Neuroimaging
Momentum
22 papers in the last four weeks, up 267% on the four weeks before. 0.2% of all new papers.
Latest papers 166
Diffusion MRI requires repeated k-space acquisitions over multiple diffusion-encoding directions, making acquisition time dependent on both spatial and angular sampling. Existing joint k-q methods either associate directional parameters with fixed voxels or separate spatial reconstruction from angular completion. However, diffusion-weighted images acquired under different directions share the same anatomical organization, while their local signal intensities vary with diffusion encoding. Existing formulations do not fully exploit the complementarity between shared anatomy and direction-dependent signal variation. Consequently, residual spatial errors may be misinterpreted as genuine angular variation and propagated to unobserved directions. We propose a subject-specific spatial-angular Gaussian field for self-supervised joint k-q dMRI reconstruction. Shared 3D Gaussian primitives provide local spatial support, with each primitive carrying a continuous q-conditioned tensor-residual response. The signal at each location is synthesized from multiple overlapping primitive responses, coupling neighboring spatial regions and diffusion directions. The field is progressively optimized from undersampled k-space measurements of observed directions, without fully sampled targets or held-out-direction supervision. Experiments on three HCP diffusion shells under multiple acceleration settings demonstrated consistent improvements in missing-direction DWI reconstruction, tensor-derived metrics, and principal diffusion orientation estimation.
Asymmetric Paired-Annotation Learning for Multi-Structure ULF Pediatric Brain MRI Segmentation
Portable ultra-low-field (ULF) MRI can expand access to pediatric neuroimaging, but segmentation at 0.064 T remains challenging because anatomical boundaries are weakly delineated, small structures may be only partially visible, and high-field references can be locally misregistered. The LISA 2026 Challenge provides two non-equivalent annotations reflecting different sources of anatomical evidence: a highfield-derived (HF) mask defining the scored target and a low-field-edited (LF) mask aligned with visible ULF anatomy. In this challenge report, we describe AURA, an nnU-Net-based asymmetric supervision strategy that treats these annotations as distinct observations rather than interchangeable ground truths. AURA anchors training to the HF mask and incorporates the LF mask through a bounded reliability gate based on label disagreement, boundaries, predictive uncertainty, class reliability, and training stage. On a 16-case development split, the HF-supervised baseline, AURA, and their ensemble achieved Dice scores of 0.7984, 0.7950, and 0.7988, respectively, while the ensemble achieved an HD95 of 1.8892 and an ASSD of 0.7855. These results provide a preliminary evaluation of AURA within the LISA 2026 Challenge and motivate further assessment on the hidden test set and external ULF cohorts. Our code and pretrained models are available at https://github.com/minhdang050806/ A-nnU-Net-based-asymmetric-supervision-strategy.
CORAL: A Benchmark for Structure-aware and Brain-wide Neuron Reconstruction in Light Microscopy
Automatic neuron reconstruction from light microscopy images is a central problem in computational neuroanatomy. While recent methods have achieved encouraging results on local image blocks, it remains unclear whether such progress translates to reconstruction that is both structurally accurate and scalable to the whole-brain scale. We present CORAL, the first benchmark for structure-aware evaluation of automatic neuron reconstruction from light microscopy images at both local and whole-brain scales. Built on a high-quality whole-brain fMOST dataset with carefully curated annotations, CORAL establishes two progressive tasks: block-level reconstruction, which evaluates reconstruction methods under limited spatial context, and brain-wide reconstruction, which assesses complete neuron reconstruction at the whole-brain scale. To account for topological correctness beyond geometric distance similarity, we introduce a structure-aware metric based on fiber prediction. To further achieve complete neuron reconstruction across the entire brain, we develop a brain-wide neuron tracing framework that extends arbitrary local reconstruction methods to the whole-brain scale through an iterative local-to-global process. Using this benchmark, we provide the first structure-aware comparison of mainstream methods for local neuron reconstruction and further evaluate their performance in brain-wide reconstruction. Our results underscore the importance of structure-aware evaluation and the need for more robust methods for complete neuron reconstruction.
Benchmarking External Generalization of SPD Matrix Learning for Resting-State fMRI Connectome Prediction
Resting-state functional magnetic resonance imaging (rs-fMRI) functional connectivity (FC) matrices are widely used for individual-level prediction, but strong performance within one cohort may not generalize to a new cohort. We ask whether within-dataset performance remains when the test data come from an entirely held-out rs-fMRI dataset. Each scan is represented as a regularized symmetric positive definite (SPD) correlation connectome, which allows methods to use the geometry of the SPD manifold. We introduce a reproducible age-prediction benchmark across six rs-fMRI datasets: COBRE, ADNIDOD, Cam-CAN, ABIDE, OASIS-3, and ADNI. The benchmark compares a vectorized correlation baseline, Tangent-Space Ridge, SPDNet, and split-wise Riemannian harmonization under within-dataset GroupKFold, pooled GroupKFold, and leave-one-dataset-out (LODO) evaluation. Within-dataset and pooled GroupKFold results are substantially more favorable than LODO results. When an entire dataset is held out, prediction error increases, differences among methods narrow, and performance is strongly affected by age-range mismatch and cohort heterogeneity. The benchmark provides common inputs, model settings, data splits, and analysis scripts so that future SPD matrix learning methods can be evaluated under the same external-validation protocol.
