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Oct 19

Heterogeneous synaptic motifs bridge microscale structure and macroscale nonlinear dynamics

Recent breakthroughs in synaptic-resolution network connectomics have revealed that brain circuits feature fine-scale structural connectivity, such as pairs of correlated synaptic couplings known as second-order motifs. Large-scale recordings of neuronal activity in networks containing nonlinear neurons reveal macroscopic heterogeneous population dynamics throughout the brain. These findings rekindle the inquiry into this intriguing question: Can microscale synaptic structures contribute to macroscopic heterogeneous dynamics and computations in ways that canonical brain circuit models cannot? To answer this question, we create random RNNs with various cell types, nonlinear non-negative neural responses, and arbitrary marginal and second-order correlated synaptic statistics. We derive mean-field low-rank equations for P-population networks in which the pre- and postsynaptic neuronal population identities determine the synaptic and motif strengths. Our framework requires 2P latent dynamic variables with P variables describing mean population activity and P variables capturing within-population variability. Theoretical and simulational results demonstrate that chain motifs induce correlations in synaptic variability, enabling microscopic fluctuations to be integrated and influence mesoscopic mean population dynamics. We apply this framework to reverse engineer network connectivity that recapitulates the heterogeneous activity across the population in the mouse primary visual cortex. By bridging the gap between synaptic organization and nonlinear heterogeneous population dynamics, our results offer a principled approach and testable predictions regarding the relationship between fine-scale connectivity, heterogeneous dynamics, and functional computations.

  • 4 authors
·
Jun 25

ConnectomeBench2: A Unified Benchmark for Automated Connectomic Proofreading

Proofreading--correcting segmentation errors in 3D brain reconstructions--is the rate-limiting step in synapse-resolution connectomics. We release ConnectomeBench2, a unified multi-species dataset of over 716,485 expert-labeled proofreading decisions with >4,500,000 associated images spanning four major open connectomes (mouse, human, zebrafish, fly), spanning both split and merge error correction. Trained on this dataset, a single Vision Transformer with shared encoders for mesh geometry and electron microscopy reaches human-level accuracy across species for split error correction and merge error identification, with performance scaling with data size and modality. Beyond accuracy, we show that the model is well-calibrated within distribution, that measures of distribution distance predict where calibration and accuracy will degrade on unseen data, and that connectomics-specific pretraining and active learning-based sample selection show potential to substantially reduce the labeling effort needed to extend to new species and brain regions. The benchmark provides the infrastructure to train and evaluate increasingly capable vision models for connectomic proofreading. Data and code availability. The ConnectomeBench2 dataset is released on Hugging Face at https://huggingface.co/datasets/jeffbbrown2/ConnectomeBench2. The accompanying codebase is available on GitHub at https://github.com/timfarkas/ConnectomeBench2.

  • 4 authors
·
Jun 18

Harnessing cortical geometry, wiring, and function as inductive biases for recurrent neural networks

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.

  • 4 authors
·
Jun 11

Beyond Pairwise Connections: Extracting High-Order Functional Brain Network Structures under Global Constraints

Functional brain network (FBN) modeling often relies on local pairwise interactions, whose limitation in capturing high-order dependencies is theoretically analyzed in this paper. Meanwhile, the computational burden and heuristic nature of current hypergraph modeling approaches hinder end-to-end learning of FBN structures directly from data distributions. To address this, we propose to extract high-order FBN structures under global constraints, and implement this as a Global Constraints oriented Multi-resolution (GCM) FBN structure learning framework. It incorporates 4 types of global constraint (signal synchronization, subject identity, expected edge numbers, and data labels) to enable learning FBN structures for 4 distinct levels (sample/subject/group/project) of modeling resolution. Experimental results demonstrate that GCM achieves up to a 30.6% improvement in relative accuracy and a 96.3% reduction in computational time across 5 datasets and 2 task settings, compared to 9 baselines and 10 state-of-the-art methods. Extensive experiments validate the contributions of individual components and highlight the interpretability of GCM. This work offers a novel perspective on FBN structure learning and provides a foundation for interdisciplinary applications in cognitive neuroscience. Code is publicly available on https://github.com/lzhan94swu/GCM.

  • 5 authors
·
Oct 10, 2025

Surface-based parcellation and vertex-wise analysis of ultra high-resolution ex vivo 7 tesla MRI in Alzheimer's disease and related dementias

Magnetic resonance imaging (MRI) is the standard modality to understand human brain structure and function in vivo (antemortem). Decades of research in human neuroimaging has led to the widespread development of methods and tools to provide automated volume-based segmentations and surface-based parcellations which help localize brain functions to specialized anatomical regions. Recently ex vivo (postmortem) imaging of the brain has opened-up avenues to study brain structure at sub-millimeter ultra high-resolution revealing details not possible to observe with in vivo MRI. Unfortunately, there has been limited methodological development in ex vivo MRI primarily due to lack of datasets and limited centers with such imaging resources. Therefore, in this work, we present one-of-its-kind dataset of 82 ex vivo T2w whole brain hemispheres MRI at 0.3 mm isotropic resolution spanning Alzheimer's disease and related dementias. We adapted and developed a fast and easy-to-use automated surface-based pipeline to parcellate, for the first time, ultra high-resolution ex vivo brain tissue at the native subject space resolution using the Desikan-Killiany-Tourville (DKT) brain atlas. This allows us to perform vertex-wise analysis in the template space and thereby link morphometry measures with pathology measurements derived from histology. We will open-source our dataset docker container, Jupyter notebooks for ready-to-use out-of-the-box set of tools and command line options to advance ex vivo MRI clinical brain imaging research on the project webpage.

  • 23 authors
·
Mar 28, 2024

PhyMRI-SR: Toward Physics-Aware MRI Image Super-Resolution

Magnetic resonance imaging (MRI) super-resolution is vital for improving diagnostic accessibility, yet most methods treat it as a deterministic mapping from a fixed low-resolution input to a high-resolution target. This overlooks a key property of MRI acquisition physics: spatial resolution and signal-to-noise ratio (SNR) are inherently coupled, making any given low-resolution scan merely one of many possible realizations under varying acquisition trade-offs. We rethink MRI super-resolution as a physics-aware reconstruction problem, in which the goal is to identify the optimal resolution-SNR configuration and then super-resolve it to obtain high-quality MRI results. A key implication of this formulation is that MRI resolution becomes dynamic rather than fixed. To handle such resolution-heterogeneous inputs, we adapt 2D Gaussian Splatting (2D GS) to MRI by formulating reconstruction as a coordinate-based, resolution-agnostic rendering problem. To further enhance fidelity, we introduce three innovations: (1) a prior-aware Gaussian representation that combines an Anatomical Structure Prior for tissue-specific kernel initialization with an Imaging System Prior that captures hardware characteristics via a covariance dictionary; (2) a physics-constrained signal modeling scheme that predicts intrinsic tissue parameters (proton density rho and effective relaxation rate R2) and synthesizes intensities through governing physical equations, ensuring biophysically plausible contrast; and (3) a meta-learning framework that alleviates paired-data scarcity by pretraining on simulated data and adapting to real-world conditions. Extensive experiments on dynamic-resolution datasets and standard benchmarks demonstrate that our method achieves state-of-the-art performance, highlighting its strong potential for clinical deployment.

Stochastic Attention: Connectome-Inspired Randomized Routing for Expressive Linear-Time Attention

The whole-brain connectome of a fruit fly comprises over 130K neurons connected with a probability of merely 0.02%, yet achieves an average shortest path of only 4.4 hops. Despite being highly structured at the circuit level, the network's long-range connections are broadly distributed across brain regions, functioning as stochastic shortcuts that enable efficient global communication. Inspired by this observation, we propose Stochastic Attention (SA), a drop-in enhancement for sliding-window attention (SWA) that applies a random permutation to the token sequence before windowed attention and restores the original order afterward. This transforms the fixed local window into a stochastic global one within the same O(nw) per-layer budget. Through depth, independently sampled permutations yield exponentially growing receptive fields, achieving full sequence coverage in O(log_w n) layers versus O(n/w) for SWA. We validate SA in two settings: pre-training language models from scratch, where a gated SA + SWA combination achieves the best average zero-shot accuracy, and training-free inference on Qwen3-8B and Qwen3-30B-A3B, where SA consistently outperforms SWA and matches or exceeds Mixture of Block Attention at comparable compute budgets. These results suggest that connectome-inspired stochastic routing is a practical primitive for improving the expressivity of efficient attention, complementary to existing linear and sparse approaches.

  • 2 authors
·
May 3

Parallelized Hierarchical Connectome: A Spatiotemporal Recurrent Framework for Spiking State-Space Models

This work presents the Parallelized Hierarchical Connectome (PHC), a general architectural framework that upgrades temporal-only State-Space Models (SSMs) into spatiotemporal recurrent networks. Conventional SSMs achieve parallel-scan training but are limited to temporal recurrence, lacking lateral or feedback interactions within a single timestep. PHC maps the diagonal SSM core to a shared Neuron Layer and inter-neuronal communication to a shared Synapse Layer of hierarchical regions, reconnected by a Multi-Transmission Loop iterating spatial recurrence within each temporal window, at parameter complexity Theta(D^2) versus Theta(D^2 L) of stacked SSMs. This spatiotemporal framework enables the seamless integration of neuro-physical priors typically intractable for standard SSMs, including adaptive LIF, synaptic delay, STP, Dale's Law with E/I-asymmetric topology, and STDP. The framework is instantiated as PHCSSM, the first spiking SSM that integrates all five biological priors and is evaluated on long-sequence data, achieving test accuracy competitive with state-of-the-art SSM baselines at 1,312 to 4,891 trainable parameters (1 to 4 orders of magnitude smaller than every baseline). PHCSSM further admits a sequential recurrent spiking neural network (RSNN) deployment mode that converges asymptotically to the parallel-scan training mode without artificial-neural-network-to-spiking-neural-network (ANN-to-SNN) conversion, with cross-backend reproducibility verified across four hardware backends (x86 CPU, H100 GPU, Cortex-A76, Cortex-M4F) including end-to-end deployment on the Cortex-M4F microcontroller (40 KB SRAM, 128 KB Flash). PHCSSM thereby bridges parallel-scan SSM and biologically grounded RSNN, two paradigms with previously incompatible training regimes, into a single architecture and trained weights.

  • 1 authors
·
May 19

Homogenized C. elegans Neural Activity and Connectivity Data

There is renewed interest in modeling and understanding the nervous system of the nematode Caenorhabditis elegans (C. elegans), as this small model system provides a path to bridge the gap between nervous system structure (connectivity) and function (physiology). However, existing physiology datasets, whether involving passive recording or stimulation, are in distinct formats, and connectome datasets require preprocessing before analysis can commence. Here we compile and homogenize datasets of neural activity and connectivity. Our neural activity dataset is derived from 11 C. elegans neuroimaging experiments, while our connectivity dataset is compiled from 9 connectome annotations based on 3 primary electron microscopy studies and 1 signal propagation study. Physiology datasets, collected under varying protocols, measure calcium fluorescence in labeled subsets of the worm's 300 neurons. Our preprocessing pipeline standardizes these datasets by consistently ordering labeled neurons and resampling traces to a common sampling rate, yielding recordings from approximately 900 worms and 250 uniquely labeled neurons. The connectome datasets, collected from electron microscopy reconstructions, represent the entire nervous system as a graph of connections. Our collection is accessible on HuggingFace, facilitating analysis of the structure-function relationship in biology using modern neural network architectures and enabling cross-lab and cross-animal comparisons.

