Moo K. Chung, Keith J. Worsley, Steve Robbins +1cs.CV q-bio.NC
We present a unified computational approach to tensor-based morphometry in detecting the brain surface shape differences between two clinical groups based on magnetic resonance images. Our approach is novel in a sense that we combined surface modeling, surface data smoothing and statistical analysis in a coherent unified mathematical framework. The cerebral cortex has the topology of a 2D highly convoluted sheet. Between two different clinical groups, the local surface area and curvature of the cortex may differ. It is highly likely that such surface shape differences are not uniform over the whole cortex. By computing how such surface metrics differ, the regions of the most rapid structural differences can be localized. To increase the signal to noise ratio, diffusion smoothing based on the explicit estimation of Laplace-Beltrami operator has been developed and applied to the surface metrics. As an illustration, we demonstrate how this new tensor-based surface morphometry can be applied in localizing the cortical regions of the gray matter tissue growth and loss in the brain images longitudinally collected in the group of children.
Structural magnetic resonance imaging (MRI) images are sometimes corrupted over a contiguous set of slices, where acquisition, motion, hardware, or reconstruction effects leave a single slice or short interval inconsistent with its neighbors while the rest of the image remains usable. Such localized corruption can bias downstream morphometric analysis, yet discarding or reacquiring an otherwise usable image is costly. We formulate this as an image restoration problem: given the location of the affected interval, reconstruct those slices from the surrounding anatomical and imaging context. We propose SliceBridge, a framework for restoring corrupted slice intervals in T1-weighted MRI using rectified flow matching conditioned on the surrounding intact slices and their relative slice positions. Through-plane consistency is encouraged by coupling the slices within the interval through interval-correlated initial noise, a shared flow time, and synchronized sampling. The restored interval is then inserted back, leaving all other slices unchanged. We trained and validated the model on 9,877 T1-weighted brain MRI volumes from four datasets and evaluated it on 581 external subjects using clean interval withholding and controlled corruptions. Compared with a matched model that reconstructed target slices independently, SliceBridge reduced error in slice-to-slice changes within repaired intervals by 32.9%-41.3% across interval lengths and achieved higher SSIM at every interval length. In controlled-corruption cases, SliceBridge reduced the median error in regional brain volume estimates produced by a downstream segmentation model from 1.95% in corrupted volumes to 1.05%.
Multimodal fusion of structural MRI (sMRI) and dynamic functional network connectivity (dFNC) can reveal how brain structure relates to changing functional states. When the same structural latent representation is coupled with multiple states, applying independent vector analysis (IVA) separately to each state can produce unrelated structural decompositions, while forcing identical decompositions may suppress state-specific relationships. In addition, not every subject expresses every dynamic state. We propose masked structural residual IVA (MSR-IVA), a state-aware framework that combines a shared structural representation with state-specific residual adaptations and masks for incomplete state expression. On an Alzheimer's Disease Neuroimaging Initiative cohort, MSR-IVA improved matched source coupling by 6.5% and reduced unmatched dependence by 15.7% relative to the independent pairwise IVA baseline. Among subjects expressing both states, mean absolute cross-state structural source correlation was 0.9177 for MSR-IVA versus 0.2978 for no sharing, demonstrating controlled structural sharing that preserves source correspondence while allowing state-specific adaptation.
Madhumitha Venkatesh, Shanawaj S Madarkar, Konda Reddy Mopurics.CV
We introduce BrainNorm, a normative foundation model, trained and tested on ~66,000 T1-weighted structural MRI (T1w sMRI) scans. By leveraging language-image style contrastive pretraining on healthy cohorts across ages, BrainNorm learns a Semantic Atlas Latent space (SAL), where each scan is represented as a set of atlas-parcel embeddings. This yields parcel-specific healthy aging template trajectories that support age-consistent template matching and localized deviation scoring relative to a subject's chronological age. Across 6 downstream cohorts, BrainNorm demonstrates generalization evaluated across 25 task-setting combinations spanning age estimation, brain-age gap estimation, parcel identification, and single- & multi-disease classification tasks under direct inference, zero-shot, few-shot & full-data linear-probe settings. The resulting deviation patterns in SAL space enable zero-shot tasks for disease prediction using parcel-wise abnormalities. Fine-tuning on healthy-only cohorts of downstream datasets further improves the performance of various tasks. Across all classification tasks, linear probing on BrainNorm's frozen embeddings outperforms 9 baselines finetuned under end-to-end supervision. Furthermore, the localized deviations identified by BrainNorm across various neurodegenerative disorders closely align with established neurodegeneration pathology in clinical literature.
