Brain

Three-dimensional (3D) brain MRI is central to clinical neurology and neuro-oncology, where generative models could augment under-represented cohorts, simulate disease trajectories, and support privacy-preserving data sharing. Latent diffusion has been the go-to solution for modeling imaging data, but it places two competing demands on the tokenizer: encoder embeddings must retain the clinical information that downstream tasks act on, and the decoder must reconstruct anatomically faithful volumes. Existing reconstruction-driven tokenizers achieve the second at the expense of the first. To address this, we introduce a fully volumetric masked-autoencoder (MAE) based tokenizer for 3D brain MRI latent diffusion, decoupling encoder and decoder: a frozen 3D MAE encoder produces clinically informative embeddings, while a dedicated CNN decoder reconstructs voxels from a linear projection of those embeddings. We pretrain the encoder on 35,309 volumes from 18 public cohorts spanning four modalities, ten disease categories, and 200+ acquisition sites, and demonstrate its dual utility in two settings. First, on a 23-task linear-probing benchmark, the encoder outperforms or matches SOTA models (i.e., BrainIAC, BrainSegFounder, and MedicalNet) on 21 of 23 tasks. Second, a conditional diffusion transformer (DiT) trained on these clinically informative embeddings supports both conditional generation across six variables and patient-specific longitudinal forecasting. Together these results establish a single 3D brain-MRI embedding space capable of both downstream clinical tasks and controllable generation.

Glioma segmentation in multiparametric MRI is a critical component of treatment planning. A segmentation model that fails silently on treatment-critical sub-regions represents a patient safety risk that overlap-based metrics such as Dice scores cannot expose. We ask whether voxel-level uncertainty estimation via Monte Carlo (MC) Dropout can reliably identify segmentation errors in clinically critical sub-regions, and whether calibration failure modes are detectable from standard reporting metrics alone. In an empirical two-model case study on 126 BraTS21 patients, we evaluate a high-performance pretrained SegResNet and a locally trained UNet with residual units (UNet-Res). MC dropout preserved segmentation accuracy ($|Δ\text{Dice}|$ $<0.01$) while achieving strong uncertainty-error alignment (AUROC for entropy (H) $\approx$0.97), indicating uncertainty correctly ranks erroneous voxels above correct ones. Entropy-based patient stratification identified a high-uncertainty subgroup with substantially lower segmentation performance (median whole-tumour Dice $0.835$ vs. $0.925$), supporting uncertainty as a practical triage signal. However, global alignment can mask important region-specific differences. Despite similar AUROC, UNet-Res exhibited near-zero enhancing tumour entropy ($0.054$) and Expected Calibration Error (ECE) of $0.915$, with a Dice of only $0.714$, indicating severely miscalibrated confidence on the most clinically critical sub-region, a failure mode invisible to standard Dice and AUROC reporting. These findings demonstrate that strong uncertainty-error alignment is necessary but insufficient for clinical safety: sub-region-specific calibration assessment must accompany AUROC evaluation when selecting models for clinical deployment.

Whole-brain 4D fMRI generation is valuable for modeling functional brain dynamics, yet existing fMRI foundation models mainly target representation learning and downstream prediction rather than conditional predictive generation. We introduce BrainWorld, a structural-prior-conditioned generative model for whole-brain 4D fMRI dynamics. BrainWorld uses sMRI as subject-level anatomical context to guide future fMRI generation, integrating structural information into the denoising process rather than treating it as a parallel modality. Evaluated on 22 datasets spanning diverse cohorts and brain states, BrainWorld generates stable 4D fMRI trajectories up to 400 frames, improves downstream performance through generated-example augmentation, and learns transferable multimodal representations that outperform baselines. Together, these results establish BrainWorld as a condition-aware generative framework for long-horizon brain dynamics modeling and multimodal representation learning.

This paper proposes an unsupervised workflow to pseudo-label extracellular spikes from human brain slice MEA recordings into two putative cell types: pyramidal cells and interneurons. Here, the raw data from the data acquisition system is used and processed. The pipeline for pre-processing includes bandpass filtering, threshold--based spike detection, frame alignment and normalization. In the ML workflow, dimensionality reduction (PCA, t-SNE, UMAP), clustering (GMM, k-means). To achieve an online system, template matching and OSort under varying curation strictness is also considered. All pipelines are evaluated by different cluster quality with within-cluster Pearson correlation, Silhouette score, and Calinski-Harabasz index. Applying stricter curation improves separation at some cost to inclusivity.

Multimodal large language models (MLLMs) hold great potential for medicine, as they inherit knowledge from LLM and allow multiple data modalities to be integrated, analysed and interpreted in natural language. However, the field of medical MLLMs is constrained by non-trivial challenges, notably the scarcity of high-quality training data and the frequent occurrence of missing data in the real-world clinical setting. Here, we propose a novel unified multimodal model, UniBrain, for brain magnetic resonance image (MRI) analysis. To address potential missing brain MRI modalities, we employ a unified training strategy to perform joint imaging modality imputation and brain image understanding. During training, an interleaved and description-enriched data flow is constructed to train the model in an autoregressive manner, enabling medical reasoning with generated multimodal data. A self-alignment strategy is introduced to leverage dense image embeddings to learn fine-grained anatomical features without requiring detailed image captions. Furthermore, we propose a dynamic hidden state mechanism to alleviate the exposure bias during long-context multimodal inference. Extensive experiments on multi-disease brain MRI dataset demonstrate that UniBrain achieves high performance for brain image imputation, understanding, and disease diagnosis under various extents of modality incompleteness.

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.

Post-traumatic epilepsy (PTE) is a severe complication of traumatic brain injury (TBI). Yet, early identification remains challenging due to the complex structural and functional alterations it induces in the brain. To address this, we propose a dynamic multimodal Mixture-of-Experts (MoE) framework that integrates functional and structural connectivity through time-aware functional-structural encoding and class-conditioned expert routing. Within this framework, modality-specific and cross-modal experts learn complementary representations, while a Modality-Class MoE (MCoE) module dynamically adjusts expert weights according to each classification objective. Experimental results across three binary classification tasks demonstrate that the framework consistently outperforms static fusion baselines, and high-interpretability analyses further reveal meaningful regions of interest (ROIs) interactions. This dynamic multimodal expert framework effectively captures class-dependent brain interaction patterns and provides an interpretable approach for PTE diagnosis and risk stratification.

Flow matching is a powerful generative modeling framework, valued for its simplicity and strong empirical performance. However, its standard formulation treats signals on structured spaces, such as fMRI data on brain graphs, as points in Euclidean space, overlooking the rich topological features of their domains. To address this, we introduce topological flow matching, a topology-aware generalization of flow matching. We interpret flow matching as a framework for solving a degenerate Schrödinger bridge problem and inject topological information by augmenting the reference process with a Laplacian-derived drift. This principled modification captures the structure of the underlying domain while preserving the desirable properties of flow matching: a stable, simulation-free objective and deterministic sample paths. As a result, our framework serves as a drop-in replacement for standard flow matching. We demonstrate its effectiveness on diverse structured datasets, including brain fMRIs, ocean currents, seismic events, and traffic flows.