A Deep RL based Framework for Targeted White Matter Tractography
Fiber tractography's ability to reconstruct the brain's structural pathways, has made it a crucial component of modern neuroimaging, enabling detailed, non-invasive mapping of structural connectivity and supporting a wide range of neurological research and clinical applications. However, despite its importance, tractography remains a challenging task due to the inherent complexity of white matter structure and its susceptibility to false positives, which can lead to the misrepresentation of critical pathways. To overcome these limitations, in this thesis, we propose a hybrid framework that integrates reinforcement learning with supervised learning for refining RL policies, specifically tailored for tract-specific tractography. Notably, our framework does not rely on ground-truth fibers for training. Moreover, the tract-specific formulation bypasses the need for an explicit segmentation process, simplifying the overall pipeline. Our work includes two main contributions, each building upon the previous. First, we introduce a hybrid approach that combines reinforcement learning with supervised learning (specifically, GPT-based policy learning) to refine policies in a tract-specific context. Second, we propose a scalable framework for data-driven multi-policy fusion, which leverages the complementary strengths of multiple RL policies to improve tractography performance and robustness. We demonstrate the effectiveness of our framework through extensive validation on benchmark public datasets including TractoInferno, HCP, and ISMRM-2015, highlighting its ability to generalize across data sources and accurately reconstruct brain white matter tracts. We believe that these contributions represent significant advancements in the field of tractography, improving robustness, reliability, and accuracy while reducing dependence on ground-truth annotations.
Decoding Phenotypes: A Framework for Fusing Genomic Language Models and Neuroimaging
Neuroimaging and genetic testing are two important clinical references for nervous system diseases, offering complementary diagnostic information. However, integrating genomic and neuroimaging data for precise disease diagnosis is challenging due to cross-modality heterogeneity. Existing imaging-genetics approaches mainly encode genetic information as hard-coded labels, which lose the local sequence context around disease-associated variants. To address this limitation, we propose GeneFuse, a multimodal learning framework that aligns genetic representations from pre-trained Genomic Language Models (GLMs) with features extracted from images. GeneFuse integrates two components: (1) Genotype-Conditioned Feature Modulation (GCFM), a FiLM-inspired module that uses genomic embeddings to modulate image feature maps; and (2) Uncertainty-aware Genomic Residual Fusion (U-GRF), a fusion strategy that uses imaging-derived predictive uncertainty to gate the contribution of genotypic features. We evaluate GeneFuse on early cognitive decline identification (NC vs. MCI) and dementia screening (NC vs. AD). In the APOE-centered setting, GeneFuse achieves AUROCs of 0.77 and 0.83, outperforming existing imaging-genetics fusion methods. These results indicate that GLM-derived genomic embeddings provide additional information to imaging.
FedDOSE: Federated Learning Framework Decomposing Site Effects for Modeling Brain Dynamic Functional Connectivity
Functional Magnetic Resonance Imaging ( fMRI ) data are often pooled into collaborative multi-site consortia, as deep learning models for analyses require large datasets to generalize well. While Federated Learning (FL) offers a privacy-preserving paradigm for collaborative training, standard approaches continue to struggle with statistical heterogeneity. In particular, site differences pose a key challenge in multi-site data settings. Additionally, existing FL approaches for fMRI rely on static Functional Connectivity ( FC), omitting dynamic information in brain networks. To address this, we propose FedDOSE, a novel framework that explicitly decomposes site differences for analysis of dynamic FC (dFC). FedDOSE introduces a Modularity-Guided Tucker Decomposition block to encode high-dimensional dFC tensors and capture modular-level spatio-temporal patterns efficiently. Class-specific prototypes are generated across all sites and subsequently aligned at the global level by using a combination of Optimal Transport (OT) barycenter formulation and Procrustes analysis. Extensive experiments for diagnosing Autism Spectrum Disorder (ASD) and Attention-Deficit Hyperactivity Disorder (ADHD) on three multi-site resting-state fMRI datasets: ABIDE-I, ABIDE-II, and ADHD-200, demonstrate that FedDOSE outperforms state-of-the-art methods in ASD and ADHD detection. Our results highlight its effectiveness in learning robust representations from multi-site datasets for reliable analysis.
