Hernando Ombao

Hwa Hui Tew, Junn Yong Loo, Fang Yu Leong et al.

Functional Magnetic Resonance Imaging (fMRI) provides non-invasive access to dynamic brain activity by measuring blood oxygen level-dependent (BOLD) signals over time. However, the resource-intensive nature of fMRI acquisition limits the availability of high-fidelity samples required for data-driven brain analysis models. While modern generative models can synthesize fMRI data, they often remain challenging in replicating their inherent non-stationarity, intricate spatiotemporal dynamics, and physiological variations of raw BOLD signals. To address these challenges, we propose Dual-Spectral Flow Matching (DSFM), a novel fMRI generative framework that cascades dual frequency representation of BOLD signals with spectral flow matching. Specifically, our framework first converts BOLD signals into a wavelet decomposition map via a discrete wavelet transform (DWT) to capture globalized transient and multi-scale variations, and projects into the discrete cosine transform (DCT) space across brain regions and time to exploit localized energy compaction of low-frequency dominant BOLD coefficients. Subsequently, a spectral flow matching model is trained to generate class-conditioned cosine-frequency representation. The generated samples are reconstructed through inverse DCT and inverse DWT operations to recover physiologically plausible time-domain BOLD signals. This dual-transform approach imposes structured frequency priors and preserves key physiological brain dynamics. Ultimately, we demonstrate the efficacy of our approach through improved downstream fMRI-based brain network classification. The code is available at https://github.com/htew0001/DSFM.git .

Yee-Fan Tan, Chee-Ming Ting, Fuad Noman et al.

Common measures of brain functional connectivity (FC) including covariance and correlation matrices are semi-positive definite (SPD) matrices residing on a cone-shape Riemannian manifold. Despite its remarkable success for Euclidean-valued data generation, use of standard generative adversarial networks (GANs) to generate manifold-valued FC data neglects its inherent SPD structure and hence the inter-relatedness of edges in real FC. We propose a novel graph-regularized manifold-aware conditional Wasserstein GAN (GR-SPD-GAN) for FC data generation on the SPD manifold that can preserve the global FC structure. Specifically, we optimize a generalized Wasserstein distance between the real and generated SPD data under an adversarial training, conditioned on the class labels. The resulting generator can synthesize new SPD-valued FC matrices associated with different classes of brain networks, e.g., brain disorder or healthy control. Furthermore, we introduce additional population graph-based regularization terms on both the SPD manifold and its tangent space to encourage the generator to respect the inter-subject similarity of FC patterns in the real data. This also helps in avoiding mode collapse and produces more stable GAN training. Evaluated on resting-state functional magnetic resonance imaging (fMRI) data of major depressive disorder (MDD), qualitative and quantitative results show that the proposed GR-SPD-GAN clearly outperforms several state-of-the-art GANs in generating more realistic fMRI-based FC samples. When applied to FC data augmentation for MDD identification, classification models trained on augmented data generated by our approach achieved the largest margin of improvement in classification accuracy among the competing GANs over baselines without data augmentation.

Malik Shahid Sultan, Samuel Horvath, Hernando Ombao

Dependence between nodes in a network is an important concept that pervades many areas including finance, politics, sociology, genomics and the brain sciences. One way to characterize dependence between components of a multivariate time series data is via Granger Causality (GC). Standard traditional approaches to GC estimation / inference commonly assume linear dynamics, however such simplification does not hold in many real-world applications where signals are inherently non-linear. In such cases, imposing linear models such as vector autoregressive (VAR) models can lead to mis-characterization of true Granger Causal interactions. To overcome this limitation, Tank et al (IEEE Transactions on Pattern Analysis and Machine Learning, 2022) proposed a solution that uses neural networks with sparse regularization penalties. The regularization encourages learnable weights to be sparse, which enables inference on GC. This paper overcomes the limitations of current methods by leveraging advances in machine learning and deep learning which have been demonstrated to learn hidden patterns in the data. We propose novel classes of models that can handle underlying non-linearity in a computationally efficient manner, simultaneously providing GC and lag order selection. Firstly, we present the Learned Kernel VAR (LeKVAR) model that learns kernel parameterized by a shared neural net followed by penalization on learnable weights to discover GC structure. Secondly, we show one can directly decouple lags and individual time series importance via decoupled penalties. This is important as we want to select the lag order during the process of GC estimation. This decoupling acts as a filtering and can be extended to any DL model including Multi-Layer Perceptrons (MLP), Recurrent Neural Networks (RNN), Long Short Term Memory Networks (LSTM), Transformers etc, for simultaneous GC estimation and lag selection.