  • 4 authors
·
Nov 18, 2024

ASD Classification on Dynamic Brain Connectome using Temporal Random Walk with Transformer-based Dynamic Network Embedding

Autism Spectrum Disorder (ASD) is a complex neurological condition characterized by varied developmental impairments, especially in communication and social interaction. Accurate and early diagnosis of ASD is crucial for effective intervention, which is enhanced by richer representations of brain activity. The brain functional connectome, which refers to the statistical relationships between different brain regions measured through neuroimaging, provides crucial insights into brain function. Traditional static methods often fail to capture the dynamic nature of brain activity, in contrast, dynamic brain connectome analysis provides a more comprehensive view by capturing the temporal variations in the brain. We propose BrainTWT, a novel dynamic network embedding approach that captures temporal evolution of the brain connectivity over time and considers also the dynamics between different temporal network snapshots. BrainTWT employs temporal random walks to capture dynamics across different temporal network snapshots and leverages the Transformer's ability to model long term dependencies in sequential data to learn the discriminative embeddings from these temporal sequences using temporal structure prediction tasks. The experimental evaluation, utilizing the Autism Brain Imaging Data Exchange (ABIDE) dataset, demonstrates that BrainTWT outperforms baseline methods in ASD classification.

  • 3 authors
·
Mar 15, 2025

BrainWideBench: Benchmarking large-scale pretraining and across-animal transfer in multi-region neural recordings

Advances in large-scale neural recording have made it possible to collect data across many animals and distributed brain regions, raising the question of whether this scale can be exploited to learn general-purpose neural representations transferable across diverse downstream tasks. Yet, progress toward this goal has been limited by fragmented evaluation protocols and a narrow focus on individual task domains. Here, we present BrainWideBench, a benchmark for evaluating across-animal transfer on multi-region neural recordings, built on the International Brain Laboratory Brainwide Map dataset of neural and behavioral recordings spanning 276 brain regions from 139 mice performing a sensory-guided decision-making task. The benchmark is organized around three complementary task suites that evaluate whether learned representations support downstream decoding of behavior, can predict masked or future neural activity, and can recover biologically meaningful anatomical organization. With this benchmark, we systematically evaluate pretraining methods across transfer settings, including finetuning on downstream objectives and zero-shot generalization to unseen animals. Our results confirm pretraining improves performance over matched single-session baselines, but we show current methods exhibit heterogeneity in transfer capabilities: gains depend strongly on the alignment between pretraining objectives and downstream tasks. No single approach performs uniformly well across all three suites, and most methods are designed to only address a subset of them. Together, these findings suggest that learning representations that jointly generalize across behavior, dynamics, and anatomy remains an open challenge. By providing a unified and reproducible evaluation suite, BrainWideBench establishes a framework for measuring progress toward general-purpose models of the mouse brain.

  • 42 authors
·
Sep 17

DISGAN: Wavelet-informed Discriminator Guides GAN to MRI Super-resolution with Noise Cleaning

MRI super-resolution (SR) and denoising tasks are fundamental challenges in the field of deep learning, which have traditionally been treated as distinct tasks with separate paired training data. In this paper, we propose an innovative method that addresses both tasks simultaneously using a single deep learning model, eliminating the need for explicitly paired noisy and clean images during training. Our proposed model is primarily trained for SR, but also exhibits remarkable noise-cleaning capabilities in the super-resolved images. Instead of conventional approaches that introduce frequency-related operations into the generative process, our novel approach involves the use of a GAN model guided by a frequency-informed discriminator. To achieve this, we harness the power of the 3D Discrete Wavelet Transform (DWT) operation as a frequency constraint within the GAN framework for the SR task on magnetic resonance imaging (MRI) data. Specifically, our contributions include: 1) a 3D generator based on residual-in-residual connected blocks; 2) the integration of the 3D DWT with 1times 1 convolution into a DWT+conv unit within a 3D Unet for the discriminator; 3) the use of the trained model for high-quality image SR, accompanied by an intrinsic denoising process. We dub the model "Denoising Induced Super-resolution GAN (DISGAN)" due to its dual effects of SR image generation and simultaneous denoising. Departing from the traditional approach of training SR and denoising tasks as separate models, our proposed DISGAN is trained only on the SR task, but also achieves exceptional performance in denoising. The model is trained on 3D MRI data from dozens of subjects from the Human Connectome Project (HCP) and further evaluated on previously unseen MRI data from subjects with brain tumours and epilepsy to assess its denoising and SR performance.

  • 6 authors
·
Aug 23, 2023

The Topology and Geometry of Neural Representations

A central question for neuroscience is how to characterize brain representations of perceptual and cognitive content. An ideal characterization should distinguish different functional regions with robustness to noise and idiosyncrasies of individual brains that do not correspond to computational differences. Previous studies have characterized brain representations by their representational geometry, which is defined by the representational dissimilarity matrix (RDM), a summary statistic that abstracts from the roles of individual neurons (or responses channels) and characterizes the discriminability of stimuli. Here we explore a further step of abstraction: from the geometry to the topology of brain representations. We propose topological representational similarity analysis (tRSA), an extension of representational similarity analysis (RSA) that uses a family of geo-topological summary statistics that generalizes the RDM to characterize the topology while de-emphasizing the geometry. We evaluate this new family of statistics in terms of the sensitivity and specificity for model selection using both simulations and functional MRI (fMRI) data. In the simulations, the ground truth is a data-generating layer representation in a neural network model and the models are the same and other layers in different model instances (trained from different random seeds). In fMRI, the ground truth is a visual area and the models are the same and other areas measured in different subjects. Results show that topology-sensitive characterizations of population codes are robust to noise and interindividual variability and maintain excellent sensitivity to the unique representational signatures of different neural network layers and brain regions.

  • 2 authors
·
Sep 19, 2023

Learning dynamic representations of the functional connectome in neurobiological networks

The static synaptic connectivity of neuronal circuits stands in direct contrast to the dynamics of their function. As in changing community interactions, different neurons can participate actively in various combinations to effect behaviors at different times. We introduce an unsupervised approach to learn the dynamic affinities between neurons in live, behaving animals, and to reveal which communities form among neurons at different times. The inference occurs in two major steps. First, pairwise non-linear affinities between neuronal traces from brain-wide calcium activity are organized by non-negative tensor factorization (NTF). Each factor specifies which groups of neurons are most likely interacting for an inferred interval in time, and for which animals. Finally, a generative model that allows for weighted community detection is applied to the functional motifs produced by NTF to reveal a dynamic functional connectome. Since time codes the different experimental variables (e.g., application of chemical stimuli), this provides an atlas of neural motifs active during separate stages of an experiment (e.g., stimulus application or spontaneous behaviors). Results from our analysis are experimentally validated, confirming that our method is able to robustly predict causal interactions between neurons to generate behavior. Code is available at https://github.com/dyballa/dynamic-connectomes.

  • 5 authors
·
Feb 21, 2024

BrainMAE: A Region-aware Self-supervised Learning Framework for Brain Signals

The human brain is a complex, dynamic network, which is commonly studied using functional magnetic resonance imaging (fMRI) and modeled as network of Regions of interest (ROIs) for understanding various brain functions. Recent studies utilize deep learning approaches to learn the brain network representation based on functional connectivity (FC) profile, broadly falling into two main categories. The Fixed-FC approaches, utilizing the FC profile which represents the linear temporal relation within the brain network, are limited by failing to capture informative brain temporal dynamics. On the other hand, the Dynamic-FC approaches, modeling the evolving FC profile over time, often exhibit less satisfactory performance due to challenges in handling the inherent noisy nature of fMRI data. To address these challenges, we propose Brain Masked Auto-Encoder (BrainMAE) for learning representations directly from fMRI time-series data. Our approach incorporates two essential components: a region-aware graph attention mechanism designed to capture the relationships between different brain ROIs, and a novel self-supervised masked autoencoding framework for effective model pre-training. These components enable the model to capture rich temporal dynamics of brain activity while maintaining resilience to inherent noise in fMRI data. Our experiments demonstrate that BrainMAE consistently outperforms established baseline methods by significant margins in four distinct downstream tasks. Finally, leveraging the model's inherent interpretability, our analysis of model-generated representations reveals findings that resonate with ongoing research in the field of neuroscience.

  • 4 authors
·
Jun 24, 2024

Whole Brain Vessel Graphs: A Dataset and Benchmark for Graph Learning and Neuroscience (VesselGraph)

Biological neural networks define the brain function and intelligence of humans and other mammals, and form ultra-large, spatial, structured graphs. Their neuronal organization is closely interconnected with the spatial organization of the brain's microvasculature, which supplies oxygen to the neurons and builds a complementary spatial graph. This vasculature (or the vessel structure) plays an important role in neuroscience; for example, the organization of (and changes to) vessel structure can represent early signs of various pathologies, e.g. Alzheimer's disease or stroke. Recently, advances in tissue clearing have enabled whole brain imaging and segmentation of the entirety of the mouse brain's vasculature. Building on these advances in imaging, we are presenting an extendable dataset of whole-brain vessel graphs based on specific imaging protocols. Specifically, we extract vascular graphs using a refined graph extraction scheme leveraging the volume rendering engine Voreen and provide them in an accessible and adaptable form through the OGB and PyTorch Geometric dataloaders. Moreover, we benchmark numerous state-of-the-art graph learning algorithms on the biologically relevant tasks of vessel prediction and vessel classification using the introduced vessel graph dataset. Our work paves a path towards advancing graph learning research into the field of neuroscience. Complementarily, the presented dataset raises challenging graph learning research questions for the machine learning community, in terms of incorporating biological priors into learning algorithms, or in scaling these algorithms to handle sparse,spatial graphs with millions of nodes and edges. All datasets and code are available for download at https://github.com/jocpae/VesselGraph .

  • 12 authors
·
Aug 30, 2021

MindBridge: A Cross-Subject Brain Decoding Framework

Brain decoding, a pivotal field in neuroscience, aims to reconstruct stimuli from acquired brain signals, primarily utilizing functional magnetic resonance imaging (fMRI). Currently, brain decoding is confined to a per-subject-per-model paradigm, limiting its applicability to the same individual for whom the decoding model is trained. This constraint stems from three key challenges: 1) the inherent variability in input dimensions across subjects due to differences in brain size; 2) the unique intrinsic neural patterns, influencing how different individuals perceive and process sensory information; 3) limited data availability for new subjects in real-world scenarios hampers the performance of decoding models. In this paper, we present a novel approach, MindBridge, that achieves cross-subject brain decoding by employing only one model. Our proposed framework establishes a generic paradigm capable of addressing these challenges by introducing biological-inspired aggregation function and novel cyclic fMRI reconstruction mechanism for subject-invariant representation learning. Notably, by cycle reconstruction of fMRI, MindBridge can enable novel fMRI synthesis, which also can serve as pseudo data augmentation. Within the framework, we also devise a novel reset-tuning method for adapting a pretrained model to a new subject. Experimental results demonstrate MindBridge's ability to reconstruct images for multiple subjects, which is competitive with dedicated subject-specific models. Furthermore, with limited data for a new subject, we achieve a high level of decoding accuracy, surpassing that of subject-specific models. This advancement in cross-subject brain decoding suggests promising directions for wider applications in neuroscience and indicates potential for more efficient utilization of limited fMRI data in real-world scenarios. Project page: https://littlepure2333.github.io/MindBridge

  • 4 authors
·
Apr 11, 2024

NeuroBOLT: Resting-state EEG-to-fMRI Synthesis with Multi-dimensional Feature Mapping

Functional magnetic resonance imaging (fMRI) is an indispensable tool in modern neuroscience, providing a non-invasive window into whole-brain dynamics at millimeter-scale spatial resolution. However, fMRI is constrained by issues such as high operation costs and immobility. With the rapid advancements in cross-modality synthesis and brain decoding, the use of deep neural networks has emerged as a promising solution for inferring whole-brain, high-resolution fMRI features directly from electroencephalography (EEG), a more widely accessible and portable neuroimaging modality. Nonetheless, the complex projection from neural activity to fMRI hemodynamic responses and the spatial ambiguity of EEG pose substantial challenges both in modeling and interpretability. Relatively few studies to date have developed approaches for EEG-fMRI translation, and although they have made significant strides, the inference of fMRI signals in a given study has been limited to a small set of brain areas and to a single condition (i.e., either resting-state or a specific task). The capability to predict fMRI signals in other brain areas, as well as to generalize across conditions, remain critical gaps in the field. To tackle these challenges, we introduce a novel and generalizable framework: NeuroBOLT, i.e., Neuro-to-BOLD Transformer, which leverages multi-dimensional representation learning from temporal, spatial, and spectral domains to translate raw EEG data to the corresponding fMRI activity signals across the brain. Our experiments demonstrate that NeuroBOLT effectively reconstructs unseen resting-state fMRI signals from primary sensory, high-level cognitive areas, and deep subcortical brain regions, achieving state-of-the-art accuracy with the potential to generalize across varying conditions and sites, which significantly advances the integration of these two modalities.