A foundation-model approach to pediatric headache classification from rs-fMRI
Headache is the most common neurological disorder in children and substantially affects quality of life. We investigated whether resting-state functional MRI (rs-fMRI) can support pediatric headache classification using machine learning. We encoded rs-fMRI data using NeuroSTORM, a recent foundation model, and fine-tuned it to distinguish healthy controls from children with headache and subsequently classify headache subtypes. We compared NeuroSTORM with a standard neuroscience approach using functional-connectivity (FC) matrices derived from brain activity as predictors. Using 189 rs-fMRI scans from 110 individuals collected across two visits (prevalence of any headache: 74%), NeuroSTORM achieved an area under the receiver operating characteristic curve (AUROC) of 0.82 (95% CI, 0.82-0.82) and an area under the precision-recall curve (AUPRC) of 0.93 (95% CI, 0.93-0.94) for discriminating headache from non-headache. In contrast, models trained on FC matrices showed lower performance (AUROC, 0.67 [95% CI, 0.67-0.67]; AUPRC, 0.85 [95% CI, 0.85-0.85]). In multiclass classification of healthy controls, chronic migraine, and non-chronic headaches (e.g., post-viral headache, new daily persistent headache, post-traumatic headache), NeuroSTORM achieved a macro-AUROC of 0.69 (95% CI, 0.68-0.69). Results suggest that the approach can distinguish chronic migraine but has difficulty differentiating other headache subtypes from chronic migraine. Overall, under limited-data conditions, NeuroSTORM appears to capture latent rs-fMRI representations that transfer to headache-related tasks without relying on FC features. These findings provide proof of concept for fMRI-based prediction of pediatric headache and highlight potential future utility for subtype identification and individualized treatment strategies.
International Transfer of Stochastic Cortical Self-Reconstruction
Stochastic cortical self-reconstruction (SCSR) enables personalized mapping of gray matter atrophy, a hallmark of neurodegenerative disorders such as Alzheimer's disease (AD), onto high-resolution cortical surfaces. Unlike conventional normative modeling approaches, which typically operate at a coarse regional level and remain inherently constrained by the covariates included during training, SCSR estimates an individualized healthy reference directly from the observed cortical thickness at the vertex level. This allows the detection of subtle, subject-specific deviations from healthy cortical shape. In this work, we investigate the generalization and transferability of SCSR, originally trained on UK Biobank (UKB) data, to an independent Chinese population dataset. Specifically, we evaluate the ability of SCSR-derived Z-scores to discriminate between healthy scans, individuals with mild cognitive impairment (MCI), and patients with AD, while also assessing model robustness across the lifespan. We compare four training strategies: direct application of the UKB-trained model, fine-tuning on Chinese data, training from scratch, and joint training on UKB and Chinese cohorts. As reconstruction backbones, we consider both a multilayer perceptron (MLP) and a Spherical UNet (SUNet). Our results demonstrate that SCSR provides robust detection of cortical atrophy in the Chinese population across all evaluated models. The highest discriminative performance was achieved by the fine-tuned SUNet model (average pairwise AUC = 0.848), followed closely by the UKB-trained SUNet. Moreover, reconstruction errors remained low across the lifespan, even when the training population exhibited a substantially narrower age distribution, indicating strong cross-population transferability.
Predicting Brain Morphometry with MT-GNN: Mesh Evolution in Continuous Time with Graph-Based Metric Tensor Embeddings
Predicting how a subcortical structure's shape will evolve from a few prior scans could support prognosis and clinical-trial enrichment. Existing longitudinal mesh predictors either extrapolate shape trajectories via high-dimensional embeddings or regress vertex deformations directly. We instead predict the surface's intrinsic geometry in continuous time: a single per-structure graph network predicts the future per-vertex first fundamental form (metric tensor) for an arbitrary causal multiple-visit history and an arbitrary prediction horizon, conditioned on a Fourier encoding of the lead time. The predicted metric is decoded into a surface by a differentiable As-Rigid-As-Possible solver, and the model is trained end-to-end on the rigid-aligned vertex error. Training through the reconstruction keeps the decoded prediction a valid surface and consistently improves it. On 14 subcortical structures from the ADNI dataset, the proposed mesh evolution model (MT-GNN) predicts best among the evaluated methods at every horizon ( mean vertex error vs. the temporal mean, , beating it on 14/14 structures), ahead of geodesic shape regression (DCM, ) and a mesh transformer (TransforMesh, ; ), with the lead widening as the horizon grows.
Towards Reliable and Reproducible Fetal Brain Biometry: A Deep Learning Approach Using MRI
Fetal brain biometry is essential for quantitative assessment of brain development, supporting gestational age estimation, developmental monitoring, and detection of abnormalities. In clinical practice, measurements are manually performed, making them time-consuming and prone to variability. While automated approaches have been proposed, reproducible methods remain limited, particularly those providing anatomically interpretable landmark localization. We present a fully automated deep learning-based framework for reliable and reproducible brain biometry from 3D super-resolution-reconstructed fetal brain MRI. The proposed four-step pipeline derives biometric parameters by jointly estimating linear measurements and their corresponding anatomical landmarks. A 3D convolutional neural network is trained to regress landmark coordinates from brain segmentation label maps, followed by measurement-specific geometric optimization to refine landmark positions and compute measurements. The pipeline is evaluated on two publicly available fetal MRI datasets comprising 150 volumes (gestational age range: 20-37 weeks) acquired across different scanners and protocols, assessing five key biometric measurements across varying acquisition settings and providing a comprehensive evaluation of both measurement accuracy and landmark localization using quantitative metrics and visual assessment. Compared with the only available automated pipeline, the proposed method achieves comparable or improved accuracy for most measurements. In conclusion, we introduce a straightforward pipeline for reliable biometry estimations, with efficiency, interpretability and scalability that support integration into clinical workflows.
