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Zhengwu Zhang

Publications and source records attributed to Zhengwu Zhang.

At least 19 recordsLinked to original sources
arXiv2026

ConSEAL: Connectivity-Informed Streamline Endpoint Alignment for Diffeomorphic Cortical Registration

Cortical surface registration is often driven by local geometric descriptors (e.g., sulcal depth and curvature). While this approach achieves geometric correspondence, it neglects the long-range wiring constraints imposed by white-matter anatomy. Diffusion MRI tractography offers these crucial constraints; however, prior connectivity-informed pipelines typically align precomputed connectivity matrices, making the optimization highly sensitive to connectivity estimation and its resolution. In this paper, we introduce ConSEAL (Connectivity-Informed Streamline Endpoint Alignment), a novel connectivity-based surface registration method that aligns cortical surfaces by operating directly on white-matter fiber-tract endpoints. We model tract endpoints as a point cloud on the product manifold $Ω\times Ω$, where $Ω$ represents the spherical domain of the inflated cortical hemispheres. Our alignment method iteratively (i) computes a small diffeomorphic warp for $Ω$ by minimizing connectivity mismatch, and (ii) updates the endpoints based on this warp. The method relies on a geometric framework that ensures output warps are diffeomorphisms and has a final goal that optimizes the matching of well-known fiber bundles. Experiments on Human Connectome Project (HCP) data demonstrate that ConSEAL improves tract-level correspondence, achieving higher connectivity-level overlap coefficients on major fiber bundles and stronger robustness across grid resolutions for $Ω$ compared to state-of-the-art methods such as ENCORE and MSMAll.

cs.CV↗
arXiv2026

Attention-Based Variational Framework for Joint and Individual Components Learning with Applications in Brain Network Analysis

Brain organization is increasingly characterized through multiple imaging modalities, most notably structural connectivity (SC) and functional connectivity (FC). Integrating these inherently distinct yet complementary data sources is essential for uncovering the cross-modal patterns that drive behavioral phenotypes. However, effective integration is hindered by the high dimensionality and non-linearity of connectome data, complex non-linear SC-FC coupling, and the challenge of disentangling shared information from modality-specific variations. To address these issues, we propose the Cross-Modal Joint-Individual Variational Network (CM-JIVNet), a unified probabilistic framework designed to learn factorized latent representations from paired SC-FC datasets. Our model utilizes a multi-head attention fusion module to capture non-linear cross-modal dependencies while isolating independent, modality-specific signals. Validated on Human Connectome Project Young Adult (HCP-YA) data, CM-JIVNet demonstrates superior performance in cross-modal reconstruction and behavioral trait prediction. By effectively disentangling joint and individual feature spaces, CM-JIVNet provides a robust, interpretable, and scalable solution for large-scale multimodal brain analysis.

cs.LG↗
arXiv2025

NeuroPMD: Neural Fields for Density Estimation on Product Manifolds

We propose a novel deep neural network methodology for density estimation on product Riemannian manifold domains. In our approach, the network directly parameterizes the unknown density function and is trained using a penalized maximum likelihood framework, with a penalty term formed using manifold differential operators. The network architecture and estimation algorithm are carefully designed to handle the challenges of high-dimensional product manifold domains, effectively mitigating the curse of dimensionality that limits traditional kernel and basis expansion estimators, as well as overcoming the convergence issues encountered by non-specialized neural network methods. Extensive simulations and a real-world application to brain structural connectivity data highlight the clear advantages of our method over the competing alternatives.

stat.ML↗
arXiv2025

Alignment of Continuous Brain Connectivity

Brain networks are typically represented by adjacency matrices, where each node corresponds to a brain region. In traditional brain network analysis, nodes are assumed to be matched across individuals, but the methods used for node matching often overlook the underlying connectivity information. This oversight can result in inaccurate node alignment, leading to inflated edge variability and reduced statistical power in downstream connectivity analyses. To overcome this challenge, we propose a novel framework for registering high resolution continuous connectivity (ConCon), defined as a continuous function on a product manifold space specifically, the cortical surface capturing structural connectivity between all pairs of cortical points. Leveraging ConCon, we formulate an optimal diffeomorphism problem to align both connectivity profiles and cortical surfaces simultaneously. We introduce an efficient algorithm to solve this problem and validate our approach using data from the Human Connectome Project (HCP). Results demonstrate that our method substantially improves the accuracy and robustness of connectome-based analyses compared to existing techniques.

