects, the resulting adjacency matrix may be mostly zero or exhibit a bizarre pattern not consistent with a functioning brain. These outlying networks may serve as influential points, contaminating subsequent statistical analyses. We propose a simple Outlier DetectIon for Networks (ODIN) method relying on an influence measure under a hierarchical generalized linear model for the adjacency matrices. An efficient computational algorithm is described, and ODIN is illustrated through simulations and an application to data from the UK Biobank. ODIN was successful in identifying moderate to extreme outliers. Removing such outliers can significantly change inferences in downstream applications.

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Amplitude Mean of Functional Data on $\mathbb{S}^2$

Manifold-valued functional data analysis (FDA) recently becomes an active area of research motivated by the raising availability of trajectories or longitudinal data observed on non-linear manifolds. The challenges of analyzing such data come from many aspects, including infinite dimensionality and nonlinearity, as well as time-domain or phase variability. In this paper, we study the amplitude part of manifold-valued functions on $\mathbb{S}^2$, which is invariant to random time warping or re-parameterization. Utilizing the nice geometry of $\mathbb{S}^2$, we develop a set of efficient and accurate tools for temporal alignment of functions, geodesic computing, and sample mean calculation. At the heart of these tools, they rely on gradient descent algorithms with carefully derived gradients. We show the advantages of these newly developed tools over its competitors with extensive simulations and real data and demonstrate the importance of considering the amplitude part of functions instead of mixing it with phase variability in manifold-valued FDA.

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Learning to Model the Relationship Between Brain Structural and Functional Connectomes

Recent advances in neuroimaging along with algorithmic innovations in statistical learning from network data offer a unique pathway to integrate brain structure and function, and thus facilitate revealing some of the brain's organizing principles at the system level. In this direction, we develop a supervised graph representation learning framework to model the relationship between brain structural connectivity (SC) and functional connectivity (FC) via a graph encoder-decoder system, where the SC is used as input to predict empirical FC. A trainable graph convolutional encoder captures direct and indirect interactions between brain regions-of-interest that mimic actual neural communications, as well as to integrate information from both the structural network topology and nodal (i.e., region-specific) attributes. The encoder learns node-level SC embeddings which are combined to generate (whole brain) graph-level representations for reconstructing empirical FC networks. The proposed end-to-end model utilizes a multi-objective loss function to jointly reconstruct FC networks and learn discriminative graph representations of the SC-to-FC mapping for downstream subject (i.e., graph-level) classification. Comprehensive experiments demonstrate that the learnt representations of said relationship capture valuable information from the intrinsic properties of the subject's brain networks and lead to improved accuracy in classifying a large population of heavy drinkers and non-drinkers from the Human Connectome Project. Our work offers new insights on the relationship between brain networks that support the promising prospect of using graph representation learning to discover more about human brain activity and function.

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Optimized Diffusion Imaging for Brain Structural Connectome Analysis

High angular resolution diffusion imaging (HARDI) is a type of diffusion magnetic resonance imaging (dMRI) that measures diffusion signals on a sphere in q-space. It has been widely used in data acquisition for human brain structural connectome analysis. To more accurately estimate the structural connectome, dense samples in q-space are often acquired, potentially resulting in long scanning times and logistical challenges. This paper proposes a statistical method to select q-space directions optimally and estimate the local diffusion function from sparse observations. The proposed approach leverages relevant historical dMRI data to calculate a prior distribution to characterize local diffusion variability in each voxel in a template space. For a new subject to be scanned, the priors are mapped into the subject-specific coordinate and used to help select the best q-space samples. Simulation studies demonstrate big advantages over the existing HARDI sampling and analysis framework. We also applied the proposed method to the Human Connectome Project data and a dataset of aging adults with mild cognitive impairment. The results indicate that with very few q-space samples (e.g., 15 or 20), we can recover structural brain networks comparable to the ones estimated from 60 or more diffusion directions with the existing methods. n Connectome Project data demonstrate that our proposed method provides substantial advantages over its competitors.

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Auto-encoding brain networks with applications to analyzing large-scale brain imaging datasets

There has been huge interest in studying human brain connectomes inferred from different imaging modalities and exploring their relationship with human traits, such as cognition. Brain connectomes are usually represented as networks, with nodes corresponding to different regions of interest (ROIs) and edges to connection strengths between ROIs. Due to the high-dimensionality and non-Euclidean nature of networks, it is challenging to depict their population distribution and relate them to human traits. Current approaches focus on summarizing the network using either pre-specified topological features or principal components analysis (PCA). In this paper, building on recent advances in deep learning, we develop a nonlinear latent factor model to characterize the population distribution of brain graphs and infer the relationships between brain structural connectomes and human traits. We refer to our method as Graph AuTo-Encoding (GATE). We applied GATE to two large-scale brain imaging datasets, the Adolescent Brain Cognitive Development (ABCD) study and the Human Connectome Project (HCP) for adults, to understand the structural brain connectome and its relationship with cognition. Numerical results demonstrate huge advantages of GATE over competitors in terms of prediction accuracy, statistical inference and computing efficiency. We found that structural connectomes have a stronger association with a wide range of human cognitive traits than was apparent using previous approaches.

