Deep learning models for medical image segmentation suffer significant performance drops due to distribution shifts, but the causal mechanisms behind these drops remain poorly understood. We extend causal attribution frameworks to high-dimensional segmentation tasks, quantifying how acquisition protocols and annotation variability independently contribute to performance degradation. We model the data-generating process through a causal graph and employ Shapley values to fairly attribute performance changes to individual mechanisms. Our framework addresses unique challenges in medical imaging: high-dimensional outputs, limited samples, and complex mechanism interactions. Validation on multiple sclerosis (MS) lesion segmentation across 4 centers and 7 annotators reveals context-dependent failure modes: annotation protocol shifts dominate when crossing annotators (7.4% $\pm$ 8.9% DSC attribution), while acquisition shifts dominate when crossing imaging centers (6.5% $\pm$ 9.1%). This mechanism-specific quantification enables practitioners to prioritize targeted interventions based on deployment context.

People with Multiple Sclerosis (MS) complain of problems with hand dexterity and cognitive fatigue. However, in many cases, impairments are subtle and difficult to detect. Functional near-infrared spectroscopy (fNIRS) is a non-invasive neuroimaging technique that measures brain hemodynamic responses during cognitive or motor tasks. We aimed to detect brain activity biomarkers that could explain subjective reports of cognitive fatigue while completing dexterous tasks and provide targets for future brain stimulation treatments. We recruited 15 people with MS who did not have a hand (Nine Hole Peg Test [NHPT]), mobility, or cognitive impairment, and 12 age- and sex-matched controls. Participants completed two types of hand dexterity tasks with their dominant hand, single task and dual task (NHPT while holding a ball between the fifth finger and hypothenar eminence of the same hand). We analyzed fNIRS data (oxygenated and deoxygenated hemoglobin levels) using a machine learning framework to classify MS patients from controls based on their brain activation patterns in bilateral prefrontal and sensorimotor cortices. The K-Nearest Neighbor classifier achieved an accuracy of 75.0% for single manual dexterity tasks and 66.7% for the more complex dual manual dexterity tasks. Using XAI, we found that the most important brain regions contributing to the machine learning model were the supramarginal/angular gyri and the precentral gyrus (sensory integration and motor regions) of the ipsilateral hemisphere, with suppressed activity and slower neurovascular response in the MS group. During both tasks, deoxygenated hemoglobin levels were better predictors than the conventional measure of oxygenated hemoglobin. This nonconventional method of fNIRS data analysis revealed novel brain activity biomarkers that can help develop personalized brain stimulation targets.

We present a machine learning pipeline for biomarker discovery in Multiple Sclerosis (MS), integrating eight publicly available microarray datasets from Peripheral Blood Mononuclear Cells (PBMC). After robust preprocessing we trained an XGBoost classifier optimized via Bayesian search. SHapley Additive exPlanations (SHAP) were used to identify key features for model prediction, indicating thus possible biomarkers. These were compared with genes identified through classical Differential Expression Analysis (DEA). Our comparison revealed both overlapping and unique biomarkers between SHAP and DEA, suggesting complementary strengths. Enrichment analysis confirmed the biological relevance of SHAP-selected genes, linking them to pathways such as sphingolipid signaling, Th1/Th2/Th17 cell differentiation, and Epstein-Barr virus infection--all known to be associated with MS. This study highlights the value of combining explainable AI (xAI) with traditional statistical methods to gain deeper insights into disease mechanism.

Integrative analysis of multi-institutional Electronic Health Record (EHR) data enhances the reliability and generalizability of translational research by leveraging larger, more diverse patient cohorts and incorporating multiple data modalities. However, harmonizing EHR data across institutions poses major challenges due to data heterogeneity, semantic differences, and privacy concerns. To address these challenges, we introduce $\textit{PEHRT}$, a standardized pipeline for efficient EHR data harmonization consisting of two core modules: (1) data pre-processing and (2) representation learning. PEHRT maps EHR data to standard coding systems and uses advanced machine learning to generate research-ready datasets without requiring individual-level data sharing. Our pipeline is also data model agnostic and designed for streamlined execution across institutions based on our extensive real-world experience. We provide a complete suite of open source software, accompanied by a user-friendly tutorial, and demonstrate the utility of PEHRT in a variety of tasks using data from diverse healthcare systems.

Depression commonly co-occurs with neurodegenerative disorders like Multiple Sclerosis (MS), yet the potential of speech-based Artificial Intelligence for detecting depression in such contexts remains unexplored. This study examines the transferability of speech-based depression detection methods to people with MS (pwMS) through cross-corpus and cross-lingual analysis using English data from the general population and German data from pwMS. Our approach implements supervised machine learning models using: 1) conventional speech and language features commonly used in the field, 2) emotional dimensions derived from a Speech Emotion Recognition (SER) model, and 3) exploratory speech feature analysis. Despite limited data, our models detect depressive mood in pwMS with moderate generalisability, achieving a 66% Unweighted Average Recall (UAR) on a binary task. Feature selection further improved performance, boosting UAR to 74%. Our findings also highlight the relevant role emotional changes have as an indicator of depressive mood in both the general population and within PwMS. This study provides an initial exploration into generalising speech-based depression detection, even in the presence of co-occurring conditions, such as neurodegenerative diseases.

