Neuroimaging

Synapses are densely packed submicron structures that dynamically reorganize during learning and memory formation. Longitudinal \textit{in vivo} imaging of fluorescently tagged synaptic receptors offers a promising opportunity to study large-scale synaptic dynamics and how these processes are disrupted in neurological disease. However, in vivo imaging with 2-photon microscopy uses low laser power and therefore suffers from low signal-to-noise ratio (SNR) and high shot noise, nonlinear tissue motion between days, nonstationary fluctuations in synaptic fluorescence, and significant blur induced by the microscope point spread function (PSF). Together, these factors make it challenging to detect and track synapses, especially in regions with high synaptic density. This paper presents a novel template-based framework for modeling synapses as varying luminance point sources that move under a nonlinear tissue deformation. Taking a unified Bayesian approach, we apply this model to microscopy data by deriving a posterior that incorporates a diffeomorphic mapping for domain warping, a Gaussian point spread function for the imaging process, and a Poisson observation model for raw photon counts. The Bayesian solution simultaneously: (1) Constructs a probabilistic template of synapse locations, (2) denoises and deconvolves the image data, (3) infers fluorescence intensities, (4) performs diffeomorphic image registration to correct for tissue motion, and (5) provides confidence regions for these parameter estimates. We demonstrate the framework on both a 2D+t simulated dataset and a 3D+t longitudinal \textit{in vivo} microscopy dataset of fluorescent synapses imaged in a mouse over two weeks.

We present Supervised Deep Multimodal Matrix Factorization (SD3MF), an interpretable framework for integrative brain network analysis that generalizes Symmetric Nonnegative Matrix Tri-Factorization (SNMTF) from unsupervised single-graph clustering to supervised prediction over populations of multimodal graphs. SD3MF learns deep hierarchical factorizations for each modality together with a shared latent representation that aligns subjects across views. An encoder-decoder formulation jointly optimizes graph reconstruction and supervised prediction, while adaptive weights enable data-driven multimodal fusion. By representing each subject through community-level interaction matrices, the model yields interpretable and discriminative features. Experiments on multimodal connectome datasets show that SD3MF consistently outperforms strong deep learning baselines such as CNNs and GNNs, while enabling biologically interpretable insights. Code for reproducibility is available at: https://github.com/amjadseyedi/SD3MF.

Decoding speech from non-invasive brain signals is challenging. For the LibriBrain 2025 Speech Detection task, we propose a novel two-step framework that bypasses direct reconstruction. First, a contrastive learning model retrieves the matching speech segment for the given test MEG from a large-scale audio library (LibriVox). Second, a speech detection model generates the binary silence/speech sequence directly from this retrieved audio. With this approach, our team Sherlock Holmes achieved first place in the extended track (F1-score: 0.962), demonstrating that leveraging external audio databases is a highly effective strategy.

Brain encoder models predict cortical fMRI responses from the internal activations of pretrained vision and language networks, and are typically evaluated by held-out prediction accuracy. This is a useful signal for training but a poor one for interpretation: it tells us an encoder fits the data without telling us whether it has internalized the functional organization of the brain. We propose feature visualization -- gradient ascent on the encoder's predicted activation for a target region of interest (ROI) -- as a complementary interpretability technique, and apply it to TRIBE v2 composed with V-JEPA 2 (ViT-G, 40 layers), holding both frozen and synthesizing still images for seven regions spanning the ventral and dorsal visual hierarchies. Under identical hyperparameters, the probe recovers a visible progression of increasing spatial scale and feature complexity across V1 to V4, matching the ventral-stream hierarchy. It also produces three distinctive downstream regimes: radial "frozen-motion" streaks for the middle temporal area (MT) despite static-only optimization, face-like features for the fusiform face area (FFA), and consistent rectilinear line patterns for the parahippocampal place area (PPA). Optimized FFA stimuli drive the predicted region ~4x as much as a natural face photograph, consistent with feature visualization producing adversarial super-stimuli rather than canonical exemplars. The probe is simple, differentiable, and applicable to any brain encoder with a differentiable backbone, allowing for qualitative evaluation of brain encoders.

