Functional Connectivity

Multimodal neuroimaging fusion of functional MRI (fMRI) and diffusion tensor imaging (DTI) provides complementary information for cognitive impairment analysis, but remains challenged by heterogeneous feature spaces and misaligned representations. We propose NeuroAlign, a hierarchical framework for structured multimodal fusion. It introduces (1) Dual-Modal Hierarchical Alignment (DMHA), which models multi-scale dynamic connectivity and aligns dynamic-static and functional-structural embeddings; and (2) Dual-Domain Hierarchical Interaction (DDHI), which enables fine-grained modulation and global interaction between connectivity- and region-level features. To support feature-level inspection, we design Synergistic Activation Mapping (SAM), a gradient-free, marker-oriented attribution method for DFC, SFC, ALFF, and FA. Evaluated on GUTCM, ADNI, and OASIS under five-fold validation, NeuroAlign achieves competitive MCI/SCD detection and preliminary cross-dataset transferability. Attribution analyses reveal modality-specific and partially consistent brain patterns, providing model-derived evidence for multimodal representation analysis.

Brain foundation models (BFMs) are self-supervised Transformers pretrained on fMRI data. We posit that these models should capture each subject's cognitive performance from their fMRI signal. Yet across three state-of-the-art BFMs and every readout we test, they predict cognition worse than a linear regression from the $\sim$80K parameters of the functional connectivity matrix (FC). The gap widens with scale: BrainLM's 650M model predicts cognition worse than its 111M. We attribute this to a variance allocation problem: BFM pretraining captures the variance components that dominate fMRI but not the higher-order structure that predicts cognition. Our per-cumulant analysis of the reconstructed signal shows that the second-order covariance is partially preserved, while the third-order co-skewness tensor is largely destroyed. To recover what BFMs lose, we design a linear pipeline that projects the fMRI signal into the subspace that best preserves its co-skewness and computes FC there. This exceeds raw FC and every pretrained BFM on every dataset and parcellation we test, outperforming prior state-of-the-art under controlled evaluation with no pretraining and no GPU. We recover the raw-FC ceiling on BrainLM's forward pass by finetuning with a loss targeted at this same subspace. This shows that the bottleneck is the pretraining objective, not the architecture or the model size.

Major depressive disorder (MDD) is a common neuropsychiatric condition whose accurate diagnosis from resting-state functional magnetic resonance imaging (rs-fMRI) remains difficult. Dynamic functional connectivity (DFC) captures time-varying interactions among brain regions and provides rich spatio-temporal information, yet current DFC-based methods face three limitations: sliding-window Pearson correlation yields noisy estimates sensitive to window length and motion artifacts; correlation-derived node features do not fully exploit frequency-domain properties of blood-oxygen-level-dependent (BOLD) signals; and most spatio-temporal graph models handle spatial structure and temporal dynamics in separate stages, restricting their ability to represent coupled brain network evolution. To overcome these issues, we reformulate DFC learning as joint spatio-temporal graph representation learning under a Hawkes-process-inspired temporal dependency prior and propose HWSTCL, a two-stage framework built on a reliability-refined joint spatio-temporal graph with a kernel-weighted pretraining objective. Within each temporal window, BOLD signals are encoded as spectral node descriptors and functional edges are refined by an exponential distance-decay prior that down-weights less reliable long-range connections. The joint graph is then formed by linking each region to itself across future windows through a Hawkes-inspired exponential kernel, allowing spatial and temporal information to be propagated together during message passing. A kernel-weighted contrastive objective further promotes temporal consistency for each region across windows while reducing redundant similarity between different regions. Experiments on a benchmark rs-fMRI dataset show that HWSTCL outperforms recent baselines and yields coherent spatio-temporal representations for MDD diagnosis.

