Brain Network Analysis

A growing number of techniques leverage the spatial structures that underlie many real-world datasets. Despite these advances, the complementary task of estimating spatial structures and understanding their role within these techniques has often been overlooked. In neurophysiological data analysis specifically, numerous methods exist to estimate brain connectivity, but most are not explicitly model-based, dynamic, multivariate, or directed. To address these limitations, we previously introduced noise-driven heat modelling on graphs for neurophysiological connectivity estimation. In this study, we extend this framework by relaxing earlier noise assumptions and adding regularisation to improve robustness. We also develop a simulation procedure to characterise and evaluate our technique in a controlled setting. Finally, we demonstrate that the technique is able to capture meaningful spatial structure across two experiments, each using two real-world datasets. The explicit model formulation of our connectivity estimator has the potential to improve the interpretability of graph-based techniques across a wide range of applications. The code implementing our method is available at https://github.com/sgoerttler/Heat_Connectivity.

This study examines how deficiencies in one brain connectome modality propagate to the other, using the Krakencoder as a simulation framework. Structural and functional connectomes from 702 healthy participants in the Human Connectome Project were analyzed, with the impact of each of the Yeo-7 functional networks assessed separately. Seven scenarios were considered, each involving the removal of a single network while the remaining networks were preserved. The resulting perturbations in cross-modal predictions were quantified using three complementary metrics: KL divergence on eigenvalue spectra, Frobenius norm, and Wasserstein distance. In addition, the persistence of sex-specific information within the predicted connectomes was evaluated. Across all metrics and both prediction directions, the Default Mode Network produced the largest perturbations, whereas the Somatomotor network yielded the smallest. Sex differences in network-level perturbation signatures were subtle, with the best result being an accuracy of 66.09% from connectomes predicted under network-removal conditions. In contrast, connectomes predicted from intact inputs achieved substantially higher sex classification accuracy, reaching up to 84.76%. These findings confirm that full predicted connectomes retain considerably more sex-discriminative information than perturbation-derived signatures alone.

Multimodal neuroimaging, integrating functional connectivity from fMRI and structural connectivity from DTI, enables non-invasive analysis of brain networks using graph neural networks. However, demographic factors such as age and sex systematically confound the relationship between brain connectivity and clinical outcomes, causing GNNs to exploit spurious shortcuts rather than learning causally invariant representations. While recent causal GNN methods introduce causality at the graph-modeling level, their causal mechanisms remain domain-agnostic without accounting for the real-world confounders inherent in clinical neuroimaging data. Moreover, brain networks are constructed from atlas-based parcellations where each region exhibits distinct sensitivity to demographic factors, necessitating region-aware adjustment. We propose Artemis, a region-level causal framework that bridges this gap with causal intervention at each brain region independently by learning region-specific confounder representations with lightweight parameters. Our adjustment comprehensively utilized the multimodal functional and structural features for graph reasoning as a plug-in module compatible with arbitrary GNN backbones. Experiments on three benchmarks, ADNI for disease diagnosis, OASIS for dementia staging, and HCP for sex classification, demonstrate consistent improvements over representative GNN-based baselines. Multiple supporting experiments further demonstrate statistical significance and neuroscientific interpretability.

Most statistical and machine learning methods for directed interactions focus on pairwise effects among variables. Even existing cyclic models represent feedback primarily through node-level dependencies, making large-scale recurrent organization difficult to estimate and compare. This limitation is particularly acute in biological and neural systems, where interactions are highly recurrent and involve many overlapping cycles. We introduce a variational framework for statistical inference on cyclic interactions. Directed interactions are represented as edge flows on a simplicial complex and evolved under an energy-minimizing dynamical system. The resulting dynamics separate transient interaction components from persistent harmonic flows, yielding a low-dimensional cycle space that captures stable recurrent organization. Rather than enumerating individual cycles, the proposed framework represents cyclic interactions as elements of a Hilbert space, enabling projection, averaging, comparison, and population-level statistical inference. We establish theoretical properties of the harmonic projection, including characterization of the cycle space, variance reduction, and population inference. Simulations demonstrate substantially improved recovery of cyclic structure in dense recurrent systems compared with existing directed-interaction methods. Applied to resting-state fMRI from 400 human subjects, the framework reveals reproducible large-scale cyclic organization that is not detectable through edgewise averaging. These results provide a scalable statistical framework for studying recurrent interactions in high-dimensional dynamical systems.

