Interpretable Cross-Network Attention for Resting-State fMRI Representation Learning

Understanding how large-scale functional brain networks reorganize during cognitive decline remains a central challenge in neuroimaging. While recent self-supervised models have shown promise for learning representations from resting-state fMRI, their internal mechanisms are difficult to interpret, limiting mechanistic insight. We propose BrainInterNet, a network-aware self-supervised framework based on masked reconstruction with cross-attention that explicitly models inter-network dependencies in rs-fMRI. By selectively masking predefined functional networks and reconstructing them from remaining context, our approach enables direct quantification of network predictability and interpretable analysis of cross-network interactions. We train BrainInterNet on multi-cohort fMRI data (from the ABCD, HCP Development, HCP Young Adults, and HCP Aging datasets) and evaluate on the Alzheimer's Disease Neuroimaging Initiative (ADNI) dataset, in total comprising 5,582 recordings. Our method reveals systematic alterations in the brain's network interactions under AD, including in the default mode, limbic, and attention networks. In parallel, the learned representations support accurate Alzheimer's-spectrum classification and yield a compact summary marker that tracks disease severity longitudinally. Together, these results demonstrate that network-guided masked modeling with cross-attention provides an interpretable and effective framework for characterizing functional reorganization in neurodegeneration.

Generating Novel Brain Morphology by Deforming Learned Templates

Designing generative models for 3D structural brain MRI that synthesize morphologically-plausible and attribute-specific (e.g., age, sex, disease state) samples is an active area of research. Existing approaches based on frameworks like GANs or diffusion models synthesize the image directly, which may limit their ability to capture intricate morphological details. In this work, we propose a 3D brain MRI generation method based on state-of-the-art latent diffusion models (LDMs), called MorphLDM, that generates novel images by applying synthesized deformation fields to a learned template. Instead of using a reconstruction-based autoencoder (as in a typical LDM), our encoder outputs a latent embedding derived from both an image and a learned template that is itself the output of a template decoder; this latent is passed to a deformation field decoder, whose output is applied to the learned template. A registration loss is minimized between the original image and the deformed template with respect to the encoder and both decoders. Empirically, our approach outperforms generative baselines on metrics spanning image diversity, adherence with respect to input conditions, and voxel-based morphometry. Our code is available at https://github.com/alanqrwang/morphldm.

Spectral Graph Sample Weighting for Interpretable Sub-cohort Analysis in Predictive Models for Neuroimaging

Recent advancements in medicine have confirmed that brain disorders often comprise multiple subtypes of mechanisms, developmental trajectories, or severity levels. Such heterogeneity is often associated with demographic aspects (e.g., sex) or disease-related contributors (e.g., genetics). Thus, the predictive power of machine learning models used for symptom prediction varies across subjects based on such factors. To model this heterogeneity, one can assign each training sample a factor-dependent weight, which modulates the subject's contribution to the overall objective loss function. To this end, we propose to model the subject weights as a linear combination of the eigenbases of a spectral population graph that captures the similarity of factors across subjects. In doing so, the learned weights smoothly vary across the graph, highlighting sub-cohorts with high and low predictability. Our proposed sample weighting scheme is evaluated on two tasks. First, we predict initiation of heavy alcohol drinking in young adulthood from imaging and neuropsychological measures from the National Consortium on Alcohol and NeuroDevelopment in Adolescence (NCANDA). Next, we detect Dementia vs. Mild Cognitive Impairment (MCI) using imaging and demographic measurements in subjects from the Alzheimer's Disease Neuroimaging Initiative (ADNI). Compared to existing sample weighting schemes, our sample weights improve interpretability and highlight sub-cohorts with distinct characteristics and varying model accuracy.