We investigate how internal representations emerge across hierarchical processing systems by introducing a neuroscience-inspired framework for analyzing deep spiking neural networks (SNN) through the lens of functional connectivity. Drawing on concepts from systems neuroscience and information theory, we form the first-order functionally-connected (1FC) group of a neuron based on its statistically significant pairwise correlations with neurons from the previous layer of a trained SNN architecture. We then track its response properties during inference under various conditions. Our analysis shows that several principles of functional connectivity previously observed in biological cortex are preserved in spiking ResNet architectures. These 1FC ensembles display interesting properties: their aggregate cofiring reliably predicts downstream neuronal responses through a robust, ReLU-like input-output relationship, whose gain scales systematically with ensemble size. Reliable encoding of the presented class emerges only during high 1FC cofiring events, which themselves occur infrequently, indicating that informative representations are concentrated in rare but highly coordinated activity patterns. Under uniform random noise or adversarial perturbations, these response profiles are disrupted, particularly in early and intermediate layers. This enables a targeted high-resolution interrogation at specific nodes and pathways. We showed that the functional connectivity structure is shaped by learning and this structure breaks under weight permutation. These establish 1FC ensembles as a functionally meaningful substrate for input encoding and information transfer, with potential implications in designing targeted fine-grained diagnostics on the information flow.

Correlation matrices are fundamental summaries of functional brain networks, yet standard analyses often treat entries independently, ignoring the curved geometry of correlation space. Existing geometric methods frequently lack closed-form operations or depend on arbitrary region ordering, limiting scalability. We introduce a scalable geometric framework with two components: (i) the Off-log metric, a smooth transformation mapping correlation matrices to symmetric zero-diagonal matrices. This enables closed-form expressions for distances, Frechet means, and linear models, allowing standard statistical modeling without complex manifold optimization. (ii) Grassmannian subspace discrimination, which compares subjects via principal-angle distances between eigenvector subspaces, resolving inherent sign and basis ambiguities. Both components integrate into standard machine-learning workflows for inference, regression, and classification. Validated across two clinical cohorts (Parkinson's and psychosis) and three ageing fMRI datasets, the Off-log metric increased sensitivity in permutation tests and matched or exceeded Riemannian and Euclidean baselines in classification. Brain-age prediction performance was comparable, with Riemannian metrics excelling in two of three cohorts. The Grassmannian method consistently outperformed Euclidean baselines, highlighting disease-relevant networks. Overall, geometry-aware representations improve sensitivity and predictive performance while remaining straightforward to deploy at scale.

Masked autoencoders (MAEs) have recently shown promise for self-supervised representation learning of resting-state brain functional connectivity (FC). However, a fundamental question remains unresolved: how should FC matrices be tokenized to align with the intrinsic modular organization of large-scale brain networks? Existing approaches typically adopt region-centric or graph-based schemes that treat FC as structurally homogeneous elements and overlook the large-scale network brain organization. We introduce NERVE (Network-Aware Representations of Brain Functional Connectivity via Bilinear Tokenization), a self-supervised learning framework that redefines FC tokenization by partitioning FC matrices into patches of intra- and inter-network connectivity blocks. Unlike image-based MAE, where fixed-size patches share a common tokenizer, FC patches defined by network pairs are heterogeneous in size and correspond to distinct functional roles. To resolve this problem, NERVE embeds FC patches through a novel structured bilinear factorization. This formulation preserves network identity and reduces parameter complexity from quadratic to linear scaling in the number of networks. We evaluate NERVE across three large-scale developmental cohorts (ABCD, PNC, and CCNP) for behavior and psychopathology prediction. Compared to structurally agnostic MAE variants and graph-based self-supervised baselines, the proposed network-aware formulation yields more stable and transferable representations, particularly in cross-cohort evaluation. Ablation studies confirm that the proposed bilinear network embedding and anatomically grounded parcellation are critical for performance. These findings highlight the importance of incorporating domain-specific structural priors into self-supervised learning for functional connectomics. Code is available at: https://github.com/leomlck/NERVE.

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.

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.

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.

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.