  • 10 authors
·
Oct 6, 2024

Explainable AI for Accelerated Microstructure Imaging: A SHAP-Guided Protocol on the Connectome 2.0 scanner

The diffusion MRI Neurite Exchange Imaging model offers a promising framework for probing gray matter microstructure by estimating parameters such as compartment sizes, diffusivities, and inter-compartmental water exchange time. However, existing protocols require long scan times. This study proposes a reduced acquisition scheme for the Connectome 2.0 scanner that preserves model accuracy while substantially shortening scan duration. We developed a data-driven framework using explainable artificial intelligence with a guided recursive feature elimination strategy to identify an optimal 8-feature subset from a 15-feature protocol. The performance of this optimized protocol was validated in vivo and benchmarked against the full acquisition and alternative reduction strategies. Parameter accuracy, preservation of anatomical contrast, and test-retest reproducibility were assessed. The reduced protocol yielded parameter estimates and cortical maps comparable to the full protocol, with low estimation errors in synthetic data and minimal impact on test-retest variability. Compared to theory-driven and heuristic reduction schemes, the optimized protocol demonstrated superior robustness, reducing the deviation in water exchange time estimates by over two-fold. In conclusion, this hybrid optimization framework enables viable imaging of neurite exchange in 14 minutes without loss of parameter fidelity. This approach supports the broader application of exchange-sensitive diffusion magnetic resonance imaging in neuroscience and clinical research, and offers a generalizable method for designing efficient acquisition protocols in biophysical parameter mapping.

  • 13 authors
·
Sep 11, 2025

Brain-IT: Image Reconstruction from fMRI via Brain-Interaction Transformer

Reconstructing images seen by people from their fMRI brain recordings provides a non-invasive window into the human brain. Despite recent progress enabled by diffusion models, current methods often lack faithfulness to the actual seen images. We present "Brain-IT", a brain-inspired approach that addresses this challenge through a Brain Interaction Transformer (BIT), allowing effective interactions between clusters of functionally-similar brain-voxels. These functional-clusters are shared by all subjects, serving as building blocks for integrating information both within and across brains. All model components are shared by all clusters & subjects, allowing efficient training with a limited amount of data. To guide the image reconstruction, BIT predicts two complementary localized patch-level image features: (i)high-level semantic features which steer the diffusion model toward the correct semantic content of the image; and (ii)low-level structural features which help to initialize the diffusion process with the correct coarse layout of the image. BIT's design enables direct flow of information from brain-voxel clusters to localized image features. Through these principles, our method achieves image reconstructions from fMRI that faithfully reconstruct the seen images, and surpass current SotA approaches both visually and by standard objective metrics. Moreover, with only 1-hour of fMRI data from a new subject, we achieve results comparable to current methods trained on full 40-hour recordings.

Brain3D: Generating 3D Objects from fMRI

Understanding the hidden mechanisms behind human's visual perception is a fundamental question in neuroscience. To that end, investigating into the neural responses of human mind activities, such as functional Magnetic Resonance Imaging (fMRI), has been a significant research vehicle. However, analyzing fMRI signals is challenging, costly, daunting, and demanding for professional training. Despite remarkable progress in fMRI analysis, existing approaches are limited to generating 2D images and far away from being biologically meaningful and practically useful. Under this insight, we propose to generate visually plausible and functionally more comprehensive 3D outputs decoded from brain signals, enabling more sophisticated modeling of fMRI data. Conceptually, we reformulate this task as a {\em fMRI conditioned 3D object generation} problem. We design a novel 3D object representation learning method, Brain3D, that takes as input the fMRI data of a subject who was presented with a 2D image, and yields as output the corresponding 3D object images. The key capabilities of this model include tackling the noises with high-level semantic signals and a two-stage architecture design for progressive high-level information integration. Extensive experiments validate the superior capability of our model over previous state-of-the-art 3D object generation methods. Importantly, we show that our model captures the distinct functionalities of each region of human vision system as well as their intricate interplay relationships, aligning remarkably with the established discoveries in neuroscience. Further, preliminary evaluations indicate that Brain3D can successfully identify the disordered brain regions in simulated scenarios, such as V1, V2, V3, V4, and the medial temporal lobe (MTL) within the human visual system. Our data and code will be available at https://brain-3d.github.io/.

  • 7 authors
·
May 24, 2024

Connectome-Based Modeling of Mutation-Specific Amyloid-β Aggregation in Familial Alzheimer's Disease

Familial amyloid-β (Aβ) variants alter aggregation kinetics, but their interaction with structural brain connectivity remains incompletely understood. We developed a mutation-aware mechanistic model coupling a coarse-grained monomer--oligomer--fibril aggregation--fragmentation system to graph diffusion on the 540-node Budapest Reference Connectome component. Experimental Aβ_{42} nucleation scores scaled primary nucleation rates for seven variants relative to wild type. Robustness was examined using mutation-score uncertainty, alternative kinetic mappings, global sensitivity analysis, seed and edge-weight perturbations, degree-preserving randomized connectomes, spatial propagation analysis, synthetic ABC-SMC parameter recovery, posterior prediction, and Chemical Langevin simulations. E22G showed the earliest threshold crossing and greatest cumulative oligomer burden, whereas A2V was delayed under the selected mapping. Mutation rankings persisted across tested network perturbations, although regional burden patterns depended on topology. Connectome distance from seed regions was associated with later oligomer arrival (Spearman ρapprox0.92). Under inferred parameter uncertainty, the mean timing-rank correlation was 0.990 and cumulative-burden ordering was preserved in every posterior draw, while exact peak-amplitude ordering was less stable. Stochastic ensemble medians retained the deterministic ordering despite overlap among trajectories. Within this proof-of-concept framework, mutation-dependent kinetics primarily influence aggregation timing and cumulative burden, while connectivity shapes spatial propagation. Nominal background rates, model-time units, and synthetic parameter recovery limit interpretation to mechanistic comparisons rather than clinically calibrated prediction.

  • 2 authors
·
Oct 6

Can Natural Image Autoencoders Compactly Tokenize fMRI Volumes for Long-Range Dynamics Modeling?

Modeling long-range spatiotemporal dynamics in functional Magnetic Resonance Imaging (fMRI) remains a key challenge due to the high dimensionality of the four-dimensional signals. Prior voxel-based models, although demonstrating excellent performance and interpretation capabilities, are constrained by prohibitive memory demands and thus can only capture limited temporal windows. To address this, we propose TABLeT (Two-dimensionally Autoencoded Brain Latent Transformer), a novel approach that tokenizes fMRI volumes using a pre-trained 2D natural image autoencoder. Each 3D fMRI volume is compressed into a compact set of continuous tokens, enabling long-sequence modeling with a simple Transformer encoder with limited VRAM. Across large-scale benchmarks including the UK-Biobank (UKB), Human Connectome Project (HCP), and ADHD-200 datasets, TABLeT outperforms existing models in multiple tasks, while demonstrating substantial gains in computational and memory efficiency over the state-of-the-art voxel-based method given the same input. Furthermore, we develop a self-supervised masked token modeling approach to pre-train TABLeT, which improves the model's performance for various downstream tasks. Our findings suggest a promising approach for scalable and interpretable spatiotemporal modeling of brain activity. Our code is available at https://github.com/beotborry/TABLeT.

Pre-Synaptic Pool Modification (PSPM): A Supervised Learning Procedure for Spiking Neural Networks

Learning synaptic weights of spiking neural network (SNN) models that can reproduce target spike trains from provided neural firing data is a central problem in computational neuroscience and spike-based computing. The discovery of the optimal weight values can be posed as a supervised learning task wherein the weights of the model network are chosen to maximize the similarity between the target spike trains and the model outputs. It is still largely unknown whether optimizing spike train similarity of highly recurrent SNNs produces weight matrices similar to those of the ground truth model. To this end, we propose flexible heuristic supervised learning rules, termed Pre-Synaptic Pool Modification (PSPM), that rely on stochastic weight updates in order to produce spikes within a short window of the desired times and eliminate spikes outside of this window. PSPM improves spike train similarity for all-to-all SNNs and makes no assumption about the post-synaptic potential of the neurons or the structure of the network since no gradients are required. We test whether optimizing for spike train similarity entails the discovery of accurate weights and explore the relative contributions of local and homeostatic weight updates. Although PSPM improves similarity between spike trains, the learned weights often differ from the weights of the ground truth model, implying that connectome inference from spike data may require additional constraints on connectivity statistics. We also find that spike train similarity is sensitive to local updates, but other measures of network activity such as avalanche distributions, can be learned through synaptic homeostasis.

  • 4 authors
·
Oct 7, 2018

Brain decoding: toward real-time reconstruction of visual perception

In the past five years, the use of generative and foundational AI systems has greatly improved the decoding of brain activity. Visual perception, in particular, can now be decoded from functional Magnetic Resonance Imaging (fMRI) with remarkable fidelity. This neuroimaging technique, however, suffers from a limited temporal resolution (approx0.5 Hz) and thus fundamentally constrains its real-time usage. Here, we propose an alternative approach based on magnetoencephalography (MEG), a neuroimaging device capable of measuring brain activity with high temporal resolution (approx5,000 Hz). For this, we develop an MEG decoding model trained with both contrastive and regression objectives and consisting of three modules: i) pretrained embeddings obtained from the image, ii) an MEG module trained end-to-end and iii) a pretrained image generator. Our results are threefold: Firstly, our MEG decoder shows a 7X improvement of image-retrieval over classic linear decoders. Second, late brain responses to images are best decoded with DINOv2, a recent foundational image model. Third, image retrievals and generations both suggest that high-level visual features can be decoded from MEG signals, although the same approach applied to 7T fMRI also recovers better low-level features. Overall, these results, while preliminary, provide an important step towards the decoding -- in real-time -- of the visual processes continuously unfolding within the human brain.

  • 3 authors
·
Oct 18, 2023

How do neurons operate on sparse distributed representations? A mathematical theory of sparsity, neurons and active dendrites

We propose a formal mathematical model for sparse representations and active dendrites in neocortex. Our model is inspired by recent experimental findings on active dendritic processing and NMDA spikes in pyramidal neurons. These experimental and modeling studies suggest that the basic unit of pattern memory in the neocortex is instantiated by small clusters of synapses operated on by localized non-linear dendritic processes. We derive a number of scaling laws that characterize the accuracy of such dendrites in detecting activation patterns in a neuronal population under adverse conditions. We introduce the union property which shows that synapses for multiple patterns can be randomly mixed together within a segment and still lead to highly accurate recognition. We describe simulation results that provide further insight into sparse representations as well as two primary results. First we show that pattern recognition by a neuron with active dendrites can be extremely accurate and robust with high dimensional sparse inputs even when using a tiny number of synapses to recognize large patterns. Second, equations representing recognition accuracy of a dendrite predict optimal NMDA spiking thresholds under a generous set of assumptions. The prediction tightly matches NMDA spiking thresholds measured in the literature. Our model matches many of the known properties of pyramidal neurons. As such the theory provides a mathematical framework for understanding the benefits and limits of sparse representations in cortical networks.

