ICLR 2026 Papers

DNA language models are emerging as powerful tools for representing genomic sequences, with recent progress driven by self-supervised learning. However, performance on downstream tasks is sensitive to tokenization strategies reflecting the complex encodings in DNA, where both regulatory elements and single-nucleotide changes can be functionally significant. Yet existing models are fixed to their initial tokenization strategy; single-nucleotide encodings result in long sequences that challenge transformer architectures, while fixed multi-nucleotide schemes like byte pair encoding struggle with character level modeling. Drawing inspiration from the Byte Latent Transformer's combining of bytes into patches, we propose that 'patching' provides a competitive and more efficient alternative to tokenization for DNA sequences. Furthermore, patching eliminates the need for a fixed vocabulary, which offers unique advantages to DNA. Leveraging this, we propose a biologically informed strategy, using evolutionary conservation scores as a guide for 'patch' boundaries. By prioritizing conserved regions, our approach directs computational resources to the most functionally relevant parts of the DNA sequence. We show that models up to an order of magnitude smaller surpass current state-of-the-art performance in existing DNA benchmarks. Importantly, our approach provides the flexibility to change patching without retraining, overcoming a fundamental limitation of current tokenization methods.

Virtual screening (VS) aims to identify bioactive compounds from vast chemical libraries, but remains difficult in low-label regimes where only a few actives are known. Existing methods largely rely on general-purpose molecular fingerprints and overlook class-discriminative substructures critical to bioactivity. Moreover, they consider molecules independently, limiting effectiveness in low-label regimes. We introduce SubDyve, a network-based VS framework that constructs a subgraph-aware similarity network and propagates activity signals from a small known actives. When few active compounds are available, SubDyve performs iterative seed refinement, incrementally promoting new candidates based on local false discovery rate. This strategy expands the seed set with promising candidates while controlling false positives from topological bias and overexpansion. We evaluate SubDyve on ten DUD-E targets under zero-shot conditions and on the CDK7 target with a 10-million-compound ZINC dataset. SubDyve consistently outperforms existing fingerprint or embedding-based approaches, achieving margins of up to +34.0 on the BEDROC and +24.6 on the $EF_{1\\%}$ metric.

Continuous learning of novel classes is crucial for edge devices to preserve data privacy and maintain reliable performance in dynamic environments. However, the scenario becomes particularly challenging when data samples are insufficient, requiring on-device few-shot class-incremental learning (FSCIL) to maintain consistent model performance. Although existing work has explored parameter-efficient FSCIL frameworks based on artificial neural networks (ANNs), their deployment is still fundamentally constrained by limited device resources. Spiking neural networks (SNNs) process spatiotemporal information efficiently, offering lower energy consumption, greater biological plausibility, and compatibility with neuromorphic hardware than ANNs. In this work, we propose an SNN-based method containing Sparsity-Aware neuronal dynamics and Fast Adaptive structure (SAFA-SNN) for On-Device FSCIL. First, neurons are sparsity-aware with dynamic thresholds, keeping most of them stable. As a result, the synaptic traces that encode base-class knowledge are naturally preserved, thereby alleviating catastrophic forgetting. To cope with spike non-differentiability in backpropagation, we employ a gradient-free estimation, i.e., zeroth-order optimization. Moreover, class prototypes can limit overfitting on few-shot data but introduce bias in incremental learning. We enhance prototype discriminability by subspace projection. Extensive experiments conducted on two standard benchmark datasets (CIFAR100 and Mini-ImageNet) and three neuromorphic datasets (CIFAR-10-DVS, DVS128gesture, and N-Caltech101) demonstrate that SAFA-SNN outperforms baseline methods, specifically achieving at least 4.01\% improvement at the last incremental session on Mini-ImageNet and 20\% lower energy cost on Spiking ResNet-20 over baselines with practical implementation.