Functional magnetic resonance imaging (fMRI) is widely used for studying and diagnosing brain disorders, with functional connectivity (FC) matrices providing powerful representations of large-scale neural interactions. However, existing diagnostic models are trained either on a single site or under full multi-site access, making them unsuitable for real-world scenarios where clinical data arrive sequentially from different institutions. This results in limited generalization and severe catastrophic forgetting. This paper presents the first continual learning framework specifically designed for fMRI-based diagnosis across heterogeneous clinical sites. Our framework introduces a structure-aware variational autoencoder that synthesizes realistic FC matrices for both patient and control groups. Built on this generative backbone, we develop a multi-level knowledge distillation strategy that aligns predictions and graph representations between new-site data and replayed samples. To further enhance efficiency, we incorporate a hierarchical contextual bandit scheme for adaptive replay sampling. Experiments on multi-site datasets for major depressive disorder (MDD), schizophrenia (SZ), and autism spectrum disorder (ASD) show that the proposed generative model enhances data augmentation quality, and the overall continual learning framework substantially outperforms existing methods in mitigating catastrophic forgetting. Our code is available at https://github.com/4me808/FORGE.

Understanding how brain structure and function interact is key to explaining intelligence yet modeling them jointly is challenging as the structural and functional connectome capture complementary aspects of organization. We introduced Multi-scale Adaptive Graph Network (MAGNet), a Transformer-style graph neural network framework that adaptively learns structure-function interactions. MAGNet leverages source-based morphometry from structural MRI to extract inter-regional morphological features and fuses them with functional network connectivity from resting-state fMRI. A hybrid graph integrates direct and indirect pathways, while local-global attention refines connectivity importance and a joint loss simultaneously enforces cross-modal coherence and optimizes the prediction objective end-to-end. On the ABCD dataset, MAGNet outperformed relevant baselines, demonstrating effective multimodal integration for advancing our understanding of cognitive function.

Early identification of adolescents at risk for substance use initiation (SUI) is vital yet difficult, as most predictors treat connectivity as static or cross-sectional and miss how brain networks change over time and with behavior. We proposed NeuroBRIDGE (Behavior conditioned RIemannian Koopman Dynamics on lonGitudinal connEctomes), a novel graph neural network-based framework that aligns longitudinal functional connectome in a Riemannian tangent space and couples dual-time attention with behavioral-conditioned Koopman dynamics to capture temporal change. Evaluated on ABCD, NeuroBRIDGE improved future SUI prediction over relevant baselines while offering interpretable insights into neural pathways, refining our understanding of neurodevelopmental risk and informing targeted prevention.

Understanding how large-scale brain networks represent visual categories is fundamental to linking perception and cortical organization. Using high-resolution 7T fMRI from the Natural Scenes Dataset, we construct parcel-level functional graphs and train a signed Graph Neural Network that models both positive and negative interactions, with a sparse edge mask and class-specific saliency. The model accurately decodes category-specific functional connectivity states (sports, food, vehicles) and reveals reproducible, biologically meaningful subnetworks along the ventral and dorsal visual pathways. This framework bridges machine learning and neuroscience by extending voxel-level category selectivity to a connectivity-based representation of visual processing.

Connectivity structure shapes neural computation, but inferring this structure from population recordings is degenerate: multiple connectivity structures can generate identical dynamics. Recent work uses low-rank recurrent neural networks (lrRNNs) to infer low-dimensional latent dynamics and connectivity from observed activity, enabling a mechanistic interpretation of the dynamics. However, standard approaches for training lrRNNs can recover spurious structures irrelevant to the underlying dynamics. We first characterize the identifiability of connectivity structures in lrRNNs and determine conditions under which a unique solution exists. To find such solutions, we develop an inference framework based on maximum entropy and continuous normalizing flows (CNFs), trained via flow matching. Instead of estimating a single connectivity matrix, our method learns a distribution over connection weights that is maximally unbiased over unidentifiable components while matching the observed dynamics. This approach captures complex yet necessary distributions such as heavy-tailed connectivity found in empirical data. We validate our method on synthetic datasets with connectivity structures that generate multistable attractors, limit cycles, and ring attractors, and demonstrate its applicability in recordings from rat frontal cortex during decision-making. Our framework shifts circuit inference from recovering connectivity to identifying which connectivity structures are computationally required, and which are artifacts of underconstrained inference.

