arXiv subjects

Guorong Wu

Publications and source records attributed to Guorong Wu.

47 records · Page 3Linked to original sources

arXiv2023

Uncovering the System Vulnerability and Criticality of Human Brain under Dynamical Neuropathological Events in Alzheimer's Disease

Background: Despite the striking efforts in investigating neurobiological factors behind the acquisition of amyloid-\b{eta} (A), protein tau (T), and neurodegeneration ([N]) biomarkers, the mechanistic pathways of how AT[N] biomarkers spreading throughout the brain remain elusive. Objectives: To disentangle the massive heterogeneities in AD progressions and identify vulnerable/critical brain regions to AD pathology. Methods: In this work, we characterized the interaction of AT[N] biomarkers and their propagation across brain networks using a novel bistable reaction-diffusion model, which allows us to establish a new systems biology underpinning of Alzheimer's disease (AD) progression. We applied our model to large-scale longitudinal neuroimages from the ADNI database and studied the systematic vulnerability and criticality of brains. Results: Our model yields long term prediction that is statistically significant linear correlated with temporal imaging data, produces clinically consistent risk prediction, and captures the Braak-like spreading pattern of AT[N] biomarkers in AD development. Conclusion: Our major findings include (i) tau is a stronger indicator of regional risk compared to amyloid, (ii) temporal lobe exhibits higher vulnerability to AD-related pathologies, (iii) proposed critical brain regions outperform hub nodes in transmitting disease factors across the brain, and (iv) comparing the spread of neuropathological burdens caused by amyloid-\b{eta} and tau diffusions, disruption of metabolic balance is the most determinant factor contributing to the initiation and progression of Alzheimer's disease.

q-bio.QM↗

arXiv2023

Correlation networks, dynamic factor models and community detection

A dynamic factor model with a mixture distribution of the loadings is introduced and studied for multivariate, possibly high-dimensional time series. The correlation matrix of the model exhibits a block structure, reminiscent of correlation patterns for many real multivariate time series. A standard $k$-means algorithm on the loadings estimated through principal components is used to cluster component time series into communities with accompanying bounds on the misclustering rate. This is one standard method of community detection applied to correlation matrices viewed as weighted networks. This work puts a mixture model, a dynamic factor model and network community detection in one interconnected framework. Performance of the proposed methodology is illustrated on simulated and real data.

stat.ME↗

arXiv2023

Re-Think and Re-Design Graph Neural Networks in Spaces of Continuous Graph Diffusion Functionals

Graph neural networks (GNNs) are widely used in domains like social networks and biological systems. However, the locality assumption of GNNs, which limits information exchange to neighboring nodes, hampers their ability to capture long-range dependencies and global patterns in graphs. To address this, we propose a new inductive bias based on variational analysis, drawing inspiration from the Brachistochrone problem. Our framework establishes a mapping between discrete GNN models and continuous diffusion functionals. This enables the design of application-specific objective functions in the continuous domain and the construction of discrete deep models with mathematical guarantees. To tackle over-smoothing in GNNs, we analyze the existing layer-by-layer graph embedding models and identify that they are equivalent to l2-norm integral functionals of graph gradients, which cause over-smoothing. Similar to edge-preserving filters in image denoising, we introduce total variation (TV) to align the graph diffusion pattern with global community topologies. Additionally, we devise a selective mechanism to address the trade-off between model depth and over-smoothing, which can be easily integrated into existing GNNs. Furthermore, we propose a novel generative adversarial network (GAN) that predicts spreading flows in graphs through a neural transport equation. To mitigate vanishing flows, we customize the objective function to minimize transportation within each community while maximizing inter-community flows. Our GNN models achieve state-of-the-art (SOTA) performance on popular graph learning benchmarks such as Cora, Citeseer, and Pubmed.

cs.LG↗

arXiv2021

Analyzing the Spatiotemporal Interaction and Propagation of ATN Biomarkers in Alzheimer's Disease using Longitudinal Neuroimaging Data