Spatio-temporal fetal brain atlases are important for characterizing normative neurodevelopment and identifying congenital anomalies. However, existing atlas construction pipelines necessitate days for slice-to-volume reconstruction (SVR) to generate high-resolution 3D brain volumes and several additional days for iterative volume registration, thereby rendering atlas construction from large-scale cohorts prohibitively impractical. We address these limitations with INFANiTE, an Implicit Neural Representation (INR) framework for high-resolution Fetal brain spatio-temporal Atlas learNing from clinical Thick-slicE MRI scans, bypassing both the costly SVR and the iterative non-rigid registration steps entirely, thereby substantially accelerating atlas construction. Extensive experiments demonstrate that INFANiTE outperforms existing baselines in subject consistency, reference fidelity, intrinsic quality and biological plausibility, even under challenging sparse-data settings. Additionally, INFANiTE reduces the end-to-end processing time (i.e., from raw scans to the final atlas) from days to hours compared to the traditional 3D volume-based pipeline (e.g., SyGN), facilitating large-scale population-level fetal brain analysis. Code: https://github.com/hu2274898/INFANiTE

This article presents a novel approach to keyframe detection in ultrasound videos, with a particular focus on fetal brain imaging. The proposed model is a composite neural network architecture that combines a Convolutional Neural Network (CNN) with a Recurrent Neural Network (RNN). The CNN extracts spatial features from individual video frames, while the RNN captures temporal dependencies between consecutive frames within each video sequence. The proposed model may improve the efficiency and accuracy of fetal brain ultrasound analysis, thereby supporting earlier detection, diagnosis, and treatment planning for selected fetal brain conditions.

Transforming neuroimaging data into clinically actionable biomarkers is a knowledge-intensive and labor-intensive process. Standardized workflows such as fMRIPrep have improved robustness and efficiency, but they are statically configured and cannot reason about downstream objectives, deliberate over alternative strategies, or close the loop between intermediate evidence and subsequent decisions in the way a human researcher would. This lack of closed-loop adaptation often leaves domain experts trapped in a cycle of manual trial-and-error to tune parameters and remediate pipeline failures, severely constraining the scalability of clinical biomarker development. To bridge this gap, we introduce NEXUS, an autonomous multi-agent framework that integrates neuroimaging workflow execution with scientific-objective understanding. Unlike conventional flat toolcalling agents, NEXUS adopts a code-centric execution paradigm where specialist agents collaboratively synthesize and optimize executable programs over composable domain-specific primitives. This design enables robust, long-horizon workflow construction that adapts dynamically to runtime observations. Furthermore, we propose a hierarchical verification framework for autonomous quality control, integrating cohort-level metric screening with agentic visual inspection to drive evidence-grounded workflow remediation. Experiments on ADHD-200 and ADNI demonstrate that NEXUS outperforms standard workflow-based baselines in predictive performance while exhibiting sophisticated agentic behaviors, including strategy exploration and adaptive refinement. The code is available at https://github.com/LearningKeqi/Virtual-Neuroscientist-NEXUS.

Deep learning models in medical imaging typically operate as parametric memory, diagnosing patients by recalling fixed knowledge learned during training. This contrasts sharply with clinical practice, where physicians employ analogical reasoning to diagnose new cases by referencing similar records from past exemplars. While In-Context Learning (ICL) frameworks such as Tabular Prior-Fitted Networks (TabPFN) offer a promising diagnosis-by-reference paradigm, they are designed with tabular-specific inductive priors and rely on non-differentiable preprocessing pipelines, leading to manifold mismatch and gradient fracture when applied to heterogeneous multimodal data. To address these limitations, we propose PromptDx, a novel diagnosis-by-reference framework that leverages a pre-trained TabPFN as an ICL engine while enabling seamless integration with multimodal representations. Our core contribution is a Differentiable Prompt Tuning (DPT) mechanism that aligns a Masked Multimodal Modeling module with the pre-trained ICL engine. By training a lightweight adapter as a differentiable surrogate for the engine's non-differentiable preprocessors, we enable an end-to-end optimization of multimodal prompts within the ICL paradigm. We validate our method on the Alzheimer's Disease Neuroimaging Initiative (ADNI) dataset using 3D MRI and tabular biomarkers. Experiments demonstrate that our approach outperforms traditional parametric baselines. Notably, our method achieves superior performance using only 1% context samples compared to 30% in standard ICL, demonstrating exceptional manifold condensation ability. We further validate the generalizability of our DPT framework across six tabular datasets with diverse scales. Overall, our method offers a more data-efficient and clinically aligned paradigm for Alzheimer's Disease diagnosis.