  • 2 authors
·
Jan 4, 2016

A community-based transcriptomics classification and nomenclature of neocortical cell types

To understand the function of cortical circuits it is necessary to classify their underlying cellular diversity. Traditional attempts based on comparing anatomical or physiological features of neurons and glia, while productive, have not resulted in a unified taxonomy of neural cell types. The recent development of single-cell transcriptomics has enabled, for the first time, systematic high-throughput profiling of large numbers of cortical cells and the generation of datasets that hold the promise of being complete, accurate and permanent. Statistical analyses of these data have revealed the existence of clear clusters, many of which correspond to cell types defined by traditional criteria, and which are conserved across cortical areas and species. To capitalize on these innovations and advance the field, we, the Copenhagen Convention Group, propose the community adopts a transcriptome-based taxonomy of the cell types in the adult mammalian neocortex. This core classification should be ontological, hierarchical and use a standardized nomenclature. It should be configured to flexibly incorporate new data from multiple approaches, developmental stages and a growing number of species, enabling improvement and revision of the classification. This community-based strategy could serve as a common foundation for future detailed analysis and reverse engineering of cortical circuits and serve as an example for cell type classification in other parts of the nervous system and other organs.

  • 71 authors
·
Sep 5, 2019

SliceBridge: context-consistent repair of corrupted slice intervals in T1-weighted MRI

Structural magnetic resonance imaging (MRI) images are sometimes corrupted over a contiguous set of slices, where acquisition, motion, hardware, or reconstruction effects leave a single slice or short interval inconsistent with its neighbors while the rest of the image remains usable. Such localized corruption can bias downstream morphometric analysis, yet discarding or reacquiring an otherwise usable image is costly. We formulate this as an image restoration problem: given the location of the affected interval, reconstruct those slices from the surrounding anatomical and imaging context. We propose SliceBridge, a framework for restoring corrupted slice intervals in T1-weighted MRI using rectified flow matching conditioned on the surrounding intact slices and their relative slice positions. Through-plane consistency is encouraged by coupling the slices within the interval through interval-correlated initial noise, a shared flow time, and synchronized sampling. The restored interval is then inserted back, leaving all other slices unchanged. We trained and validated the model on 9,877 T1-weighted brain MRI volumes from four datasets and evaluated it on 581 external subjects using clean interval withholding and controlled corruptions. Compared with a matched model that reconstructed target slices independently, SliceBridge reduced error in slice-to-slice changes within repaired intervals by 32.9%-41.3% across interval lengths and achieved higher SSIM at every interval length. In controlled-corruption cases, SliceBridge reduced the median error in regional brain volume estimates produced by a downstream segmentation model from 1.95% in corrupted volumes to 1.05%.

Characterizing and Optimizing the Spatial Kernel of Multi Resolution Hash Encodings

Multi-Resolution Hash Encoding (MHE), the foundational technique behind Instant Neural Graphics Primitives, provides a powerful parameterization for neural fields. However, its spatial behavior lacks rigorous understanding from a physical systems perspective, leading to reliance on heuristics for hyperparameter selection. This work introduces a novel analytical approach that characterizes MHE by examining its Point Spread Function (PSF), which is analogous to the Green's function of the system. This methodology enables a quantification of the encoding's spatial resolution and fidelity. We derive a closed-form approximation for the collision-free PSF, uncovering inherent grid-induced anisotropy and a logarithmic spatial profile. We establish that the idealized spatial bandwidth, specifically the Full Width at Half Maximum (FWHM), is determined by the average resolution, N_{avg}. This leads to a counterintuitive finding: the effective resolution of the model is governed by the broadened empirical FWHM (and therefore N_{avg}), rather than the finest resolution N_{max}, a broadening effect we demonstrate arises from optimization dynamics. Furthermore, we analyze the impact of finite hash capacity, demonstrating how collisions introduce speckle noise and degrade the Signal-to-Noise Ratio (SNR). Leveraging these theoretical insights, we propose Rotated MHE (R-MHE), an architecture that applies distinct rotations to the input coordinates at each resolution level. R-MHE mitigates anisotropy while maintaining the efficiency and parameter count of the original MHE. This study establishes a methodology based on physical principles that moves beyond heuristics to characterize and optimize MHE.

  • 2 authors
·
Feb 10

BrainDyn: A Sheaf Neural ODE for Generative Brain Dynamics

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.

YaleUniversity Yale University
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May 18

Learning Alzheimer's Disease Signatures by bridging EEG with Spiking Neural Networks and Biophysical Simulations

As the prevalence of Alzheimer's disease (AD) rises, improving mechanistic insight from non-invasive biomarkers is increasingly critical. Recent work suggests that circuit-level brain alterations manifest as changes in electroencephalography (EEG) spectral features detectable by machine learning. However, conventional deep learning approaches for EEG-based AD detection are computationally intensive and mechanistically opaque. Spiking neural networks (SNNs) offer a biologically plausible and energy-efficient alternative, yet their application to AD diagnosis remains largely unexplored. We propose a neuro-bridge framework that links data-driven learning with minimal, biophysically grounded simulations, enabling bidirectional interpretation between machine learning signatures and circuit-level mechanisms in AD. Using resting-state clinical EEG, we train an SNN classifier that achieves competitive performance (AUC = 0.839) and identifies the aperiodic 1/f slope as a key discriminative marker. The 1/f slope reflects excitation-inhibition balance. To interpret this mechanistically, we construct spiking network simulations in which inhibitory-to-excitatory synaptic ratios are systematically varied to emulate healthy, mild cognitive impairment, and AD-like states. Using both membrane potential-based and synaptic current-based EEG proxies, we reproduce empirical spectral slowing and altered alpha organization. Incorporating empirical functional connectivity priors into multi-subnetwork simulations further enhances spectral differentiation, demonstrating that large-scale network topology constrains EEG signatures more strongly than excitation-inhibition balance alone. Overall, this neuro-bridge approach connects SNN-based classification with interpretable circuit simulations, advancing mechanistic understanding of EEG biomarkers while enabling scalable, explainable AD detection.

  • 3 authors
·
Jan 29

Neuro-inspired Ensemble-to-Ensemble Communication Primitives for Sparse and Efficient ANNs

The structure of biological neural circuits-modular, hierarchical, and sparsely interconnected-reflects an efficient trade-off between wiring cost, functional specialization, and robustness. These principles offer valuable insights for artificial neural network (ANN) design, especially as networks grow in depth and scale. Sparsity, in particular, has been widely explored for reducing memory and computation, improving speed, and enhancing generalization. Motivated by systems neuroscience findings, we explore how patterns of functional connectivity in the mouse visual cortex-specifically, ensemble-to-ensemble communication, can inform ANN design. We introduce G2GNet, a novel architecture that imposes sparse, modular connectivity across feedforward layers. Despite having significantly fewer parameters than fully connected models, G2GNet achieves superior accuracy on standard vision benchmarks. To our knowledge, this is the first architecture to incorporate biologically observed functional connectivity patterns as a structural bias in ANN design. We complement this static bias with a dynamic sparse training (DST) mechanism that prunes and regrows edges during training. We also propose a Hebbian-inspired rewiring rule based on activation correlations, drawing on principles of biological plasticity. G2GNet achieves up to 75% sparsity while improving accuracy by up to 4.3% on benchmarks, including Fashion-MNIST, CIFAR-10, and CIFAR-100, outperforming dense baselines with far fewer computations.

  • 3 authors
·
Aug 19, 2025

Deep Generative Modeling with Spatial and Network Images: An Explainable AI (XAI) Approach

This article addresses the challenge of modeling the amplitude of spatially indexed low frequency fluctuations (ALFF) in resting state functional MRI as a function of cortical structural features and a multi-task coactivation network in the Adolescent Brain Cognitive Development (ABCD) Study. It proposes a generative model that integrates effects of spatially-varying inputs and a network-valued input using deep neural networks to capture complex non-linear and spatial associations with the output. The method models spatial smoothness, accounts for subject heterogeneity and complex associations between network and spatial images at different scales, enables accurate inference of each images effect on the output image, and allows prediction with uncertainty quantification via Monte Carlo dropout, contributing to one of the first Explainable AI (XAI) frameworks for heterogeneous imaging data. The model is highly scalable to high-resolution data without the heavy pre-processing or summarization often required by Bayesian methods. Empirical results demonstrate its strong performance compared to existing statistical and deep learning methods. We applied the XAI model to the ABCD data which revealed associations between cortical features and ALFF throughout the entire brain. Our model performed comparably to existing methods in predictive accuracy but provided superior uncertainty quantification and faster computation, demonstrating its effectiveness for large-scale neuroimaging analysis. Open-source software in Python for XAI is available.

  • 3 authors
·
May 19, 2025

Brain Diffusion for Visual Exploration: Cortical Discovery using Large Scale Generative Models

A long standing goal in neuroscience has been to elucidate the functional organization of the brain. Within higher visual cortex, functional accounts have remained relatively coarse, focusing on regions of interest (ROIs) and taking the form of selectivity for broad categories such as faces, places, bodies, food, or words. Because the identification of such ROIs has typically relied on manually assembled stimulus sets consisting of isolated objects in non-ecological contexts, exploring functional organization without robust a priori hypotheses has been challenging. To overcome these limitations, we introduce a data-driven approach in which we synthesize images predicted to activate a given brain region using paired natural images and fMRI recordings, bypassing the need for category-specific stimuli. Our approach -- Brain Diffusion for Visual Exploration ("BrainDiVE") -- builds on recent generative methods by combining large-scale diffusion models with brain-guided image synthesis. Validating our method, we demonstrate the ability to synthesize preferred images with appropriate semantic specificity for well-characterized category-selective ROIs. We then show that BrainDiVE can characterize differences between ROIs selective for the same high-level category. Finally we identify novel functional subdivisions within these ROIs, validated with behavioral data. These results advance our understanding of the fine-grained functional organization of human visual cortex, and provide well-specified constraints for further examination of cortical organization using hypothesis-driven methods.

  • 4 authors
·
Jun 5, 2023

MRI Super-Resolution with Deep Learning: A Comprehensive Survey

High-resolution (HR) magnetic resonance imaging (MRI) is crucial for many clinical and research applications. However, achieving it remains costly and constrained by technical trade-offs and experimental limitations. Super-resolution (SR) presents a promising computational approach to overcome these challenges by generating HR images from more affordable low-resolution (LR) scans, potentially improving diagnostic accuracy and efficiency without requiring additional hardware. This survey reviews recent advances in MRI SR techniques, with a focus on deep learning (DL) approaches. It examines DL-based MRI SR methods from the perspectives of computer vision, computational imaging, inverse problems, and MR physics, covering theoretical foundations, architectural designs, learning strategies, benchmark datasets, and performance metrics. We propose a systematic taxonomy to categorize these methods and present an in-depth study of both established and emerging SR techniques applicable to MRI, considering unique challenges in clinical and research contexts. We also highlight open challenges and directions that the community needs to address. Additionally, we provide a collection of essential open-access resources, tools, and tutorials, available on our GitHub: https://github.com/mkhateri/Awesome-MRI-Super-Resolution. IEEE keywords: MRI, Super-Resolution, Deep Learning, Computational Imaging, Inverse Problem, Survey.