A common objection to artificial or simulated consciousness is that a simulated brain is no more conscious than simulated water is wet. We address this from the perspective of Intrinsic Computational Functionalism (ICF): if consciousness is computationally constituted, it depends not on externally imposed descriptions but on the computational structures a system physically realizes in virtue of its own causal-dynamical organization. In previous work we developed Canonical Functionalism as a mathematically precise special case of this anti-interpretivist program, identifying functional states by their complete future input-output roles under a fixed interface. Here we argue that this input-output construction, though important, is incomplete: as a behavioral boundary case of ICF, it makes lookup tables and unfolded systems that preserve the same boundary behavior canonically equivalent. A consciousness-relevant canonical representation must instead include internal mechanisms, interventions, and joint readouts belonging to the relevant intrinsic organization. We therefore define a mechanism-enriched canonical structure and use it to formulate Intrinsic Causal-Computational Realization (ICCR), a realization relation preserving physical implementation, intrinsic state individuation, transition structure, intervention profiles, and the relevant agent-body-world boundary. The central result is conditional: if conscious properties are invariants of intrinsic causal-computational organization, then any system satisfying ICCR realizes the same consciousness-relevant properties, whether biological, artificial, or simulated. We discuss objections including biological naturalism and integrated information theory. We conclude that to deny consciousness to a simulation, one must identify a consciousness-relevant intrinsic causal-computational structure that the simulation fails to realize.

Affective and cognitive disorders manifest as distributed, time-varying brain network dynamics across regions, channels, and time, challenging robust representation learning from EEG/sEEG for clinical diagnosis. We propose RECTOR (Masked Region-Channel-Temporal Modeling), an end-to-end self-supervised framework that unifies joint region-channel-temporal representation learning beyond fixed anatomical priors. At its core, RECTOR-SA is a hierarchical, block-sparse self-attention induced by Adaptive Functional Partitioning that evolves region structures from static anatomical definitions to adaptive functional regions. The self-supervision is driven by Masked Topology and Representation Learning, which jointly optimizes three complementary objectives: Masked Predictive Modeling, Topological Structure Modeling, and Cross-View Consistency. Across diverse benchmarks, RECTOR sets a new state-of-the-art in EEG emotion recognition and sEEG task-engagement classification. Crucially, its strong robustness to missing channels and cross-montage generalization underscores its potential for large-scale pre-training on heterogeneous EEG/sEEG, providing interpretable insights at both region and channel levels.

How the wiring and functional organization of cortex shape recurrent computation remains a central question in both neuroscience and machine learning. Here, we leverage data released through the Machine Intelligence from Cortical Networks (MICrONS) program--a functional connectomics resource spanning multiple areas of mouse visual cortex, in which dense calcium imaging is co-registered with high-resolution electron microscopy reconstruction from the same animal--to build biologically grounded recurrent neural networks. Using neuronal spatial coordinates, anatomical connectivity, and function-derived relationships from nearly 12,000 coregistered excitatory neurons, we initialize recurrent weights and impose communication-aware spatial constraints during learning. Across three cognitive decision-making tasks, networks constrained by cortical structure and function consistently outperform baseline and partially constrained models. Functional weight initialization provides the largest gain, while real spatial embedding yields robust additional improvements across conditions. These biologically grounded networks also develop low-entropy, modular, and small-world organization, and retain strong performance even when recurrence is restricted to positive weights. Together, our results show that the machinery of cortex--its geometry, wiring, and functional structure--can be harnessed as a powerful inductive basis for building recurrent networks that learn more effectively while converging toward key organizational principles of biological computation.

Alzheimer's Disease (AD) is a progressive neurodegenerative disorder that affects millions of older adults, with prevalence expected to rise significantly in the coming years. Early diagnosis, particularly during the mild cognitive impairment (MCI) stage, is critical for timely intervention. Structural Magnetic Resonance Imaging (sMRI) has emerged as a key modality for detecting AD-related brain changes, but traditional graph-based approaches often struggle with modality and inter-site heterogeneity, limiting diagnostic performance. In this paper, we propose Graph Matching Network for Alzheimer's Disease Diagnosis (GMN4AD), designed to model interactions between heterogeneous brain graphs derived from neuroimaging data. Unlike conventional methods that treat each brain graph independently, GMN4AD leverages graph matching to capture cross-graph relationships, enhancing diagnostic precision. Furthermore, we introduce a test-time domain adaptation strategy that combines contrastive learning to mitigate domain shifts during inference. Extensive experiments on three public AD datasets demonstrate that GMN4AD achieves superior performance compared to state-of-the-art methods, offering a robust and generalizable solution for AD diagnosis.

Flow matching and diffusion models enable conditional generation across domains ranging from images to proteins, with recent extensions to out-of-distribution contexts. Yet generative models of neural time series have largely remained restricted to categorical conditioning, precluding compositional and zero-shot generalization. In this work, we propose a per-timestep conditioned diffusion transformer for generating realistic fMRI brain dynamics during unseen cognitive tasks by injecting both compositional language and optional spatial priors in-context. Such zero-shot generation could enable counterfactual neuroscience by supporting in-silico design and evaluation of novel cognitive experiments before empirical validation. Leveraging this model, we evaluate across hundreds of held-out task conditions and characterize predictive performance in relation to the training manifold. From language alone, the model recovers region-specific recruitment across tasks and held-out spatial activation patterns. Spatial priors, when available, complement the text pathway by anchoring generation in regions of task space where language alone degrades, while retaining the compositional structure needed for counterfactual task specification. To our knowledge this is the first generative model of whole-cortex fMRI dynamics for unseen cognitive tasks, advancing counterfactual neuroscience and data-driven experimental design.

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.

The success of large-scale deep learning models in neuroscience is fundamentally constrained by severe data heterogeneity. Native fMRI data aggregated from diverse sources exhibit substantial variation in both spatial and temporal resolutions. Consequently, most existing frameworks rely on lengthy, rigid preprocessing pipelines that enforce uniformity across datasets. This practice introduces two critical limitations: (1) potential degradation of subject-specific anatomical information; (2) significant computational overhead, often requiring hours of processing per subject. Here, we propose FlexiBrain, a resolution-agnostic voxel-level encoding framework for native fMRI based on Mamba-JEPA. FlexiBrain defines patch sizes in real-world physical units and employs a dynamic patch resizing, thereby bypassing destructive spatial standardization while enabling direct ingestion of data in native space. We instantiate the framework using an efficient Mamba-JEPA backbone to model high-dimensional 4D fMRI signals. Across five diverse downstream neuroscience tasks, FlexiBrain consistently outperforms recent state-of-the-art methods, achieving gains of up to 12 percentage points without external data augmentation. Importantly, FlexiBrain functions as a seamless plug-in module, substantially reducing preprocessing costs and accelerating the development of robust voxel-level fMRI foundation models. Code is available at https://github.com/OneMore1/FlexiBrain.

Recent developments in brain recording are driving a demand for machine learning tools capable of decoding the latent structure of large populations of neurons. In this paper, we provide a comprehensive survey that outlines the trajectory of Latent Variable Models (LVMs) from early state-space models to more recent deep generative models. We organize the literature into three closely related domains: (1) Single-Region Latent Dynamics, which includes models such as linear dynamical systems to more complex dynamics represented by Recurrent Neural Networks (RNNs) and Neural Ordinary Differential Equations (ODEs); (2) Multi-Region Communication, which employs probabilistic as well as subspace methods to study how information is transferred across different brain areas considering synaptic propagation delays and network connectivity; and (3) Behavior-Aligned Modeling, which seeks to disentangle neural activity related to task performance from other internal states via supervised or contrastive learning. This survey also includes large-scale neural foundation models, such as Transformers and diffusion models, that rely on large-scale pre-training for optimal performance across subjects. Finally, we conclude and discuss benchmarks, evaluation criteria, and open challenges, such as the ability to identify causal links or directionality of communication, to facilitate future research for bridging interpretable brain dynamics with reliable neural decoding.