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Soft Tensor Regression

Statistical methods relating tensor predictors to scalar outcomes in a regression model generally vectorize the tensor predictor and estimate the coefficients of its entries employing some form of regularization, use summaries of the tensor covariate, or use a low dimensional approximation of the coefficient tensor. However, low rank approximations of the coefficient tensor can suffer if the true rank is not small. We propose a tensor regression framework which assumes a soft version of the parallel factors (PARAFAC) approximation. In contrast to classic PARAFAC, where each entry of the coefficient tensor is the sum of products of row-specific contributions across the tensor modes, the soft tensor regression (Softer) framework allows the row-specific contributions to vary around an overall mean. We follow a Bayesian approach to inference, and show that softening the PARAFAC increases model flexibility, leads to improved estimation of coefficient tensors, more accurate identification of important predictor entries, and more precise predictions, even for a low approximation rank. From a theoretical perspective, we show that employing Softer leads to a weakly consistent posterior distribution of the coefficient tensor, irrespective of the true or approximation tensor rank, a result that is not true when employing the classic PARAFAC for tensor regression. In the context of our motivating application, we adapt Softer to symmetric and semi-symmetric tensor predictors and analyze the relationship between brain network characteristics and human traits.soft

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High-Dimensional Spatial Quantile Function-on-Scalar Regression

This paper develops a novel spatial quantile function-on-scalar regression model, which studies the conditional spatial distribution of a high-dimensional functional response given scalar predictors. With the strength of both quantile regression and copula modeling, we are able to explicitly characterize the conditional distribution of the functional or image response on the whole spatial domain. Our method provides a comprehensive understanding of the effect of scalar covariates on functional responses across different quantile levels and also gives a practical way to generate new images for given covariate values. Theoretically, we establish the minimax rates of convergence for estimating coefficient functions under both fixed and random designs. We further develop an efficient primal-dual algorithm to handle high-dimensional image data. Simulations and real data analysis are conducted to examine the finite-sample performance.

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Multivariate functional responses low rank regression with an application to brain imaging data

We propose a multivariate functional responses low rank regression model with possible high dimensional functional responses and scalar covariates. By expanding the slope functions on a set of sieve basis, we reconstruct the basis coefficients as a matrix. To estimate these coefficients, we propose an efficient procedure using nuclear norm regularization. We also derive error bounds for our estimates and evaluate our method using simulations. We further apply our method to the Human Connectome Project neuroimaging data to predict cortical surface motor task-evoked functional magnetic resonance imaging signals using various clinical covariates to illustrate the usefulness of our results.

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Multi-scale graph principal component analysis for connectomics

In brain connectomics, the cortical surface is parcellated into different regions of interest (ROIs) prior to statistical analysis. The brain connectome for each individual can then be represented as a graph, with the nodes corresponding to ROIs and edges to connections between ROIs. Such a graph can be summarized as an adjacency matrix, with each cell containing the strength of connection between a pair of ROIs. These matrices are symmetric with the diagonal elements corresponding to self-connections typically excluded. A major disadvantage of such representations of the connectome is their sensitivity to the chosen ROIs, including critically the number of ROIs and hence the scale of the graph. As the scale becomes finer and more ROIs are used, graphs become increasingly sparse. Clearly, the results of downstream statistical analyses can be highly dependent on the chosen parcellation. To solve this problem, we propose a multi-scale graph factorization, which links together scale-specific factorizations through a common set of individual-specific scores. These scores summarize an individual's brain structure combining information across measurement scales. We obtain a simple and efficient algorithm for implementation, and illustrate substantial advantages over single scale approaches in simulations and analyses of the Human Connectome Project dataset.