stat.ME↗
arXiv2024

Motion-Invariant Variational Auto-Encoding of Brain Structural Connectomes

Mapping of human brain structural connectomes via diffusion MRI offers a unique opportunity to understand brain structural connectivity and relate it to various human traits, such as cognition. However, head displacement during image acquisition can compromise the accuracy of connectome reconstructions and subsequent inference results. We develop a generative model to learn low-dimensional representations of structural connectomes invariant to motion-induced artifacts, so that we can link brain networks and human traits more accurately, and generate motion-adjusted connectomes. We apply the proposed model to data from the Adolescent Brain Cognitive Development (ABCD) study and the Human Connectome Project (HCP) to investigate how our motion-invariant connectomes facilitate understanding of the brain network and its relationship with cognition. Empirical results demonstrate that the proposed motion-invariant variational auto-encoder (inv-VAE) outperforms its competitors in various aspects. In particular, motion-adjusted structural connectomes are more strongly associated with a wide array of cognition-related traits than other approaches without motion adjustment.

q-bio.NC↗
arXiv2024

Multi-faceted Neuroimaging Data Integration via Analysis of Subspaces

Neuroimaging studies, such as the Human Connectome Project (HCP), often collect multi-faceted and multi-block data to study the complex human brain. However, these data are often analyzed in a pairwise fashion, which can hinder our understanding of how different brain-related measures interact with each other. In this study, we comprehensively analyze the multi-block HCP data using the Data Integration via Analysis of Subspaces (DIVAS) method. We integrate structural and functional brain connectivity, substance use, cognition, and genetics in an exhaustive five-block analysis. This gives rise to the important finding that genetics is the single data modality most predictive of brain connectivity, outside of brain connectivity itself. Nearly 14\% of the variation in functional connectivity (FC) and roughly 12\% of the variation in structural connectivity (SC) is attributed to shared spaces with genetics. Moreover, investigations of shared space loadings provide interpretable associations between particular brain regions and drivers of variability, such as alcohol consumption in the substance-use data block. Novel Jackstraw hypothesis tests are developed for the DIVAS framework to establish statistically significant loadings. For example, in the (FC, SC, and Substance Use) shared space, these novel hypothesis tests highlight largely negative functional and structural connections suggesting the brain's role in physiological responses to increased substance use. Furthermore, our findings have been validated using a subset of genetically relevant siblings or twins not studied in the main analysis.

q-bio.NC↗
arXiv2024

Unpaired Volumetric Harmonization of Brain MRI with Conditional Latent Diffusion

Multi-site structural MRI is increasingly used in neuroimaging studies to diversify subject cohorts. However, combining MR images acquired from various sites/centers may introduce site-related non-biological variations. Retrospective image harmonization helps address this issue, but current methods usually perform harmonization on pre-extracted hand-crafted radiomic features, limiting downstream applicability. Several image-level approaches focus on 2D slices, disregarding inherent volumetric information, leading to suboptimal outcomes. To this end, we propose a novel 3D MRI Harmonization framework through Conditional Latent Diffusion (HCLD) by explicitly considering image style and brain anatomy. It comprises a generalizable 3D autoencoder that encodes and decodes MRIs through a 4D latent space, and a conditional latent diffusion model that learns the latent distribution and generates harmonized MRIs with anatomical information from source MRIs while conditioned on target image style. This enables efficient volume-level MRI harmonization through latent style translation, without requiring paired images from target and source domains during training. The HCLD is trained and evaluated on 4,158 T1-weighted brain MRIs from three datasets in three tasks, assessing its ability to remove site-related variations while retaining essential biological features. Qualitative and quantitative experiments suggest the effectiveness of HCLD over several state-of-the-arts

eess.IV↗
arXiv2024

Nonparametric Modeling of Diffusion MRI Signal in Q-space

This paper describes a novel nonparametric model for modeling diffusion MRI signals in q-space. In q-space, diffusion MRI signal is measured for a sequence of magnetic strengths (b-values) and magnetic gradient directions (b-vectors). We propose a Poly-RBF model, which employs a bidirectional framework with polynomial bases to model the signal along the b-value direction and Gaussian radial bases across the b-vectors. The model can accommodate sparse data on b-values and moderately dense data on b-vectors. The utility of Poly-RBF is inspected for two applications: 1) prediction of the dMRI signal, and 2) harmonization of dMRI data collected under different acquisition protocols with different scanners. Our results indicate that the proposed Poly-RBF model can more accurately predict the unmeasured diffusion signal than its competitors such as the Gaussian process model in {\tt Eddy} of FSL. Applying it to harmonizing the diffusion signal can significantly improve the reproducibility of derived white matter microstructure measures.