The state-of-the-art generative models, such as CycleGAN, Pix2Pix, and diffusion models have demonstrated remarkable performance in the face generation task. However, they fail to effectively capture cross-modality semantic information in craniofacial reconstruction when translating from the skull (x-ray) to the face (optical) domain, due to a mismatch in the alignment of structural identity across modalities. To address this issue, we propose Cranio-Diff, a diffusion-based framework for cross-domain cranio-facial reconstruction from 2D X-ray skull images. The proposed approach integrates skull-conditioned structural guidance through ControlNet with biometric text conditioning to generate a face which is more semantically and structurally aligned with the given skull. The proposed Cranio-diff method is evaluated on skull-face dataset obtained from X-ray scans of 120 subjects in lateral and frontal views. To enable controlled evaluation, each face image is synthesised across three age groups (25, 45, 65) and three BMI variations of -10%, baseline and +10%, yielding 4320 paired samples. To the best of our knowledge, this is the only X-ray-face dataset with this magnitude. Extensive experiments showed that the proposed method outperforms recent existing approaches in both generated image quality and retrieval task. Finally, to evaluate the performance of our proposed method, we have evaluated the quality of the generated image using FID, IS, SSIM, LPIPS, PSNR and ArcFace score. Additionally, retrieval performance is evaluated using recall@k, mAP@k and MRR@k. Obtained experimental results demonstrate that the proposed method can be used as an alternate tool in providing aid in forensic investigations.

Reservoir computing exploits the fixed dynamics of a recurrent network for temporal processing, requiring only a trained linear readout. Biological neural connectomes, shaped by millions of years of evolution, may encode computational structure beyond what random reservoirs provide, yet whether that structure can be further enhanced by principled optimisation remains an open question. We address it by applying four gradient-free, bio-inspired optimisers (Particle Swarm Optimisation, Differential Evolution, Grey Wolf Optimiser, and Whale Optimisation Algorithm) to the edge weights of connectome-based echo-state networks across six species spanning six orders of magnitude in neural complexity: C. elegans (279 neurons), Drosophila (49 nodes), mouse (112), rat (73), macaque (29 regions, continuous FLNe synaptic strengths), and human structural MRI connectivity (83 parcels). Each connectome is evaluated on four canonical reservoir computing benchmarks: Memory Capacity (MC), Lorenz attractor prediction, NARMA-10 system identification, and Mackey-Glass chaotic time-series prediction. All four optimisers consistently outperform unoptimised biological baselines across every task and species when initialised from biological weights. WOA achieves the largest gains on every task: up to a 17x MC improvement (C. elegans: 1.39 to 23.91) and up to 89% NRMSE reduction (Mackey-Glass, human), corresponding to an average 214% improvement across all species and tasks. Crucially, random initialisation on the same topology reliably underperforms biology, establishing biological weight values as an essential inductive bias that topology alone cannot recover. These results position bio-inspired, biologically-initialised optimisation as a principled and broadly effective strategy for connectome reservoir computing across the animal kingdom.

Decoding emotional states from neural signals has been typically framed as a discrete, single-label classification task based on emotionally stable stimuli, a formulation that oversimplifies the continuous, fluid, and co-occurring nature of human affect. This study reconceptualizes emotion decoding by adopting a multi-target regression framework to track multiple overlapping emotional dimensions as continuous trajectories over time. Leveraging the robust generalization capabilities of Large Language Models (LLMs), we extracted fine-grained, continuous sentiment profiles from a naturalistic auditory narrative, Alice in Wonderland, to serve as scalable proxies for subjective affect from human fMRI dataset. Departing from standard classification paradigms or mass-univariate subtractive contrasts that filter out network dynamics, we leverage regularized and kernel-based machine learning algorithms as continuous estimators to track the magnitude of macroscale neural state variations. We demonstrate that models trained on temporal snapshots of Dynamic Functional Connectivity (DFC) significantly outperform static region-of-interest (ROI) amplitude representations, effectively capturing continuous emotional trajectories under rapidly fluctuating narrative input. Furthermore, by implementing graph-theoretical Explainable AI (XAI) techniques, we deconstruct the underlying predictive features to reveal highly interpretable, emotion-specific topological configurations. Collectively, these results highlight the utility of LLM-automated annotation in affective neuroscience and provide compelling empirical evidence for psychological constructionist frameworks, demonstrating that dynamic, distributed network interactions offer superior explanatory power over strictly locationist accounts of emotion.

Diffusion MRI (dMRI) tractography is the only noninvasive approach for mapping white-matter pathways in the living human brain. It represents each brain as a tractogram: a large, unordered set of three-dimensional streamlines that includes information about both local streamline geometry and whole-brain anatomical organization. This structure makes tractograms a natural but challenging target for representation learning. Existing methods treat streamline classification and subject-level prediction as separate problems: streamline classifiers focus on geometric patterns, whereas subject-level prediction often depends on hand-crafted features. As a result, current methods do not learn reusable representations that connect streamline anatomy with whole-brain inter-subject variation. Here we introduce TractFM, a tractogram foundation model that learns reusable representations directly from whole-brain streamline sets. TractFM combines a local streamline encoder with a permutation-equivariant tractogram encoder, allowing all streamlines from a subject to be contextualized jointly in a single forward pass. Pretraining on dense anatomical tract parcellation, i.e., assigning anatomical labels to individual streamlines, yields two complementary representations: contextualized streamline-level embeddings for tract parcellation and compact subject-level descriptors for downstream prediction of subject phenotypes. Across three tractography algorithms and five dMRI datasets, TractFM transfers to both streamline-level and subject-level tasks. Its frozen representations achieve accurate tract parcellation and predict age and sex across independent datasets. These results show that whole-brain geometric context, learned once, can generalize across tractography pipelines, datasets, and prediction tasks.

Understanding the relationship between deep visual representations and the human visual system is a fundamental challenge in computational neuroscience. While modern vision models achieve strong performance in image recognition, their correspondence with the hierarchical organization of the human visual cortex remains an open question. In this study, we propose CHASMBrain, a novel hierarchical two-stage framework for image-to-fMRI encoding. Our architecture leverages a dual-stream Mamba design to explicitly separate and process global semantic tokens and local spatial patches, motivated by the functional organization of the visual cortex. A coarse-to-fine strategy is employed: Stage 1 predicts denoised ROI-level activations, while Stage 2 refines these coarse responses into full voxel-level predictions using a Mamba-VAE. Experiments on the Natural Scenes Dataset (NSD) demonstrate that our method achieves a Pearson correlation of 0.429 and an MSE of 0.261, outperforming all evaluated baselines including ridge regression and DINOv2 linear probes. Beyond predictive performance, causal branch-ablation experiments reveal an asymmetric specialization: the patch stream is specifically locked to early visual cortex (retinotopic regions), while the CLS stream contributes broader semantic context to higher-order areas -- a correspondence that holds causally, not merely correlationally. Cross-subject transfer experiments further show that the learned backbone generalizes across individuals with minimal per-subject adaptation, suggesting the model captures a shared, subject-agnostic visual representation.