Integrating structural and functional connectomes remains challenging because their relationship is non-linear and organized over nested modular hierarchies. We propose a hierarchical multiscale structure-function coupling framework for connectome integration that jointly learns individualized modular organization and hierarchical coupling across structural connectivity (SC) and functional connectivity (FC). The framework includes: (i) Prototype-based Modular Pooling (PMPool), which learns modality-specific multiscale communities by selecting prototypical ROIs and optimizing a differentiable modularity-inspired objective; (ii) an Attention-based Hierarchical Coupling Module (AHCM) that models both within-hierarchy and cross-hierarchy SC-FC interactions to produce enriched hierarchical coupling representations; and (iii) a Coupling-guided Clustering loss (CgC-Loss) that regularizes SC and FC community assignments with coupling signals, allowing cross-modal interactions to shape community alignment across hierarchies. We evaluate the model's performance across four cohorts for predicting brain age, cognitive score, and disease classification. Our model consistently outperforms baselines and other state-of-the-art approaches across three tasks. Ablation and sensitivity analyses verify the contributions of key components. Finally, the visualizations of learned coupling reveal interpretable differences, suggesting that the framework captures biologically meaningful structure-function relationships.

Brain network analysis provides an interpretable framework for characterizing brain organization and has been widely used for neurological disorder identification. Recent advances in self-supervised learning have motivated the development of brain network foundation models. However, existing approaches are often limited by atlas dependency, insufficient exploitation of multiple network views, and weak incorporation of anatomical priors. In this work, we propose MV-BrainFM, a multi-view brain network foundation model designed to learn generalizable and scalable representations from brain networks constructed with arbitrary atlases. MV-BrainFM explicitly incorporates anatomical distance information into Transformer-based modeling to guide inter-regional interactions, and introduces an unsupervised cross-view consistency learning strategy to align representations from multiple atlases of the same subject in a shared latent space. By jointly enforcing within-view robustness and cross-view alignment during pretraining, the model effectively captures complementary information across heterogeneous network views while remaining atlas-aware. In addition, MV-BrainFM adopts a unified multi-view pretraining paradigm that enables simultaneous learning from multiple datasets and atlases, significantly improving computational efficiency compared to conventional sequential training strategies. The proposed framework also demonstrates strong scalability, consistently benefiting from increasing data diversity while maintaining stable performance across unseen atlas configurations. Extensive experiments on more than 20K subjects from 17 fMRI datasets show that MV-BrainFM consistently outperforms 14 existing brain network foundation models and task-specific baselines under both single-atlas and multi-atlas settings.

Inferring the connectivity of neural circuits from incomplete observations is a fundamental challenge in neuroscience. We present a covariance-based method for estimating the weight matrix of a recurrent neural network from sparse, partial measurements across multiple recording sessions. By accumulating pairwise covariance estimates across sessions where different subsets of neurons are observed, we reconstruct the full connectivity matrix without requiring simultaneous recording of all neurons. A Granger-causality refinement step enforces biological constraints via projected gradient descent. Through systematic experiments on synthetic networks modeling small brain circuits, we characterize a fundamental control-estimation tradeoff: stimulation aids identifiability but disrupts intrinsic dynamics, with the optimal level depending on measurement density. We discover that the ``incorrect'' linear approximation acts as implicit regularization -- outperforming the oracle estimator with known nonlinearity at all operating regimes -- and provide an exact characterization via the Stein--Price identity.

