arXiv subjects

Eardi Lila

Publications and source records attributed to Eardi Lila.

13 recordsLinked to original sources

arXiv2026

Biophysics-informed deep operator learning for inverse problems with application to electrophysiological source reconstruction

Electrophysiological brain signals are typically acquired through indirect and noisy measurements, providing transformed representations of the underlying neural activity. Source reconstruction---the inverse problem of resolving underlying neural signals from these measurements---is essential for mapping brain function but remains challenging because it is ill-posed and sensitive to noise. Deep learning methods have shown promise across a range of inverse problems, yet many do not explicitly incorporate the biophysical principles governing data generation, limiting data efficiency and adaptation across subjects. Here, we introduce DeepOp-Informed, a biophysics-informed geometric deep operator learning framework that embeds the biophysics of the sensing process into the model through a custom differentiable layer, enabling more efficient learning and improved reconstruction performance. This layer enables the neural network to adapt to subject-specific variations in the physics of signal generation, resulting from differences in brain anatomy and sensor positioning. In realistic magnetoencephalography simulations, DeepOp-Informed generalizes to forward models from held-out subjects, reducing reconstruction error relative to several neural-network and classical baselines. Applied to adolescent auditory-evoked recordings, it produces anatomically plausible reconstructions localized to the auditory cortex. While our application focuses on magnetoencephalography, the framework is general and may be adaptable to other imaging modalities.

stat.ME↗

arXiv2026

Learned Hemodynamic Coupling Inference in Resting-State Functional MRI

Functional magnetic resonance imaging (fMRI) provides an indirect measurement of neuronal activity via hemodynamic responses that vary across brain regions and individuals. Ignoring this hemodynamic variability can bias downstream connectivity estimates. Furthermore, the hemodynamic parameters themselves may serve as important imaging biomarkers. Estimating spatially varying hemodynamics from resting-state fMRI (rsfMRI) is therefore an important but challenging blind inverse problem, since both the latent neural activity and the hemodynamic coupling are unknown. In this work, we propose a methodology for inferring hemodynamic coupling on the cortical surface from rsfMRI. Our approach avoids the highly unstable joint recovery of neural activity and hemodynamics by marginalizing out the latent neural signal and basing inference on the resulting marginal likelihood. To enable scalable, high-resolution estimation, we employ a deep neural network combined with conditional normalizing flows to accurately approximate this intractable marginal likelihood, while enforcing spatial coherence through priors defined on the cortical surface that admit sparse representations. Uncertainty in the hemodynamic estimates is quantified via a double-bootstrap procedure. The proposed approach is extensively validated using synthetic data and real fMRI datasets, demonstrating clear improvements over current methods for hemodynamic estimation and downstream connectivity analysis.

eess.IV↗

arXiv2026

Asymmetric canonical correlation analysis of Riemannian and high-dimensional data

In this paper, we introduce a novel statistical model for the integrative analysis of Riemannian-valued functional data and high-dimensional data. We apply this model to explore the dependence structure between each subject's dynamic functional connectivity -- represented by a temporally indexed collection of positive definite covariance matrices -- and high-dimensional data representing lifestyle, demographic, and psychometric measures. Specifically, we employ a reformulation of canonical correlation analysis that enables efficient control of the complexity of the functional canonical directions using tangent space sieve approximations. Additionally, we enforce an interpretable group structure on the high-dimensional canonical directions via a sparsity-promoting penalty. The proposed method shows improved empirical performance over alternative approaches and comes with theoretical guarantees. Its application to data from the Human Connectome Project reveals a dominant mode of covariation between dynamic functional connectivity and lifestyle, demographic, and psychometric measures. This mode aligns with results from static connectivity studies but reveals a unique temporal non-stationary pattern that such studies fail to capture.

stat.ME↗

arXiv2026

Dimension-reduced outcome-weighted learning for estimating individualized treatment regimes in observational studies

Individualized treatment regimes (ITRs) aim to improve clinical outcomes by assigning treatment based on patient-specific characteristics. However, existing methods often struggle with high-dimensional covariates, limiting accuracy, interpretability, and real-world applicability. We propose a novel sufficient dimension reduction approach that directly targets the contrast between potential outcomes and identifies a low-dimensional subspace of the covariates capturing treatment effect heterogeneity. This reduced representation enables more accurate estimation of optimal ITRs through outcome-weighted learning. To accommodate observational data, our method incorporates kernel-based covariate balancing, allowing treatment assignment to depend on the full covariate set and avoiding the restrictive assumption that the subspace sufficient for modeling heterogeneous treatment effects is also sufficient for confounding adjustment. We show that the proposed method achieves universal consistency, i.e., its risk converges to the Bayes risk, under mild regularity conditions. We demonstrate its finite sample performance through simulations and an analysis of intensive care unit sepsis patient data to determine who should receive transthoracic echocardiography.