Maximal safe resection is the primary objective in glioma surgery. Neuronavigation guidance is progressively degraded by brain shift after dural opening. Intraoperative MRI can compensate but needs dedicated infrastructure and is rarely available, whereas intraoperative ultrasound (ioUS) is inexpensive, repeatable, and compatible with routine workflows. Navigation systems combining ioUS with preoperative MRI usually rely on rigid registration; even deformable multimodal registration is limited by ultrasound speckle contrast, a narrow field of view, and the inability to represent structures absent from the preoperative scan, most critically the resection cavity and residual tumor. We propose an end-to-end pipeline that generates a new whole-brain MRI volume in the preoperative imaging space by merging the preoperative MRI, a synthetic MRI generated from the ioUS, and a deformable registration anchored on that synthetic image. It integrates a 2.5D residual-transformer synthesis backbone (ResViT-2.5D) and a two-stage registration coupling NiftyReg with a synthesis-anchored SynthMorph stage, operating directly on raw scanner inputs. On a post-resection ReMIND cohort, ResViT-2.5D produced synthetic images closely matching the intraoperative T2 across structural, intensity, and perceptual metrics. In 14 subjects with 215 expert landmarks, the synthesis-anchored registration reduced the mean target registration error from 6.27 to 5.86 mm, matching a strong classical NiftyReg baseline (5.85 mm) while yielding a diffeomorphic deformation field in every subject. The contribution is not a gain in registration accuracy but the integrated volume itself, which inside the ultrasound field of view it reflects the intraoperative post-resection state. This provides the surgeon with an MRI-like update of the operative field with potential for integration into surgical-navigation workflows.

Computational models of epilepsy promise patient-specific treatment design, but most optimization workflows still search for parameters that perform well on average. In neuromodulation, this is a weak target: a protocol that improves the mean response can still fail in the patient whose network is least tolerant to stimulation. We present a literature-guided minimax pipeline that couples PubMed-scale hypothesis extraction, The Virtual Brain (TVB) Epileptor simulations, and large-language-model-guided black-box optimization. The optimizer proposes either intrinsic model-control parameters or clinically interpretable external-stimulation protocols; TVB evaluates each proposal across sampled virtual patients; and the objective maximizes worst-case reward, defined as the negative variance of simulated seizure activity. In the intrinsic model-control experiment, the best archived parameter set improved worst-case reward from -0.5285 to -0.3182, a 39.8% gain over baseline. The clinical-style external-stimulation search produced a much smaller worst-case improvement (1.7%), and a 20-patient virtual cohort showed no aggregate benefit (p=0.9019), despite a 55% responder rate and a positive temporal-lobe subgroup signal. The study should be read as an in silico proof of concept for robust, literature-aware neurostimulation design, not as clinical evidence.

The graphical representation of the brain offers critical insights into diagnosing and prognosing neurodegenerative disease via relationships between regions of interest (ROIs). Despite recent emergence of various Graph Neural Networks (GNNs) to effectively capture the relational information, there remain inherent limitations in interpreting the brain networks. Specifically, convolutional approaches ineffectively aggregate information from distant neighborhoods, while attention-based methods exhibit deficiencies in capturing node-centric information, particularly in retaining critical characteristics from pivotal nodes. These shortcomings reveal challenges for identifying disease-specific variation from diverse features from different modalities. In this regard, we propose an integrated framework guiding diffusion process at each node by a downstream transformer where both short- and long-range properties of graphs are aggregated via diffusion-kernel and multi-head attention respectively. We demonstrate the superiority of our model by improving performance of pre-clinical Alzheimer's disease (AD) classification with various modalities. Also, our model adeptly identifies key ROIs that are closely associated with the preclinical stages of AD, marking a significant potential for early diagnosis and prevision of the disease.

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.

We introduce Convex Distance Operator Transport (CDOT), the first convex optimal transport framework that aligns distributions across heterogeneous domains by jointly preserving feature correspondence and intrinsic geometric structure. Specifically, CDOT employs an operator-based regularization that aligns aggregated distance structures by introducing distance and conditional expectation operators. Consequently, the proposed regularization improves the robustness to local geometric variations. We further prove that the resulting CDOT discrepancy is a valid pseudometric on the space of attributed compact metric-measure spaces. In addition, we characterize the relationship between CDOT and Gromov--Wasserstein (GW) through a new notion of dispersion gap, formally elucidating the geometric source of non-convexity in GW compared to the convexity of CDOT. In the finite-sample regime, we derive a non-asymptotic risk bound decomposed into optimization and statistical errors, establishing risk consistency under a globally convergent Frank--Wolfe algorithm. Experiments on synthetic point clouds, brain connectomes, and graph classification benchmarks demonstrate better performance over existing methods, with stable and reliable behavior in practice.

Electroencephalography (EEG) is the cornerstone of non-invasive brain-computer interfaces (BCIs), yet conventional decoding relies on fragmented, task-specific architectures that severely limit cross-task scalability. While EEG foundation models pre-trained on massive corpora promise universal brain decoding, current post-training depends on task-isolated fine-tuning. This static paradigm restricts knowledge transfer across heterogeneous tasks, hinders model scalability, and incurs computational and storage overheads that scale linearly with task count. To overcome these bottlenecks, we formulate downstream adaptation as a cross-task continual learning problem and propose EvoBrain, a dynamic, task-aware continual learning framework for unified EEG decoding. EvoBrain addresses the plasticity-stability trade-off via two complementary components: (1) Neuro-Spectral Task Normalization (NSN) aligns incoming tasks with historical statistics while recalibrating spectral responses to handle distributional and neuro-spectral shifts; and (2) Response-Affinity Distillation (RAD), combined with time-dependent replay, preserves old-task response geometry and promotes selective knowledge transfer between spectrally compatible tasks, effectively mitigating forgetting. Extensive evaluations across six distinct BCI tasks demonstrate that EvoBrain consistently surpasses state-of-the-art methods across diverse foundation backbones, optimally balancing plasticity and stability. To our knowledge, this work pioneers cross-task continual learning in the EEG domain, advancing the realization of a unified, one-for-all brain decoding system.

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 \textit{NeuroAlign}, a hierarchical framework for structured multimodal fusion. It introduces (1) \textit{Dual-Modal Hierarchical Alignment} (DMHA), which models multi-scale dynamic connectivity and aligns dynamic-static and functional-structural embeddings; and (2) \textit{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 \textit{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.

Mild cognitive impairment (MCI) and subjective cognitive decline (SCD) are closely associated with the early Alzheimer's disease continuum, where accurate and explainable diagnosis is important for early risk assessment and intervention. Existing connectome-based deep learning models can improve classification performance but often provide limited insight into disease-related functional and structural connectivity changes. This paper proposes an atlas-knowledge-guided Generative Counterfactual Attention-guided Network (GCAN) for explainable cognitive decline diagnosis using multimodal brain connectomes. GCAN formulates diagnosis as a source-to-target counterfactual generation problem, where target-label connectomes are generated from source-label inputs and their differences are used to construct counterfactual attention maps. To preserve connectome topology, an Atlas-aware Bidirectional Transformer (AABT) performs network-level token encoding and decoding under brain-atlas constraints. The framework is further extended from functional connectivity (FC) to joint functional and structural connectivity (SC) modeling, enabling counterfactual analysis of complementary functional reorganization and structural topology changes. Experiments on hospital-collected and ADNI datasets show that GCAN achieves competitive performance across HC vs. SCD, HC vs. MCI, and SCD vs. MCI classification tasks. Visualization, circular connectome analysis, CAM-based comparison, ablation studies, and confidence interval analysis further support the interpretability and reliability of the proposed framework. Modality-specific FC and SC pre-trained classifiers are used to provide target-state priors for counterfactual generation while being separated from the downstream diagnostic classifier to prevent data leakage.