Sarbojit Roy, Malik Shahid Sultan, Hernando Ombao

Interpretable classification of time series presents significant challenges in high dimensions. Traditional feature selection methods in the frequency domain often assume sparsity in spectral density matrices (SDMs) or their inverses, which can be restrictive for real-world applications. In this article, we propose a model-based approach for classifying high-dimensional stationary time series by assuming sparsity in the difference between inverse SDMs. Our approach emphasizes the interpretability of model parameters, making it especially suitable for fields like neuroscience, where understanding differences in brain network connectivity across various states is crucial. The estimators for model parameters demonstrate consistency under appropriate conditions. We further propose using standard deep learning optimizers for parameter estimation, employing techniques such as mini-batching and learning rate scheduling. Additionally, we introduce a method to screen the most discriminatory frequencies for classification, which exhibits the sure screening property under general conditions. The flexibility of the proposed model allows the significance of covariates to vary across frequencies, enabling nuanced inferences and deeper insights into the underlying problem. The novelty of our method lies in the interpretability of the model parameters, addressing critical needs in neuroscience. The proposed approaches have been evaluated on simulated examples and the `Alert-vs-Drowsy' EEG dataset.

Md Nurul Muttakin, Malik Shahid Sultan, Robert Hoehndorf et al.

Generative Adversarial Networks are used for generating the data using a generator and a discriminator, GANs usually produce high-quality images, but training GANs in an adversarial setting is a difficult task. GANs require high computation power and hyper-parameter regularization for converging. Projected GANs tackle the training difficulty of GANs by using transfer learning to project the generated and real samples into a pre-trained feature space. Projected GANs improve the training time and convergence but produce artifacts in the generated images which reduce the quality of the generated samples, we propose an optimized architecture called Stylized Projected GANs which integrates the mapping network of the Style GANs with Skip Layer Excitation of Fast GAN. The integrated modules are incorporated within the generator architecture of the Fast GAN to mitigate the problem of artifacts in the generated images.

Yee-Fan Tan, Jun Lin Liow, Pei-Sze Tan et al.

Modern brain imaging technologies have enabled the detailed reconstruction of human brain connectomes, capturing structural connectivity (SC) from diffusion MRI and functional connectivity (FC) from functional MRI. Understanding the intricate relationships between SC and FC is vital for gaining deeper insights into the brain's functional and organizational mechanisms. However, obtaining both SC and FC modalities simultaneously remains challenging, hindering comprehensive analyses. Existing deep generative models typically focus on synthesizing a single modality or unidirectional translation between FC and SC, thereby missing the potential benefits of bi-directional translation, especially in scenarios where only one connectome is available. Therefore, we propose Structural-Functional Connectivity GAN (SFC-GAN), a novel framework for bidirectional translation between SC and FC. This approach leverages the CycleGAN architecture, incorporating convolutional layers to effectively capture the spatial structures of brain connectomes. To preserve the topological integrity of these connectomes, we employ a structure-preserving loss that guides the model in capturing both global and local connectome patterns while maintaining symmetry. Our framework demonstrates superior performance in translating between SC and FC, outperforming baseline models in similarity and graph property evaluations compared to ground truth data, each translated modality can be effectively utilized for downstream classification.

Hwa Hui Tew, Junn Yong Loo, Yee-Fan Tan et al.

Functional Magnetic Resonance Imaging (fMRI) is an advanced neuroimaging method that enables in-depth analysis of brain activity by measuring dynamic changes in the blood oxygenation level-dependent (BOLD) signals. However, the resource-intensive nature of fMRI data acquisition limits the availability of high-fidelity samples required for data-driven brain analysis models. While modern generative models can synthesize fMRI data, they often underperform because they overlook the complex non-stationarity and nonlinear BOLD dynamics. To address these challenges, we introduce T2I-Diff, an fMRI generation framework that leverages time-frequency representation of BOLD signals and classifier-free denoising diffusion. Specifically, our framework first converts BOLD signals into windowed spectrograms via a time-dependent Fourier transform, capturing both the underlying temporal dynamics and spectral evolution. Subsequently, a classifier-free diffusion model is trained to generate class-conditioned frequency spectrograms, which are then reverted to BOLD signals via inverse Fourier transforms. Finally, we validate the efficacy of our approach by demonstrating improved accuracy and generalization in downstream fMRI-based brain network classification.