We developed a ResNet-based human activity recognition (HAR) model with minimal overhead to detect gait versus non-gait activities and everyday activities (walking, running, stairs, standing, sitting, lying, sit-to-stand transitions). The model was trained and evaluated using smartphone sensor data from adult healthy controls (HC) and people with multiple sclerosis (PwMS) with Expanded Disability Status Scale (EDSS) scores between 0.0-6.5. Datasets included the GaitLab study (ISRCTN15993728), an internal Roche dataset, and publicly available data sources (training only). Data from 34 HC and 68 PwMS (mean [SD] EDSS: 4.7 [1.5]) were included in the evaluation. The HAR model showed 98.4% and 99.6% accuracy in detecting gait versus non-gait activities in the GaitLab and Roche datasets, respectively, similar to a comparative state-of-the-art ResNet model (99.3% and 99.4%). For everyday activities, the proposed model not only demonstrated higher accuracy than the state-of-the-art model (96.2% vs 91.9%; internal Roche dataset) but also maintained high performance across 9 smartphone wear locations (handbag, shopping bag, crossbody bag, backpack, hoodie pocket, coat/jacket pocket, hand, neck, belt), outperforming the state-of-the-art model by 2.8% - 9.0%. In conclusion, the proposed HAR model accurately detects everyday activities and shows high robustness to various smartphone wear locations, demonstrating its practical applicability.

In recent years, the advent of deep learning and, in particular, transformer-based architectures, has significantly revolutionized the field of Artificial Intelligence (AI) in many scientific domains, including computer vision, natural language processing, and sequence modeling, thanks to the increasing availability of computational power and large-scale data-sets. However, classical Machine Learning (ML) methods, such as decision trees, gradient-boosted trees, Support V ector Machines (SVMs), and regression--based techniques, continue to be considered as the state-of-the-art for tabular data, which are still nowadays widely used in healthcare, finance, industrial monitoring, and other structured-data domains. There are several reasons for this. Notably, conventional AI models tend to perform reasonably well on datasets of limited size, whereas state-of-the-art deep learning techniques typically require substantially larger amounts of data to generalize effectively. Moreover, many classical AI methods, such as regression, Bayesian approaches, rule-based systems, and tree-based models, are inherently more interpretable, a characteristic that is particularly valuable in high-stakes domains such as healthcare. In contrast, deep learning models often work as black boxes, limiting their explainability. As an example, Grinsztajn et al. [1] showed that tree-based ensembles like XGBoost and Random Forests consistently outperformed a wide range of contemporary deep learning models across dozens of medium-sized tabular datasets (

Early multiple sclerosis (MS) disability progression prediction is challenging due to disease heterogeneity. This work predicts 48- and 72-week disability using sparse baseline clinical data and 12 weeks of daily digital Floodlight data from the CONSONANCE clinical trial. We employed state-of-the-art tabular and time-series foundation models (FMs), a custom multimodal attention-based transformer, and machine learning methods. Despite the difficulty of early prediction (AUROC 0.63), integrating digital data via advanced models improved performance over clinical data alone. A transformer model using unimodal embeddings from the Moment FM yielded the best result, but our multimodal transformer consistently outperformed its unimodal counterpart, confirming the advantages of combining clinical with digital data. Our findings demonstrate the promise of FMs and multimodal approaches to extract predictive signals from complex and diverse clinical and digital life sciences data (e.g., imaging, omics), enabling more accurate prognostics for MS and potentially other complex diseases.

Quantitative susceptibility maps from magnetic resonance images can provide both prognostic and diagnostic information in multiple sclerosis, a neurodegenerative disease characterized by the formation of lesions in white matter brain tissue. In particular, susceptibility maps provide adequate contrast to distinguish between "rim" lesions, surrounded by deposited paramagnetic iron, and "non-rim" lesion types. These paramagnetic rim lesions (PRLs) are an emerging biomarker in multiple sclerosis. Much effort has been devoted to both detection and segmentation of such lesions to monitor longitudinal change. As paramagnetic rim lesions are rare, addressing this problem requires confronting the class imbalance between rim and non-rim lesions. W e produce synthetic quantitative susceptibility maps of paramagnetic rim lesions and show that inclusion of such synthetic data improves classifier performance and provide a multi-channel extension to generate accompanying contrasts and probabilistic segmentation maps. W e exploit the projection capability of our trained generative network to demonstrate a novel denoising approach that allows us to train on ambiguous rim cases and substantially increase the minority class. W e show that both synthetic lesion synthesis and our proposed rim lesion label denoising method best approximate the unseen rim lesion distribution and improve detection in a clinically interpretable manner . W e release our code and generated data at https://github.com/agr78/PRLx-GAN

Electronic Health Records (EHR) offer rich real-world data for personalized medicine, providing insights into disease progression, treatment responses, and patient outcomes. However, their sparsity, heterogeneity, and high dimensionality make them difficult to model, while the lack of standardized ground truth further complicates predictive modeling. To address these challenges, we propose SCORE, a semi-supervised representation learning framework that captures multi-domain disease profiles through patient embeddings. SCORE employs a Poisson-Adapted Latent factor Mixture (PALM) Model with pre-trained code embeddings to characterize codified features and extract meaningful patient phenotypes and embeddings. To handle the computational challenges of large-scale data, it introduces a hybrid Expectation-Maximization (EM) and Gaussian Variational Approximation (GVA) algorithm, leveraging limited labeled data to refine estimates on a vast pool of unlabeled samples. We theoretically establish the convergence of this hybrid approach, quantify GVA errors, and derive SCORE's error rate under diverging embedding dimensions. Our analysis shows that incorporating unlabeled data enhances accuracy and reduces sensitivity to label scarcity. Extensive simulations confirm SCORE's superior finite-sample performance over existing methods. Finally, we apply SCORE to predict disability status for patients with multiple sclerosis (MS) using partially labeled EHR data, demonstrating that it produces more informative and predictive patient embeddings for multiple MS-related conditions compared to existing approaches.