Intraoperative ultrasound (ioUS) is a versatile, cost-effective modality in brain tumour surgery, but its interpretation is difficult: acquisition planes are non-standard, artefacts are modality-specific, and its appearance differs markedly from the preoperative MRI on which surgical-planning tools, segmentation models and the surgeon's experience rely. Synthesising MRI-like images from ioUS could let this MRI-based infrastructure be reused intraoperatively without an extra scan. Most prior work evaluates a single architecture in isolation; to our knowledge, no benchmark has spanned architectural paradigms, inference regimes and downstream-task endpoints under a common protocol. We address this gap on the public ReMIND data set (76 patients; 153 paired ioUS/T2w and 104 paired ioUS/FLAIR studies; 60/16 patient-level train/held-out split). Six generators (four GAN baselines: Pix2Pix, SwinPix2Pix, CycleGAN, CUT; the transformer-augmented ResViT; and the few-step diffusion model SynDiff) were each trained under four inference regimes (2D, 2.5D, 2D + 3D-refinement, full-3D) and two targets (T2w only; T2w + FLAIR multi-task), yielding 48 experiments. Image-fidelity metrics (SSIM, PSNR, MAE, LPIPS) were complemented by an nnU-Net v2 downstream segmentation evaluation (tumour and resection cavity) and by subgroup analyses by histological grade and reoperation. No architecture dominated every axis, and, critically, perceptual quality tracked downstream utility most closely (LPIPS, r=-0.66, p<0.001), whereas higher SSIM was associated with worse utility (r=-0.64, p<0.001); SynDiff-2.5D best preserved downstream segmentation (U_Dice=0.55). Perceptual and downstream-task metrics should therefore be reported alongside or in preference to global SSIM, and architecture choice conditioned on surgical phase, patient history and clinical objective.

Forecasting the progression of neurodegenerative diseases, such as Parkinson's disease, is essential for effective long-term planning and personalized therapeutic intervention. Existing systems typically produce scalar clinical scores that ignore the rich structure of longitudinal neuroimaging, while traditional generative approaches suffer from a loss of anatomical details and blurring subtle progression patterns. To address this, we introduce a novel treatment-conditioned diffusion framework that predicts high-fidelity future brain states by conditioning the generative process on patients' screening DaTscan images and levodopa equivalent daily dose over one year. The pipeline uses a Transformer-based encoder to represent non-linear, time-dependent pharmacological dynamics and optimizes generation through a multi-weight region-of-interest mask that focuses on biologically critical areas. Experimental evaluation shows that our framework maintains sharp anatomical boundaries and significantly improves clinical fidelity relative to the baseline, achieving 14.0% lower MSE, 7.2% lower MAE, and 4.9% higher SSIM.

Decoding visual content from fMRI signals recorded while a person views images, and specifically answering questions about the seen images, is a long-standing challenge. While significant progress has been made in recent years in visual question answering (VQA) from fMRI, performance remains limited. Moreover, although recent models can make increasingly accurate predictions, they have rarely been used as tools for understanding the structure of visual representations in the brain. We present Brain-IT-VQA, a framework for visual question answering from fMRI. Building on the Brain Interaction Transformer (Brain-IT), our method decodes language tokens from brain activity and integrates them with a language model to answer visual questions. Our model substantially outperforms previous fMRI-based captioning and VQA approaches. We further introduce NSD-VQA, a new dataset and benchmark for visual question answering from fMRI. Unlike existing image-fMRI VQA datasets, which typically provide only a few broad and weakly controlled questions per image, NSD-VQA provides on average 20 question-answer pairs per image across 20 controlled question categories that disentangle multiple levels of visual understanding. This enables more reliable and interpretable evaluation despite limited fMRI test data. Together, Brain-IT-VQA and NSD-VQA provide both a strong predictive framework and a tool for studying brain representations. Using this benchmark, we quantify which forms of visual and semantic information can be reliably decoded from fMRI responses to natural images. We further analyze the contributions of different brain regions across question types.

Functional magnetic resonance imaging (fMRI) is a powerful tool for investigating human brain function. However, the high cost of data acquisition and the inherent subjectivity of psychiatric rating scales often lead to datasets with small sample sizes and variable label quality, especially when targeting a specific neurological condition. Combined with the inherently high dimensionality of fMRI data, these limitations substantially increase the risk of model overfitting. Recent years have seen growing interest in developing fMRI foundation models by combining multiple datasets; however, the computational resources needed for pretraining and fine-tuning are often prohibitive. We show that a lightweight self-supervised framework yields representations that generalize across diverse downstream tasks, outperforming fully supervised baselines and approaching the performance of large-scale models. We introduce BrainSimSiam, a data-efficient self-supervised representation learning framework that leverages positive-only data pairs to learn robust and generalizable features. We demonstrate that the learned representations achieve strong performance across multiple downstream classification and regression tasks, highlighting the potential of BrainSimSiam for data-limited neuroimaging applications.

Electroencephalography (EEG) is a critical, non-invasive method to monitor electrical brain activity. EEGs can span anywhere from a couple seconds to multiple hours, posing a major hurdle for existing deep learning methods due to two major factors: (1) existing EEG models are predominantly built upon the attention mechanism, incurring quadratic scaling as the sequence length increases, and (2) raw EEG signals must be processed in a sliding-window fashion due to fixed-length input requirements, preventing global understanding of the entire signal. To this extent, we propose CaMBRAIN - the first Causal, Mamba-based state space model (SSM) capable of real-time inference of EEG signals, arguing that bidirectional approaches are needlessly expensive given the causal, unidirectional nature of EEG. However, training such a model is non-trivial, as crucial EEG events can be extremely brief - within fractions of a second - yet separated by long intervals spanning minutes. Current EEG methods use self-supervised objectives that optimize for signal reconstruction, but these are not well suited for streaming SSMs; they fail to explicitly train the hidden state to retain the salient long-range context needed for streaming inference. We therefore introduce a multi-stage self-supervised training pipeline specifically tailored to encourage long-range memory retention and strong performance on EEG signals, while preserving the linear-time complexity of state space models. CaMBRAIN achieves state-of-the-art (SOTA) results across 3 different EEG datasets with >10x higher throughput than existing models, enabling the first model capable of long-range, continuous inference of variable-length EEG signals.

Electroencephalogram (EEG)-based emotion recognition is an important affective computing task, and recent EEG foundation models provide useful generic representations for downstream adaptation. However, under the fine-tuning setting, three limitations remain prominent: insufficient modeling of multi-scale emotional dynamics, inadequate exploitation of inter-channel functional connectivity, and the limited expressive power of simple linear classification heads. To address these issues, this paper proposes a new EEG emotion recognition method, termed MSCGC-KAN, which introduces a structured task head composed of multi-scale causal graph convolution and Kolmogorov--Arnold feature mapping. Built on a pre-trained CBraMod backbone, MSCGC-KAN enhances downstream adaptation by jointly strengthening multi-scale temporal modeling, learnable inter-channel connectivity modeling, and nonlinear discriminative mapping within a compact task-specific head. This design preserves the representation advantage of the foundation model while making the classifier more sensitive to emotion-related spatiotemporal patterns. Extensive experiments are conducted on the public FACED and SEED-VII datasets. The proposed method achieves a balanced accuracy of 60.66%, a Cohen's Kappa of 0.5525, and a weighted F1-score of 60.40% on FACED, and obtains 33.27%, 0.2223, and 33.64%, respectively, on SEED-VII. Compared with the CBraMod+Linear baseline, the balanced accuracy is improved by 5.91 and 2.03 percentage points on the two datasets, respectively. These results indicate that structured task-head design is an effective way to improve EEG emotion recognition when fine-tuning pre-trained EEG models.