Three major biomarkers: beta-amyloid (A), pathologic tau (T), and neurodegeneration (N), are recognized as valid proxies for neuropathologic changes of Alzheimer's disease. While there are extensive studies on cerebrospinal fluids biomarkers (amyloid, tau), the spatial propagation pattern across brain is missing and their interactive mechanisms with neurodegeneration are still unclear. To this end, we aim to analyze the spatiotemporal associations between ATN biomarkers using large-scale neuroimaging data. We first investigate the temporal appearances of amyloid plaques, tau tangles, and neuronal loss by modeling the longitudinal transition trajectories. Second, we propose linear mixed-effects models to quantify the pathological interactions and propagation of ATN biomarkers at each brain region. Our analysis of the current data shows that there exists a temporal latency in the build-up of amyloid to the onset of tau pathology and neurodegeneration. The propagation pattern of amyloid can be characterized by its diffusion along the topological brain network. Our models provide sufficient evidence that the progression of pathological tau and neurodegeneration share a strong regional association, which is different from amyloid.

q-bio.QM↗

arXiv2020

A Network-Guided Reaction-Diffusion Model of AT[N] Biomarkers in Alzheimer's Disease

Currently, many studies of Alzheimer's disease (AD) are investigating the neurobiological factors behind the acquisition of beta-amyloid (A), pathologic tau (T), and neurodegeneration ([N]) biomarkers from neuroimages. However, a system-level mechanism of how these neuropathological burdens promote neurodegeneration and why AD exhibits characteristic progression is largely elusive. In this study, we combined the power of systems biology and network neuroscience to understand the dynamic interaction and diffusion process of AT[N] biomarkers from an unprecedented amount of longitudinal Amyloid PET scan, MRI imaging, and DTI data. Specifically, we developed a network-guided biochemical model to jointly (1) model the interaction of AT[N] biomarkers at each brain region and (2) characterize their propagation pattern across the fiber pathways in the structural brain network, where the brain resilience is also considered as a moderator of cognitive decline. Our biochemical model offers a greater mathematical insight to understand the physiopathological mechanism of AD progression by studying the system dynamics and stability. Thus, an in-depth system-level analysis allows us to gain a new understanding of how AT[N] biomarkers spread throughout the brain, capture the early sign of cognitive decline, and predict the AD progression from the preclinical stage.

q-bio.NC↗

arXiv2020

Learning Common Harmonic Waves on Stiefel Manifold -- A New Mathematical Approach for Brain Network Analyses

Converging evidence shows that disease-relevant brain alterations do not appear in random brain locations, instead, its spatial pattern follows large scale brain networks. In this context, a powerful network analysis approach with a mathematical foundation is indispensable to understand the mechanism of neuropathological events spreading throughout the brain. Indeed, the topology of each brain network is governed by its native harmonic waves, which are a set of orthogonal bases derived from the Eigen-system of the underlying Laplacian matrix. To that end, we propose a novel connectome harmonic analysis framework to provide enhanced mathematical insights by detecting frequency-based alterations relevant to brain disorders. The backbone of our framework is a novel manifold algebra appropriate for inference across harmonic waves that overcomes the limitations of using classic Euclidean operations on irregular data structures. The individual harmonic difference is measured by a set of common harmonic waves learned from a population of individual Eigen systems, where each native Eigen-system is regarded as a sample drawn from the Stiefel manifold. Specifically, a manifold optimization scheme is tailored to find the common harmonic waves which reside at the center of Stiefel manifold. To that end, the common harmonic waves constitute the new neuro-biological bases to understand disease progression. Each harmonic wave exhibits a unique propagation pattern of neuro-pathological burdens spreading across brain networks. The statistical power of our novel connectome harmonic analysis approach is evaluated by identifying frequency-based alterations relevant to Alzheimer's disease, where our learning-based manifold approach discovers more significant and reproducible network dysfunction patterns compared to Euclidian methods.

eess.IV↗

arXiv2016

Synergetic and redundant information flow detected by unnormalized Granger causality: application to resting state fMRI