Recent advances in neuroimaging have deepened our understanding of the brain's complex functional and structural organization. Among these, functional Magnetic Resonance Imaging (fMRI) - particularly resting-state fMRI (rs-fMRI) - has emerged as a tool for identifying biomarkers of intrinsic brain connectivity and delineating large-scale neural networks. These networks are typically represented as volumetric spatial maps that capture functionally coherent brain regions and reflect individual differences in brain activity and structure. The spatial resolution of these maps plays an important role, as it determines the ability to localize functional units with precision, perform reliable brain parcellation, and detect subtle, spatially specific neurobiological alterations associated with development, aging, or disease. Therefore, improving the effective resolution of neuroimaging-derived maps holds significant promise for enabling more detailed insights into brain architecture and its relationship to behavior and pathology. To address this need, we propose NeuroGAN-3D, a novel 3D generative super-resolution model tailored to the computational demands of volumetric neuroimaging. Our model leverages a generative adversarial network architecture to enhance the spatial resolution of rs-fMRI spatial maps, significantly outperforming a conventional baseline.

Decoding imagined speech from non-invasive brain recordings is challenging because imagined datasets are scarce and difficult to align temporally across subjects and sessions In this work, we propose a new approach to the decoding of imagined speech that leverages the richer and more reliably labeled recordings during listening to speech. We collected paired listened and imagined MEG recordings to rhythmic melodic and spoken stimuli from trained musicians. Using trained musicians helped improve temporal alignment across conditions. We then developed a three-stage decoding pipeline that revealed consistent and meaningful relationships between neural activity evoked by imagining and listening to the same stimuli. First, we trained six linear and neural models to map imagined MEG responses to listened responses. We evaluated these models against a null baseline from unseen subjects to validate that the predicted-listening responses preserve stimulus-specific information. In the second stage, we trained a contrastive word decoder exclusively on the listened MEG responses, and evaluated it using four embedding strategies including semantic, acoustic, and phonetic representations. In the third stage, we process the imagined MEG responses from held-out subjects through the mapping pipeline to compute the corresponding listening responses that are then decoded by the listened decoder. Using rank-based analysis, we show that the imagined words are decodable significantly above chance. We shall report here the results of a proof-of-concept implementation to decode imagined speech, where all evaluations are performed on held-out subjects. We also demonstrate that performance improves with training data size, suggesting that this approach is scalable and can directly be made applicable to realistic brain-computer interface scenarios.

Functional connectivity (FC) derived from resting-state fMRI is widely used to characterize large-scale brain network alterations in neurological and psychiatric disorders. However, FC construction critically depends on the choice of brain atlas, and different parcellations may emphasize distinct organizational features, leading to heterogeneous and sometimes inconsistent representations. Existing multi-atlas approaches partially alleviate this issue but often fuse atlas-derived features or predictions at a relatively shallow level, while single-atlas disentanglement methods do not explicitly address cross-atlas heterogeneity. We propose Multi-Atlas Disentangled Connectivity LEarning (MADCLE), a multi-branch representation learning framework that jointly encodes FC matrices derived from different brain atlases. Rather than introducing a single explicitly shared latent variable across parcellations, MADCLE learns atlas-wise disease-related representations and encourages them to be cross-atlas consistent through distributional alignment. Meanwhile, covariate-related and atlas-dependent residual factors are modeled separately using covariate similarity supervision, atlas-specific reconstruction, and decorrelation constraints, thereby reducing the leakage of non-disease and parcellation-dependent information into the disease-related embeddings. Experiments on the ADNI and ADHD-200 datasets suggest that MADCLE achieves competitive or improved performance compared with single-atlas baselines, multi-atlas GNN/Transformer models, and recent multi-atlas consistency frameworks. These results support the potential value of structured disentanglement for FC-based disorder identification under heterogeneous parcellation schemes.

Multimodal neuroimaging analysis often involves complex, modality-specific preprocessing workflows that require careful configuration, quality control, and coordination across heterogeneous toolchains. Beyond preprocessing, downstream statistical analysis and disease classification commonly require task-specific code, evaluation protocols, and data-format conventions, creating additional barriers between raw acquisitions and reproducible scientific analysis. We present NeuroAgent, an LLM-driven agentic framework that automates key preprocessing and analysis steps for heterogeneous neuroimaging data, including sMRI, fMRI, dMRI, and PET, and supports interactive downstream analysis through natural-language queries. NeuroAgent employs a hierarchical multi-agent architecture with a feedback-driven Generate-Execute-Validate engine: agents autonomously generate executable preprocessing code, detect and recover from runtime errors, and validate output integrity. We evaluate the system on 1,470 subjects pooled across all ADNI phases (CN=1,000, AD=470), where all subjects have sMRI and tabular data, with subsets also having Tau-PET (n=469), fMRI (n=278), and DTI ($n=620$). Pipeline ablation studies across multiple LLM backends show that capable models reach up to 100% intent-parsing accuracy, with the strongest backend (Qwen3.5-27B) reaching 84.8% end-to-end preprocessing step correctness. Automated recovery limits manual intervention to edge cases where human review is required via the Human-In-The-Loop interface. For Alzheimer's Disease classification using automatically preprocessed multimodal data, our agent ensemble achieves an AUC of 0.9518 with four modalities, outperforming all single-modality baselines. These results show that NeuroAgent can reduce the manual effort required for neuroimaging preprocessing and enable end-to-end automated analysis pipelines for neuroimaging research.