Dynamic functional connectivity (dFC) derived from resting-state functional magnetic resonance imaging (fMRI) has been extensively utilized in brain science research. The sliding window correlation (SWC) method is a widely used approach for constructing dFC by computing correlation coefficients between amplitude time series of signals from pairs of brain regions. In this study, we propose an integrated approach that incorporates both amplitude and phase information of fMRI signals to improve the detection of brain disorders. Specifically, we introduce a multi-scale fusion learning framework, namely MSFL, which leverages two complementary dFC features derived from SWC and phase synchronization (PS). Here, SWC captures amplitude correlations, while PS measures phase coherence within dFC. We evaluated the efficacy of MSFL in classifying autism spectrum disorder and major depressive disorder using two publicly available datasets: ABIDE I and REST-meta-MDD, respectively. The results indicate that MSFL significantly outperforms existing comparative models. Moreover, we performed model explanation analysis using the SHAP framework, which showed that both types of dFC features from SWC and PS contribute to detecting brain disorders.

Modeling the complex interactions among functional subnetworks is crucial for the diagnosis of mental disorders and the identification of functional pathways. However, learning the interactions of the underlying subnetworks remains a significant challenge for existing Transformer-based methods due to the limited number of training samples. To address these challenges, we propose KD-Brain, a Prior-Informed Graph Learning framework for explicitly encoding prior knowledge to guide the learning process. Specifically, we design a Semantic-Conditioned Interaction mechanism that injects semantic priors into the attention query, explicitly navigating the subnetwork interactions based on their functional identities. Furthermore, we introduce a Pathology-Consistent Constraint, which regularizes the model optimization by aligning the learned interaction distributions with clinical priors. Additionally, KD-Brain leads to state-of-the-art performance on a wide range of disorder diagnosis tasks and identifies interpretable biomarkers consistent with psychiatric pathophysiology. Our code is available at https://anonymous.4open.science/r/KDBrain.

Brain network analysis based on functional Magnetic Resonance Imaging (fMRI) is pivotal for diagnosing brain disorders. Existing approaches typically rely on predefined functional sub-networks to construct sub-network associations. However, we identified many cross-network interaction patterns with high Pearson correlations that this strict, prior-based organization fails to capture. To overcome this limitation, we propose the Brain Hierarchical Organization Learning (BrainHO) to learn inherently hierarchical brain network dependencies based on their intrinsic features rather than predefined sub-network labels. Specifically, we design a hierarchical attention mechanism that allows the model to aggregate nodes into a hierarchical organization, effectively capturing intricate connectivity patterns at the subgraph level. To ensure diverse, complementary, and stable organizations, we incorporate an orthogonality constraint loss, alongside a hierarchical consistency constraint strategy, to refine node-level features using high-level graph semantics. Extensive experiments on the publicly available ABIDE and REST-meta-MDD datasets demonstrate that BrainHO not only achieves state-of-the-art classification performance but also uncovers interpretable, clinically significant biomarkers by precisely localizing disease-related sub-networks.

Brain activity is intrinsically a neural dynamic process constrained by anatomical space. This leads to significant variations in spatial distribution patterns and correlation patterns of neural activity across variable and heterogeneous scenarios. However, dominant brain functional network construction methods, which relies on pre-defined brain atlases and linear assumptions, fails to precisely capture varying neural activity patterns in heterogeneous scenarios. This limits the consistency and generalizability of the brain functional networks constructed by dominant methods. Here, a neural dynamics-informed pre-trained framework is proposed for personalized brain functional network construction. The proposed framework extracts personalized representations of neural activity patterns in heterogeneous scenarios. Personalized brain functional networks are obtained by utilizing these representations to guide brain parcellation and neural activity correlation estimation. Systematic evaluations were employed on 18 datasets across tasks, such as virtual neural modulation and abnormal neural circuit identification. Experimental results demonstrate that the proposed framework attains superior performance in heterogeneous scenarios. Overall, the proposed framework challenges the dominant brain functional network construction method.