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Bayesian Hierarchical Modeling on Covariance Valued Data

Analysis of structural and functional connectivity (FC) of human brains is of pivotal importance for diagnosis of cognitive ability. The Human Connectome Project (HCP) provides an excellent source of neural data across different regions of interest (ROIs) of the living human brain. Individual specific data were available from an existing analysis (Dai et al., 2017) in the form of time varying covariance matrices representing the brain activity as the subjects perform a specific task. As a preliminary objective of studying the heterogeneity of brain connectomics across the population, we develop a probabilistic model for a sample of covariance matrices using a scaled Wishart distribution. We stress here that our data units are available in the form of covariance matrices, and we use the Wishart distribution to create our likelihood function rather than its more common usage as a prior on covariance matrices. Based on empirical explorations suggesting the data matrices to have low effective rank, we further model the center of the Wishart distribution using an orthogonal factor model type decomposition. We encourage shrinkage towards a low rank structure through a novel shrinkage prior and discuss strategies to sample from the posterior distribution using a combination of Gibbs and slice sampling. We extend our modeling framework to a dynamic setting to detect change points. The efficacy of the approach is explored in various simulation settings and exemplified on several case studies including our motivating HCP data. We extend our modeling framework to a dynamic setting to detect change points.

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Learning Signal Subgraphs from Longitudinal Brain Networks with Symmetric Bilinear Logistic Regression

Modern neuroimaging technologies, combined with state-of-the-art data processing pipelines, have made it possible to collect longitudinal observations of an individual's brain connectome at different ages. It is of substantial scientific interest to study how brain connectivity varies over time in relation to human cognitive traits. In brain connectomics, the structural brain network for an individual corresponds to a set of interconnections among brain regions. We propose a symmetric bilinear logistic regression to learn a set of small subgraphs relevant to a binary outcome from longitudinal brain networks as well as estimating the time effects of the subgraphs. We enforce the extracted signal subgraphs to have clique structure which has appealing interpretations as they can be related to neurological circuits. The time effect of each signal subgraph reflects how its predictive effect on the outcome varies over time, which may improve our understanding of interactions between the aging of brain structure and neurological disorders. Application of this method on longitudinal brain connectomics and cognitive capacity data shows interesting discovery of relevant interconnections among a small set of brain regions in frontal and temporal lobes with better predictive performance than competitors.

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Analyzing Dynamical Brain Functional Connectivity As Trajectories on Space of Covariance Matrices

Human brain functional connectivity (FC) is often measured as the similarity of functional MRI responses across brain regions when a brain is either resting or performing a task. This paper aims to statistically analyze the dynamic nature of FC by representing the collective time-series data, over a set of brain regions, as a trajectory on the space of covariance matrices, or symmetric-positive definite matrices (SPDMs). We use a recently developed metric on the space of SPDMs for quantifying differences across FC observations, and for clustering and classification of FC trajectories. To facilitate large scale and high-dimensional data analysis, we propose a novel, metric-based dimensionality reduction technique to reduce data from large SPDMs to small SPDMs. We illustrate this comprehensive framework using data from the Human Connectome Project (HCP) database for multiple subjects and tasks, with task classification rates that match or outperform state-of-the-art techniques.

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Discovering Common Change-Point Patterns in Functional Connectivity Across Subjects

This paper studies change-points in human brain functional connectivity (FC) and seeks patterns that are common across multiple subjects under identical external stimulus. FC relates to the similarity of fMRI responses across different brain regions when the brain is simply resting or performing a task. While the dynamic nature of FC is well accepted, this paper develops a formal statistical test for finding {\it change-points} in times series associated with FC. It represents short-term connectivity by a symmetric positive-definite matrix, and uses a Riemannian metric on this space to develop a graphical method for detecting change-points in a time series of such matrices. It also provides a graphical representation of estimated FC for stationary subintervals in between the detected change-points. Furthermore, it uses a temporal alignment of the test statistic, viewed as a real-valued function over time, to remove inter-subject variability and to discover common change-point patterns across subjects. This method is illustrated using data from Human Connectome Project (HCP) database for multiple subjects and tasks.

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Symmetric Bilinear Regression for Signal Subgraph Estimation

There is increasing interest in learning a set of small outcome-relevant subgraphs in network-predictor regression. The extracted signal subgraphs can greatly improve the interpretation of the association between the network predictor and the response. In brain connectomics, the brain network for an individual corresponds to a set of interconnections among brain regions and there is a strong interest in linking the brain connectome to human cognitive traits. Modern neuroimaging technology allows a very fine segmentation of the brain, producing very large structural brain networks. Therefore, accurate and efficient methods for identifying a set of small predictive subgraphs become crucial, leading to discovery of key interconnected brain regions related to the trait and important insights on the mechanism of variation in human cognitive traits. We propose a symmetric bilinear model with $L_1$ penalty to search for small clique subgraphs that contain useful information about the response. A coordinate descent algorithm is developed to estimate the model where we derive analytical solutions for a sequence of conditional convex optimizations. Application of this method on human connectome and language comprehension data shows interesting discovery of relevant interconnections among several small sets of brain regions and better predictive performance than competitors.