CyberNeuro: A Privacy-Preserving Agentic Workbench for Cohort-Scale Neuroimage and Clinical Data Analysis
Despite tremendous success in neuroimaging methodology, making large-scale, high-dimensional datasets ready for AI/ML applications remains a critical operational bottleneck. Conventional workflows require extensive manual effort across metadata curation, pipeline execution, post-processing quality control, and data management, a burden that disproportionately excludes laboratories with limited manpower and computational infrastructure. To address this real-world barrier, there is an urgent need for scalable, cost-effective computational platforms that democratize advanced neuroimaging analytics and accelerate discoveries in mental health and clinical translation. Capitalizing on multi-agent LLM breakthroughs, we introduce CyberNeuro, an agentic workbench with a tailored local LLM-model ('WandaMind') for automated neuroimaging and health-data analysis. Driven by four dedicated agents (Planner, Validator, Dispatcher, and Reporter) communicating via a secure MCP bridge and a pinned execution layer, CyberNeuro enables researchers to execute complex workflows using natural language while maintaining clinical-grade data privacy. On the public NeuroBench suite, CyberNeuro increases held-out domain accuracy from 40% to 69% over the baseline model. Beyond automated metrics, the platform integrates a human-in-the-loop verification panel to ensure rigorous biomedical quality control. Across the same end-to-end 10-batch cohort workflow suite, the local WandaMind configuration completed all tasks with an estimated aggregate token count of about 10.6% using WandaMind and 61.7% using cloud providers of token usage, compared to Neuroclaw, respectively. The platform and its production-ready modules are available at https://wanda-cyberbench.com.
NeuroPilot: An Agent-Driven Smart Pipeline for Processing, Quality Control, and Managing Neuroimages
Transforming raw neuroimage archives into analysis-ready derivatives relies on three brittle stages: data standardization, modality-specific preprocessing, and quality control (QC). While individual neuroimaging tools are well developed, their orchestration requires project-specific scripts, environment-adaptive tuning, and labor-intensive manual QC. To address this, we introduce NeuroPilot, a multi-agent system that digitalizes the expertise of neuroimage processing, QC, and data management into three LLM-invocable skills: dcm2bids-skill, neuroimage-pre-skill, and qc-agent-skill. The LLM-driven agent autonomously orchestrates workflows, generalizing various infrastructure settings into a single configuration to achieve the highest scalability. Demonstrating the system's generalizability, we deployed NeuroPilot across 17 cohorts (>123,000 subjects) spanning infant to aging populations and multiple MRI modalities (structural, diffusion, functional). In practice, after standardizing data via the dcm2bids-skill, the agent dynamically routes datasets to the optimal neuroimage-pre-skill based on available modalities and cohort traits (e.g., dispatching T1w and fMRI data to fMRIPrep, or selecting specialized pipelines for infant cohorts). The qc-agent-skill then drives an evidence-based, semi-automated QC via a 3-D browser dashboard, utilizing a multi-tiered verification system to optimize failed cases and escalate complex issues for supervisor inspection. Quantitatively, our QC agent screened 558 production subjects, validating its automated flags against FreeSurfer's topology-defect metrics. The infant processing pipeline achieved a 100% (201/201) completion rate on QC-validated inputs. Importantly, NeuroPilot compresses the traditional 2--3 month timeline for training staff and processing complete datasets into a single week. NeuroPilot is deployed in https://wanda-cyberbench.com/.
Do Medical Foundation Models Generalize on the African Brain?
Medical foundation models (FMs) are increasingly used for brain MRI analysis. However, their evaluation remains dominated by high-resource datasets, leaving generalization to African cohorts underexplored. We assess whether FMs generalize equally to African and non-African brain MRI data across two tasks: dementia classification using a Nigerian dataset and brain tumor segmentation using BraTS-Africa. We evaluate two generalist FMs (BrainIAC, 3DINO) and two segmentation-specific FMs (MedSAM2, Medical-SAM2) against a from-scratch baseline. For classification, FMs provide limited gains (highest ROC-AUC of 0.86 with BrainIAC), whereas for segmentation they consistently improve performance, reaching up to 0.86 Dice with MedSAM2. Performance differences between African and non-African cohorts are inconsistent and appear more related to dataset size than data origin. These results suggest that FMs do not exhibit an inherent bias against African cohorts, and highlight the limited availability and diversity of African neuroimaging datasets as the main barrier to robust evaluation and deployment.