Graph-based learning from functional magnetic resonance imaging (fMRI) has shown strong potential for brain network analysis. However, existing methods often degrade under cross-site out-of-distribution (OOD) settings, as site-dependent confounder effects can obscure disease-related connectivity patterns and static functional connectivity (FC) does not explicitly capture informative within-scan variations. In this paper, we propose Cross-site OOD Robust brain nEtwork (CORE), a unified framework for brain network learning across unseen sites. First, CORE estimates site-specific confounder effects and aggregates the resulting deconfounders by cross-source reliability for unseen-site correction, while extracting a population scaffold of reproducible label-associated connections from site-wise residualized FC. It then summarizes temporal variations on scaffold edges into compact descriptors for line-graph modeling. Finally, prior-guided subject-adaptive gating modulates message passing, balancing population priors with individual variability. Extensive leave-one-site-out experiments on ABIDE, REST-meta-MDD, SRPBS, and ABCD demonstrate that CORE consistently outperforms competitive baselines, with up to a 10.3% relative improvement in accuracy. These gains also persist across different brain parcellation schemes on ABIDE.

Cognitive neuroscience is fragmented into specialized models, each tailored to specific experimental paradigms, hence preventing a unified model of cognition in the human brain. Here, we introduce TRIBE v2, a tri-modal (video, audio and language) foundation model capable of predicting human brain activity in a variety of naturalistic and experimental conditions. Leveraging a unified dataset of over 1,000 hours of fMRI across 720 subjects, we demonstrate that our model accurately predicts high-resolution brain responses for novel stimuli, tasks and subjects, superseding traditional linear encoding models, delivering several-fold improvements in accuracy. Critically, TRIBE v2 enables in silico experimentation: tested on seminal visual and neuro-linguistic paradigms, it recovers a variety of results established by decades of empirical research. Finally, by extracting interpretable latent features, TRIBE v2 reveals the fine-grained topography of multisensory integration. These results establish artificial intelligence as a unifying framework for exploring the functional organization of the human brain.

The lack of analytical models describing diffusion time dependence at intermediate time scales in complex tissue microstructure limits the accurate quantification of extracellular diffusivity and tissue microstructure. We introduce TRACED, a biophysical model that incorporates diffusion time dependence in cell distributions to quantify pathologically-relevant properties in solid tumors. Neural networks were trained on Monte Carlo diffusion simulations using sphere distribution-based geometries to enable the rapid computation of time-dependent diffusion MRI signals in cell populations of variable cell size. Model sensitivity and fit performance were assessed via simulation. Diffusion data from eight mixed-grade glioma patients was fitted using the TRACED model. Data fitting was performed using a novel physics-informed transfer learning pipeline, Sim2PINN. In two patients, cell size measurements were compared directly with image-localized histology. Simulation results indicate improved parameter estimation compared to the simple two-compartment model. TRACED enabled the simultaneous in vivo quantification of intracellular volume fraction, cell size distribution, extracellular intrinsic diffusivity, and tortuosity in glioma patients. Neural network implementations of diffusion time-dependence and tortuosity showed behavior consistent with coarse-graining and effective medium theory, respectively. Future work will explore the clinical utility of TRACED parameters in additional patients.