Functional Magnetic Resonance Imaging(fMRI) has now become a classic way for measuring brain activity, and recent trend is shifting toward utilizing fMRI brain data for AI-driven diagnosis. Given that the brain functions as not a discrete but interconnected whole, Graph-based architectures represented by Graph Convolutional Network(GCN) has emerged as a dominant framework for such task, since they are capable of treating ROIs as dynamically interconnected nodes and extracting relational architecture between them. Ironically, however, it is the very nature of GCN's architecture that acts as an obstacle to its performance. The mathematical foundation of GCN, effective for capturing global regularities, acts as a tradeoff; by smoothing features across the connected nodes repeatedly, traditional GCN tend to blur out the contrastive dynamics that might be crucial in identifying certain neurological disorders. In order to break through this structural bottleneck, we propose LUMINA, a Laplacian-Unifying Mechanism for Interpretable Neurodevelopmental Analysis. Our model is a Quad-Stream GCN that employs a bipolar RELU activation and a dual-spectrum graph Laplacian filtering mechanism, thereby capturing heterogeneous dynamics that were often blurred out in conventional GCN. By doing so, we can preserve the diverse range and characteristics of neural connections in each fMRI data. Through 5-fold cross validation on the ADHD200(N=144) and ABIDE(N=579) dataset, LUMINA demonstrates stable diagnostic performance in two of the most critical neurodevelopmental disorder in childhood, ADHD and ASD, outperforming existing models with an accuracy of 84.66% and 88.41% each.

Robust and interpretable dementia diagnosis from noisy, non-stationary electroencephalography (EEG) is clinically essential yet remains challenging. To this end, we propose SeeGraph, a Sparse-Explanatory dynamic EEG-graph network that models time-evolving functional connectivity and employs a node-guided sparse edge mask to reveal the connections that drive diagnostic decisions, while remaining robust to noise and cross-site variability. SeeGraph comprises four components: (1) a dual-trajectory temporal encoder that models dynamic EEG with two streams, where node signals capture regional oscillations and edge signals capture interregional coupling; (2) a topology-aware positional encoder that derives graph-spectral Laplacian coordinates from the fused connectivity and augments node embeddings; (3) a node-guided sparse explanatory edge mask that gates the connectivity into a compact subgraph; and (4) a gated graph predictor that operates on the sparsified graph. The framework is trained using cross-entropy loss together with a sparsity regularizer on the mask, yielding noise-robust and interpretable diagnoses. The effectiveness of SeeGraph is validated on public and in-house EEG cohorts, including patients with neurodegenerative dementias and healthy controls, under both raw and noise-perturbed conditions. Its sparse, node-guided explanations highlight disease-relevant connections and align with established clinical findings on functional connectivity alterations, thereby offering transparent cues for neurological evaluation.

Anatomical brain parcellations dominate rs-fMRI-based Autism Spectrum Disorder (ASD) classification, yet their rigid boundaries may fail to capture the idiosyncratic connectivity patterns that characterise ASD. We present a graph-based deep learning framework comparing anatomical (AAL, 116 ROIs) and functionally-derived (MSDL, 39 ROIs) parcellation strategies on the ABIDE I dataset. Our FSL preprocessing pipeline handles multi-site heterogeneity across 400 balanced subjects, with site-stratified 70/15/15 splits to prevent data leakage. Gaussian noise augmentation within training folds expands samples from 280 to 1,680. A three phase pipeline progresses from a baseline GCN with AAL (73.3% accuracy, AUC=0.74), to an optimised GCN with MSDL (84.0%, AUC=0.84), to a Graph Attention Network ensemble achieving 95.0% accuracy (AUC=0.98), outperforming all recent GNN-based benchmarks on ABIDE I. The 10.7-point gain from atlas substitution alone demonstrates that functional parcellation is the most impactful modelling decision. Gradient-based saliency and GNNExplainer analyses converge on the Posterior Cingulate Cortex and Precuneus as core Default Mode Network hubs, validating that model decisions reflect ASD neuropathology rather than acquisition artefacts. All code and datasets will be publicly released upon acceptance.