EEG-based emotion recognition holds significant promise for objective diagnosis of mood disorders. Graph neural networks (GNNs) have emerged as the dominant paradigm for modeling inter-channel dependencies in EEG, yet existing approaches rely on symmetric adjacency matrices derived from spatial proximity or functional correlations that fundamentally capture statistical associations rather than directed causal influences, which conflicts with the inherently asymmetric, causally-driven nature of neural information flow. To bridge this gap, we propose GL-LFGNN, a Global-Local Dual-branch Causal Graph Neural Network grounded in Liang-Kleeman information flow theory. Unlike Granger causality that merely assesses temporal precedence, our approach rigorously quantifies causal strength from a dynamical systems perspective, yielding neurophysiologically interpretable directed graphs. A dual-branch architecture further integrates whole-brain connectivity with region-specific processing aligned to established functional neuroanatomy. On the MEEG dataset, GL-LFGNN achieves 86.17% (Arousal) and 86.71% (Valence) accuracy with only 37K parameters -- approximately 10% of the current state-of-the-art -- demonstrating that principled causal modeling can simultaneously enhance interpretability, generalization, and computational efficiency. Code will be released.

Large language models (LLMs) display strong comprehensive abilities, yet the internal mechanisms that support these behaviors remain insufficiently understood. In this work, we show that across a wide range of open-weight Transformers, a subset of neurons remains consistently highly activated during inference across tasks of multiple capability dimensions. By probing along the cross-task activation strength, an extremely sparse subset is isolated, whose removal causes a collapse in model behavior, which we term keystone neurons. Our analysis reveals that keystone neurons are a stable and intrinsic neuron subset of the model that is largely established during pretraining. The parameters associated with these neurons are tightly calibrated during the training process, and their precise values are critical for the capabilities of the model. Building on these insights, we propose a supervised fine-tuning approach that updates only keystone neurons, achieving task gains comparable to or even better than full-parameter fine-tuning while better preserving performance in other capability dimensions, despite modifying a much smaller number of parameters.

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.

Brain-LLM alignment is well established in English, yet the brain's language network is neuroanatomically universal across languages. Does alignment also generalize cross-linguistically, and what governs the variation? We test this using fMRI data from 112 participants across English, Chinese, and French (the Le Petit Prince corpus) and seven LLMs spanning English-dominant, Chinese-dominant, and multilingual architectures. Our central finding is that training-language dominance, not an inherent property of English, drives the alignment pattern: a Chinese-dominant model (Baichuan2-7B), architecture-matched to LLaMA-2-7B, reverses the gradient entirely, aligning best with Chinese brains and worst with English. Beyond training dominance, formal typological distance independently covaries with alignment degradation, syntax-associated brain regions (IFG) show $2.3\times$ steeper typological gradients than lexico-semantic regions (PTL), and tokenization fertility accounts for $\sim$60% of a cross-linguistic shift in optimal encoding layer. These results reveal that the apparent "English advantage" in brain-LLM alignment is an artifact of training data composition, while the remaining variation reflects genuine typological structure concentrated in syntactic processing.

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.

The Thousand Brains Theory (TBT) and its open-source Monty framework model object recognition through sensorimotor inference -- identifying objects by actively moving a sensor across their surface and building evidence contact by contact. The current implementation encodes each contact as a dense floating-point vector. While Monty tracks inter-step displacement and accumulates evidence across contacts, it treats the feature activation pattern at each contact as an unordered set - the directional sequence in which features are encountered carries no representational weight. In TBT, the sequence of contacts carries spatial meaning: knowing that feature A was felt before feature B during a left-to-right sweep tells you something about where A and B sit on the object. Dense vectors discard this ordering. We propose replacing dense vectors with rank-order spike packets: each contact produces a brief burst of neural events where the most strongly activated neuron fires first. The time gap between successive bursts implicitly encodes sensor displacement without explicit coordinate calculations. A biologically motivated learning rule (STDP) encodes traversal direction into synaptic weights. A learnable parameter lambda adjusts reliance on earlier versus recent contacts, adapting to each object's geometry. We derive three testable predictions and specify an implementation of four components in approximately 450 lines of NumPy. Three synthetic experiments confirm the core claims: temporal coding achieves perfect discrimination accuracy on objects with identical features in different spatial arrangements, where dense accumulation performs at chance; temporal coding maintains a 30-50 percentage point advantage across all tested noise levels; the adaptive lambda converges to distinct values, reflecting object geometric complexity. End-to-end evaluation on Monty's YCB benchmark is left for future work.

Efficient neural network models that generate brain-like dynamic activity can be a valuable resource for generating synthetic data, analyzing differences in brain transients under conditions such as testing perturbation activity or inferring the underlying generative dynamics. However, large language models (LLMs) or standard recurrent neural networks (RNNs) ignore the anatomical organization and therefore do not produce components that align with brain regions. On the other hand, graph-based networks often have very simple message passing rules that are not sufficiently expressive for brain-like dynamics. To address this, we introduce BrainDyn, a sheaf neural ordinary differential equation (neural ODE) model for continuous-time dynamics on structured brain graphs. BrainDyn encodes the recent activity history of each brain region using a long short-term memory (LSTM) model over a sliding temporal window to produce hidden states, or stalks, that are projected through learnable restriction maps into edge-specific shared spaces. Discrepancies between neighboring nodes in these shared spaces are characterized by a sheaf Laplacian that can facilitate message passing between neuronal units. The output of these messages is then fed to a neural ODE that governs the continuous-time evolution of neuronal activity. We evaluated BrainDyn on resting-state fMRI (PNC dataset), scalp EEG with focal epilepsy (TUSZ dataset), and simulated activity from the NEST spiking network simulator. BrainDyn achieves strong forecasting ability across modalities, and the resulting representations support downstream tasks including in silico perturbation prediction.

Visual image reconstruction from functional Magnetic Resonance Imaging (fMRI) is a fundamental task in brain decoding, providing a crucial pathway for understanding human perceptual mechanisms and developing advanced brain-computer interfaces (BCIs). However, most current methods simply flatten fMRI signals from localized visual cortices into one-dimensional (1D) vectors, mapping them directly into latent spaces such as that of Contrastive Language-Image Pre-training (CLIP). This paradigm not only disrupts the inherent network topology of the brain-leading to limited neuroscientific interpretability-but also overlooks the synergistic contributions of other distributed functional networks in processing high-level visual semantics. To address these limitations, we propose FPED, a Functional-Network Prior-Guided Mixture of Experts (MoE) framework for interpretable brain decoding. FPED explicitly models different functional brain networks as specialized experts and employs adaptive routing to capture their complementary contributions to visual semantic understanding. Unlike conventional homogeneous decoding paradigms, our framework incorporates neurobiologically grounded priors to enable structured and interpretable network-level representation learning. Experimental results demonstrate that FPED achieves highly competitive semantic reconstruction performance with only 0.68B parameters. The learned routing dynamics reveal biologically meaningful correspondence between functional brain networks and modality-specific semantic processing, providing transparent neuroscientific interpretability. This suggests that brain network-aware expert modeling is a promising direction for bridging neural decoding and biologically inspired artificial intelligence.

Cortical surface registration is often driven by local geometric descriptors (e.g., sulcal depth and curvature). While this approach achieves geometric correspondence, it neglects the long-range wiring constraints imposed by white-matter anatomy. Diffusion MRI tractography offers these crucial constraints; however, prior connectivity-informed pipelines typically align precomputed connectivity matrices, making the optimization highly sensitive to connectivity estimation and its resolution. In this paper, we introduce a novel connectivity-based surface registration method that aligns cortical surfaces by operating directly on white-matter fiber-tract endpoints. We model tract endpoints as a point cloud on the product manifold $Ω\times Ω$, where $Ω$ represents the spherical domain of the inflated cortical hemispheres. Our alignment method iteratively (i) computes a small diffeomorphic warp for $Ω$ by minimizing connectivity mismatch, and (ii) updates the endpoints based on this warp. The method relies on a geometric framework that ensures output warps are diffeomorphisms and has a final goal that optimizes the matching of well-known fiber bundles. Experiments on Human Connectome Project (HCP) data demonstrate improved tract-level correspondence, achieving higher connectivity-level overlap coefficients on major fiber bundles and stronger robustness across grid resolutions for $Ω$ compared to state-of-the-art methods such as ENCORE and MSMAll.