Self-supervised pretraining is promising for large-scale neuroimaging, yet the impact of region-aware masking and hybrid sequence modeling remains underexplored. In this work, we introduce Rhamba, a region-aware pretraining framework that integrates anatomically guided masking with hybrid Attention-Mamba architectures for resting state functional magnetic resonance imaging (fMRI) analysis. Models were pretrained on the ABIDE dataset using region-aligned patch embeddings and three masking strategies (Any, Majority, and Pure) with increasing spatial specificity. We evaluated four architectural variants: a Mamba only model, an Alternate architecture with interleaved Mamba and Attention blocks, and two hybrid encoder-decoder configurations (Attention-Mamba (AM) and Mamba-Attention (MA)). The pretrained models were fine-tuned on downstream classification tasks using the COBRE and ADHD-200 datasets for schizophrenia and attention-deficit/hyperactivity disorder discrimination. We employed Integrated Gradients, an explainable AI method, to identify the brain regions contributing to model predictions. Masking strategy strongly influenced reconstruction behavior, with reconstruction loss following a consistent ordering (Any > Majority > Pure). However, this trend did not directly translate into downstream performance, where differences were modest and dataset-dependent. The hybrid architecture with the MA configuration achieved the highest average AUROC across both datasets, and Rhamba outperformed state-of-the-art methods in comparative evaluation. Region-wise analysis showed that peak performance depends on the interaction between masking strategy and architecture rather than a single dominant configuration. Overall, Rhamba offers a flexible framework for balancing interpretability, scalability, and performance in large-scale fMRI representation learning.

Despite being resource-intensive to train, 3D convolutional neural networks (CNNs) have been the standard approach to classify CT and MRI scans. Recent work suggests that deep multiple instance learning (MIL) may be a more efficient alternative for 3D brain scans, especially when the pre-trained image encoder used to embed each 2D slice is frozen and only the pooling operation and classifier are trained. In this paper, we provide a systematic comparison of simple MIL, attention-based MIL, 3D CNNs, and 3D ViTs across three CT and four MRI datasets, including two large datasets of at least 10,000 scans. Our goal is to help resource-constrained practitioners understand which neural networks work well for 3D neuroimages and why. We further compare design choices for attention-based MIL, including different encoders, pooling operations, and architectural orderings. We find that simple mean pooling MIL, without any learnable attention, matches or outperforms recent MIL or 3D CNN alternatives on 4 of 6 moderate-sized tasks. This baseline remains competitive on two large datasets while being 25x faster to train. To explain mean pooling's success, we examine per-slice attention quality and a semi-synthetic dataset where we can derive the best possible classifier via a Bayes estimator. This analysis reveals the limits of existing MIL approaches and suggests routes for future improvements.

Brain encoding models not only serve to decipher how visual stimuli are transformed into neural responses, but also represent a critical step toward visual prostheses that restore vision for patients with severe vision disorders. Brain encoding involves two fundamental steps: achieving faithful reconstruction of neural responses and establishing cross-modal alignment between visual stimuli and neural responses. To this end, we propose ViBE, a novel brain encoding framework for generating magnetoencephalography (MEG) and electroencephalography (EEG) signals from visual stimuli. Specifically, we first design a spatio-temporal convolutional variational autoencoder (TSC-VAE) that captures the spatio-temporal characteristics of M/EEG signals for effective neural response reconstruction. To bridge the modality gap between visual features and neural representations, we employ Q-Former to map CLIP image embeddings to the TSC-VAE latent space, producing neural proxy embeddings. For comprehensive cross-modal alignment, we combine mean squared error (MSE) loss for point-wise feature matching with sliced Wasserstein distance (SWD) for probability distribution alignment between the neural proxy embeddings and TSC-VAE latent embeddings. We conduct extensive experiments on the THINGS-EEG2 and THINGS-MEG datasets, demonstrating the effectiveness of our approach in generating high-quality M/EEG signals from visual stimuli.

Encoding models provide a powerful framework for linking continuous stimulus features to neural activity; however, traditional voxelwise approaches are limited by measurement noise, inter-subject variability, and redundancy arising from spatially correlated voxels encoding overlapping neural signals. Here, we propose an independent component (IC)-based encoding framework that dissociates stimulus-driven and noise-driven signals in fMRI data. We decompose continuous fMRI data from naturalistic story listening into ICs using one subset of the data, and train encoding models on independent data to predict IC time series from large language model representations of linguistic input. Across subjects, a subset of ICs exhibited consistently high predictivity. These ICs were spatially and temporally consistent across subjects and included cognitive networks known to respond during story listening (auditory and language). Auditory component time series were strongly correlated with acoustic stimulus features, highlighting the interpretability of identified component time series. Components identified as noise or motion-related artifacts by ICA-AROMA showed uniformly poor predictive performance, confirming that highly predicted components reflect genuine stimulus-related neural signals rather than confounds. Overall, IC-based encoding models enable analyses at the level of functional networks, accommodating the variability in network locations across individuals and providing interpretable results that are easy to compare across subjects. Code provided at: https://github.com/kamyahari/IC-Encoding-Models.git