stat.AP↗
arXiv2023

Joint Semi-Symmetric Tensor PCA for Integrating Multi-modal Populations of Networks

Multi-modal populations of networks arise in many scenarios including in large-scale multi-modal neuroimaging studies that capture both functional and structural neuroimaging data for thousands of subjects. A major research question in such studies is how functional and structural brain connectivity are related and how they vary across the population. we develop a novel PCA-type framework for integrating multi-modal undirected networks measured on many subjects. Specifically, we arrange these networks as semi-symmetric tensors, where each tensor slice is a symmetric matrix representing a network from an individual subject. We then propose a novel Joint, Integrative Semi-Symmetric Tensor PCA (JisstPCA) model, associated with an efficient iterative algorithm, for jointly finding low-rank representations of two or more networks across the same population of subjects. We establish one-step statistical convergence of our separate low-rank network factors as well as the shared population factors to the true factors, with finite sample statistical error bounds. Through simulation studies and a real data example for integrating multi-subject functional and structural brain connectivity, we illustrate the advantages of our method for finding joint low-rank structures in multi-modal populations of networks.

stat.ME↗
arXiv2023

Interpretable AI for relating brain structural and functional connectomes

One of the central problems in neuroscience is understanding how brain structure relates to function. Naively one can relate the direct connections of white matter fiber tracts between brain regions of interest (ROIs) to the increased co-activation in the same pair of ROIs, but the link between structural and functional connectomes (SCs and FCs) has proven to be much more complex. To learn a realistic generative model characterizing population variation in SCs, FCs, and the SC-FC coupling, we develop a graph auto-encoder that we refer to as Staf-GATE. We trained Staf-GATE with data from the Human Connectome Project (HCP) and show state-of-the-art performance in predicting FC and joint generation of SC and FC. In addition, as a crucial component of the proposed approach, we provide a masking-based algorithm to extract interpretable inferences about SC-FC coupling. Our interpretation methods identified important SC subnetworks for FC coupling and relating SC and FC with sex.

q-bio.NC↗
arXiv2023

Continuous and Atlas-free Analysis of Brain Structural Connectivity

Brain structural networks are often represented as discrete adjacency matrices with elements summarizing the connectivity between pairs of regions of interest (ROIs). These ROIs are typically determined a-priori using a brain atlas. The choice of atlas is often arbitrary and can lead to a loss of important connectivity information at the sub-ROI level. This work introduces an atlas-free framework that overcomes these issues by modeling brain connectivity using smooth random functions. In particular, we assume that the observed pattern of white matter fiber tract endpoints is driven by a latent random function defined over a product manifold domain. To facilitate statistical analysis of these high dimensional functional data objects, we develop a novel algorithm to construct a data-driven reduced-rank function space that offers a desirable trade-off between computational complexity and flexibility. Using real data from the Human Connectome Project, we show that our method outperforms state-of-the-art approaches that use the traditional atlas-based structural connectivity representation on a variety of connectivity analysis tasks. We further demonstrate how our method can be used to detect localized regions and connectivity patterns associated with group differences.

stat.CO↗
arXiv2023

Low Tree-Rank Bayesian Vector Autoregression Model

Vector autoregression has been widely used for modeling and analysis of multivariate time series data. In high-dimensional settings, model parameter regularization schemes inducing sparsity yield interpretable models and achieved good forecasting performance. However, in many data applications, such as those in neuroscience, the Granger causality graph estimates from existing vector autoregression methods tend to be quite dense and difficult to interpret, unless one compromises on the goodness-of-fit. To address this issue, this paper proposes to incorporate a commonly used structural assumption -- that the ground-truth graph should be largely connected, in the sense that it should only contain at most a few components. We take a Bayesian approach and develop a novel tree-rank prior distribution for the regression coefficients. Specifically, this prior distribution forces the non-zero coefficients to appear only on the union of a few spanning trees. Since each spanning tree connects $p$ nodes with only $(p-1)$ edges, it effectively achieves both high connectivity and high sparsity. We develop a computationally efficient Gibbs sampler that is scalable to large sample size and high dimension. In analyzing test-retest functional magnetic resonance imaging data, our model produces a much more interpretable graph estimate, compared to popular existing approaches. In addition, we show appealing properties of this new method, such as efficient computation, mild stability conditions and posterior consistency.