Mohammad Mehedi Hasan, Pedro G. Lind, Hernando Ombao et al.

Dementia (DEM) is a growing global health challenge, underscoring the need for early and accurate diagnosis. Electroencephalography (EEG) provides a non-invasive window into brain activity, but conventional methods struggle to capture its transient complexity. We present the \textbf{EEG Microstate Analysis Framework (EEG-MSAF)}, an end-to-end pipeline that leverages EEG microstates discrete, quasi-stable topographies to identify DEM-related biomarkers and distinguish DEM, mild cognitive impairment (MCI), and normal cognition (NC). EEG-MSAF comprises three stages: (1) automated microstate feature extraction, (2) classification with machine learning (ML), and (3) feature ranking using Shapley Additive Explanations (SHAP) to highlight key biomarkers. We evaluate on two EEG datasets: the public Chung-Ang University EEG (CAUEEG) dataset and a clinical cohort from Thessaloniki Hospital. Our framework demonstrates strong performance and generalizability. On CAUEEG, EEG-MSAF-SVM achieves \textbf{89\% $\pm$ 0.01 accuracy}, surpassing the deep learning baseline CEEDNET by \textbf{19.3\%}. On the Thessaloniki dataset, it reaches \textbf{95\% $\pm$ 0.01 accuracy}, comparable to EEGConvNeXt. SHAP analysis identifies mean correlation and occurrence as the most informative metrics: disruption of microstate C (salience/attention network) dominates DEM prediction, while microstate F, a novel default-mode pattern, emerges as a key early biomarker for both MCI and DEM. By combining accuracy, generalizability, and interpretability, EEG-MSAF advances EEG-based dementia diagnosis and sheds light on brain dynamics across the cognitive spectrum.

Malik Shahid Sultan, Hernando Ombao

Granger Causality (GC) offers an elegant statistical framework to study the association between multivariate time series data. Linear Vector Autoregressive models (VAR) though have nice interpretation properties but have limited practical application due to underlying assumptions on the kind of associations that can be captured by these models. Numerous attempts have already been made in the literature that exploit the functional approximation power of Deep Neural Networks (DNNs) for the task of GC estimation. These methods however treat GC as a variable selection problem. We present a novel paradigm for approaching GC. We present this idea that GC is essentially linked with prediction and if a deep learning model is used to model the time series collectively or jointly, a well regularized model may learn the true granger causal structure from the data, given that there is enough training data. We propose to uncover the learned GC structure by comparing the model uncertainty or distribution of the residuals when the past of everything is used as compared to the one where a specific time series component is dropped from the model. We also compare the effect of input layer dropout on the ability of a neural network to learn granger causality from the data. We show that a well regularized model infact can learn the true GC structure from the data without explicitly adding terms in the loss function that guide the model to select variables or perform sparse regression.

Chee-Ming Ting, Fuad Noman, Raphaël C. -W. Phan et al.

The low-rank plus sparse (L+S) decomposition model has enabled better reconstruction of dynamic magnetic resonance imaging (dMRI) with separation into background (L) and dynamic (S) component. However, use of low-rank prior alone may not fully explain the slow variations or smoothness of the background part at the local scale. In this paper, we propose a smoothness-regularized L+S (SR-L+S) model for dMRI reconstruction from highly undersampled k-t-space data. We exploit joint low-rank and smooth priors on the background component of dMRI to better capture both its global and local temporal correlated structures. Extending the L+S formulation, the low-rank property is encoded by the nuclear norm, while the smoothness by a general \ell_{p}-norm penalty on the local differences of the columns of L. The additional smoothness regularizer can promote piecewise local consistency between neighboring frames. By smoothing out the noise and dynamic activities, it allows accurate recovery of the background part, and subsequently more robust dMRI reconstruction. Extensive experiments on multi-coil cardiac and synthetic data shows that the SR-L+S model outp

Fuad Noman, Chee-Ming Ting, Hakmook Kang et al.