Agentic artificial intelligence systems promise to accelerate scientific workflows, but neuroimaging poses unique challenges: heterogeneous modalities (sMRI, fMRI, dMRI, EEG), long multi-stage pipelines, and persistent reproducibility risks. To address this gap, we present NeuroClaw, a domain-specialized multi-agent research assistant for executable and reproducible neuroimaging research. NeuroClaw operates directly on raw neuroimaging data across formats and modalities, grounding decisions in dataset semantics and BIDS metadata so users need not prepare curated inputs or bespoke model code. The platform combines harness engineering with end-to-end environment management, including pinned Python environments, Docker support, automated installers for common neuroimaging tools, and GPU configuration. In practice, this layer emphasizes checkpointing, post-execution verification, structured audit traces, and controlled runtime setup, making toolchains more transparent while improving reproducibility and auditability. A three-tier skill/agent hierarchy separates user-facing interaction, high-level orchestration, and low-level tool skills to decompose complex workflows into safe, reusable units. Alongside the NeuroClaw framework, we introduce NeuroBench, a system-level benchmark for executability, artifact validity, and reproducibility readiness. Across multiple multimodal LLMs, NeuroClaw-enabled runs yield consistent and substantial score improvements compared with direct agent invocation. Project homepage: https://cuhk-aim-group.github.io/NeuroClaw/index.html

Understanding and predicting the progression of neurodegenerative diseases remains a major challenge in medical AI, with significant implications for early diagnosis, disease monitoring, and treatment planning. However, most available longitudinal neuroimaging datasets are temporally sparse with a few follow-up scans per subject. This scarcity of temporal data limits our ability to model and accurately capture the continuous anatomical changes related to disease progression in individual subjects. To address this problem, we propose a novel 4D (3DxT) diffusion-based generative framework that effectively models and synthesizes longitudinal brain anatomy over time, conditioned on available clinical variables such as health status, age, sex, and other relevant factors. Moreover, while most current approaches focus on manipulating image intensity or texture, our method explicitly learns the data distribution of topology-preserving spatiotemporal deformations to effectively capture the geometric changes of brain structures over time. This design enables the realistic generation of future anatomical states and the reconstruction of anatomically consistent disease trajectories, providing a more faithful representation of longitudinal brain changes. We validate our model through both synthetic sequence generation and downstream longitudinal disease classification, as well as brain segmentation. Experiments on two large-scale longitudinal neuroimage datasets demonstrate that our method outperforms state-of-the-art baselines in generating anatomically accurate, temporally consistent, and clinically meaningful brain trajectories. Our code is available on Github.

Several brain foundation models (FM) have recently been proposed to predict brain disorders by modelling dynamic functional connectivity (FC). While they demonstrate remarkable model performance and zero- or few-shot generalization, the salient features identified as potential biomarkers are yet to be thoroughly evaluated. We propose RE-CONFIRM, a framework for evaluating the robustness of potential biomarker candidates elucidated by deep learning (DL) models including FMs. From experiments on five large datasets of Autism Spectrum Disorder (ASD), Attention-deficit Hyperactivity Disorder (ADHD), and Alzheimer's Disease (AD), we found that although commonly used performance metrics provide an intuitive assessment of model predictions, they are insufficient for evaluating the robustness of biomarkers identified by these models. RE-CONFIRM metrics revealed that simply finetuning FMs leads to models that fail to capture regional hubs effectively, even in disorders where hubs are known to be implicated, such as ASD and ADHD. In view of this, we propose Hub-LoRA (Low-Rank Adaptation) as a fine-tuning technique that enables FMs to not only outperform customised DL models but also produce neurobiologically faithful biomarkers supported by meta-analyses. RE-CONFIRM is generalizable and can be easily applied to ascertain the robustness of DL models trained on functional MRI datasets. Code is available at: https://github.com/SCSE-Biomedical-Computing-Group/RE-CONFIRM.

