Abstract In biomedical Subgroup Discovery, practitioners are interested in discovering interpretable and homogeneous subgroups within a group of patients. In this paper, assuming that healthy subjects (i.e., controls) share common but irrelevant factors of variation with the patients, we motivate and develop a Contrastive Subgroup Discovery method, entitled Deep UCSL. By contrasting patients with controls, Deep UCSL identifies subgroups driven solely by pathological factors, ignoring common variability shared with healthy subjects. Our framework employs a deep feature extractor to learn a discriminative representation space. Mathematically, we derive a novel loss based on the conditional joint likelihood of latent clusters and patient/control labels, optimized via an Expectation-Maximization strategy alternating between subgroup inference and feature encoder updates. A regularization term further encourages representations to capture disease-specific variability while ignoring variability shared with controls. Compared to previous related works, our approach quantitatively improves the quality of the estimated subgroups, as demonstrated on a MNIST example and four distinct real medical imaging datasets. Code and datasets are available at: ( https://github.com/rlouiset/deep_ucsl ).

Deep Learning (DL) in neuroimaging has become increasingly relevant for detecting neurological conditions and neurodegenerative disorders. One of the predominant biomarkers in neuroimaging is represented by brain age, which has been shown to be a good indicator for different conditions, such as Alzheimer’s Disease. Using brain age for weakly supervised pre-training of DL models in transfer learning settings has also recently shown promising results, especially when dealing with data scarcity of different conditions. On the other hand, anatomical information of brain MRIs (e.g. cortical thickness) can provide important information for learning good representations that can be transferred to many downstream tasks. In this work, we propose AnatCL, an anatomical foundation model for structural brain MRIs that (i.) leverages anatomical information in a weakly contrastive learning approach, and (ii.) achieves state-of-the-art performances across many different downstream tasks. To validate our approach we consider 12 different downstream tasks for the diagnosis of different conditions such as Alzheimer’s Disease, autism spectrum disorder, and schizophrenia. Furthermore, we also target the prediction of 10 different clinical assessment scores using structural MRI data. Our findings show that incorporating anatomical information during pre-training leads to more robust and generalizable representations. Pre-trained models can be found at: https://github.com/EIDOSLAB/AnatCL . • We propose AnatCL, a novel brain MRI foundation model; • AnatCL accounts for age and anatomical measures; • We benchmark AnatCL on 22 deep-learning-based phenotyping tasks; • Our method achieves SOTA results on many downstream phenotyping tasks; • We publicly release pre-trained models.

Estimating brain age from structural MRI has emerged as a powerful tool for characterizing normative and pathological aging. In this work, we explore contrastive learning as a scalable and robust alternative to L1-supervised approaches for brain age estimation. We introduce a novel contrastive loss function, L e x p , and evaluate it across multiple public neuroimaging datasets comprising over 20,000 scans. Our experiments reveal four key findings. First, scaling pre-training on diverse, multi-site data consistently improves generalization performance, cutting external mean absolute error (MAE) nearly in half. Second, L e x p is robust to site-related confounds, maintaining low scanner-predictability as training size increases. Third, contrastive models reliably capture accelerated aging in patients with cognitive impairment and Alzheimer’s disease, as shown through brain age gap analysis, ROC curves, and longitudinal trends. Lastly, unlike L1-supervised baselines, L e x p maintains a strong correlation between brain age accuracy and downstream diagnostic performance, supporting its potential as a foundation model for neuroimaging. These results position contrastive learning as a promising direction for building generalizable and clinically meaningful brain representations.

Humans perceive the world through multisensory integration, blending the information of different modalities to adapt their behavior. Contrastive learning offers an appealing solution for multimodal self-supervised learning. Indeed, by considering each modality as a different view of the same entity, it learns to align features of different modalities in a shared representation space. However, this approach is intrinsically limited as it only learns shared or redundant information between modalities, while multimodal interactions can arise in other ways. In this work, we introduce CoMM, a Contrastive Multimodal learning strategy that enables the communication between modalities in a single multimodal space. Instead of imposing cross- or intra- modality constraints, we propose to align multimodal representations by maximizing the mutual information between augmented versions of these multimodal features. Our theoretical analysis shows that shared, synergistic and unique terms of information naturally emerge from this formulation, allowing us to estimate multimodal interactions beyond redundancy. We test CoMM both in a controlled and in a series of real-world settings: in the former, we demonstrate that CoMM effectively captures redundant, unique and synergistic information between modalities. In the latter, CoMM learns complex multimodal interactions and achieves state-of-the-art results on seven multimodal tasks.

Data augmentation is a crucial component in unsupervised contrastive learning (CL). It determines how positive samples are defined and, ultimately, the quality of the learned representation. In this work, we open the door to new perspectives for CL by integrating prior knowledge, given either by generative models - viewed as prior representations - or weak attributes in the positive and negative sampling. To this end, we use kernel theory to propose a novel loss, called decoupled uniformity, that i) allows the integration of prior knowledge and ii) removes the positive-negative coupling in the original InfoNCE loss. We draw a connection between contrastive learning and the conditional mean embedding theory to derive tight bounds on the downstream classification loss. In an unsupervised setting, we empirically demonstrate that CL benefits from generative models to improve its representation both on natural and medical images. In a weakly supervised scenario, our framework outperforms other unconditional and conditional CL approaches.