Data-driven techniques for translational neuroscience and personalized neuro-health

Neurodegenexrative diseases such as Alzheimer's disease and Parkinson's disease are diagnosed most reliably only after substantial, often irreversible, neuronal loss has already occurred, creating an urgent need for quantitative tools that can detect subtle, early, and individual-specific brain changes from neuroimaging data. This review surveys a broad and rapidly evolving toolkit of data-driven techniques for translational neuroscience and personalized neuro-health, organized around four complementary methodological pillars. Throughout, we emphasize how these methodologically diverse approaches converge on a common translational goal: personalized, mechanistically grounded, and clinically actionable models of individual brain health, and we close by discussing the principal open statistical, computational, and clinical challenges that remain.

Surv-IPTB: An Attention-Based Model for Estimating Individual Probability of Treatment Benefit with Survival Data

This work presents a novel attention-based framework for estimating the Individual Probability of Treatment Benefit (IPTB) in survival analysis contexts. The proposed model, called Surv-IPTB, directly quantifies the probability that a specific patient will experience extended survival time under treatment versus control. We reformulate IPTB estimation as a binary classification problem, leveraging pairwise patient comparisons across treatment and control cohorts. The framework incorporates a principled handling of right-censored observations through imprecise probability representations, where uncertain treatment effects are characterized by interval-valued probabilities. An attention mechanism with learnable query-key transformations enables flexible, data-driven aggregation of pairwise comparisons, while simultaneously learning soft class probabilities for censored cases. Through extensive experiments on synthetic datasets with complex nonlinear structures, including spiral, bell-shaped, and circular feature spaces, we demonstrate that our approach maintains robust performance across varying censoring rates and treatment effect strengths. The model consistently outperforms meta-learner baselines (T-learner and S-learner) equipped with random survival forests, Cox proportional hazards, and Beran estimators, particularly in challenging nonlinear scenarios where conventional methods exhibit significant degradation. The results establish the proposed attention-based framework as a scalable and statistically principled solution for personalized treatment benefit assessment in survival settings. The code implementing the model is publicly available.

Subject-Conditioned Glucose Forecasting in Type-1 Diabetes

Accurate forecasting of blood glucose concentration is key in the management of Type 1 Diabetes, facilitating early detection of adverse glycemic events and supporting timely therapeutic interventions. Despite recent advances in glucose prediction, most existing approaches rely on population-level representations or implicit personalization strategies that fail to deliver effective subject-specific forecasts. In this work, we propose Subject-Conditioned Glucose Prediction (SCGP), a novel multimodal deep learning architecture conceived for personalized blood glucose prediction. SCGP conditions glucose predictions based on observed glucose data and a compact subject-specific representation learned from contextual information. By explicitly separating subject characterization from glucose dynamics modeling and avoiding early fusion of heterogeneous inputs, the proposed framework effectively captures inter-subject variability while preserving robust and reliable temporal modeling. Experiments on two state-of-the-art benchmark datasets demonstrate that SCGP consistently improves forecasting performance, enabling reliable detection of adverse glycemic events across multiple prediction horizons, highlighting the benefits of explicit subject conditioning for personalized diabetes management.

HAPI-EP: Towards Hybrid, Adaptive, and Predictive Digital Twins of Cardiac Electrophysiology

A digital twin (DT) of a patient-specific heart offers significant potential in personalized medicine. However, its rapid and dynamic adaptation to an individual's live data and its predictive capability after adaptation remains central challenges. We examine this challenge from its two building blocks: DT formulation where mechanistic and data-driven models show competing merits and limitations, and DT optimization strategies that are largely driven by a reconstruction objective leading to un-identifiable models. We address both bottlenecks via HAPI -- an AI framework for building hybrid, adaptive, and predictive DTs with three key enablers. First, HAPI constructs a physics-integrated gray-box model in which an interpretable mechanistic backbone is augmented by a neural component that models its residual to the observed data. Second, rather than attempting to pre-encode all possible variations in a static hybrid model, HAPI enables rapid on-the-fly adaptation of the hybrid model to few-shot live data, achieved by feedforward meta-learners realizing amortized inference of both mechanistic and neural parameters of the hybrid model trained with predictive objectives. Finally, we show that this adaptivity corresponds to the construction of a conditional generative model (i.e., the hybrid DT) that endows it with theoretical identifiability and thus strong performance in predictive scenarios. We demonstrate the proof-of-concept of HAPI in cardiac electrophysiology using a hybrid monodomain model with mechanistic reaction kinetics and neural graph diffusion. Across synthetic and real-data studies, we show that HAPI's mechanistic-neural hybridization and predictive adaptation are critical for obtaining identifiable DTs with strong predictive and out-of-distribution capabilities.

Attention-Based Estimation of the Individual Treatment Benefit Probability under Dose Variation

Estimating the probability that a treatment outperforms a control for an individual patient, called the Individual Probability of Treatment Benefit (IPTB), offers a clinically intuitive alternative to population-average metrics. However, existing methods for IPTB estimation are largely confined to binary treatment settings, despite the prevalence of dose-varying interventions in clinical practice. We propose a general framework for IPTB estimation with ordinal outcomes under discrete dose assignments, called Dose-AIPTB (Dose Attention-based IPTB). Our approach recasts the problem as binary classification over the unobserved sign of the individual treatment effect, constructing pseudo-labels from covariate-similar pairwise comparisons and aggregating them via attention mechanisms or Nadaraya-Watson kernel regression. This formulation naturally accommodates multiple discrete dose levels, extending beyond the binary treatment paradigm. Through numerical experiments on real-world and synthetic data under covariate shift, varying sample sizes, and heterogeneous outcomes, we demonstrate that attention-based aggregation consistently outperforms kernel alternatives. The framework provides a foundation for personalized dose selection grounded in individual-level benefit probabilities. Codes implementing the model are publicly available at https://github.com/NTAILab/AIPTBDose.

A Guide to Estimating Conditional Average Treatment Effects in Competing Risks Settings

Conditional average treatment effects (CATEs) are central to treatment decision-making in personalized medicine. In competing risks settings, estimating CATEs from survival data allows for patient-specific assessments of treatment effectiveness for a specific event of interest while properly accounting for alternative event types. This distinction is essential in the presence of comorbidities, where competing causes of death may otherwise confound the therapeutic benefit. Focusing on right-censored survival times with binary treatment, we examine CATEs defined as covariate-conditional differences in the absolute risk for the event of interest at a fixed time. To this end, we study meta-learners which adapt machine learning algorithms for CATE estimation in competing risks scenarios. We systematically compare six meta-learners, combining Cox regression or random survival forests for risk modeling with elastic net regression or random forests for direct CATE modeling. To provide practical guidance on model selection, we evaluate their performance in multiple simulation settings, that differ in hazard complexity, treatment heterogeneity, treatment assignment, event type distribution and censoring. To facilitate applied use, we provide the R package, crsurvlearners, which implements all considered approaches.