Linear models are widely used in computational neuroimaging to identify biomarkers associated with brain pathologies. However, interpreting the learned weights remains challenging, as they do not always yield clinically meaningful insights. This difficulty arises in part from the inherent correlation between brain regions, which causes linear weights to reflect shared rather than region-specific contributions. In particular, some groups of regions, including homologous structures in the left and right hemispheres, are known to exhibit strong anatomical correlations. In this work, we leverage this prior neuroanatomical knowledge to introduce a whitening approach applied to groups of regions with known shared variance, designed to disentangle overlapping information across correlated brain measures. We additionally propose a regularized variant that allows controlled tuning of the degree of decorrelation. We evaluate this method using region-of-interest features in two psychiatric classification tasks, distinguishing individuals with bipolar disorder or schizophrenia from healthy controls. Importantly, unlike PCA or ICA which use whitening as a dimensionality reduction step, our approach decorrelates anatomically informed pairs of neuroanatomical regions while retaining the full input signal, making it specifically suited for feature interpretation rather than feature selection. Our findings demonstrate that whitening improves the interpretability of model weights while preserving predictive performance, providing a robust framework for linking linear model outputs to neurobiological mechanisms.

Resting-state functional magnetic resonance imaging (fMRI) has emerged as a cornerstone for psychiatric diagnosis, yet most approaches rely on pairwise brain cortical or sub-cortical connectivities that overlooks higher-order interactions (HOIs) central to complex brain dynamics. While hypergraph methods encode HOIs through predefined hyperedges, their construction typically relies on heuristic similarity metrics and does not explicitly characterize whether interactions are synergy- or redundancy-dominated. In this paper, we introduce $O$-information, a signed measure that characterizes the informational nature of HOIs, and integrate third- and fourth-order $O$-information into a unified multi-view information bottleneck framework for fMRI-based psychiatric diagnosis. To enable scalable $O$-information estimation, we further develop two independent acceleration strategies: a Gaussian analytical approximation and a randomized matrix-based Rényi entropy estimator, achieving over a 30-fold computational speedup compared with conventional estimators. Our tri-view architecture systematically fuses pairwise, triadic, and tetradic brain interactions, capturing comprehensive brain connectivity while explicitly penalizing redundancy. Extensive evaluation across four benchmark datasets (REST-meta-MDD, ABIDE, UCLA, ADNI) demonstrates consistent improvements, outperforming 11 baseline methods including state-of-the-art graph neural network (GNN) and hypergraph based approaches. Moreover, our method reveals interpretable region-level synergy-redundancy patterns which are not explicitly characterized by conventional hypergraph formulations.

The scarcity of labeled clinical data in oncology makes Few-Shot Learning (FSL) a critical framework for Computer Aided Diagnostics, but we observed that standard Prototypical Networks often struggle with the "prototype instability" caused by morphological noise and high intra-class variance in brain tumor scans. Our work attempts to minimize this by integrating a non-linear Logistic Chaos Module into a fine-tuned ResNet-18 backbone creating the Chaos-Enhanced ProtoNet(CE-ProtoNet). Using the deterministic ergodicity of the logistic chaos map we inject controlled perturbations into support features during episodic training-essentially for "stress testing" the embedding space. This process makes the model to converge on noise-invariant representations without increasing computational overhead. Testing this on a 4-way 5-shot brain tumor classification task, we found that a 15% chaotic injection level worked efficiently to stabilize high-dimensional clusters and reduce class dispersion. Our method achieved a peak test accuracy of 84.52%, outperforming standard ProtoNet. Our results suggest the idea of using chaotic perturbation as an efficient, low-overhead regularization tool, for the data-scarce regimes.

The accurate quantification of brain age from MRI has emerged as an important biomarker of brain health. However, existing approaches are often restricted to narrow age ranges and single-modality MRI data, limiting their capacity to capture the coordinated macro- and microstructural changes that unfold across the human lifespan. To address these limitations, we develop a multi-modal brain age framework to characterize the integrated evolution of brain morphology and white matter organization. Our model adopts a two-stage architecture, where modalities are processed independently and integrated via late fusion in both stages: first to estimate a probability distribution over six developmental stages, and then to predict age via probability-weighted stage-specialized experts. Experiments on nine datasets spanning fetal to elderly stages demonstrate competitive in-domain performance and out-of-domain generalization, with our method reducing MAE by 13% and 78% over existing baselines and multi-modal integration yielding 12-13% gains. Analysis of ADNI clinical groups further suggests the potential of the predicted brain age gap to characterize Alzheimer's-related brain aging.