Objectives: We develop a framework for the analysis of synergy and redundancy in the pattern of information flow between subsystems of a complex network. Methods: The presence of redundancy and/or synergy in multivariate time series data renders difficult to estimate the neat flow of information from each driver variable to a given target. We show that adopting an unnormalized definition of Granger causality one may put in evidence redundant multiplets of variables influencing the target by maximizing the total Granger causality to a given target, over all the possible partitions of the set of driving variables. Consequently we introduce a pairwise index of synergy which is zero when two independent sources additively influence the future state of the system, differently from previous definitions of synergy. Results: We report the application of the proposed approach to resting state fMRI data from the Human Connectome Project, showing that redundant pairs of regions arise mainly due to space contiguity and interhemispheric symmetry, whilst synergy occurs mainly between non-homologous pairs of regions in opposite hemispheres. Conclusions: Redundancy and synergy, in healthy resting brains, display characteristic patterns, revealed by the proposed approach. Significance: The pairwise synergy index, here introduced, maps the informational character of the system at hand into a weighted complex network: the same approach can be applied to other complex systems whose normal state corresponds to a balance between redundant and synergetic circuits.

cs.IT↗

arXiv2014

Beam energy distribution influences on density modulation efficiency in seeded free-electron lasers

The beam energy spread at the entrance of undulator system is of paramount importance for efficient density modulation in high-gain seeded free-electron lasers (FELs). In this paper, the dependences of high harmonic micro-bunching in the high-gain harmonic generation (HGHG), echo-enabled harmonic generation (EEHG) and phase-merging enhanced harmonic generation (PEHG) schemes on the electron energy spread distribution are studied. Theoretical investigations and multi-dimensional numerical simulations are applied to the cases of uniform and saddle beam energy distributions and compared to a traditional Gaussian distribution. It shows that the uniform and saddle electron energy distributions significantly enhance the performance of HGHG-FELs, while they almost have no influence on EEHG and PEHG schemes. A numerical example demonstrates that, with about 84keV RMS uniform and/or saddle slice energy spread, the 30th harmonic radiation can be directly generated by a single-stage seeding scheme for a soft x-ray FEL facility.

physics.acc-ph↗

arXiv2013

Point-process deconvolution of fMRI reveals effective connectivity alterations in chronic pain patients

It is now recognized that important information can be extracted from the brain spontaneous activity, as exposed by recent analysis using a repertoire of computational methods. In this context a novel method, based on a blind deconvolution technique, is used in this paper to analyze potential changes due to chronic pain in the brain pain matrix's effective connectivity. The approach is able to deconvolve the hemodynamic response function to spontaneous neural events, i.e., in the absence of explicit onset timings, and to evaluate information transfer between two regions as a joint probability of the occurrence of such spontaneous events. The method revealed that the chronic pain patients exhibit important changes in the Insula's effective connectivity which can be relevant to understand the overall impact of chronic pain on brain function.

q-bio.NC↗

arXiv2013

Information transfer of an Ising model on a brain network

We implement the Ising model on a structural connectivity matrix describing the brain at a coarse scale. Tuning the model temperature to its critical value, i.e. at the susceptibility peak, we find a maximal amount of total information transfer between the spin variables. At this point the amount of information that can be redistributed by some nodes reaches a limit and the net dynamics exhibits signature of the law of diminishing marginal returns, a fundamental principle connected to saturated levels of production. Our results extend the recent analysis of dynamical oscillators models on the connectome structure, taking into account lagged and directional influences, focusing only on the nodes that are more prone to became bottlenecks of information. The ratio between the outgoing and the incoming information at each node is related to the number of incoming links.

q-bio.NC↗

arXiv2012

Information flow in a network model and the law of diminishing marginal returns

We analyze a simple dynamical network model which describes the limited capacity of nodes to process the input information. For a suitable choice of the parameters, the information flow pattern is characterized by exponential distribution of the incoming information and a fat-tailed distribution of the outgoing information, as a signature of the law of diminishing marginal returns. The analysis of a real EEG data-set shows that similar phenomena may be relevant for brain signals.

physics.data-an↗