Brain functional connectivity (FC) reveals biomarkers for identification of various neuropsychiatric disorders. Recent application of deep neural networks (DNNs) to connectome-based classification mostly relies on traditional convolutional neural networks using input connectivity matrices on a regular Euclidean grid. We propose a graph deep learning framework to incorporate the non-Euclidean information about graph structure for classifying functional magnetic resonance imaging (fMRI)-derived brain networks in major depressive disorder (MDD). We design a novel graph autoencoder (GAE) architecture based on the graph convolutional networks (GCNs) to embed the topological structure and node content of large-sized fMRI networks into low-dimensional latent representations. In network construction, we employ the Ledoit-Wolf (LDW) shrinkage method to estimate the high-dimensional FC metrics efficiently from fMRI data. We consider both supervised and unsupervised approaches for the graph embedding learning. The learned embeddings are then used as feature inputs for a deep fully-connected neural network (FCNN) to discriminate MDD from healthy controls. Evaluated on two resting-state fMRI (rs-fMRI) MDD datasets, results show that the proposed GAE-FCNN model significantly outperforms several state-of-the-art methods for brain connectome classification, achieving the best accuracy using the LDW-FC edges as node features. The graph embeddings of fMRI FC networks learned by the GAE also reveal apparent group differences between MDD and HC. Our new framework demonstrates feasibility of learning graph embeddings on brain networks to provide discriminative information for diagnosis of brain disorders.

Moo K. Chung, Hernando Ombao

Persistent homology has undergone significant development in recent years. However, one outstanding challenge is to build a coherent statistical inference procedure on persistent diagrams. In this paper, we first present a new lattice path representation for persistent diagrams. We then develop a new exact statistical inference procedure for lattice paths via combinatorial enumerations. The lattice path method is applied to the topological characterization of the protein structures of the COVID-19 virus. We demonstrate that there are topological changes during the conformational change of spike proteins.

Chee-Ming Ting, Jeremy I. Skipper, Steven L. Small et al.

We consider the challenges in extracting stimulus-related neural dynamics from other intrinsic processes and noise in naturalistic functional magnetic resonance imaging (fMRI). Most studies rely on inter-subject correlations (ISC) of low-level regional activity and neglect varying responses in individuals. We propose a novel, data-driven approach based on low-rank plus sparse (L+S) decomposition to isolate stimulus-driven dynamic changes in brain functional connectivity (FC) from the background noise, by exploiting shared network structure among subjects receiving the same naturalistic stimuli. The time-resolved multi-subject FC matrices are modeled as a sum of a low-rank component of correlated FC patterns across subjects, and a sparse component of subject-specific, idiosyncratic background activities. To recover the shared low-rank subspace, we introduce a fused version of principal component pursuit (PCP) by adding a fusion-type penalty on the differences between the rows of the low-rank matrix. The method improves the detection of stimulus-induced group-level homogeneity in the FC profile while capturing inter-subject variability. We develop an efficient algorithm via a linearized alternating direction method of multipliers to solve the fused-PCP. Simulations show accurate recovery by the fused-PCP even when a large fraction of FC edges are severely corrupted. When applied to natural fMRI data, our method reveals FC changes that were time-locked to auditory processing during movie watching, with dynamic engagement of sensorimotor systems for speech-in-noise. It also provides a better mapping to auditory content in the movie than ISC.

Chee-Ming Ting, S. Balqis Samdin, Meini Tang et al.

We present a unified statistical framework for characterizing community structure of brain functional networks that captures variation across individuals and evolution over time. Existing methods for community detection focus only on single-subject analysis of dynamic networks; while recent extensions to multiple-subjects analysis are limited to static networks. To overcome these limitations, we propose a multi-subject, Markov-switching stochastic block model (MSS-SBM) to identify state-related changes in brain community organization over a group of individuals. We first formulate a multilayer extension of SBM to describe the time-dependent, multi-subject brain networks. We develop a novel procedure for fitting the multilayer SBM that builds on multislice modularity maximization which can uncover a common community partition of all layers (subjects) simultaneously. By augmenting with a dynamic Markov switching process, our proposed method is able to capture a set of distinct, recurring temporal states with respect to inter-community interactions over subjects and the change points between them. Simulation shows accurate community recovery and tracking of dynamic community regimes over multilayer networks by the MSS-SBM. Application to task fMRI reveals meaningful non-assortative brain community motifs, e.g., core-periphery structure at the group level, that are associated with language comprehension and motor functions suggesting their putative role in complex information integration. Our approach detected dynamic reconfiguration of modular connectivity elicited by varying task demands and identified unique profiles of intra and inter-community connectivity across different task conditions. The proposed multilayer network representation provides a principled way of detecting synchronous, dynamic modularity in brain networks across subjects.