Latent diffusion models have emerged as powerful generative models in medical imaging, enabling the synthesis of high quality brain magnetic resonance imaging scans. In particular, predicting the evolution of a patients brain can aid in early intervention, prognosis, and treatment planning. In this study, we introduce CLIMB, Controllable Longitudinal brain Image generation via state space based latent diffusion model, an advanced framework for modeling temporal changes in brain structure. CLIMB is designed to model the structural evolution of the brain structure over time, utilizing a baseline MRI scan and its acquisition age as foundational inputs. Additionally, multiple conditional variables, including projected age, gender, disease status, genetic information, and brain structure volumes, are incorporated to enhance the temporal modeling of anatomical changes. Unlike existing LDM methods that rely on self attention modules, which effectively capture contextual information from input images but are computationally expensive, our approach leverages state space, a state space model architecture that substantially reduces computational overhead while preserving high-quality image synthesis. Furthermore, we introduce a Gaussian-aligned autoencoder that extracts latent representations conforming to prior distributions without the sampling noise inherent in conventional variational autoencoders. We train and evaluate our proposed model on the Alzheimers Disease Neuroimaging Initiative dataset, consisting of 6,306 MRI scans from 1,390 participants. By comparing generated images with real MRI scans, CLIMB achieves a structural similarity index of 0.9433, demonstrating notable improvements over existing methods.

Alzheimer's disease (AD) confirmation often relies on positron emission tomography (PET) or cerebrospinal fluid (CSF) analysis, which are costly and invasive. Consequently, structural MRI biomarkers such as cortical thickness (CT) are widely used for non-invasive AD screening. Multiscale structural mapping (MSSM) was recently proposed to integrate gray-white matter contrasts (GWCs) with CT from a single T1-weighted MRI (T1w) scan. Building on this framework, we propose MSSM+, together with surface supervertex mapping (SSVM) and a Supervertex Vision Transformer (SV-ViT). 3D T1w images from individuals with AD and cognitively normal (CN) controls were analyzed. MSSM+ extends MSSM by incorporating sulcal depth and cortical curvature at the vertex level. SSVM partitions the cortical surface into supervertices (surface patches) that effectively represent inter- and intra-regional spatial relationships. SV-ViT is a Vision Transformer architecture operating on these supervertices, enabling anatomically informed learning from surface mesh representations. Compared with MSSM, MSSM+ identified more spatially extensive and statistically significant group differences between AD and CN. In AD vs. CN classification, MSSM+ achieved a 3%p higher area under the precision-recall curve than MSSM. Vendor-specific analyses further demonstrated reduced signal variability and consistently improved classification performance across MR manufacturers relative to CT, GWCs, and MSSM. These findings suggest that MSSM+ combined with SV-ViT is a promising MRI-based imaging marker for AD detection prior to CSF/PET confirmation.

Recent progress in visual brain decoding from fMRI has been enabled by large-scale datasets such as the Natural Scenes Dataset (NSD) and powerful diffusion-based generative models. While current pipelines are primarily optimized for perception, their performance under mental-imagery remains less well understood. In this work, we study how a state-of-the-art (SOTA) perception decoder (DynaDiff) can be adapted to reconstruct imagined content from the NSD-Imagery benchmark. We propose a latent functional alignment (LFA) approach that maps imagery-evoked activity to the pretrained model's semantic content-enriched conditioning space, by adding a simple alignment module, while keeping the original remaining components frozen. To mitigate the limited amount of matched imagery-perception supervision, we further introduce a neural retrieval-based augmentation strategy that selects semantically related NSD perception trials from the same participants. Across four subjects, LFA consistently improves high-level semantic reconstruction metrics relative to the frozen pretrained baseline and a voxel-space ridge alignment baseline, and enables above-chance decoding from multiple cortical regions. These results suggest that semantic structure learned from perception can be leveraged to stabilize and improve visual imagery decoding under out-of-distribution conditions.

Current fMRI foundation models primarily rely on a limited range of brain states and mismatched pretraining tasks, restricting their ability to learn generalized representations across diverse brain states. We present Brain-DiT, a universal multi-state fMRI foundation model pretrained on 349,898 sessions from 24 datasets spanning resting, task, naturalistic, disease, and sleep states. Unlike prior fMRI foundation models that rely on masked reconstruction in the raw-signal space or a latent space, Brain-DiT adopts metadata-conditioned diffusion pretraining with a Diffusion Transformer (DiT), enabling the model to learn multi-scale representations that capture both fine-grained functional structure and global semantics. Across extensive evaluations and ablations on 7 downstream tasks, we find consistent evidence that diffusion-based generative pretraining is a stronger proxy than reconstruction or alignment, with metadata-conditioned pretraining further improving downstream performance by disentangling intrinsic neural dynamics from population-level variability. We also observe that downstream tasks exhibit distinct preferences for representational scale: ADNI classification benefits more from global semantic representations, whereas age/sex prediction comparatively relies more on fine-grained local structure.