Harvard Harvard University
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Nov 20, 2025 2

Comparison Against Task Driven Artificial Neural Networks Reveals Functional Organization of Mouse Visual Cortex

Partially inspired by features of computation in visual cortex, deep neural networks compute hierarchical representations of their inputs. While these networks have been highly successful in machine learning, it remains unclear to what extent they can aid our understanding of cortical function. Several groups have developed metrics that provide a quantitative comparison between representations computed by networks and representations measured in cortex. At the same time, neuroscience is well into an unprecedented phase of large-scale data collection, as evidenced by projects such as the Allen Brain Observatory. Despite the magnitude of these efforts, in a given experiment only a fraction of units are recorded, limiting the information available about the cortical representation. Moreover, only a finite number of stimuli can be shown to an animal over the course of a realistic experiment. These limitations raise the question of how and whether metrics that compare representations of deep networks are meaningful on these datasets. Here, we empirically quantify the capabilities and limitations of these metrics due to limited image presentations and neuron samples. We find that the comparison procedure is robust to different choices of stimuli set and the level of subsampling that one might expect in a large-scale brain survey with thousands of neurons. Using these results, we compare the representations measured in the Allen Brain Observatory in response to natural image presentations to deep neural network. We show that the visual cortical areas are relatively high order representations (in that they map to deeper layers of convolutional neural networks). Furthermore, we see evidence of a broad, more parallel organization rather than a sequential hierarchy, with the primary area VISp(V1) being lower order relative to the other areas.

  • 3 authors
·
Nov 18, 2019

Neuro-Vision to Language: Enhancing Visual Reconstruction and Language Interaction through Brain Recordings

Decoding non-invasive brain recordings is pivotal for advancing our understanding of human cognition but faces challenges due to individual differences and complex neural signal representations. Traditional methods often require customized models and extensive trials, lacking interpretability in visual reconstruction tasks. Our framework integrates 3D brain structures with visual semantics using a Vision Transformer 3D. This unified feature extractor efficiently aligns fMRI features with multiple levels of visual embeddings, eliminating the need for subject-specific models and allowing extraction from single-trial data. The extractor consolidates multi-level visual features into one network, simplifying integration with Large Language Models (LLMs). Additionally, we have enhanced the fMRI dataset with diverse fMRI-image-related textual data to support multimodal large model development. Integrating with LLMs enhances decoding capabilities, enabling tasks such as brain captioning, complex reasoning, concept localization, and visual reconstruction. Our approach demonstrates superior performance across these tasks, precisely identifying language-based concepts within brain signals, enhancing interpretability, and providing deeper insights into neural processes. These advances significantly broaden the applicability of non-invasive brain decoding in neuroscience and human-computer interaction, setting the stage for advanced brain-computer interfaces and cognitive models.

  • 8 authors
·
Apr 30, 2024

FISBe: A real-world benchmark dataset for instance segmentation of long-range thin filamentous structures

Instance segmentation of neurons in volumetric light microscopy images of nervous systems enables groundbreaking research in neuroscience by facilitating joint functional and morphological analyses of neural circuits at cellular resolution. Yet said multi-neuron light microscopy data exhibits extremely challenging properties for the task of instance segmentation: Individual neurons have long-ranging, thin filamentous and widely branching morphologies, multiple neurons are tightly inter-weaved, and partial volume effects, uneven illumination and noise inherent to light microscopy severely impede local disentangling as well as long-range tracing of individual neurons. These properties reflect a current key challenge in machine learning research, namely to effectively capture long-range dependencies in the data. While respective methodological research is buzzing, to date methods are typically benchmarked on synthetic datasets. To address this gap, we release the FlyLight Instance Segmentation Benchmark (FISBe) dataset, the first publicly available multi-neuron light microscopy dataset with pixel-wise annotations. In addition, we define a set of instance segmentation metrics for benchmarking that we designed to be meaningful with regard to downstream analyses. Lastly, we provide three baselines to kick off a competition that we envision to both advance the field of machine learning regarding methodology for capturing long-range data dependencies, and facilitate scientific discovery in basic neuroscience.

  • 9 authors
·
Mar 29, 2024

Fine-tuning deep learning model parameters for improved super-resolution of dynamic MRI with prior-knowledge

Dynamic imaging is a beneficial tool for interventions to assess physiological changes. Nonetheless during dynamic MRI, while achieving a high temporal resolution, the spatial resolution is compromised. To overcome this spatio-temporal trade-off, this research presents a super-resolution (SR) MRI reconstruction with prior knowledge based fine-tuning to maximise spatial information while reducing the required scan-time for dynamic MRIs. An U-Net based network with perceptual loss is trained on a benchmark dataset and fine-tuned using one subject-specific static high resolution MRI as prior knowledge to obtain high resolution dynamic images during the inference stage. 3D dynamic data for three subjects were acquired with different parameters to test the generalisation capabilities of the network. The method was tested for different levels of in-plane undersampling for dynamic MRI. The reconstructed dynamic SR results after fine-tuning showed higher similarity with the high resolution ground-truth, while quantitatively achieving statistically significant improvement. The average SSIM of the lowest resolution experimented during this research (6.25~\% of the k-space) before and after fine-tuning were 0.939 pm 0.008 and 0.957 pm 0.006 respectively. This could theoretically result in an acceleration factor of 16, which can potentially be acquired in less than half a second. The proposed approach shows that the super-resolution MRI reconstruction with prior-information can alleviate the spatio-temporal trade-off in dynamic MRI, even for high acceleration factors.

  • 6 authors
·
Feb 4, 2021

BrainDINO: A Brain MRI Foundation Model for Generalizable Clinical Representation Learning

Brain MRI underpins a wide range of neuroscientific and clinical applications, yet most learning-based methods remain task-specific and require substantial labeled data. Here we show that a single self-supervised representation can generalize across heterogeneous brain MRI endpoints. We trained BrainDINO, a self-distilled foundation model, on approximately 6.6 million unlabeled axial slices from 20 datasets encompassing broad variation in population, disease, and acquisition setting. Using a frozen encoder with lightweight task heads, BrainDINO supported transfer across tumor segmentation, neurodegenerative and neurodevelopmental conditions classification, brain age estimation, post-stroke temporal prediction, molecular status prediction, MRI sequence classification, and survival modeling. Across tasks and supervision regimes, BrainDINO consistently equaled or exceeded natural-image and MRI-specific self-supervised baselines, with particularly strong advantages under label scarcity. Representation analyses further showed anatomically organized and pathology-sensitive feature structure in the absence of task-specific supervision. Our findings indicate that large-scale slice-wise self-supervised learning can yield a unified brain MRI representation that supports diverse neuroimaging tasks without volumetric pretraining or full-network fine-tuning, establishing a scalable foundation for robust and data-efficient brain imaging analysis.

  • 8 authors
·
Apr 29

One Brain, Omni Modalities: Towards Unified Non-Invasive Brain Decoding with Large Language Models

Deciphering brain function through non-invasive recordings requires synthesizing complementary high-frequency electromagnetic (EEG/MEG) and low-frequency metabolic (fMRI) signals. However, despite their shared neural origins, extreme discrepancies have traditionally confined these modalities to isolated analysis pipelines, hindering a holistic interpretation of brain activity. To bridge this fragmentation, we introduce NOBEL, a neuro-omni-modal brain-encoding large language model (LLM) that unifies these heterogeneous signals within the LLM's semantic embedding space. Our architecture integrates a unified encoder for EEG and MEG with a novel dual-path strategy for fMRI, aligning non-invasive brain signals and external sensory stimuli into a shared token space, then leverages an LLM as a universal backbone. Extensive evaluations demonstrate that NOBEL serves as a robust generalist across standard single-modal tasks. We also show that the synergistic fusion of electromagnetic and metabolic signals yields higher decoding accuracy than unimodal baselines, validating the complementary nature of multiple neural modalities. Furthermore, NOBEL exhibits strong capabilities in stimulus-aware decoding, effectively interpreting visual semantics from multi-subject fMRI data on the NSD and HAD datasets while uniquely leveraging direct stimulus inputs to verify causal links between sensory signals and neural responses. NOBEL thus takes a step towards unifying non-invasive brain decoding, demonstrating the promising potential of omni-modal brain understanding.

  • 11 authors
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Feb 24

BaRISTA: Brain Scale Informed Spatiotemporal Representation of Human Intracranial Neural Activity

Intracranial recordings have opened a unique opportunity to simultaneously measure activity across multiregional networks in the human brain. Recent works have focused on developing transformer-based neurofoundation models of such recordings that can generalize across subjects and datasets. However, these recordings exhibit highly complex spatiotemporal interactions across diverse spatial scales, from the single-channel scale to the scale of brain regions. As such, there remain critical open questions regarding how best to encode spatial information and how to design self-supervision tasks that enable the learning of brain network patterns and enhance downstream decoding performance using such high-dimensional, multiregional recordings. To allow for exploring these questions, we propose a new spatiotemporal transformer model of multiregional neural activity and a corresponding self-supervised masked latent reconstruction task, designed to enable flexibility in the spatial scale used for token encoding and masking. Applying this model on publicly available multiregional intracranial electrophysiology (iEEG) data, we demonstrate that adjusting the spatial scale for both token encoding and masked reconstruction significantly impacts downstream decoding. Further, we find that spatial encoding at larger scales than channel-level encoding, which is commonly used in existing iEEG transformer models, improves downstream decoding performance. Finally, we demonstrate that our method allows for region-level token encoding while also maintaining accurate channel-level neural reconstruction. Taken together, our modeling framework enables exploration of the spatial scales used for token encoding and masking, reveals their importance towards self-supervised pretraining of neurofoundation models of multiregional human brain activity, and enhances downstream decoding performance.

  • 3 authors
·
Dec 12, 2025

Neuroformer: Multimodal and Multitask Generative Pretraining for Brain Data

State-of-the-art systems neuroscience experiments yield large-scale multimodal data, and these data sets require new tools for analysis. Inspired by the success of large pretrained models in vision and language domains, we reframe the analysis of large-scale, cellular-resolution neuronal spiking data into an autoregressive spatiotemporal generation problem. Neuroformer is a multimodal, multitask generative pretrained transformer (GPT) model that is specifically designed to handle the intricacies of data in systems neuroscience. It scales linearly with feature size, can process an arbitrary number of modalities, and is adaptable to downstream tasks, such as predicting behavior. We first trained Neuroformer on simulated datasets, and found that it both accurately predicted simulated neuronal circuit activity, and also intrinsically inferred the underlying neural circuit connectivity, including direction. When pretrained to decode neural responses, the model predicted the behavior of a mouse with only few-shot fine-tuning, suggesting that the model begins learning how to do so directly from the neural representations themselves, without any explicit supervision. We used an ablation study to show that joint training on neuronal responses and behavior boosted performance, highlighting the model's ability to associate behavioral and neural representations in an unsupervised manner. These findings show that Neuroformer can analyze neural datasets and their emergent properties, informing the development of models and hypotheses associated with the brain.

