Georgi Hrusanov

Narmina Baghirova, Duy-Thanh Vũ, Duy-Cat Can et al.

Alzheimer's disease (AD) affects 50 million people worldwide and is projected to overwhelm 152 million by 2050. AD is characterized by cognitive decline due partly to disruptions in metabolic brain connectivity. Thus, early and accurate detection of metabolic brain network impairments is crucial for AD management. Chief to identifying such impairments is FDG-PET data. Despite advancements, most graph-based studies using FDG-PET data rely on group-level analysis or thresholding. Yet, group-level analysis can veil individual differences and thresholding may overlook weaker but biologically critical brain connections. Additionally, machine learning-based AD prediction largely focuses on univariate outcomes, such as disease status. Here, we introduce explainable graph-theoretical machine learning (XGML), a framework employing kernel density estimation and dynamic time warping to construct individual metabolic brain graphs that capture the distance between pair-wise brain regions and identify subgraphs most predictive of multivariate AD-related outcomes. Using FDG-PET data from the Alzheimer's Disease Neuroimaging Initiative, XGML builds metabolic brain graphs and uncovers subgraphs predictive of eight AD-related cognitive scores in new subjects. XGML shows robust performance, particularly for predicting scores measuring learning, memory, language, praxis, and orientation, such as CDRSB ($r = 0.74$), ADAS11 ($r = 0.73$), and ADAS13 ($r = 0.71$). Moreover, XGML unveils key edges jointly but differentially predictive of several AD-related outcomes; they may serve as potential network biomarkers for assessing overall cognitive decline. Together, we show the promise of graph-theoretical machine learning in biomarker discovery and disease prediction and its potential to improve our understanding of network neural mechanisms underlying AD.

Georgi Hrusanov, Oliver Y. Chén, Julien S. Bodelet

Deep Generative models (DGMs) play two key roles in modern machine learning: (i) producing new information (e.g., image synthesis) and (ii) reducing dimensionality. However, traditional architectures often rely on auxiliary networks such as encoders in Variational Autoencoders (VAEs) or discriminators in Generative Adversarial Networks (GANs), which introduce training instability, computational overhead, and risks like mode collapse. We present NeuroSQL, a new generative paradigm that eliminates the need for auxiliary networks by learning low-dimensional latent representations implicitly. NeuroSQL leverages an asymptotic approximation that expresses the latent variables as the solution to an optimal transportation problem. Specifically, NeuroSQL learns the latent variables by solving a linear assignment problem and then passes the latent information to a standalone generator. We benchmark its performance against GANs, VAEs, and a budget-matched diffusion baseline on four datasets: handwritten digits (MNIST), faces (CelebA), animal faces (AFHQ), and brain images (OASIS). Compared to VAEs, GANs, and diffusion models: (1) in terms of image quality, NeuroSQL achieves overall lower mean pixel distance between synthetic and authentic images and stronger perceptual/structural fidelity; (2) computationally, NeuroSQL requires the least training time; and (3) practically, NeuroSQL provides an effective solution for generating synthetic data with limited training samples. By embracing quantile assignment rather than an encoder, NeuroSQL provides a fast, stable, and robust way to generate synthetic data with minimal information loss.

Georgi Hrusanov, Duy-Thanh Vu, Duy-Cat Can et al.

Early forecasting of individual cognitive decline in Alzheimer's disease (AD) is central to disease evaluation and management. Despite advances, it is as of yet challenging for existing methodological frameworks to integrate multimodal data for longitudinal personalized forecasting while maintaining interpretability. To address this gap, we present the Neural Koopman Machine (NKM), a new machine learning architecture inspired by dynamical systems and attention mechanisms, designed to forecast multiple cognitive scores simultaneously using multimodal genetic, neuroimaging, proteomic, and demographic data. NKM integrates analytical ($α$) and biological ($β$) knowledge to guide feature grouping and control the hierarchical attention mechanisms to extract relevant patterns. By implementing Fusion Group-Aware Hierarchical Attention within the Koopman operator framework, NKM transforms complex nonlinear trajectories into interpretable linear representations. To demonstrate NKM's efficacy, we applied it to study the Alzheimer's Disease Neuroimaging Initiative (ADNI) dataset. Our results suggest that NKM consistently outperforms both traditional machine learning methods and deep learning models in forecasting trajectories of cognitive decline. Specifically, NKM (1) forecasts changes of multiple cognitive scores simultaneously, (2) quantifies differential biomarker contributions to predicting distinctive cognitive scores, and (3) identifies brain regions most predictive of cognitive deterioration. Together, NKM advances personalized, interpretable forecasting of future cognitive decline in AD using past multimodal data through an explainable, explicit system and reveals potential multimodal biological underpinnings of AD progression.