stat.ML↗

arXiv2025

Why Text Prevails: Vision May Undermine Multimodal Medical Decision Making

With the rapid progress of large language models (LLMs), advanced multimodal large language models (MLLMs) have demonstrated impressive zero-shot capabilities on vision-language tasks. In the biomedical domain, however, even state-of-the-art MLLMs struggle with basic Medical Decision Making (MDM) tasks. We investigate this limitation using two challenging datasets: (1) three-stage Alzheimer's disease (AD) classification (normal, mild cognitive impairment, dementia), where category differences are visually subtle, and (2) MIMIC-CXR chest radiograph classification with 14 non-mutually exclusive conditions. Our empirical study shows that text-only reasoning consistently outperforms vision-only or vision-text settings, with multimodal inputs often performing worse than text alone. To mitigate this, we explore three strategies: (1) in-context learning with reason-annotated exemplars, (2) vision captioning followed by text-only inference, and (3) few-shot fine-tuning of the vision tower with classification supervision. These findings reveal that current MLLMs lack grounded visual understanding and point to promising directions for improving multimodal decision making in healthcare.

cs.CV↗

arXiv2025

Genetic Regression Analysis of Human Brain Connectivity Using an Efficient Estimator of Genetic Covariance

Non-invasive measurements of the human brain using magnetic resonance imaging (MRI) have significantly improved our understanding the brain's network organization by enabling measurement of anatomical connections between brain regions (structural connectivity) and their coactivation (functional connectivity). Heritability analyses have established that genetics account for considerable intersubject variability in structural and functional connectivity. However, characterizing how genetics shape the relationship between structural and functional connectomes remains challenging, since this association is obscured by unique environmental exposures in observed data. To address this, we develop a regression analysis framework that enables characterization of the relationship between latent genetic contributions to structural and functional connectivity. Implementing the proposed framework requires estimating genetic covariance matrices in multivariate random effects models, which is computationally intractable for high-dimensional connectome data using existing methods. We introduce a constrained method-of-moments estimator that is several orders of magnitude faster than existing methods without sacrificing estimation accuracy. For the genetic regression analysis, we develop regularized estimation approaches, including ridge, lasso, and tensor regression. Applying our method to Human Connectome Project data, we find that functional connectivity is moderately predictable from structure at the genetic level (max R^2 = 0.34), though it is not directly predictable in the observed data (max R^2 = 0.03). This stark contrast suggests that unique environmental factors mask strong genetically-encoded structure-function relationships.

stat.AP↗

arXiv2024

Interpretable discriminant analysis for functional data supported on random nonlinear domains with an application to Alzheimer's disease

We introduce a novel framework for the classification of functional data supported on nonlinear, and possibly random, manifold domains. The motivating application is the identification of subjects with Alzheimer's disease from their cortical surface geometry and associated cortical thickness map. The proposed model is based upon a reformulation of the classification problem as a regularized multivariate functional linear regression model. This allows us to adopt a direct approach to the estimation of the most discriminant direction while controlling for its complexity with appropriate differential regularization. Our approach does not require prior estimation of the covariance structure of the functional predictors, which is computationally prohibitive in our application setting. We provide a theoretical analysis of the out-of-sample prediction error of the proposed model and explore the finite sample performance in a simulation setting. We apply the proposed method to a pooled dataset from the Alzheimer's Disease Neuroimaging Initiative and the Parkinson's Progression Markers Initiative. Through this application, we identify discriminant directions that capture both cortical geometric and thickness predictive features of Alzheimer's disease that are consistent with the existing neuroscience literature.

stat.ME↗

arXiv2024

Inference for Heterogeneous Graphical Models using Doubly High-Dimensional Linear-Mixed Models