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Tensor network factorizations: Relationships between brain structural connectomes and traits

Advanced brain imaging techniques make it possible to measure individuals' structural connectomes in large cohort studies non-invasively. The structural connectome is initially shaped by genetics and subsequently refined by the environment. It is extremely interesting to study relationships between structural connectomes and environment factors or human traits, such as substance use and cognition. Due to limitations in structural connectome recovery, previous studies largely focus on functional connectomes. Questions remain about how well structural connectomes can explain variance in different human traits. Using a state-of-the-art structural connectome processing pipeline and a novel dimensionality reduction technique applied to data from the Human Connectome Project (HCP), we show strong relationships between structural connectomes and various human traits. Our dimensionality reduction approach uses a tensor characterization of the connectome and relies on a generalization of principal components analysis. We analyze over 1100 scans for 1076 subjects from the HCP and the Sherbrooke test-retest data set, as well as $175$ human traits that measure domains including cognition, substance use, motor, sensory and emotion. We find that structural connectomes are associated with many traits. Specifically, fluid intelligence, language comprehension, and motor skills are associated with increased cortical-cortical brain structural connectivity, while the use of alcohol, tobacco, and marijuana are associated with decreased cortical-cortical connectivity.

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Robust Comparison of Kernel Densities on Spherical Domains

While spherical data arises in many contexts, including in directional statistics, the current tools for density estimation and population comparison on spheres are quite limited. Popular approaches for comparing populations (on Euclidean domains) mostly involvea two-step procedure: (1) estimate probability density functions (pdfs) from their respective samples, most commonly using the kernel density estimator, and, (2) compare pdfs using a metric such as the L2 norm. However, both the estimated pdfs and their differences depend heavily on the chosen kernels, bandwidths, and sample sizes. Here we develop a framework for comparing spherical populations that is robust to these choices. Essentially, we characterize pdfs on spherical domains by quantifying their smoothness. Our framework uses a spectral representation, with densities represented by their coefficients with respect to the eigenfunctions of the Laplacian operator on a sphere. The change in smoothness, akin to using different kernel bandwidths, is controlled by exponential decays in coefficient values. Then we derive a proper distance for comparing pdf coefficients while equalizing smoothness levels, negating influences of sample size and bandwidth. This signifies a fair and meaningful comparisons of populations, despite vastly different sample sizes, and leads to a robust and improved performance. We demonstrate this framework using examples of variables on S1 and S2, and evaluate its performance using a number of simulations and real data experiments.

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Common and Individual Structure of Brain Networks

This article focuses on the problem of studying shared- and individual-specific structure in replicated networks or graph-valued data. In particular, the observed data consist of $n$ graphs, $G_i, i=1,\ldots,n$, with each graph consisting of a collection of edges between $V$ nodes. In brain connectomics, the graph for an individual corresponds to a set of interconnections among brain regions. Such data can be organized as a $V \times V$ binary adjacency matrix $A_i$ for each $i$, with ones indicating an edge between a pair of nodes and zeros indicating no edge. When nodes have a shared meaning across replicates $i=1,\ldots,n$, it becomes of substantial interest to study similarities and differences in the adjacency matrices. To address this problem, we propose a method to estimate a common structure and low-dimensional individual-specific deviations from replicated networks. The proposed Multiple GRAph Factorization (M-GRAF) model relies on a logistic regression mapping combined with a hierarchical eigenvalue decomposition. We develop an efficient algorithm for estimation and study basic properties of our approach. Simulation studies show excellent operating characteristics and we apply the method to human brain connectomics data.

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Nonparametric Bayes Models of Fiber Curves Connecting Brain Regions

In studying structural inter-connections in the human brain, it is common to first estimate fiber bundles connecting different regions of the brain relying on diffusion MRI. These fiber bundles act as highways for neural activity and communication, snaking through the brain and connecting different regions. Current statistical methods for analyzing these fibers reduce the rich information into an adjacency matrix, with the elements containing a count of the number of fibers or a mean diffusion feature (such as fractional anisotropy) along the fibers. The goal of this article is to avoid discarding the rich functional data on the shape, size and orientation of fibers, developing flexible models for characterizing the population distribution of fibers between brain regions of interest within and across different individuals. We start by decomposing each fiber in each individual's brain into a corresponding rotation matrix, shape and translation from a global reference curve. These components can be viewed as data lying on a product space composed of different Euclidean spaces and manifolds. To non-parametrically model the distribution within and across individuals, we rely on a hierarchical mixture of product kernels specific to the component spaces. Taking a Bayesian approach to inference, we develop an efficient method for posterior sampling. The approach automatically produces clusters of fibers within and across individuals, and yields interesting new insights into variation in fiber curves, while providing a useful starting point for more elaborate models relating fibers to covariates and neuropsychiatric traits.

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