  • 5 authors
·
Oct 31, 2023

Accelerating Benchmarking of Functional Connectivity Modeling via Structure-aware Core-set Selection

Benchmarking the hundreds of functional connectivity (FC) modeling methods on large-scale fMRI datasets is critical for reproducible neuroscience. However, the combinatorial explosion of model-data pairings makes exhaustive evaluation computationally prohibitive, preventing such assessments from becoming a routine pre-analysis step. To break this bottleneck, we reframe the challenge of FC benchmarking by selecting a small, representative core-set whose sole purpose is to preserve the relative performance ranking of FC operators. We formalize this as a ranking-preserving subset selection problem and propose Structure-aware Contrastive Learning for Core-set Selection (SCLCS), a self-supervised framework to select these core-sets. SCLCS first uses an adaptive Transformer to learn each sample's unique FC structure. It then introduces a novel Structural Perturbation Score (SPS) to quantify the stability of these learned structures during training, identifying samples that represent foundational connectivity archetypes. Finally, while SCLCS identifies stable samples via a top-k ranking, we further introduce a density-balanced sampling strategy as a necessary correction to promote diversity, ensuring the final core-set is both structurally robust and distributionally representative. On the large-scale REST-meta-MDD dataset, SCLCS preserves the ground-truth model ranking with just 10% of the data, outperforming state-of-the-art (SOTA) core-set selection methods by up to 23.2% in ranking consistency (nDCG@k). To our knowledge, this is the first work to formalize core-set selection for FC operator benchmarking, thereby making large-scale operators comparisons a feasible and integral part of computational neuroscience. Code is publicly available on https://github.com/lzhan94swu/SCLCS

  • 4 authors
·
Feb 5

Decoding Alignment without Encoding Alignment: A critique of similarity analysis in neuroscience

Decoding approaches are widely used in neuroscience and machine learning to compare stimulus representations across neural systems, such as different brain regions, organisms, and deep learning models. Popular methods include decoding (perceptual) manifolds and alignment metrics such as Representational Similarity Analysis (RSA) and Dynamic Similarity Analysis (DSA), where similarity in decoding representations is interpreted as evidence for similar computation. This paper demonstrates a fundamental weakness behind this approach: it is misleading to assume that representational geometry is representative of a neuronal population as a whole, when such representations may actually be shaped by a very small subset of neurons. We show that the complementary encoding paradigm addresses this issue directly: it characterizes how neurons are organized globally in terms of their responses to a set of data, providing insight into how the decoding representation is implemented by neurons within a population. We demonstrate across experiments in biological systems and deep learning models that (i) surprisingly, similar decoding behavior and high representational alignment can arise from small, non-representative subpopulations of neurons; and critically, (ii) alignment metrics are insensitive to encoding manifold topology (how function is distributed across neurons), despite this being a key signature of differentiation across biological systems. A controlled MNIST experiment provides causal evidence: decoding metrics remain unchanged even when encoding topology is causally manipulated via the training loss. Overall, similarity in decoding behavior, as measured by classic alignment metrics, does not imply similarity in function or computation, motivating the use of encoding manifolds as a complementary tool for comparing neural systems.

  • 5 authors
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May 6

Reconstructing the Mind's Eye: fMRI-to-Image with Contrastive Learning and Diffusion Priors

We present MindEye, a novel fMRI-to-image approach to retrieve and reconstruct viewed images from brain activity. Our model comprises two parallel submodules that are specialized for retrieval (using contrastive learning) and reconstruction (using a diffusion prior). MindEye can map fMRI brain activity to any high dimensional multimodal latent space, like CLIP image space, enabling image reconstruction using generative models that accept embeddings from this latent space. We comprehensively compare our approach with other existing methods, using both qualitative side-by-side comparisons and quantitative evaluations, and show that MindEye achieves state-of-the-art performance in both reconstruction and retrieval tasks. In particular, MindEye can retrieve the exact original image even among highly similar candidates indicating that its brain embeddings retain fine-grained image-specific information. This allows us to accurately retrieve images even from large-scale databases like LAION-5B. We demonstrate through ablations that MindEye's performance improvements over previous methods result from specialized submodules for retrieval and reconstruction, improved training techniques, and training models with orders of magnitude more parameters. Furthermore, we show that MindEye can better preserve low-level image features in the reconstructions by using img2img, with outputs from a separate autoencoder. All code is available on GitHub.

  • 12 authors
·
May 29, 2023 1

A Generative Self-Supervised Framework using Functional Connectivity in fMRI Data

Deep neural networks trained on Functional Connectivity (FC) networks extracted from functional Magnetic Resonance Imaging (fMRI) data have gained popularity due to the increasing availability of data and advances in model architectures, including Graph Neural Network (GNN). Recent research on the application of GNN to FC suggests that exploiting the time-varying properties of the FC could significantly improve the accuracy and interpretability of the model prediction. However, the high cost of acquiring high-quality fMRI data and corresponding phenotypic labels poses a hurdle to their application in real-world settings, such that a model na\"ively trained in a supervised fashion can suffer from insufficient performance or a lack of generalization on a small number of data. In addition, most Self-Supervised Learning (SSL) approaches for GNNs to date adopt a contrastive strategy, which tends to lose appropriate semantic information when the graph structure is perturbed or does not leverage both spatial and temporal information simultaneously. In light of these challenges, we propose a generative SSL approach that is tailored to effectively harness spatio-temporal information within dynamic FC. Our empirical results, experimented with large-scale (>50,000) fMRI datasets, demonstrate that our approach learns valuable representations and enables the construction of accurate and robust models when fine-tuned for downstream tasks.

  • 5 authors
·
Dec 4, 2023

Exploring Synaptic Resonance in Large Language Models: A Novel Approach to Contextual Memory Integration

Contextual memory integration remains a high challenge in the development of language models, particularly in tasks that require maintaining coherence over extended sequences. Traditional approaches, such as self-attention mechanisms and memory-augmented architectures, often prioritize short-term dependencies, leading to fragmentation and inconsistency in long-range contextual understanding. Inspired by principles of synaptic plasticity observed in biological neural systems, a novel mechanism, Synaptic Resonance, is introduced to dynamically reinforce relevant memory pathways during training and inference. Unlike static memory representations, this mechanism continuously adjusts synaptic weight matrices based on contextual relevance, allowing for improved information retention without excessive computational overhead. Evaluations conducted on an open-source language model demonstrate reductions in perplexity, enhancements in contextual coherence, and increased robustness against input noise, highlighting the effectiveness of reinforcement-driven memory modulation. Comparative analysis against baseline models further reveals that the proposed approach achieves higher memory retention efficiency while maintaining computational feasibility. The architectural modifications integrate seamlessly into existing transformer-based frameworks, ensuring stable convergence and efficient inference without sacrificing scalability. Applications benefiting from improved long-term contextual consistency, such as dialogue systems and document summarization, stand to gain from this approach. Empirical findings suggest that dynamically reinforced memory pathways offer a promising alternative to conventional memory mechanisms, addressing longstanding limitations in extended sequence modeling.

  • 5 authors
·
Feb 15, 2025

Du-IN: Discrete units-guided mask modeling for decoding speech from Intracranial Neural signals

Invasive brain-computer interfaces have garnered significant attention due to their high performance. The current intracranial stereoElectroEncephaloGraphy (sEEG) foundation models typically build univariate representations based on a single channel. Some of them further use Transformer to model the relationship among channels. However, due to the locality and specificity of brain computation, their performance on more difficult tasks, e.g., speech decoding, which demands intricate processing in specific brain regions, is yet to be fully investigated. We hypothesize that building multi-variate representations within certain brain regions can better capture the specific neural processing. To explore this hypothesis, we collect a well-annotated Chinese word-reading sEEG dataset, targeting language-related brain networks, over 12 subjects. Leveraging this benchmark dataset, we developed the Du-IN model that can extract contextual embeddings from specific brain regions through discrete codebook-guided mask modeling. Our model achieves SOTA performance on the downstream 61-word classification task, surpassing all baseline models. Model comparison and ablation analysis reveal that our design choices, including (i) multi-variate representation by fusing channels in vSMC and STG regions and (ii) self-supervision by discrete codebook-guided mask modeling, significantly contribute to these performances. Collectively, our approach, inspired by neuroscience findings, capitalizing on multi-variate neural representation from specific brain regions, is suitable for invasive brain modeling. It marks a promising neuro-inspired AI approach in BCI.

  • 9 authors
·
May 19, 2024

Identifying Connectivity Distributions from Neural Dynamics Using Flows

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

  • 5 authors
·
May 28

BrainAnytime: Anatomy-Aware Cross-Modal Pretraining for Brain Image Analysis with Arbitrary Modality Availability

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.

  • 7 authors
·
May 12

BrainSCUBA: Fine-Grained Natural Language Captions of Visual Cortex Selectivity

Understanding the functional organization of higher visual cortex is a central focus in neuroscience. Past studies have primarily mapped the visual and semantic selectivity of neural populations using hand-selected stimuli, which may potentially bias results towards pre-existing hypotheses of visual cortex functionality. Moving beyond conventional approaches, we introduce a data-driven method that generates natural language descriptions for images predicted to maximally activate individual voxels of interest. Our method -- Semantic Captioning Using Brain Alignments ("BrainSCUBA") -- builds upon the rich embedding space learned by a contrastive vision-language model and utilizes a pre-trained large language model to generate interpretable captions. We validate our method through fine-grained voxel-level captioning across higher-order visual regions. We further perform text-conditioned image synthesis with the captions, and show that our images are semantically coherent and yield high predicted activations. Finally, to demonstrate how our method enables scientific discovery, we perform exploratory investigations on the distribution of "person" representations in the brain, and discover fine-grained semantic selectivity in body-selective areas. Unlike earlier studies that decode text, our method derives voxel-wise captions of semantic selectivity. Our results show that BrainSCUBA is a promising means for understanding functional preferences in the brain, and provides motivation for further hypothesis-driven investigation of visual cortex.

  • 4 authors
·
Oct 6, 2023

Omni-iEEG: A Large-Scale, Comprehensive iEEG Dataset and Benchmark for Epilepsy Research

Epilepsy affects over 50 million people worldwide, and one-third of patients suffer drug-resistant seizures where surgery offers the best chance of seizure freedom. Accurate localization of the epileptogenic zone (EZ) relies on intracranial EEG (iEEG). Clinical workflows, however, remain constrained by labor-intensive manual review. At the same time, existing data-driven approaches are typically developed on single-center datasets that are inconsistent in format and metadata, lack standardized benchmarks, and rarely release pathological event annotations, creating barriers to reproducibility, cross-center validation, and clinical relevance. With extensive efforts to reconcile heterogeneous iEEG formats, metadata, and recordings across publicly available sources, we present Omni-iEEG, a large-scale, pre-surgical iEEG resource comprising 302 patients and 178 hours of high-resolution recordings. The dataset includes harmonized clinical metadata such as seizure onset zones, resections, and surgical outcomes, all validated by board-certified epileptologists. In addition, Omni-iEEG provides over 36K expert-validated annotations of pathological events, enabling robust biomarker studies. Omni-iEEG serves as a bridge between machine learning and epilepsy research. It defines clinically meaningful tasks with unified evaluation metrics grounded in clinical priors, enabling systematic evaluation of models in clinically relevant settings. Beyond benchmarking, we demonstrate the potential of end-to-end modeling on long iEEG segments and highlight the transferability of representations pretrained on non-neurophysiological domains. Together, these contributions establish Omni-iEEG as a foundation for reproducible, generalizable, and clinically translatable epilepsy research. The project page with dataset and code links is available at omni-ieeg.github.io/omni-ieeg.

  • 12 authors
·
Feb 17

Learning Multi-resolution Functional Maps with Spectral Attention for Robust Shape Matching

In this work, we present a novel non-rigid shape matching framework based on multi-resolution functional maps with spectral attention. Existing functional map learning methods all rely on the critical choice of the spectral resolution hyperparameter, which can severely affect the overall accuracy or lead to overfitting, if not chosen carefully. In this paper, we show that spectral resolution tuning can be alleviated by introducing spectral attention. Our framework is applicable in both supervised and unsupervised settings, and we show that it is possible to train the network so that it can adapt the spectral resolution, depending on the given shape input. More specifically, we propose to compute multi-resolution functional maps that characterize correspondence across a range of spectral resolutions, and introduce a spectral attention network that helps to combine this representation into a single coherent final correspondence. Our approach is not only accurate with near-isometric input, for which a high spectral resolution is typically preferred, but also robust and able to produce reasonable matching even in the presence of significant non-isometric distortion, which poses great challenges to existing methods. We demonstrate the superior performance of our approach through experiments on a suite of challenging near-isometric and non-isometric shape matching benchmarks.