stat.ME↗
arXiv2023

High-dimensional Response Growth Curve Modeling for Longitudinal Neuroimaging Analysis

There is increasing interest in modeling high-dimensional longitudinal outcomes in applications such as developmental neuroimaging research. Growth curve model offers a useful tool to capture both the mean growth pattern across individuals, as well as the dynamic changes of outcomes over time within each individual. However, when the number of outcomes is large, it becomes challenging and often infeasible to tackle the large covariance matrix of the random effects involved in the model. In this article, we propose a high-dimensional response growth curve model, with three novel components: a low-rank factor model structure that substantially reduces the number of parameters in the large covariance matrix, a re-parameterization formulation coupled with a sparsity penalty that selects important fixed and random effect terms, and a computational trick that turns the inversion of a large matrix into the inversion of a stack of small matrices and thus considerably speeds up the computation. We develop an efficient expectation-maximization type estimation algorithm, and demonstrate the competitive performance of the proposed method through both simulations and a longitudinal study of brain structural connectivity in association with human immunodeficiency virus.

stat.ME↗
arXiv2022

Genetic underpinnings of brain structural connectome for young adults

With distinct advantages in power over behavioral phenotypes, brain imaging traits have become emerging endophenotypes to dissect molecular contributions to behaviors and neuropsychiatric illnesses. Among different imaging features, brain structural connectivity (i.e., structural connectome), which summarizes the anatomical connections between different brain regions, is one of the most cutting-edge while under-investigated traits; and the genetic influence on the structural connectome variation remains highly elusive. Relying on a landmark imaging genetics study for young adults, we develop a biologically plausible brain network response shrinkage model to comprehensively characterize the relationship between high dimensional genetic variants and the structural connectome phenotype. Under a unified Bayesian framework, we accommodate the topology of brain network and biological architecture within the genome; and eventually establish a mechanistic mapping between genetic biomarkers and the associated brain sub-network units. An efficient expectation-maximization algorithm is developed to estimate the model and ensure computing feasibility. In the application to the Human Connectome Project Young Adult (HCP-YA) data, we establish the genetic underpinnings which are highly interpretable under functional annotation and brain tissue eQTL analysis, for the brain white matter tracts connecting the hippocampus and two cerebral hemispheres. We also show the superiority of our method in extensive simulations.

stat.AP↗
arXiv2022

Tree Representations of Brain Structural Connectivity via Persistent Homology

The brain structural connectome is generated by a collection of white matter fiber bundles constructed from diffusion weighted MRI (dMRI), acting as highways for neural activity. There has been abundant interest in studying how the structural connectome varies across individuals in relation to their traits, ranging from age and gender to neuropsychiatric outcomes. After applying tractography to dMRI to get white matter fiber bundles, a key question is how to represent the brain connectome to facilitate statistical analyses relating connectomes to traits. The current standard divides the brain into regions of interest (ROIs), and then relies on an adjacency matrix (AM) representation. Each cell in the AM is a measure of connectivity, e.g., number of fiber curves, between a pair of ROIs. Although the AM representation is intuitive, a disadvantage is the high-dimensionality due to the large number of cells in the matrix. This article proposes a simpler tree representation of the brain connectome, which is motivated by ideas in computational topology and takes topological and biological information on the cortical surface into consideration. We demonstrate that our tree representation preserves useful information and interpretability, while reducing dimensionality to improve statistical and computational efficiency. Applications to data from the Human Connectome Project (HCP) are considered and code is provided for reproducing our analyses.

stat.ME↗
arXiv2022

Analyzing Brain Structural Connectivity as Continuous Random Functions

This work considers a continuous framework to characterize the population-level variability of structural connectivity. Our framework assumes the observed white matter fiber tract endpoints are driven by a latent random function defined over a product manifold domain. To overcome the computational challenges of analyzing such complex latent functions, we develop an efficient algorithm to construct a data-driven reduced-rank function space to represent the latent continuous connectivity. Using real data from the Human Connectome Project, we show that our method outperforms state-of-the-art approaches applied to the traditional atlas-based structural connectivity matrices on connectivity analysis tasks of interest. We also demonstrate how our method can be used to identify localized regions and connectivity patterns on the cortical surface associated with significant group differences. Code will be made available at https://github.com/sbci-brain.

stat.CO↗
arXiv2022

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.

stat.ME↗
arXiv2022

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.

stat.ML↗