MPP-GNN: Subject-Adaptive Community Detection for fMRI-Based Alzheimer's Disease Classification
Functional magnetic resonance imaging (fMRI) is a widely used technique for studying the brain. Recent methods that utilize graph neural networks (GNNs) for analysis of brain functional connectivity have shown great potential for the classification of brain disorders, such as Alzheimer's disease (AD). However, these methods often assume a preset number of functional modules across all subjects, which overlooks inter-subject variability. In addition, the discovered modules are rarely used to directly guide the learned connectivity patterns. Here, to address these issues, we propose a Meta Probabilistic Pooling GNN (MPP-GNN). We frame the model's task as a coupled, bilevel optimization that performs adaptive graph partitioning hierarchically to discover subject-specific modules and then uses the discovered brain modules as an explicit prior to guide edge refinement and representation learning. We validate MPP-GNN on two public datasets for AD classification, achieving the highest AUC in comparison to established baselines for both datasets. Furthermore, our analysis demonstrates that MPP-GNN shows significant alignment with the canonical functional-network organization defined by the Yeo brain atlas and reveals a network-level dedifferentiation pattern for AD.
An Attention-Based Framework for Alzheimers Disease Classification Using Resting-State fMRI
Accurate identification of Alzheimers disease (AD) using resting-state functional magnetic resonance imaging (rs-fMRI) remains challenging due to the high dimensionality, noise, and complex inter-regional dependencies inherent in functional brain connectivity, which limit the effectiveness of traditional approaches based on handcrafted connectivity features or conventional machine learning models. In this work, we present an attention-based deep learning framework for Alzheimers disease classification that operates directly on rs-fMRI functional connectivity matrices by treating brain regions as tokens and employing a Transformer-inspired self-attention mechanism to model long-range and global functional dependencies across distributed brain networks. The proposed framework learns discriminative functional representations without reliance on manual feature engineering and is evaluated on a longitudinal cohort from the Alzheimers Disease Neuroimaging Initiative (ADNI) comprising cognitively normal and Alzheimers disease subjects with multiple visits. A subject-wise evaluation protocol is adopted to prevent information leakage across visits, and class-weighted optimization is incorporated to address mild class imbalance. Experimental results for binary AD versus cognitively normal classification demonstrate that the proposed attention- based rs-fMRI model achieves an accuracy of 88.95% and a ROC-AUC of 0.90, along with a favorable precision-recall balance, highlighting the effectiveness of self-attention-driven functional connectivity modeling as a robust and interpretable approach for Alzheimers disease detection using resting-state fMRI.
When Language Models Meet NeuroGraphs: Exploring Enhanced Agentic LLM Framework Towards Brain Network Analysis
Brain network analysis is crucial for understanding cognition and neurological disorders, yet existing deep learning methods mainly treat connectome analysis as a graph-to-logit classification problem, offering limited explanatory reasoning. Large language models (LLMs) provide a promising interface for knowledge-intensive scientific analysis, but directly applying general-purpose LLMs to brain networks remains challenging due to the structure-language gap, limited neuroscience grounding, and overconfident positive predictions. In this paper, we propose \textbf{BrainAgent}, an agentic LLM framework for knowledge-enhanced brain network analysis. BrainAgent reformulates connectome classification as an iterative process of topology-aware understanding, external retrieval, reasoning, and reflection. Specifically, it first converts raw brain networks into compact multi-level structural descriptions through brain-specific analysis tools, then retrieves relevant neuroscience knowledge and task-specific cases to ground the reasoning process, and finally generates structured predictions with reflective verification. Experiments on four public rs-fMRI datasets show that BrainAgent consistently improves different closed-source and open-source LLM backbones over direct prompting and standard reasoning baselines. Further ablation and interpretability analyses demonstrate the effectiveness of each component and show that BrainAgent produces more comprehensive, multi-level, and verifiable explanations.These results indicate that agentic LLMs provide a practical route toward interpretable and knowledge-grounded brain network analysis.
Toward High-Fidelity 3D Point-Cloud Learning for Brain Folding Morphology Prediction Using Trans-Unet
Learning high-fidelity point-cloud features in the 3D space poses significant challenges, including permutation invariance, lack of local context, difficulty in fine-grained surface reconstruction, and high computational cost. In this article, we propose Trans-Unet, a novel framework that addresses these issues by first tansforming 3D point-cloud data into a 2D grid domain and then employing a U-shaped hybrid model that integrates Convolutional Neural Networks, and self-attention mechanisms. The proposed Trans-Unet effectively learns and reconstructs precise features from high-resolution 3D point-cloud data (with 40,401 points in surface and 2,382 points in fiber) derived from a predefined finite element brain patch growth model, enabling accurate prediction of brain folding patterns. By combining multiple techniques, Trans-Unet leverages the complementary strengths: the 3D-to-2D transformation preserves fine-grained structural information while significantly reducing computational cost and the curse of dimensionality; convolutional blocks capture hierarchical, low-level local representations; and the self-attention mechanism models global, high-level semantics and long-range dependencies. The dataset consists of 3D point-clouds containing both brain surface patches and fiber information generated by a large-scale finite element model. Trans-Unet is applied to predict brain surface folding from the initial state (state 0 or states 0-2) to the final state (state 3). Experimental results demonstrate that Trans-Unet achieves high-resolution predictions of brain patch growth, surpassing existing methods in both fidelity and accuracy.