  • 3 authors
·
Oct 11, 2022

Scalable Learning in Structured Recurrent Spiking Neural Networks without Backpropagation

Spiking Neural Networks (SNNs) provide a promising framework for energy-efficient and biologically grounded computation; however, scalable learning in deep recurrent architectures with sparse connectivity remains a major challenge. In this work, we propose a structured multi-layer recurrent SNN architecture composed of locally dense recurrent layers augmented with sparse small-world long-range projections to a readout population. The long-range connectivity is largely fixed, preserving routing efficiency and hardware scalability, while synaptic adaptation is performed using strictly local plasticity mechanisms. To enable supervised learning without backpropagation or surrogate gradients, we introduce a biologically motivated learning framework that combines: (i) population-based winner-take-all (WTA) teaching signals at the output layer, (ii) fixed random broadcast alignment feedback pathways, and (iii) low-dimensional modulatory neuron populations that gate synaptic updates through three-factor learning rules with eligibility traces. This design supports deep recurrent computation with sparse global communication and purely local synaptic updates. We analyze the algorithmic properties, computational complexity, and hardware feasibility of the proposed approach, and demonstrate stable learning and competitive performance on benchmark classification tasks. The results highlight the potential of structured recurrence and neuromodulatory learning to enable scalable, hardware-compatible SNN training beyond gradient-based methods.

  • 2 authors
·
Apr 30

Lattice-Based Pruning in Recurrent Neural Networks via Poset Modeling

Recurrent neural networks (RNNs) are central to sequence modeling tasks, yet their high computational complexity poses challenges for scalability and real-time deployment. Traditional pruning techniques, predominantly based on weight magnitudes, often overlook the intrinsic structural properties of these networks. We introduce a novel framework that models RNNs as partially ordered sets (posets) and constructs corresponding dependency lattices. By identifying meet irreducible neurons, our lattice-based pruning algorithm selectively retains critical connections while eliminating redundant ones. The method is implemented using both binary and continuous-valued adjacency matrices to capture different aspects of network connectivity. Evaluated on the MNIST dataset, our approach exhibits a clear trade-off between sparsity and classification accuracy. Moderate pruning maintains accuracy above 98%, while aggressive pruning achieves higher sparsity with only a modest performance decline. Unlike conventional magnitude-based pruning, our method leverages the structural organization of RNNs, resulting in more effective preservation of functional connectivity and improved efficiency in multilayer networks with top-down feedback. The proposed lattice-based pruning framework offers a rigorous and scalable approach for reducing RNN complexity while sustaining robust performance, paving the way for more efficient hierarchical models in both machine learning and computational neuroscience.

  • 1 authors
·
Feb 23, 2025

Domain Elastic Transform: Bayesian Function Registration for High-Dimensional Scientific Data

Nonrigid registration is conventionally divided into point set registration, which aligns sparse geometries, and image registration, which aligns continuous intensity fields on regular grids. However, this dichotomy creates a critical bottleneck for emerging scientific data, such as spatial transcriptomics, where high-dimensional vector-valued functions, e.g., gene expression, are defined on irregular, sparse manifolds. Consequently, researchers currently face a forced choice: either sacrifice single-cell resolution via voxelization to utilize image-based tools, or ignore the critical functional signal to utilize geometric tools. To resolve this dilemma, we propose Domain Elastic Transform (DET), a grid-free probabilistic framework that unifies geometric and functional alignment. By treating data as functions on irregular domains, DET registers high-dimensional signals directly without binning. We formulate the problem within a rigorous Bayesian framework, modeling domain deformation as an elastic motion guided by a joint spatial-functional likelihood. The method is fully unsupervised and scalable, utilizing feature-sensitive downsampling to handle massive atlases. We demonstrate that DET achieves 92\% topological preservation on MERFISH data where state-of-the-art optimal transport methods struggle (<5\%), and successfully registers whole-embryo Stereo-seq atlases across developmental stages -- a task involving massive scale and complex nonrigid growth. The implementation of DET is available on {https://github.com/ohirose/bcpd} (since Mar, 2025).

  • 2 authors
·
Mar 21

VoxStruct3D: Structure-Leading Flow Matching for Voxel-Space 3D MRI Synthesis

High-fidelity 3D MRI synthesis requires both globally coherent anatomy and fine-grained voxel-level detail. Although latent diffusion makes volumetric generation tractable, its image autoencoder introduces a reconstruction bottleneck that can limit the fine detail recoverable in the final volume. We present VoxStruct3D, a voxel-space flow-matching framework that directly models full-resolution MRI volumes using a clean-data prediction objective. Its Volumetric Voxel Generator (VVG) combines factorized 3D patch embedding with overlapping upsampling, time-modulated residual refinement, and skip fusion, enabling neighboring tokens to jointly reconstruct shared voxel regions and suppress patch-boundary artifacts. To complement direct voxel-space modeling with an explicit anatomical prior, we further introduce a Structure-First, Image-Follows (SFIF) strategy. A frozen pretrained 3D medical encoder and a StructVAE extract compact structure tokens that preserve dominant anatomy, while a structure-leading schedule keeps their trajectory ahead of the image trajectory. Patch-Aligned RoPE spatially aligns the unequal token grids, and asymmetric attention enforces one-way guidance from structure to image. Experiments on pathological and healthy T1-weighted brain MRI datasets show that VoxStruct3D achieves the strongest overall performance across feature-distribution alignment, sample diversity, and perceptual quality, producing anatomically coherent and visually realistic volumes.

  • 8 authors
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Aug 4

A Unified Model for Compressed Sensing MRI Across Undersampling Patterns

Compressed Sensing MRI reconstructs images of the body's internal anatomy from undersampled measurements, thereby reducing scan time. Recently, deep learning has shown great potential for reconstructing high-fidelity images from highly undersampled measurements. However, one needs to train multiple models for different undersampling patterns and desired output image resolutions, since most networks operate on a fixed discretization. Such approaches are highly impractical in clinical settings, where undersampling patterns and image resolutions are frequently changed to accommodate different real-time imaging and diagnostic requirements. We propose a unified MRI reconstruction model robust to various measurement undersampling patterns and image resolutions. Our approach uses neural operators, a discretization-agnostic architecture applied in both image and measurement spaces, to capture local and global features. Empirically, our model improves SSIM by 11% and PSNR by 4 dB over a state-of-the-art CNN (End-to-End VarNet), with 600times faster inference than diffusion methods. The resolution-agnostic design also enables zero-shot super-resolution and extended field-of-view reconstruction, offering a versatile and efficient solution for clinical MR imaging. Our unified model offers a versatile solution for MRI, adapting seamlessly to various measurement undersampling and imaging resolutions, making it highly effective for flexible and reliable clinical imaging. Our code is available at https://armeet.ca/nomri.

  • 7 authors
·
Oct 5, 2024 1

fMRI-LM: Towards a Universal Foundation Model for Language-Aligned fMRI Understanding

Recent advances in multimodal large language models (LLMs) have enabled unified reasoning across images, audio, and video, but extending such capability to brain imaging remains largely unexplored. Bridging this gap is essential to link neural activity with semantic cognition and to develop cross-modal brain representations. To this end, we present fMRI-LM, a foundational model that bridges functional MRI (fMRI) and language through a three-stage framework. In Stage 1, we learn a neural tokenizer that maps fMRI into discrete tokens embedded in a language-consistent space. In Stage 2, a pretrained LLM is adapted to jointly model fMRI tokens and text, treating brain activity as a sequence that can be temporally predicted and linguistically described. To overcome the lack of natural fMRI-text pairs, we construct a large descriptive corpus that translates diverse imaging-based features into structured textual descriptors, capturing the low-level organization of fMRI signals. In Stage 3, we perform multi-task, multi-paradigm instruction tuning to endow fMRI-LM with high-level semantic understanding, supporting diverse downstream applications. Across various benchmarks, fMRI-LM achieves strong zero-shot and few-shot performance, and adapts efficiently with parameter-efficient tuning (LoRA), establishing a scalable pathway toward a language-aligned, universal model for structural and semantic understanding of fMRI.

  • 6 authors
·
May 13

A brain basis of dynamical intelligence for AI and computational neuroscience

The deep neural nets of modern artificial intelligence (AI) have not achieved defining features of biological intelligence, including abstraction, causal learning, and energy-efficiency. While scaling to larger models has delivered performance improvements for current applications, more brain-like capacities may demand new theories, models, and methods for designing artificial learning systems. Here, we argue that this opportunity to reassess insights from the brain should stimulate cooperation between AI research and theory-driven computational neuroscience (CN). To motivate a brain basis of neural computation, we present a dynamical view of intelligence from which we elaborate concepts of sparsity in network structure, temporal dynamics, and interactive learning. In particular, we suggest that temporal dynamics, as expressed through neural synchrony, nested oscillations, and flexible sequences, provide a rich computational layer for reading and updating hierarchical models distributed in long-term memory networks. Moreover, embracing agent-centered paradigms in AI and CN will accelerate our understanding of the complex dynamics and behaviors that build useful world models. A convergence of AI/CN theories and objectives will reveal dynamical principles of intelligence for brains and engineered learning systems. This article was inspired by our symposium on dynamical neuroscience and machine learning at the 6th Annual US/NIH BRAIN Initiative Investigators Meeting.

  • 3 authors
·
May 15, 2021

A Demographic-Conditioned Variational Autoencoder for fMRI Distribution Sampling and Removal of Confounds

Objective: fMRI and derived measures such as functional connectivity (FC) have been used to predict brain age, general fluid intelligence, psychiatric disease status, and preclinical neurodegenerative disease. However, it is not always clear that all demographic confounds, such as age, sex, and race, have been removed from fMRI data. Additionally, many fMRI datasets are restricted to authorized researchers, making dissemination of these valuable data sources challenging. Methods: We create a variational autoencoder (VAE)-based model, DemoVAE, to decorrelate fMRI features from demographics and generate high-quality synthetic fMRI data based on user-supplied demographics. We train and validate our model using two large, widely used datasets, the Philadelphia Neurodevelopmental Cohort (PNC) and Bipolar and Schizophrenia Network for Intermediate Phenotypes (BSNIP). Results: We find that DemoVAE recapitulates group differences in fMRI data while capturing the full breadth of individual variations. Significantly, we also find that most clinical and computerized battery fields that are correlated with fMRI data are not correlated with DemoVAE latents. An exception are several fields related to schizophrenia medication and symptom severity. Conclusion: Our model generates fMRI data that captures the full distribution of FC better than traditional VAE or GAN models. We also find that most prediction using fMRI data is dependent on correlation with, and prediction of, demographics. Significance: Our DemoVAE model allows for generation of high quality synthetic data conditioned on subject demographics as well as the removal of the confounding effects of demographics. We identify that FC-based prediction tasks are highly influenced by demographic confounds.

  • 10 authors
·
May 13, 2024

HA-HI: Synergising fMRI and DTI through Hierarchical Alignments and Hierarchical Interactions for Mild Cognitive Impairment Diagnosis

Early diagnosis of mild cognitive impairment (MCI) and subjective cognitive decline (SCD) utilizing multi-modal magnetic resonance imaging (MRI) is a pivotal area of research. While various regional and connectivity features from functional MRI (fMRI) and diffusion tensor imaging (DTI) have been employed to develop diagnosis models, most studies integrate these features without adequately addressing their alignment and interactions. This limits the potential to fully exploit the synergistic contributions of combined features and modalities. To solve this gap, our study introduces a novel Hierarchical Alignments and Hierarchical Interactions (HA-HI) method for MCI and SCD classification, leveraging the combined strengths of fMRI and DTI. HA-HI efficiently learns significant MCI- or SCD- related regional and connectivity features by aligning various feature types and hierarchically maximizing their interactions. Furthermore, to enhance the interpretability of our approach, we have developed the Synergistic Activation Map (SAM) technique, revealing the critical brain regions and connections that are indicative of MCI/SCD. Comprehensive evaluations on the ADNI dataset and our self-collected data demonstrate that HA-HI outperforms other existing methods in diagnosing MCI and SCD, making it a potentially vital and interpretable tool for early detection. The implementation of this method is publicly accessible at https://github.com/ICI-BCI/Dual-MRI-HA-HI.git.