Decoding visual experience from brain activity has advanced substantially, but current brain-to-text systems largely recover semantic content while discarding affect. Additionally, language models can generate emotional text when prompted with categorical labels, but such labels collapse rich inter-subject variability into coarse discrete bins. We present EmoMind, the first end-to-end pipeline for decoding affective captions directly from fMRI signals. EmoMind first retrieves a semantically grounded neutral scene description from brain-decoded visual features, then rewrites it using a continuous 34-dimensional emotion vector decoded from the same fMRI recording. To control the balance between content preservation and affective expression, we train the rewriter with classifier-free guidance against an identity-preserving null branch, enabling smooth interpolation between semantic fidelity and affective expressivity. We evaluate affective caption generation with a three-axis validation framework spanning subject-specificity, structural geometry, and causal control. We further augment this framework with a synthetic-brain substitution test that probes robustness to the measurement apparatus, and we benchmark each axis against GPT-4 prompted with brain-decoded top-5 emotion labels as a strong discrete baseline. Across two independent emotion fMRI datasets, EmoMind significantly outperforms label-prompted GPT-4 on all three axes, with the largest gains on metrics that require person-specific affective structure rather than population-level emotion aggregation. These results establish continuous brain-decoded affect as a viable control signal for individualized affective caption generation and open new directions for studying individual affective brain organisation.

Learning meaningful latent representations from nonlinear fMRI data remains a fundamental challenge in neuroimaging analysis. Traditional independent component analysis, widely used due to its ability to estimate interpretable functional brain networks, relies on a linear mixing assumption for latent sources, limiting its ability to capture the inherently nonlinear and complex organization of brain dynamics. More recently, deep representation learning methods have emerged as promising alternatives for modeling nonlinear latent structure. However, many of these approaches have been evaluated primarily on simulated datasets or natural image benchmarks, with comparatively limited validation on real-world neuroimaging data such as fMRI. In this work, we are motivated by the $β$-TCVAE (Total Correlation Variational Autoencoder), a refinement of the $β$-VAE framework for learning latent representations without introducing additional hyperparameters during training. We adapt and modify this model to fMRI data for nonlinear source disentanglement, aiming to separate mixed spatial and temporal brain signals into interpretable components. We show that the $β$-TCVAE framework can recover meaningful nonlinear spatial components with biological relevance, including well-established intrinsic connectivity networks such as the default mode network. Furthermore, we evaluate the learned representations using functional network connectivity, showing that the latent structure captures coherent and interpretable brain organization patterns. This study provides a pilot investigation that bridges nonlinear representation learning and fMRI analysis.

Reconstructing dynamic visual experiences as videos from functional magnetic resonance imaging (fMRI) is pivotal for advancing the understanding of neural processes. However, current fMRI-to-video reconstruction methods are hindered by a semantic gap between noisy fMRI signals and the rich content of videos, stemming from a reliance on incomplete semantic embeddings that neither capture video-specific cues (e.g., actions) nor integrate prior knowledge. To this end, we draw inspiration from the dual-pathway processing mechanism in human brain and introduce CineNeuron, a novel hierarchical framework for semantically enhanced video reconstruction from fMRI signals with two synergistic stages. First, a bottom-up semantic enrichment stage maps fMRI signals to a rich embedding space that comprehensively captures textual semantics, image contents, action concepts, and object categories. Second, a top-down memory integration stage utilizes the proposed Mixture-of-Memories method to dynamically select relevant "memories" from previously seen data and fuse them with the fMRI embedding to refine the video reconstruction. Extensive experimental results on two fMRI-to-video benchmarks demonstrate that CineNeuron surpasses state-of-the-art methods across various metrics.

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.

Brain-language model comparisons often interpret neural prediction scores as evidence that model representations capture brain-relevant language computation. We asked whether language models align with brains, and whether prediction scores are enough to support that claim, using L-PACT, a source-audited framework that evaluates predictive, relational, mechanism-stripping, and reliability-bounded evidence. Across primary naturalistic language neural datasets and derived language-model representations, L-PACT compared real model features with nuisance baselines and severe controls, tested whether model-to-brain profiles reproduced brain-to-brain patterns, recomputed held-out scores after mechanism stripping, and normalized evidence against brain-brain ceilings. The locked analysis set contains 414 predictive-control rows, 2304 relational profile rows, 4320 mechanism-stripping rows, 420 brain-brain ceiling rows, and 146 integrated decision rows. Assay-sensitivity checks showed that brain-brain reliability, brain-as-model run-to-run relational profiles, independent low-level neural and WAV-derived acoustic-envelope gates, and a deterministic implanted-signal simulation can produce positive evidence when expected. Nevertheless, no real model row passed the predictive, relational, mechanism-stripping, or operational Turing-bounded reliability gates; all 146 integrated rows were control-explained. Less stringent single-criterion rules would have counted raw positive predictive, relational, stripping-delta, and ceiling-normalized effects, but L-PACT downgraded them because controls explained the apparent evidence. In the analyzed derived artifact set, the tested language-model representations do not satisfy L-PACT alignment gates; apparent positives are converted into an auditable control-explained taxonomy rather than treated as structural alignment.

Acquisition differences across sites, scanners, and protocols in dMRI introduce variability that complicates structural connectome analysis. This motivates deep learning models that can represent high-dimensional connectomes in a low-dimensional space while explicitly separating acquisition-related effects from biological variation. Conventional dimensionality reduction methods model all variance as continuous, so acquisition effects often get absorbed into a continuous latent space. Recent hybrid latent-space models combine discrete and continuous components to address this, but typically require manual capacity tuning to ensure the discrete component captures the intended variability. We introduce an unsupervised framework that removes this manual tuning by architecturally annealing encoder outputs before decoding, allowing the model to adaptively balance discrete and continuous latent variables during training. To evaluate it, we curated a dataset of N=7,416 structural connectomes derived from dMRI, spanning ages 2 to 102 and 13 studies with 25 unique acquisition-parameter combinations. Of these, 5,900 are cognitively unimpaired, 877 have mild cognitive impairment (MCI), and 639 have Alzheimer's disease (AD). We compare against a standard VAE, PCA with k-means clustering, and hybrid models that anneal only through the loss function. Our architectural annealing produces stronger site learning (ARI=0.53, p<0.05) than these baselines. Results show that a hybrid continuous-discrete latent space, with architectural rather than loss-based annealing, provides a useful unsupervised mechanism for capturing acquisition variability in dMRI: by jointly modeling smooth and categorical structure, the Joint-VAE recovers clusters aligned with scanner and protocol differences.

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.