Understanding how structural connections are associated with tau propagation in Alzheimer's disease (AD) remains a central open question, yet existing computational models either rely heavily on biophysical assumptions or lack neurobiologically interpretable pathway maps. We present SC-TauPath, a structural connectivity (SC) attribution framework that maps tau propagation pathways from in vivo neuroimaging data. SC-TauPath combines a Network Diffusion Model (NDM)-augmented multilayer perceptron with gradient $\times$ input attribution to score each SC edge's contribution to tau prediction, then translates these attribution scores into multi-scale pathway maps (backbone edges, high-traffic routes, and hub ROIs), which validates established Braak staging anatomy. Applied to 234 ADNI participants with paired DTI SC and 18F-Flortaucipir PET, SC-TauPath achieves strong cross-validated tau prediction and yields attribution-based pathway maps consistent with established Braak staging anatomy, demonstrating that SC encode spatially specific information about regional tau distribution in AD.

Understanding complex interactions between brain regions is critical for early neurodegenerative disease classification such as Alzheimer's Disease (AD) and Parkinson's Disease (PD). While graph-based models are widely used to analyze brain networks, most existing approaches primarily focus on pairwise interactions between directly connected nodes, limiting their ability to capture higher-order dependencies across multiple regions. Although hypergraph-based methods have been proposed to model higher-order relations, many rely on predefined hyperedges or restrict learning to hyperedge weights, reducing flexibility and limiting their capacity to capture multi-resolution structural patterns. In this regard, we introduce an adaptive multi-scale hyperedge learning framework, i.e., MuHL, which constructs hierarchical node features and dynamically learns high-order interactions through continuous hyperedge construction over multi-resolution graph signals. Extensive experiments on multiple brain network benchmarks demonstrate that MuHL consistently improves disease classification performance across different stages, and further identifies key regions of interest (ROIs) and their group-wise interactions from the learned hyperedges that are associated with disease progression, highlighting its potential as a powerful tool for brain network analysis in neurodegenerative disorders.

Brain activity unfolds as coordinated patterns across regions over time, and modeling these dynamics is a central goal in computational neuroscience. Because activity is distributed over connected brain regions, it is naturally represented on a graph whose nodes are brain regions or recording electrodes and whose edges capture relationships between these nodes, with message-passing modeling regional communication. However, standard message-passing networks place every node in a single shared feature space and typically aggregate messages from neighbors by scalar summation, which does not align with neurobiological evidence of brain communication. In order to model the heterogeneous nature of the brain, we introduce BrainDyn, a graph ordinary differential equation (ODE) network built on a cellular sheaf with dynamic restriction maps, recomputed from the forecasting context window rather than fixed once, mediating region-to-region communication through learned linear transformations that drive the time evolution of neural activity. We evaluate BrainDyn on resting-state fMRI, EEG, and simulated activity from the NEST simulator. Across these modalities, we test multi-region forecasting and autoregressive generation of brain transients, and, using NEST, prediction of altered transients following controlled perturbations. BrainDyn outperforms competing models across modalities, while analysis of the learned features shows that they are expressive, interpretable, and biologically aligned.

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.

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.

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.

Connectome-constrained neural networks are often evaluated against sparse random controls and then interpreted as evidence that biological graph topology improves learning efficiency. We revisit that claim in a controlled flyvis-based study using a Drosophila connectome, a naive self-loop-matched random graph, and a degree-preserving rewired null. Under weak controls, in which both models were recovered from a connectome-trained checkpoint and the null matched only global graph counts, the connectome appeared substantially better in early loss, mean activity, and runtime. That picture changed under stricter controls. Training both graphs from a shared random initialization removed the early loss advantage, and replacing the naive null by a degree-preserving null removed the apparent activity advantage. A five-sample degree-preserving ensemble and a pre-training activity-scale diagnostic further strengthened this revised interpretation. We also report a descriptive mechanism analysis of the earlier weak-control comparison, but we treat it as behavioral characterization rather than proof of causal superiority. We show that previously reported topology advantages in connectome-constrained neural networks can arise from initialization and null-model confounds, and largely disappear under fair from-scratch initialization and degree-preserving controls.