Real-time Reconstruction of Human Visual Perception from fMRI
Real-time closed-loop neurofeedback based on functional magnetic resonance imaging (fMRI) has led to important scientific and clinical advances. However, the sophistication of the analysis methods used in real-time fMRI lags behind the state-of-the-art in fMRI decoding, largely due to computational factors: Most advanced decoding pipelines do not fit within the envelope of real-time processing, where the analysis needs to be conducted in a matter of seconds and without leveraging data acquired later in the session. Here, we present a real-time compatible adaptation of a computationally intensive state-of-the-art pipeline for reconstructing perceived natural images (MindEye2), and we demonstrate that reliable fine-grained decoding is still achievable in this setting. Using RT-Cloud, an open-source, scalable cloud-based platform, we performed a real-time scan where we decoded single-trial visual perception within seconds after an image was shown to the participant. Finally, we use simulated analyses to document the factors driving changes in performance from offline to real-time analysis. This work serves as a proof-of-concept that it is feasible to deploy these powerful fMRI decoding pipelines in real-time analysis, paving the way for their use in brain-computer interfaces for scientific discovery and clinical treatment.
SIINR: Structurally Informed Implicit Neural Representations for super-resolution with uncertainty quantification of clinical quality diffusion MRI datasets
Diffusion Magnetic Resonance Imaging (dMRI) is a powerful tool for probing brain microstructure, but clinical acquisitions are often limited by low out-of-plane resolution, resulting in degraded structural information and reduced utility for advanced analysis. We introduce SIINR (Structurally Informed Implicit Neural Representations), a general framework for super-resoltion of clinical dMRI datasets while quantifying uncertainty in the reconstructed outputs. SIINR utilizes a supervised 3D U-net as a prior and combines it with a self-supervised implicit neural representation (INR) that fuses the high-resolution prior and the original low-resolution data. The INR enables joint modeling across spatial and angular domains, enforces data consistency, and provides analytic approximate posterior distributions for downstream uncertainty quantification. We validate the framework on a diverse set of open-access dMRI datasets, demonstrating that SIINR outperforms standard interpolation methods in both quantitative error metrics and qualitative anatomical fidelity. Experiments on clinical cases, including subjects with multiple sclerosis and brain lesions, illustrate the framework its ability to propagate intensity changes and flag uncertain regions in challenging scenarios. SIINR is flexible, modular, and can be adapted to different upsampling ratios and downstream tasks, providing a principled approach for enhancing clinical dMRI and supporting robust interpretation of derived neuroimaging metrics.
Imputation-free transformer learning enables robust Alzheimer's disease prediction and calibrated uncertainty quantification across heterogeneous clinical cohorts
Accurate diagnostic classification and disease-severity prediction for Alzheimer's disease are hampered by the incompleteness and heterogeneity of real-world clinical data. Left unaddressed, these barriers prevent reliable disease modelling and hinder effective clinical evaluation. Conventional imputation strategies introduce systematic bias, distort inter-feature relationships, and yield overconfident predictions, limitations especially consequential in diagnostic settings. Here, we propose NITROGEN, an imputation-free transformer that jointly models within-patient feature dependencies and between-patient relational structure through masked and intersample attention, enabling robust multimodal learning directly from partially observed records. We trained NITROGEN on ADNI (N=7858 scans), and evaluated it on two independent cohorts: OASIS-3 (N=2675 scans) and AIBL (N=1286 scans). Across cohorts and diagnostic and cognitive score prediction tasks, NITROGEN showed robust calibration and uncertainty quantification advantages over tree-based ensemble methods, while maintaining competitive discriminative performance. Cross-cohort and cross-method analyses identified cortical thickness in the temporal pole, age, and APOE genotype as important, though not individually sufficient, features for AD classification. We further introduced a modality-aware uncertainty adjustment that augments predictive uncertainty proportionally to the importance of absent modalities, enabling calibrated confidence when diagnostic information is unavailable. Together, our results show that imputation-free attention learning preserved meaningful discrimination under cohort shift, revealing expected degradation on more distributionally different cohorts, and demonstrate that evaluating models along calibration, interpretability, and cross-cohort reliability, not accuracy alone, is essential for clinical deployment.
Fast Whole-Brain, Geometry-Aware Functional Alignment for Cross-Subject Decoding
Decoding brain activity is useful for characterizing brain processes and understanding the functional architecture underlying cognition. However, the inter-individual variability in brain response patterns limits the development of decoders that generalize across individuals. A solution to this challenge is functional alignment: aligning functional data across individuals before training population-level decoders. The core issue is to strike the balance between aligning functional features and preserving the anatomical structure, while maintaining computational efficiency. We introduce a new functional alignment method for fMRI, SpectralOT, that embeds cortical geometry into Laplace-Beltrami eigenmodes along functional data to regularize the alignment.