Representational similarity analysis (RSA) is increasingly used to ask which learning rules give convolutional networks brain-like representations. Because biologically plausible rules such as feedback alignment, predictive coding and STDP do not scale, studies that include them train small networks on small images (typically 32x32 CIFAR) and then compare them to brain responses recorded for naturalistic stimuli modeled at far higher resolution. We find that a common result here -- that untrained or locally trained networks rival or beat backpropagation at early visual cortex -- depends strongly on the resolution at which the network is evaluated. The V1 gap between an untrained and a backprop-trained network widens from -0.001 +/- 0.007 at the 32 px training resolution to +0.044 +/- 0.006 at 224 px, growing monotonically across six resolutions (n = 5 seeds). It holds in human fMRI and, directionally, in single-seed macaque electrophysiology, along the training trajectory, and for an ImageNet ResNet-50 and a Swin-Tiny transformer trained at 224 px. We test four candidate mechanisms and none accounts for it: train/eval resolution matching, low-level Gabor and pixel structure, the normalization state of the untrained baseline, and convergence of the pooled descriptor toward a global brightness statistic. A fifth experiment locates it: capping image detail at the training resolution while letting the pooled positions grow 12-fold removes about 90% of the effect, so the dependence lives on the image-content axis. One control result is worth stating separately: a single scalar luminance value per image reaches rho = 0.074 against V1, matching the untrained network's 0.075, bounding what this comparison can resolve at V1 here. The one learning effect that holds across resolution sits at LOC. Comparisons at early visual cortex must control, and report, the evaluation resolution.
T2-weighted (T2w) brain MRI provides fluid-sensitive soft-tissue contrast that is important for neuro-oncology and radiotherapy planning. However, T2w scans are acquired with anisotropic voxels and appear blurred or stair-stepped on coronal and sagittal views, which obscures small structures and weakens any downstream 3D analysis. We propose VIPP-SR (View-Independent Patched Projection Super-Resolution), a cross-contrast guided super-resolution framework that restores the inter-plane resolution of an existing anisotropic T2w volume without an isotropic ground-truth T2w. VIPP-SR first trains a view-independent patched generator (VIP-GAN) to learn local T1c-to-T2w anatomical correspondence from high-resolution axial slices. The trained generator is then applied to axial, coronal, and sagittal views of the T1c volume to generate three orthogonal T2w estimates. Shape-preserving patching and deepest-skip removal reduce view-specific shortcuts, thereby constraining the generator to learn patch-local representations and enabling the zero-shot inter-plane transfer. Central to VIPP-SR, a projection-based optimization then enforces anatomical consistency across the three view-specific volumes, fusing them by balancing inter-plane self-consistency against per-view data fidelity. The generator is trained on BraTS-MET and evaluated on both the held-out BraTS-MET testing set and the BraTS-GLI cohort without retraining, assessing the cross-cohort generalizability. The results validate that VIPP-SR improves downstream segmentation over the real anisotropic T2w baseline, raising mean-label Dice from 0.330 to 0.465 on BraTS-MET and, zero-shot, from 0.473 to 0.563 on BraTS-GLI and ablation studies identify inter-plane self-consistency as the main source of the gain.
Damian Brzyski, Aaron Cohen, Zijian Wang +3stat.ME math.OC stat.ML
We introduce a new convex optimization framework for logistic scalar-on-matrix regression which incorporates nuclear and $\ell_1$ norm penalties to enforce simultaneously low-rank and sparse structures in the estimated coefficient matrix. The proposed method enables interpretable modeling of high-dimensional matrix-valued predictors in the presence of binary responses. We derive a custom algorithm based on the Alternating Direction Method of Multipliers (ADMM) to efficiently solve the resulting convex optimization problem and establish the theoretical properties of the obtained solution. Numerical experiments clearly demonstrate the effectiveness of our method in recovering meaningful predictive patterns. Finally, we apply our method to the brain imaging data to identify structures in functional brain connectivity matrices that are characteristic of subjects with a family history of alcohol use disorders (AUDs).