Multi-modal fusion is of great significance in neuroscience which integrates information from different modalities and can achieve better performance than uni-modal methods in downstream tasks. Current multi-modal fusion methods in brain networks, which mainly focus on structural connectivity (SC) and functional connectivity (FC) modalities, are static in nature. They feed different samples into the same model with identical computation, ignoring inherent difference between input samples. This lack of sample adaptation hinders model's further performance. To this end, we innovatively propose a multi-stage dynamic fusion strategy (M3D-BFS) for sample-adaptive multi-modal brain network analysis. Unlike other static fusion methods, we design different mixture-of-experts (MoEs) for uni- and multi-modal representations where modules can adaptively change as input sample changes during inference. To alleviate issue of MoE where training of experts may be collapsed, we divide our method into 3 stages. We first train uni-modal encoders respectively, then pretrain single experts of MoEs before finally finetuning the whole model. A multi-modal disentanglement loss is designed to enhance the final representations. To the best of our knowledge, this is the first work for dynamic fusion for multi-modal brain network analysis. Extensive experiments on different real-world datasets demonstrates the superiority of M3D-BFS.

Seizure detection from EEG signals is highly challenging due to complex spatiotemporal dynamics and extreme inter-patient variability. To model them, recent methods construct dynamic graphs via statistical correlations, predefined similarity measures, or implicit learning, yet rarely account for EEG's noisy nature. Consequently, these graphs usually contain redundant or task-irrelevant connections, undermining model performance even with state-of-the-art architectures. In this paper, we present a new perspective for EEG seizure detection: jointly learning denoised dynamic graph structures and informative spatial-temporal representations guided by the Information Bottleneck (IB). Unlike prior approaches, our graph constructor explicitly accounts for the noisy characteristics of EEG data, producing compact and reliable connectivity patterns that better support downstream seizure detection. To further enhance representation learning, we employ a self-supervised Graph Masked AutoEncoder that reconstructs masked EEG signals based on dynamic graph context, promoting structure-aware and compact representations aligned with the IB principle. Bringing things together, we introduce Information Bottleneck-guided EEG SeizuRE DetectioN via SElf-Supervised Learning (IRENE), which explicitly learns dynamic graph structures and interpretable spatial-temporal EEG representations. IRENE addresses three core challenges: (i) Identifying the most informative nodes and edges; (ii) Explaining seizure propagation in the brain network; and (iii) Enhancing robustness against label scarcity and inter-patient variability. Extensive experiments on benchmark EEG datasets demonstrate that our method outperforms state-of-the-art baselines in seizure detection and provides clinically meaningful insights into seizure dynamics. The source code is available at https://github.com/LabRAI/IRENE.

Graph Neural Networks (GNNs) have been widely used in diverse brain network analysis tasks based on preprocessed functional magnetic resonance imaging (fMRI) data. However, their performances are constrained due to high feature sparsity and inherent limitations of domain knowledge within uni-modal neurographs. Meanwhile, large language models (LLMs) have demonstrated powerful representation capabilities. Combining LLMs with GNNs presents a promising direction for brain network analysis. While LLMs and MLLMs have emerged in neuroscience, integration of LLMs with graph-based data remains unexplored. In this work, we deal with these issues by incorporating LLM's powerful representation and generalization capabilities. Considering great cost for directly tuning LLMs, we instead function LLM as enhancer to boost GNN's performance on downstream tasks. Our method, namely BLEG, can be divided into three stages. We firstly prompt LLM to get augmented texts for fMRI graph data, then we design a LLM-LM instruction tuning method to get enhanced textual representations at a relatively lower cost. GNN is trained together for coarsened alignment. Finally we finetune an adapter after GNN for given downstream tasks. Alignment loss between LM and GNN logits is designed to further enhance GNN's representation. Extensive experiments on different datasets confirmed BLEG's superiority.Code can be available at https://github.com/KamonRiderDR/BLEG.

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.

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.