Attention-Based Segmentation of WMHs and Differentiation of Vascular vs. Demyelinating Lesions
White Matter Hyperintensities (WMHs) are commonly observed in brain Magnetic Resonance Imaging (MRI) scans. They are associated with various neurological conditions, including vascular and inflammatory demyelinating diseases. Despite differing in etiology, WMHs from these conditions often appear similar on Fluid Attenuated Inversion Recovery (FLAIR) images. This similarity makes differential diagnosis challenging. In this work, we highlight the potential of combining attention-based segmentation with feature-driven classification. This approach supports more accurate and efficient classification between vascular and demyelinating white matter pathologies. For segmentation, we evaluate the effectiveness of attention mechanisms, specifically the Bottleneck Attention Module (BAM) and the Convolutional Block Attention Module (CBAM). We also test different architectures, particularly Attention U-Net. In addition, we explore advanced training strategies, such as patch-based learning and a 2.5D approach, to enhance lesion detection. After segmentation, we extract morphological features from the lesion masks. We then use them to classify WMHs based on their underlying cause. Our experiments utilize five publicly available datasets with diverse imaging protocols to promote model generalizability, despite limited sample sizes. The results suggest that attention-based segmentation and feature-driven classification offer a promising direction for discriminating vascular and demyelinating white matter lesions. Further validation in larger clinical cohorts is still needed.
AT-Attn: Temporal-Aware Cross-Attention for Longitudinal Multimodal Alzheimer's Disease Diagnosis
In longitudinal Alzheimer's disease (AD) diagnosis support, clinical and imaging information is often collected at irregular visits. Integrating these multimodal observations may improve diagnostic assessment, but naive fusion can degrade performance when MRI is noisy or intermittently unavailable. We propose AT-Attn, a temporal-aware multimodal framework that combines Change-and-Time encoding, time-biased asymmetric cross-attention, and gated fusion to integrate MRI with longitudinal clinical information. We evaluate AT-Attn on an MRI-retained ADNI cohort of 1,520 patients using structural MRI, six cognitive-scale trajectories, and seven static clinical variables under patient-level five-fold cross-validation. The main asymmetric AT-Attn model achieves accuracy 0.719+/-0.024, macro F1 0.721+/-0.023, ROC-AUC 0.873+/-0.013, and PR-AUC 0.783+/-0.018, outperforming unimodal and naive multimodal fusion baselines while remaining competitive with strong tabular baselines. These results suggest that a temporal-aware and constrained fusion strategy can help structural MRI contribute clinically relevant complementary information for patient-level AD diagnosis support.
Navigating Hierarchy: Hyperbolic Learning on Brain Graphs for Disorder Diagnosis
Functional brain networks exhibit a hierarchical organization across ROI, community, and whole-brain levels, supporting local processing, inter-community coordination, and global integration. Recent studies have demonstrated that brain community-aware modeling is beneficial for both diagnosis and biomarker identification of brain networks. However, existing brain graph modeling methods often struggle to model ROI-community interactions, thereby failing to fully exploit the hierarchy across ROI, community, and whole-brain network levels. To address this issue, inspired by deep hyperbolic learning in modeling hierarchical structures, we propose a novel framework, termed Hyperbolic Learning on Brain Graphs (HLBG), for brain network analysis. The core idea of HLBG is to exploit the inherent hierarchical geometry of hyperbolic space to model the hierarchical relationships among ROIs, functional communities, and the whole-brain network, thereby learning hierarchy-aware and highly discriminative representations for brain network data. Specifically, HLBG first projects representations from ROIs, communities, and the whole-brain network into Lorentzian hyperbolic space. Then, the multi-level hierarchy is imposed via two geometric entailment constraints. In addition, we introduce a new Graph-aware Mamba (GaMamba) model, which incorporates topology-derived structural prompts into Mamba to capture long-range dependencies while preserving graph topological information. Experiments on ABIDE-I and REST-MDD demonstrate that HLBG outperforms state-of-the-art methods and identifies disorder-relevant functional biomarkers.
Latent graph encoding of multimodal neuroimaging features with generative AI architectures
While generative models enable encoding of complex neuroimaging data for feature generation and reconstruction, developing optimal architectural frameworks with appropriate encoding and latent space processes is crucial for studying structural and functional properties of the brain. We design a multimodal generative framework for structural and functional magnetic resonance imaging (MRI) features through systematic evaluation of encoding strategies, latent multimodal fusion, and generative model selection. Using structural gray matter volume (GMV) and static functional network connectivity (sFNC) features from a large neuroimaging dataset, we analyze generative frameworks involving variational autoencoders (VAEs), transformers, generative adversarial networks (GANs), and diffusion models. Architectures that employ modality-aware graph encoding of functional connectivity into a lower-dimensional latent space outperform vectorized encoders or direct data space approaches. The proposed multimodal graph VAE (gMMVAE) surpasses alternative generative variants across multiple metrics for generation fidelity, reconstruction quality, efficiency, and latent space discriminability, highlighting its potential for robust multimodal neuroimaging analysis.