Alzheimer's Disease (AD) is a progressive neurodegenerative disorder that affects millions of older adults, with prevalence expected to rise significantly in the coming years. Early diagnosis, particularly during the mild cognitive impairment (MCI) stage, is critical for timely intervention. Structural Magnetic Resonance Imaging (sMRI) has emerged as a key modality for detecting AD-related brain changes, but traditional graph-based approaches often struggle with modality and inter-site heterogeneity, limiting diagnostic performance. In this paper, we propose Graph Matching Network for Alzheimer's Disease Diagnosis (GMN4AD), designed to model interactions between heterogeneous brain graphs derived from neuroimaging data. Unlike conventional methods that treat each brain graph independently, GMN4AD leverages graph matching to capture cross-graph relationships, enhancing diagnostic precision. Furthermore, we introduce a test-time domain adaptation strategy that combines contrastive learning to mitigate domain shifts during inference. Extensive experiments on three public AD datasets demonstrate that GMN4AD achieves superior performance compared to state-of-the-art methods, offering a robust and generalizable solution for AD diagnosis.
Badr AlKhamissi, Johannes Mehrer, Lara Marinov +3q-bio.NC cs.LG
Nearby neurons in cortex share similar response profiles, producing systematic spatial organization across sensory and cognitive systems. Recent topographic models reproduce aspects of this structure but remain unimodal and spatially constrain each layer separately, yielding fragmented maps that capture neither the contiguity of cortical processing streams nor their integration across modalities. We introduce Topo-Omni, a topographic multimodal model in which visual, auditory, and language/cognitive processing share a single contiguous in-silico sheet. Built by fine-tuning a pretrained foundation model with a spatial smoothness objective, this architecture develops clusters across modalities that are consistent with human neuroimaging, from sensory to cognitive systems. Driving or suppressing a cluster selectively biases or impairs perception, paralleling human intervention studies. Finally, we use our model to screen for novel clusters in-silico and discover new natural landscape and animal networks which we validate in human data. A single spatial principle thus organizes representations across modalities and processing stages, yielding testable hypotheses about cortical organization.
Danilo Danese, Angela Lombardi, Giuseppe Fasano +2cs.CV
Large and demographically balanced datasets are essential for reliable neuroimaging biomarkers. Full-resolution 3D brain MRI synthesis can support data augmentation in this setting, but existing approaches either incur prohibitive computational cost at volumetric scale or rely on lossy latent compression that may compromise anatomical detail. As a result, practical 3D generative augmentation often requires specialized compute infrastructure. We propose WaveDiT, a conditional flow matching framework operating in the coefficient space of a 3D Haar Discrete Wavelet Transform. The model combines factorized spatio-depth attention with band-wise heteroscedastic uncertainty modeling derived from higher-order wavelet statistics. Predicted log-variance is integrated directly into both the flow objective and conditioning pathway, enabling adaptive precision consistent with the heavy-tailed and input-dependent variance structure of anatomical detail. This formulation supports full-resolution 3D synthesis under practical memory and time constraints on a single modern GPU. Evaluation on a multi-site cohort demonstrates improved alignment between generated and real MRI distributions, together with enhanced downstream brain age prediction and region-level anatomical agreement relative to diffusion, latent, and wavelet-based baselines. Code is available at https://github.com/sisinflab/WaveDiT
Guikun Chen, Yuqian Chen, Yijie Li +5eess.IV cs.AI cs.LG
Diffusion MRI (dMRI) tractography is the only noninvasive approach for mapping white-matter pathways in the living human brain. It represents each brain as a tractogram: a large, unordered set of three-dimensional streamlines that includes information about both local streamline geometry and whole-brain anatomical organization. This structure makes tractograms a natural but challenging target for representation learning. Existing methods treat streamline classification and subject-level prediction as separate problems: streamline classifiers focus on geometric patterns, whereas subject-level prediction often depends on hand-crafted features. As a result, current methods do not learn reusable representations that connect streamline anatomy with whole-brain inter-subject variation. Here we introduce TractFM, a tractogram foundation model that learns reusable representations directly from whole-brain streamline sets. TractFM combines a local streamline encoder with a permutation-equivariant tractogram encoder, allowing all streamlines from a subject to be contextualized jointly in a single forward pass. Pretraining on dense anatomical tract parcellation, i.e., assigning anatomical labels to individual streamlines, yields two complementary representations: contextualized streamline-level embeddings for tract parcellation and compact subject-level descriptors for downstream prediction of subject phenotypes. Across three tractography algorithms and five dMRI datasets, TractFM transfers to both streamline-level and subject-level tasks. Its frozen representations achieve accurate tract parcellation and predict age and sex across independent datasets. These results show that whole-brain geometric context, learned once, can generalize across tractography pipelines, datasets, and prediction tasks.