Motivated by the problem of inferring the graph structure of functional connectivity networks from multi-level functional magnetic resonance imaging data, we develop a valid inference framework for high-dimensional graphical models that accounts for group-level heterogeneity. We introduce a neighborhood-based method to learn the graph structure and reframe the problem as that of inferring fixed effect parameters in a doubly high-dimensional linear mixed model. Specifically, we propose a LASSO-based estimator and a de-biased LASSO-based inference framework for the fixed effect parameters in the doubly high-dimensional linear mixed model, leveraging random matrix theory to deal with challenges induced by the identical fixed and random effect design matrices arising in our setting. Moreover, we introduce consistent estimators for the variance components to identify subject-specific edges in the inferred graph. To illustrate the generality of the proposed approach, we also adapt our method to account for serial correlation by learning heterogeneous graphs in the setting of a vector autoregressive model. We demonstrate the performance of the proposed framework using real data and benchmark simulation studies.

stat.ME↗

arXiv2022

Eigen-Adjusted Functional Principal Component Analysis

Functional Principal Component Analysis (FPCA) has become a widely-used dimension reduction tool for functional data analysis. When additional covariates are available, existing FPCA models integrate them either in the mean function or in both the mean function and the covariance function. However, methods of the first kind are not suitable for data that display second-order variation, while those of the second kind are time-consuming and make it difficult to perform subsequent statistical analyses on the dimension-reduced representations. To tackle these issues, we introduce an eigen-adjusted FPCA model that integrates covariates in the covariance function only through its eigenvalues. In particular, different structures on the covariate-specific eigenvalues -- corresponding to different practical problems -- are discussed to illustrate the model's flexibility as well as utility. To handle functional observations under different sampling schemes, we employ local linear smoothers to estimate the mean function and the pooled covariance function, and a weighted least square approach to estimate the covariate-specific eigenvalues. The convergence rates of the proposed estimators are further investigated under the different sampling schemes. In addition to simulation studies, the proposed model is applied to functional Magnetic Resonance Imaging scans, collected within the Human Connectome Project, for functional connectivity investigation.

stat.ME↗

arXiv2022

Functional random effects modeling of brain shape and connectivity

We present a statistical framework that jointly models brain shape and functional connectivity, which are two complex aspects of the brain that have been classically studied independently. We adopt a Riemannian modeling approach to account for the non-Euclidean geometry of the space of shapes and the space of connectivity that constrains trajectories of co-variation to be valid statistical estimates. In order to disentangle genetic sources of variability from those driven by unique environmental factors, we embed a functional random effects model in the Riemannian framework. We apply the proposed model to the Human Connectome Project dataset to explore spontaneous co-variation between brain shape and connectivity in young healthy individuals.

stat.ME↗

arXiv2020

Representation and reconstruction of covariance operators in linear inverse problems

We introduce a framework for the reconstruction and representation of functions in a setting where these objects cannot be directly observed, but only indirect and noisy measurements are available, namely an inverse problem setting. The proposed methodology can be applied either to the analysis of indirectly observed functional images or to the associated covariance operators, representing second-order information, and thus lying on a non-Euclidean space. To deal with the ill-posedness of the inverse problem, we exploit the spatial structure of the sample data by introducing a flexible regularizing term embedded in the model. Thanks to its efficiency, the proposed model is applied to MEG data, leading to a novel approach to the investigation of functional connectivity.

stat.ME↗

arXiv2019

Statistical Analysis of Functions on Surfaces, with an application to Medical Imaging

In Functional Data Analysis, data are commonly assumed to be smooth functions on a fixed interval of the real line. In this work, we introduce a comprehensive framework for the analysis of functional data, whose domain is a two-dimensional manifold and the domain itself is subject to variability from sample to sample. We formulate a statistical model for such data, here called Functions on Surfaces, which enables a joint representation of the geometric and functional aspects, and propose an associated estimation framework. We assess the validity of the framework by performing a simulation study and we finally apply it to the analysis of neuroimaging data of cortical thickness, acquired from the brains of different subjects, and thus lying on domains with different geometries.

stat.ME↗

arXiv2016

Smooth Principal Component Analysis over two-dimensional manifolds with an application to Neuroimaging

Motivated by the analysis of high-dimensional neuroimaging signals located over the cortical surface, we introduce a novel Principal Component Analysis technique that can handle functional data located over a two-dimensional manifold. For this purpose a regularization approach is adopted, introducing a smoothing penalty coherent with the geodesic distance over the manifold. The model introduced can be applied to any manifold topology, can naturally handle missing data and functional samples evaluated in different grids of points. We approach the discretization task by means of finite element analysis and propose an efficient iterative algorithm for its resolution. We compare the performances of the proposed algorithm with other approaches classically adopted in literature. We finally apply the proposed method to resting state functional magnetic resonance imaging data from the Human Connectome Project, where the method shows substantial differential variations between brain regions that were not apparent with other approaches.

stat.AP↗