CLABTOOLKIT: An Open-Source Toolkit for Routine Processing, Manipulation, and Visualization of Neuroimaging Data
Neuroimaging research requires manipulating heterogeneous data structures, including raw MRI volumes, volumetric parcellations, cortical surface meshes, tractograms, and connectivity matrices, across tools with incompatible interfaces and file formats, forcing researchers to repeatedly re-implement routine but technically demanding operations. We present CLABTOOLKIT, an open-source Python package that consolidates these operations into a single, coherent framework by representing volumetric, surface, and streamline data as interoperable Python objects. Five core data structures (Parcellation, Surface, AnnotParcellation, Tractogram, and Connectome) encapsulate common neuroanatomical entities and provide consistent methods for loading, processing, and exporting data across standard neuroimaging formats (e.g., NIfTI, GIFTI, FreeSurfer annotations, TCK/TRK), including connectome generation from a parcellation and scalar-map projection onto tractogram streamlines. Complementary modules support BIDS dataset management, FreeSurfer integration, diffusion MRI processing, morphometric analysis, graph-theoretical network analysis, and GPU-accelerated multi-panel visualization via PyVista. The toolkit comprises 19 modules organised into six layers, exposing 13 object-oriented classes with 234 methods and 207 standalone functions, and a JSON-based configuration system enables workflow customization without code changes. Unlike existing neuroimaging libraries, which typically address these tasks separately, CLABTOOLKIT combines color and lookup-table management, parcellation manipulation, multi-surface visualization, and tractography utilities within a single framework. CLABTOOLKIT is compatible with Python 3.9-3.12 and released under the Apache 2.0 license. Source code, documentation, and example workflows are available at https://github.com/connectomicslab/clabtoolkit.
SABER: A Semantic-Aligned Brain Network Analysis Framework via Multi-scale Hypergraphs
Effective brain disease diagnosis requires the synergy of brain connectivity patterns and high-level semantic knowledge. Existing methods, however, largely treat semantics from large language models (LLMs) as auxiliary features or supervision, limiting their direct role in decision-making and constraining classification stability and robustness. To overcome this, we propose a semantic-aligned brain network framework that actively integrates LLM-derived semantics into the prediction process. Specifically, ROI-level semantics are first incorporated via global self-attention to enrich node representations and provide whole-brain context. Multi-scale hypergraphs are then constructed to explicitly model functional subnetworks and multi-ROI interactions, addressing the locality limitations of traditional GNNs and capturing high-order dependencies. Finally, a decision-level semantic alignment mechanism selectively injects patient-specific textual embeddings into graph representations, enabling semantics to directly guide predictions without perturbing the underlying network structure. Experiments on public brain network datasets ABIDE and ADHD-200 demonstrate state-of-the-art performance, enhanced stability, and improved interpretability, particularly in small-sample settings.
CALM: Interpretable Cross-Modal Alignment for Biomarker Discovery from Unpaired Data
The interaction between brain structure and genetic influences is key to understanding neuropsychiatric disorders. However, most large-scale datasets are unimodal, providing either neuroimaging or genetics data. We propose CALM, a framework that learns interpretable associations between brain ROIs and genetic pathways from completely disjoint populations. CALM aligns the two modalities in a shared latent space via linear projections that simultaneously match the class-conditional latent distributions and ensure group separability. These projections provide interpretable pathway--ROI associations. When trained on unimodal imaging and genetics datasets, CALM generalizes to an unseen paired dataset, outperforming several state-of-the-art methods and ablation baselines. We also demonstrate stability of the learned associations against a paired baseline. Our experiments on autism spectrum disorder reveal immune and metabolic pathways linked to specific cortical regions and are consistent with established literature. Thus, CALM opens the door to leveraging large unimodal repositories for studying cross-modal interactions in brain disorders across disparate datasets.
Progressive Self-Supervised Learning with Individualized Community Assignment for Brain Network Analysis
Brain networks exhibit a modular community structure that varies across individuals and neurological conditions. However, existing self-supervised learning (SSL) methods often overlook this heterogeneity, relying on generic masking strategies that fail to capture subject-specific functional organization. We propose BrainPICM, a self-supervised framework for brain network analysis via progressive individualized community aware masking. BrainPICM formulates ROI-to-community mapping as a progressive unbalanced optimal transport process, yielding soft assignments and per-ROI confidence scores. Guided by these confidence estimates, a curriculum-style masking strategy gradually incorporates low-confidence, potentially pathological regions into training, enabling the model to learn both stable modular structures and individual variations. Additionally, a deviation-aware aggregation module quantifies functional reorganization by measuring mass redistribution relative to a population template, enhancing interpretability and downstream prediction. Experiments on three fMRI datasets (ABIDE-I, ADHD-200, ADNI) show that BrainPICM consistently outperforms state-of-the-art supervised and SSL methods in diagnostic accuracy, indicating that explicitly injecting modular community structure into masked modeling yields more functionally consistent and generalizable representations. The source code for this approach will be released at https://github.com/Hrychen7/BrainPICM.