  • 7 authors
·
Jan 2, 2024

A differentiable brain simulator bridging brain simulation and brain-inspired computing

Brain simulation builds dynamical models to mimic the structure and functions of the brain, while brain-inspired computing (BIC) develops intelligent systems by learning from the structure and functions of the brain. The two fields are intertwined and should share a common programming framework to facilitate each other's development. However, none of the existing software in the fields can achieve this goal, because traditional brain simulators lack differentiability for training, while existing deep learning (DL) frameworks fail to capture the biophysical realism and complexity of brain dynamics. In this paper, we introduce BrainPy, a differentiable brain simulator developed using JAX and XLA, with the aim of bridging the gap between brain simulation and BIC. BrainPy expands upon the functionalities of JAX, a powerful AI framework, by introducing complete capabilities for flexible, efficient, and scalable brain simulation. It offers a range of sparse and event-driven operators for efficient and scalable brain simulation, an abstraction for managing the intricacies of synaptic computations, a modular and flexible interface for constructing multi-scale brain models, and an object-oriented just-in-time compilation approach to handle the memory-intensive nature of brain dynamics. We showcase the efficiency and scalability of BrainPy on benchmark tasks, highlight its differentiable simulation for biologically plausible spiking models, and discuss its potential to support research at the intersection of brain simulation and BIC.

  • 6 authors
·
Nov 8, 2023

GridPE: Unifying Positional Encoding in Transformers with a Grid Cell-Inspired Framework

Understanding spatial location and relationships is a fundamental capability for modern artificial intelligence systems. Insights from human spatial cognition provide valuable guidance in this domain. Neuroscientific discoveries have highlighted the role of grid cells as a fundamental neural component for spatial representation, including distance computation, path integration, and scale discernment. In this paper, we introduce a novel positional encoding scheme inspired by Fourier analysis and the latest findings in computational neuroscience regarding grid cells. Assuming that grid cells encode spatial position through a summation of Fourier basis functions, we demonstrate the translational invariance of the grid representation during inner product calculations. Additionally, we derive an optimal grid scale ratio for multi-dimensional Euclidean spaces based on principles of biological efficiency. Utilizing these computational principles, we have developed a Grid-cell inspired Positional Encoding technique, termed GridPE, for encoding locations within high-dimensional spaces. We integrated GridPE into the Pyramid Vision Transformer architecture. Our theoretical analysis shows that GridPE provides a unifying framework for positional encoding in arbitrary high-dimensional spaces. Experimental results demonstrate that GridPE significantly enhances the performance of transformers, underscoring the importance of incorporating neuroscientific insights into the design of artificial intelligence systems.

  • 4 authors
·
Sep 13, 2024

MADE-for-ASD: A Multi-Atlas Deep Ensemble Network for Diagnosing Autism Spectrum Disorder

In response to the global need for efficient early diagnosis of Autism Spectrum Disorder (ASD), this paper bridges the gap between traditional, time-consuming diagnostic methods and potential automated solutions. We propose a multi-atlas deep ensemble network, MADE-for-ASD, that integrates multiple atlases of the brain's functional magnetic resonance imaging (fMRI) data through a weighted deep ensemble network. Our approach integrates demographic information into the prediction workflow, which enhances ASD diagnosis performance and offers a more holistic perspective on patient profiling. We experiment with the well-known publicly available ABIDE (Autism Brain Imaging Data Exchange) I dataset, consisting of resting state fMRI data from 17 different laboratories around the globe. Our proposed system achieves 75.20% accuracy on the entire dataset and 96.40% on a specific subset - both surpassing reported ASD diagnosis accuracy in ABIDE I fMRI studies. Specifically, our model improves by 4.4 percentage points over prior works on the same amount of data. The model exhibits a sensitivity of 82.90% and a specificity of 69.70% on the entire dataset, and 91.00% and 99.50%, respectively, on the specific subset. We leverage the F-score to pinpoint the top 10 ROI in ASD diagnosis, such as precuneus and anterior cingulate/ventromedial. The proposed system can potentially pave the way for more cost-effective, efficient and scalable strategies in ASD diagnosis. Codes and evaluations are publicly available at https://github.com/hasan-rakibul/MADE-for-ASD.

  • 4 authors
·
Jul 9, 2024

NeuroPilot: An Agent-Driven Smart Pipeline for Processing, Quality Control, and Managing Neuroimages

Transforming raw neuroimage archives into analysis-ready derivatives relies on three brittle stages: data standardization, modality-specific preprocessing, and quality control (QC). While individual neuroimaging tools are well developed, their orchestration requires project-specific scripts, environment-adaptive tuning, and labor-intensive manual QC. To address this, we introduce NeuroPilot, a multi-agent system that digitalizes the expertise of neuroimage processing, QC, and data management into three LLM-invocable skills: dcm2bids-skill, neuroimage-pre-skill, and qc-agent-skill. The LLM-driven agent autonomously orchestrates workflows, generalizing various infrastructure settings into a single configuration to achieve the highest scalability. Demonstrating the system's generalizability, we deployed NeuroPilot across 17 cohorts (>123,000 subjects) spanning infant to aging populations and multiple MRI modalities (structural, diffusion, functional). In practice, after standardizing data via the dcm2bids-skill, the agent dynamically routes datasets to the optimal neuroimage-pre-skill based on available modalities and cohort traits (e.g., dispatching T1w and fMRI data to fMRIPrep, or selecting specialized pipelines for infant cohorts). The qc-agent-skill then drives an evidence-based, semi-automated QC via a 3-D browser dashboard, utilizing a multi-tiered verification system to optimize failed cases and escalate complex issues for supervisor inspection. Quantitatively, our QC agent screened 558 production subjects, validating its automated flags against FreeSurfer's topology-defect metrics. The infant processing pipeline achieved a 100% (201/201) completion rate on QC-validated inputs. Importantly, NeuroPilot compresses the traditional 2--3 month timeline for training staff and processing complete datasets into a single week. NeuroPilot is deployed in https://wanda-cyberbench.com/.

  • 10 authors
·
Jul 29

HiDiffusion: Unlocking High-Resolution Creativity and Efficiency in Low-Resolution Trained Diffusion Models

We introduce HiDiffusion, a tuning-free framework comprised of Resolution-Aware U-Net (RAU-Net) and Modified Shifted Window Multi-head Self-Attention (MSW-MSA) to enable pretrained large text-to-image diffusion models to efficiently generate high-resolution images (e.g. 1024times1024) that surpass the training image resolution. Pretrained diffusion models encounter unreasonable object duplication in generating images beyond the training image resolution. We attribute it to the mismatch between the feature map size of high-resolution images and the receptive field of U-Net's convolution. To address this issue, we propose a simple yet scalable method named RAU-Net. RAU-Net dynamically adjusts the feature map size to match the convolution's receptive field in the deep block of U-Net. Another obstacle in high-resolution synthesis is the slow inference speed of U-Net. Our observations reveal that the global self-attention in the top block, which exhibits locality, however, consumes the majority of computational resources. To tackle this issue, we propose MSW-MSA. Unlike previous window attention mechanisms, our method uses a much larger window size and dynamically shifts windows to better accommodate diffusion models. Extensive experiments demonstrate that our HiDiffusion can scale diffusion models to generate 1024times1024, 2048times2048, or even 4096times4096 resolution images, while simultaneously reducing inference time by 40\%-60\%, achieving state-of-the-art performance on high-resolution image synthesis. The most significant revelation of our work is that a pretrained diffusion model on low-resolution images is scalable for high-resolution generation without further tuning. We hope this revelation can provide insights for future research on the scalability of diffusion models.

  • 8 authors
·
Nov 29, 2023

Exploiting the Brain's Network Structure for Automatic Identification of ADHD Subjects

Attention Deficit Hyperactive Disorder (ADHD) is a common behavioral problem affecting children. In this work, we investigate the automatic classification of ADHD subjects using the resting state Functional Magnetic Resonance Imaging (fMRI) sequences of the brain. We show that the brain can be modeled as a functional network, and certain properties of the networks differ in ADHD subjects from control subjects. We compute the pairwise correlation of brain voxels' activity over the time frame of the experimental protocol which helps to model the function of a brain as a network. Different network features are computed for each of the voxels constructing the network. The concatenation of the network features of all the voxels in a brain serves as the feature vector. Feature vectors from a set of subjects are then used to train a PCA-LDA (principal component analysis-linear discriminant analysis) based classifier. We hypothesized that ADHD-related differences lie in some specific regions of the brain and using features only from those regions is sufficient to discriminate ADHD and control subjects. We propose a method to create a brain mask that includes the useful regions only and demonstrate that using the feature from the masked regions improves classification accuracy on the test data set. We train our classifier with 776 subjects and test on 171 subjects provided by The Neuro Bureau for the ADHD-200 challenge. We demonstrate the utility of graph-motif features, specifically the maps that represent the frequency of participation of voxels in network cycles of length 3. The best classification performance (69.59%) is achieved using 3-cycle map features with masking. Our proposed approach holds promise in being able to diagnose and understand the disorder.

  • 3 authors
·
Jun 15, 2023

Brain Captioning: Decoding human brain activity into images and text

Every day, the human brain processes an immense volume of visual information, relying on intricate neural mechanisms to perceive and interpret these stimuli. Recent breakthroughs in functional magnetic resonance imaging (fMRI) have enabled scientists to extract visual information from human brain activity patterns. In this study, we present an innovative method for decoding brain activity into meaningful images and captions, with a specific focus on brain captioning due to its enhanced flexibility as compared to brain decoding into images. Our approach takes advantage of cutting-edge image captioning models and incorporates a unique image reconstruction pipeline that utilizes latent diffusion models and depth estimation. We utilized the Natural Scenes Dataset, a comprehensive fMRI dataset from eight subjects who viewed images from the COCO dataset. We employed the Generative Image-to-text Transformer (GIT) as our backbone for captioning and propose a new image reconstruction pipeline based on latent diffusion models. The method involves training regularized linear regression models between brain activity and extracted features. Additionally, we incorporated depth maps from the ControlNet model to further guide the reconstruction process. We evaluate our methods using quantitative metrics for both generated captions and images. Our brain captioning approach outperforms existing methods, while our image reconstruction pipeline generates plausible images with improved spatial relationships. In conclusion, we demonstrate significant progress in brain decoding, showcasing the enormous potential of integrating vision and language to better understand human cognition. Our approach provides a flexible platform for future research, with potential applications in various fields, including neural art, style transfer, and portable devices.

  • 5 authors
·
May 19, 2023

Brain-Like Object Recognition with High-Performing Shallow Recurrent ANNs

Deep convolutional artificial neural networks (ANNs) are the leading class of candidate models of the mechanisms of visual processing in the primate ventral stream. While initially inspired by brain anatomy, over the past years, these ANNs have evolved from a simple eight-layer architecture in AlexNet to extremely deep and branching architectures, demonstrating increasingly better object categorization performance, yet bringing into question how brain-like they still are. In particular, typical deep models from the machine learning community are often hard to map onto the brain's anatomy due to their vast number of layers and missing biologically-important connections, such as recurrence. Here we demonstrate that better anatomical alignment to the brain and high performance on machine learning as well as neuroscience measures do not have to be in contradiction. We developed CORnet-S, a shallow ANN with four anatomically mapped areas and recurrent connectivity, guided by Brain-Score, a new large-scale composite of neural and behavioral benchmarks for quantifying the functional fidelity of models of the primate ventral visual stream. Despite being significantly shallower than most models, CORnet-S is the top model on Brain-Score and outperforms similarly compact models on ImageNet. Moreover, our extensive analyses of CORnet-S circuitry variants reveal that recurrence is the main predictive factor of both Brain-Score and ImageNet top-1 performance. Finally, we report that the temporal evolution of the CORnet-S "IT" neural population resembles the actual monkey IT population dynamics. Taken together, these results establish CORnet-S, a compact, recurrent ANN, as the current best model of the primate ventral visual stream.

  • 14 authors
·
Oct 27, 2019