Chun-Ren Phang, Chee-Ming Ting, Fuad Noman et al.

We exploit altered patterns in brain functional connectivity as features for automatic discriminative analysis of neuropsychiatric patients. Deep learning methods have been introduced to functional network classification only very recently for fMRI, and the proposed architectures essentially focused on a single type of connectivity measure. We propose a deep convolutional neural network (CNN) framework for classification of electroencephalogram (EEG)-derived brain connectome in schizophrenia (SZ). To capture complementary aspects of disrupted connectivity in SZ, we explore combination of various connectivity features consisting of time and frequency-domain metrics of effective connectivity based on vector autoregressive model and partial directed coherence, and complex network measures of network topology. We design a novel multi-domain connectome CNN (MDC-CNN) based on a parallel ensemble of 1D and 2D CNNs to integrate the features from various domains and dimensions using different fusion strategies. Hierarchical latent representations learned by the multiple convolutional layers from EEG connectivity reveal apparent group differences between SZ and healthy controls (HC). Results on a large resting-state EEG dataset show that the proposed CNNs significantly outperform traditional support vector machine classifiers. The MDC-CNN with combined connectivity features further improves performance over single-domain CNNs using individual features, achieving remarkable accuracy of $93.06\%$ with a decision-level fusion. The proposed MDC-CNN by integrating information from diverse brain connectivity descriptors is able to accurately discriminate SZ from HC. The new framework is potentially useful for developing diagnostic tools for SZ and other disorders.

Fuad Noman, Chee-Ming Ting, Sh-Hussain Salleh et al.

This paper proposes a framework based on deep convolutional neural networks (CNNs) for automatic heart sound classification using short-segments of individual heart beats. We design a 1D-CNN that directly learns features from raw heart-sound signals, and a 2D-CNN that takes inputs of two- dimensional time-frequency feature maps based on Mel-frequency cepstral coefficients (MFCC). We further develop a time-frequency CNN ensemble (TF-ECNN) combining the 1D-CNN and 2D-CNN based on score-level fusion of the class probabilities. On the large PhysioNet CinC challenge 2016 database, the proposed CNN models outperformed traditional classifiers based on support vector machine and hidden Markov models with various hand-crafted time- and frequency-domain features. Best classification scores with 89.22% accuracy and 89.94% sensitivity were achieved by the ECNN, and 91.55% specificity and 88.82% modified accuracy by the 2D-CNN alone on the test set.

Fuad Noman, Sh-Hussain Salleh, Chee-Ming Ting et al.

Objective: This paper considers challenges in developing algorithms for accurate segmentation and classification of heart sound (HS) signals. Methods: We propose an approach based on Markov switching autoregressive model (MSAR) to segmenting the HS into four fundamental components each with distinct second-order structure. The identified boundaries are then utilized for automated classification of pathological HS using the continuous density hidden Markov model (CD-HMM). The MSAR formulated in a state-space form is able to capture simultaneously both the continuous hidden dynamics in HS, and the regime switching in the dynamics using a discrete Markov chain. This overcomes the limitation of HMM which uses a single-layer of discrete states. We introduce three schemes for model estimation: (1.) switching Kalman filter (SKF); (2.) refined SKF; (3.) fusion of SKF and the duration-dependent Viterbi algorithm (SKF-Viterbi). Results: The proposed methods are evaluated on Physionet/CinC Challenge 2016 database. The SKF-Viterbi significantly outperforms SKF by improvement of segmentation accuracy from 71% to 84.2%. The use of CD-HMM as a classifier and Mel-frequency cepstral coefficients (MFCCs) as features can characterize not only the normal and abnormal morphologies of HS signals but also morphologies considered as unclassifiable (denoted as X-Factor). It gives classification rates with best gross F1 score of 90.19 (without X-Factor) and 82.7 (with X-Factor) for abnormal beats. Conclusion: The proposed MSAR approach for automatic localization and detection of pathological HS shows a noticeable performance on large HS dataset. Significance: It has potential applications in heart monitoring systems to assist cardiologists for pre-screening of heart pathologies.