Dictionary learning is a powerful tool for creating interpretable representations. When applied to functional magnetic resonance imaging (fMRI) data, the resulting patterns of brain activity can be used for various downstream tasks, such as brain state classification or population-level analysis. However, a major challenge is the variability in brain geometry across individuals. This is usually addressed by projecting each individual brain geometry onto a common template, which removes subject-specific information. In this work, we introduce a novel approach to dictionary learning on fMRI data that explicitly accounts for this variability. We use the optimal transport-based Fused Gromov-Wasserstein (FGW) distance to compare graphs with different geometries and features. To address the challenge of computing multiple FGW distances for large graphs such as those arising from fMRI data, we rely on amortized optimization to learn a neural network that predicts an approximation of the optimal transport plans, which substantially reduces the computational cost. Additionally, we learn dictionary atoms that depend on the FGW trade-off parameter, which controls the balance between feature alignment and structural consistency. Numerical experiments on the HCP dataset demonstrate that the proposed approach captures different levels of geometric variability in the data and provides representations that preserve essential information.
Romain Valabregue, Ines Khemir, Eric Badinet +3cs.CV
Synthetic training has recently advanced brain MRI segmentation by enabling contrast-agnostic models trained entirely on generated data. However, most existing approaches rely on hundreds of automatically labeled templates, introducing systematic biases and limiting their flexibility to incorporate new anatomical structures. We present the Segment It All Model (SIAM), a 3D whole-head segmentation framework for 16 anatomical structures, trained using only six high-quality, manually annotated templates. SIAM extends domain randomization to both intensity and shape domains: synthetic image generation ensures contrast variability, while high-resolution spatial transformations model anatomical differences in cortical thickness and deep nuclei morphology. Unlike prior synthetic models, SIAM simultaneously segments brain as well as extra-cerebral tissues, including cerebrospinal fluid, vessels, dura mater, skull, and skin, enabling fully automated, preprocessing-free analysis. Evaluation across eight heterogeneous datasets (N=301), that include multiple contrasts (T1-weighted, T2-weighted, CT) and span a wide range of ages, demonstrates that SIAM matches or outperforms state-of-the-art methods for brain structures, in addition to extending automated segmentation to non-brain structures. The model also exhibits superior consistency across contrasts and repeated acquisitions, together with improved sensitivity to subtle gray matter atrophy. We openly release the model and the label templates at https://github.com/romainVala/SIAM.
Existing cross-subject fMRI decoding methods typically train a model on multiple scanned subjects and then adapt it to a new subject using substantial paired fMRI-image data. However, in realistic scenarios, new-subject fMRI data are often limited due to costly data acquisition, and raw data from previous subjects may be inaccessible, leading existing methods to suffer performance degradation during new-subject adaptation. In this paper, we identify that this degradation stems from two key issues: brain-side instability caused by large subject differences in fMRI responses, and image-side supervision unreliability caused by fine-grained visual details that are not reliably supported by limited fMRI signals. To address these challenges, we propose StableMind, a regularized adaptation framework designed to improve brain-side representation stability and image-side supervision reliability. (1) To stabilize brain representations, StableMind reuses ridge projections from the pretrained model as adaptation priors to constrain limited-data new-subject adaptation, and applies Fourier-based feature-level brain augmentation to improve robustness to individual variability. (2) To improve image supervision reliability, StableMind introduces difficulty-aware image blur for brain-image alignment, reducing the influence of fine-grained visual details that are weakly supported by limited fMRI signals while preserving stable visual structure. Experiments on the Natural Scenes Dataset under a unified 1-hour adaptation protocol demonstrate that StableMind achieves 84.02% image retrieval accuracy and 81.66% brain retrieval accuracy averaged over four subjects, surpassing the state-of-the-art method by 5.71% brain retrieval accuracy with fewer trainable adaptation parameters. Our code is available at https://github.com/lingeringlight/StableMind.