Large Language Models have achieved remarkable success in language understanding and reasoning, and their multimodal extensions enable comprehension of images, video, and audio. Inspired by this, foundation models for brain functional connectivity networks derived from resting-state fMRI have shown promise in clinical tasks. However, existing methods do not align FCNs with the text modality, limiting the ability of LLMs to directly understand FCNs. To address this, we propose FCN-LLM, a framework that enables LLMs to understand FCNs through graph-level, multi-task instruction tuning. Our approach employs a multi-scale FCN encoder capturing brain-region, functional subnetwork, and whole-brain features, projecting them into the semantic space of LLM. We design multi-paradigm instruction tasks covering 19 subject-specific attributes across demographics, phenotypes, and psychiatric conditions. A multi-stage learning strategy first aligns FCN embeddings with the LLM and then jointly fine-tunes the entire model to capture high-level semantic information. Experiments on a large-scale, multi-site FCN database show that FCN-LLM achieves strong zero-shot generalization on unseen datasets, outperforming conventional supervised and foundation models. This work introduces a new paradigm for integrating brain functional networks with LLMs, offering a flexible and interpretable framework for neuroscience.

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

Recent deep learning methods for fMRI-based diagnosis have achieved promising accuracy by modeling functional connectivity networks. However, standard approaches often struggle with noisy interactions, and conventional post-hoc attribution methods may lack reliability, potentially highlighting dataset-specific artifacts. To address these challenges, we introduce PIME, an interpretable framework that bridges intrinsic interpretability with minimal-sufficient subgraph optimization by integrating prototype-based classification and consistency training with structural perturbations during learning. This encourages a structured latent space and enables Monte Carlo Tree Search (MCTS) under a prototype-consistent objective to extract compact minimal-sufficient explanatory subgraphs post-training. Experiments on three benchmark fMRI datasets demonstrate that PIME achieves state-of-the-art performance. Furthermore, by constraining the search space via learned prototypes, PIME identifies critical brain regions that are consistent with established neuroimaging findings. Stability analysis shows 90% reproducibility and consistent explanations across atlases.

The white matter of the brain is organised into axonal bundles that support long-range neural communication. Although diffusion MRI (dMRI) enables detailed mapping of these pathways through tractography, how white matter pathways directly facilitate large-scale neural synchronisation remains poorly understood. We developed a data-driven framework that integrates dMRI and functional MRI (fMRI) to model the dynamic coupling supported by white matter tracks. Specifically, we employed track dynamic functional connectivity (Track-DFC) to characterise functional coupling of remote grey matter connected by individual white matter tracks. Using independent component analysis followed by k-medoids clustering, we derived functionally-coherent clusters of white matter tracks from the Human Connectome Project young adult cohort. When applied to the HCP ageing cohort, these clusters exhibited widespread age-related declines in both functional coupling strength and temporal variability. Importantly, specific clusters encompassing pathways linking control, default mode, attention, and visual systems significantly mediated the relationship between age and cognitive performance. Together, these findings depict the functional organisation of white matter tracks and provide a powerful tool to study brain ageing and cognitive decline.

Functional Magnetic Resonance Imaging (fMRI) is an imaging technique widely used to study human brain activity. fMRI signals in areas across the brain transiently synchronise and desynchronise their activity in a highly structured manner, even when an individual is at rest. These functional connectivity dynamics may be related to behaviour and neuropsychiatric disease. To model these dynamics, temporal brain connectivity representations are essential, as they reflect evolving interactions between brain regions and provide insight into transient neural states and network reconfigurations. However, conventional graph neural networks (GNNs) often struggle to capture long-range temporal dependencies in dynamic fMRI data. To address this challenge, we propose BrainATCL, an unsupervised, nonparametric framework for adaptive temporal brain connectivity learning, enabling functional link prediction and age estimation. Our method dynamically adjusts the lookback window for each snapshot based on the rate of newly added edges. Graph sequences are subsequently encoded using a GINE-Mamba2 backbone to learn spatial-temporal representations of dynamic functional connectivity in resting-state fMRI data of 1,000 participants from the Human Connectome Project. To further improve spatial modeling, we incorporate brain structure and function-informed edge attributes, i.e., the left/right hemispheric identity and subnetwork membership of brain regions, enabling the model to capture biologically meaningful topological patterns. We evaluate our BrainATCL on two tasks: functional link prediction and age estimation. The experimental results demonstrate superior performance and strong generalization, including in cross-session prediction scenarios.