Autism Spectrum Disorder (ASD) is a neurodevelopmental condition characterized by atypical brain connectivity. One of the crucial steps in addressing ASD is its early detection. This study introduces a novel computational framework that employs an Attention-Based Graph Convolutional Network, referred to as the GATGraphClassifier, for detecting ASD. We utilize Functional Magnetic Resonance Imaging (fMRI) data from the Autism Brain Imaging Data Exchange (ABIDE) repository to construct functional connectivity matrices using Pearson correlation, which captures interactions between various brain regions. These matrices are then transformed into graph representations, where the nodes and edges represent the brain regions and functional connections, respectively. The GATGraphClassifier employs attention mechanisms to identify critical connectivity patterns, thereby enhancing the model's interpretability and diagnostic accuracy. Our proposed framework demonstrates superior performance across all standard classification metrics compared to existing state-of-the-art methods. Notably, we achieved an average accuracy of 88.79% on the test data over 30 independent runs, surpassing the benchmark model's performance by 12.27%. In addition, we identified the crucial brain regions associated with ASD, consistent with the previous studies, and a few novel regions. This study not only contributes to the advancement of ASD detection but also shows the potential for broader adaptability of GATGraphClassifier in analyzing complex relational data in various fields, where understanding intricate connectivity and interaction patterns is essential.

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.

Neural circuits must balance local connectivity constraints against the need for global integration. Here we introduce a minimal wiring rule motivated by synaptic crowding: as a neuron accumulates incoming connections, each additional synapse becomes progressively harder to form. This single-parameter model admits an exact finite-size solution for the induced in-degree distribution and yields simple scaling laws: mean connectivity grows only logarithmically with network size while variance remains bounded -- consistent with homeostatic regulation of synaptic density. When candidates are encountered in order of spatial proximity, the crowding rule produces a broad, approximately power-law distribution of connection lengths without prescribing any explicit distance-dependent wiring law; combined with shortcut rewiring, this yields networks with small-world characteristics. We further show that the induced degree statistics largely determine attractor basin boundaries in threshold network dynamics, while local clustering primarily modulates the prevalence of long-lived non-absorbing outcomes near these boundaries. The model provides testable predictions linking local developmental constraints to macroscopic network organization and dynamics.

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.

Dynamic functional connectivity captures time-varying brain states for better neuropsychiatric diagnosis and spatio-temporal interpretability, i.e., identifying when discriminative disease signatures emerge and where they reside in the connectivity topology. Reliable interpretability faces major challenges: diagnostic signals are often subtle and sparsely distributed across both time and topology, while nuisance fluctuations and non-diagnostic connectivities are pervasive. To address these issues, we propose BrainSTR, a spatio-temporal contrastive learning framework for interpretable dynamic brain network modeling. BrainSTR learns state-consistent phase boundaries via a data-driven Adaptive Phase Partition module, identifies diagnostically critical phases with attention, and extracts disease-related connectivity within each phase using an Incremental Graph Structure Generator regularized by binarization, temporal smoothness, and sparsity. Then, we introduce a spatio-temporal supervised contrastive learning approach that leverages diagnosis-relevant spatio-temporal patterns to refine the similarity metric between samples and capture more discriminative spatio-temporal features, thereby constructing a well-structured semantic space for coherent and interpretable representations. Experiments on ASD, BD, and MDD validate the effectiveness of BrainSTR, and the discovered critical phases and subnetworks provide interpretable evidence consistent with prior neuroimaging findings. Our code: https://anonymous.4open.science/r/BrainSTR1.

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.

Brain-wide recordings of large-scale networks of neurons now provide an unprecedented view into how the brain drives behavior. However, brain activity contains both information directly related to behavior as well as the potential for many internal computations. Moreover, observable behavior is executed not only by the brain, but also by the spinal cord and peripheral nervous system. Behavior is a coarse-grained product of neural activity, and we thus take the view that it can be best represented by lower-dimensional latent neural dynamics. Capturing this indirect relationship while disambiguating behavior-generating networks from internal computations running in parallel requires new modeling approaches that can embody the parallel and distributed nature of large-scale neural populations. We thus present behavior-decomposed linear dynamical systems (b-dLDS) to disentangle simultaneously recorded subsystems and identify how the latent neural subsystems relate to behavior. We demonstrate the ability of b-dLDS to decouple behavioral vs. internal computations on controlled, simulated data, showing improvements over a state-of-the-art model that uses behavior to supervise all dynamics based on behavior. We also demonstrate b-dLDS's interpretability benefits on a task-driven RNN dataset featuring a nonlinear relationship between behavior and activations. We then show that b-dLDS can further scale up to tens of thousands of neurons by applying our model to a large-scale recording of a zebrafish hindbrain during the complex positional homeostasis behavior, wherein b-dLDS highlights asymmetry in behavior-related dynamic connectivity networks.

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.