While EEG foundation models have shown significant potential in universal neural decoding across tasks, their advancement remains constrained by the inadequacy modeling of complex spatiotemporal topology, as well as the inherent modality gap between low-level physiological signals and high-level textual semantics. To address these challenges, we propose a Knowledge-Anchored Semantically-Dynamic Topology Brain Autoregressive Model (KAST-BAR), which dynamically aligns physiological representations derived from multi-level brain topology with an expert-level semantic space. Specifically, we design a Dual-Stream Hierarchical Attention (DSHA) encoder that accurately captures the brain's intrinsic non-Euclidean topology by modeling local temporal dynamics with global spatial contexts. On this basis, a Knowledge-Anchored Semantic Profiler (KASP) is proposed to synthesize physically-grounded and instance-level textual profiles, which subsequently drive a Semantic Text-Aware Refiner (STAR) to dynamically reconstruct EEG representations using Latent Expert Queries. By conducting large-scale pre-training on 21 diverse datasets to build a foundation model, KAST-BAR effectively integrates expert-level medical knowledge into EEG signal representations, consistently achieving superior performance across six downstream tasks. Our code is available at https://github.com/KAST-BAR/KAST-BAR

Clinical diagnostic workups typically follow a modality escalation pathway: after initial clinical evaluation, clinicians begin with routine structural imaging (e.g., MRI), selectively add sequences such as FLAIR or T2 to refine the differential, and reserve molecular imaging (e.g., amyloid-PET) for cases that remain uncertain after standard evaluation. Consequently, patients are observed with heterogeneous and often incomplete modality subsets. However, most current AI models assume fixed data modalities as the model inputs. In this paper, we present BrainAnytime, a unified pretraining framework pretrained on 34,899 3D brain scans from five datasets that support brain image analysis under arbitrary modality availability spanning multi-sequence MRI and amyloid-PET. A single model accepts whatever imaging is available, from a lone T1 scan to a full multimodal workup. Pretraining learns structural-molecular correspondences between MRI and PET via cross-modal distillation (RCMD) and prioritizes disease-vulnerable anatomy via atlas-guided curriculum masking (PACM), all within a shared 3D masked autoencoder (Multi-MAE3D). Across four downstream tasks and five clinically motivated modality settings, BrainAnytime largely outperforms modality-specific models, missing-modality baselines, and large-scale brain MRI pretrained foundation models on most modality settings. Notably, it surpasses the strongest missing-modality baselines with relative improvements of 6.2% and 7.0% in average accuracy on CN vs. AD and CN vs. MCI classification, respectively. Code is available at https://github.com/SDH-Lab/BrainAnytime.

Structural MRI-to-amyloid PET synthesis has been proposed as a non-invasive alternative for amyloid assessment in Alzheimer's disease (AD). However, reported performance of identical models varies widely across studies, and increasingly complex architectures have not led to consistent gains. This inconsistency is thought to be caused by a fundamental biological ambiguity: MRI captures neurodegeneration, while PET measures amyloid pathology - two processes that are often temporally decoupled in AD. As a result, similar MRI patterns may correspond to different amyloid states, creating ambiguous one-to-many mappings. MRI-to-amyloid PET synthesis may therefore be intrinsically ill-posed; however, this idea has yet to be tested scientifically. The aim of this work is to test this hypothesis through two controlled experiments. We first control the training distribution by stratifying paired MRI-PET data by amyloid and neurodegeneration status. Using two standard synthesis models under a controlled design, we show that biologically unambiguous mappings are learnable in isolation, but performance collapses when data ambiguity is introduced. This demonstrates that ambiguity in the data distribution, rather than architectural capacity, constrains performance. Second, we show that introducing orthogonal biological information in the form of plasma biomarkers resolves this ambiguity. When multimodal inputs are incorporated, performance improves and stability is restored. Together, these findings suggest that limited and inconsistent performance in MRI-to-amyloid PET synthesis is explained by intrinsic biological ambiguity, and that stable, meaningful progress requires multimodal integration rather than architectural complexity.

Clinical electroencephalogram (EEG) analysis rests on a hand-crafted feature catalog refined over decades, \emph{e.g.,} band power, connectivity, complexity, and more. Modern EEG foundation models bypass this catalog, learn directly from raw signals via self-supervised pretraining, and match or outperform feature-engineered baselines on most clinical benchmarks. Whether the two representations align is an open question, which we decompose into three sub-questions: \emph{what does the model learn}, \emph{what does the model use}, and \emph{how much can be explained}. We answer them with layer-wise ridge probing, LEACE-style cross-covariance subspace erasure, and a transparent classifier benchmarked against a random-feature baseline. The audit covers three foundation models (CSBrain, CBraMod, LaBraM), five clinical tasks (MDD, Stress, ISRUC-Sleep, TUSL, Siena), and a 6-family 63-feature lexicon. Of the $945$ (model, task, feature) units, $648$ ($68.6\%$) are representation-causal and $199$ ($21.1\%$) are encoded-only. Across tasks, $50$ features qualify as universal candidates with strong support (all three architectures RC) in two or more tasks. Frequency-domain features dominate, but the other five families each contribute substantial causal mass. Confirmed features recover, on average, $79.3\%$ of the foundation model's advantage over the random baseline, with a clean task gradient (MDD $\approx 0.99$ down to Stress $\approx 0.56$): tasks near ceiling are almost fully recovered by the lexicon, while harder tasks leave a non-trivial residual that pinpoints a concrete target for future concept discovery.

How much thinking can a civilisation do? Kardashev's (1964) typology ranks civilisations by total power: planetary (Type I, ~10^16 W), stellar (Type II, ~10^26 W), galactic (Type III). This paper builds an analogous Cognitive Kardashev Scale: how much sustained AI-grade computation each tier could support. Four ingredients enter the calculation: total power P (watts), the share f of it devoted to cognition, the efficiency $η$ at which energy becomes compute (operations per joule), and the brain's own processing rate $C_{\mathrm{brain}}$ as a reference unit. Anchoring on 2024-2026 hardware (El Capitan, NVIDIA Blackwell, Vera Rubin) gives $η_{2026} = 10^{12}$ FLOP/J. Contemporary humanity sits at $K \approx 0.73$, three-quarters of the way to Type I. At Type I and $f = 1\%$, available compute is, within an order of magnitude, one personal AI's worth of cognition per human inhabitant; at Type II it is essentially incomprehensible. Three trajectories for frontier compute through 2035 are reported as conditional projections, not predictions. Whether the long-run binding constraint is energy or efficiency depends on engineering choices not yet made; the political economy of who has access may matter more than either.

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.

Electroencephalography (EEG) is a cornerstone of brain-computer interfaces and clinical neuroscience, yet deep learning models are typically trained and evaluated under a single, unreported preprocessing pipeline. We formalize preprocessing choices as a counterfactual intervention space and show that EEG predictions are surprisingly unstable under this space: across six datasets spanning four paradigms, up to 42% of trial-level predictions flip when only the preprocessing changes, a variability that standard uncertainty methods do not explicitly quantify because they condition on a fixed preprocessing pipeline. We provide three tools to make this instability measurable, decomposable, and reducible. First, a Walsh-Hadamard decomposition of the 2^7 pipeline space reveals that sensitivity is near-additive in practice under the binary intervention design, enabling efficient step-by-step optimization. Second, we introduce Preprocessing Uncertainty (PU), a per-trial diagnostic that captures a dimension of instability complementary to model-based confidence. Third, we study Normalized Adaptive PGI (NA-PGI), a graph-structured regularizer that exploits the compositional structure of preprocessing interventions as one mitigation strategy with clear scope conditions.

Accurate 3D brain MRI subtype classification benefits from both localized anatomical cues and long-range contextual reasoning. We present AGA3DNet, a report-grounded framework that incorporates brief anatomical phrases extracted from radiology reports as a soft anatomical prior channel and fuses it with a lightweight 3D CNN and multi-view xLSTM aggregation. Specifically, extracted anatomical phrases are mapped to atlas-defined regions and converted into smooth spatial priors using a signed-distance transform followed by Gaussian weighting, providing interpretable, anatomy-grounded guidance without requiring dense voxel annotations. We evaluate AGA3DNet on a retrospective institutional brain MRI cohort for abnormal subtype discrimination and compare against reproducible 3D classification baselines. AGA3DNet achieves improved overall balance across performance metrics and supports clinically interpretable localization through the prior channel. We discuss limitations related to single-cohort evaluation and the lack of large-scale public brain MRI datasets paired with radiology reports under broadly usable terms.