We present CogniMap3D, a bioinspired framework for dynamic 3D scene understanding and reconstruction that emulates human cognitive processes. Our approach maintains a persistent memory bank of static scenes, enabling efficient spatial knowledge storage and rapid retrieval. CogniMap3D integrates three core capabilities: a multi-stage motion cue framework for identifying dynamic objects, a cognitive mapping system for storing, recalling, and updating static scenes across multiple visits, and a factor graph optimization strategy for refining camera poses. Given an image stream, our model identifies dynamic regions through motion cues with depth and camera pose priors, then matches static elements against its memory bank. When revisiting familiar locations, CogniMap3D retrieves stored scenes, relocates cameras, and updates memory with new observations. Evaluations on video depth estimation, camera pose reconstruction, and 3D mapping tasks demonstrate its state-of-the-art performance, while effectively supporting continuous scene understanding across extended sequences and multiple visits.

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 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.

Modeling neural population dynamics is crucial for foundational neuroscientific research and various clinical applications. Conventional latent variable methods typically model continuous brain dynamics through discretizing time with recurrent architecture, which necessarily results in compounded cumulative prediction errors and failure of capturing instantaneous, nonlinear characteristics of EEGs. We propose ODEBrain, a Neural ODE latent dynamic forecasting framework to overcome these challenges by integrating spatio-temporal-frequency features into spectral graph nodes, followed by a Neural ODE modeling the continuous latent dynamics. Our design ensures that the latent representations can capture stochastic variations of complex brain state at any given time point. Extensive experiments verifies that ODEBrain can improve significantly over existing methods in forecasting EEG dynamics with enhanced robustness and generalization capabilities.

Autonomous science agents, built on large language models (LLMs), are increasingly being investigated to generate hypotheses, design experiments, and produce reports. Prior science agents primarily focus on open-ended scientific problems, where such outputs—hypotheses, experiments, or analyses are inherently subjective and thus difficult to evaluate rigorously. In contrast, existing scientific coding benchmarks provide tasks with clearly defined, executable outputs that enable objective assessment. However, current agent-based approaches to these benchmarks remain engineering-driven pipelines, lacking principled framework design. This mismatch exposes a gap: the absence of end-to-end, principled science agent frameworks for scientific coding tasks. We address this gap by focusing on scientific coding tasks, where evaluation can be made rigorously, and introducing an agent framework SciNav (Scientific Navigator) that enables more effective solution exploration. Our framework is designed to operate efficiently under constrained search budgets, moving beyond reliance on pre-defined success metrics and prolonged search cycles. Inspired by findings that comparative judgments often reveal finer-grained quality differences and therefore provide greater discriminative power than absolute scoring, our framework leverages pairwise relative judgments within a tree search process to select top-K promising solution branches, prune low-potential ones, and progressively narrow down the solution candidates on the selected branches guided by relative comparisons. We demonstrate our agent's effectiveness across different types of tasks on two benchmarks. Experiments show that SciNav significantly outperforms direct prompting and prior agents like OpenHands and Self-Debug across different base models, task types, and difficulty levels, and exceeds different frontier comparators such as random selection and LLM absolute scoring. These results confirm the strength of our agent design and highlight the effectiveness of relative judgment–guided top-K search for high-quality scientific coding, marking a step toward more practical science agents.

Training recurrent neural networks (RNNs) to perform neuroscience-style tasks has become a popular way to generate hypotheses for how neural circuits in the brain might perform computations. Recent work has demonstrated that task-trained RNNs possess a strong simplicity bias. In particular, this inductive bias often causes RNNs trained on the same task to collapse on effectively the same solution, typically comprised of fixed-point attractors or other low-dimensional dynamical motifs. While such solutions are readily interpretable, this collapse proves counterproductive for the sake of generating a set of genuinely unique hypotheses for how neural computations might be performed. Here we propose Iterative Neural Similarity Deflation (INSD), a simple method to break this inductive bias. By penalizing linear predictivity of neural activity produced by standard task-trained RNNs, we find an alternative class of solutions to classic neuroscience-style RNN tasks. These solutions appear distinct across a battery of analysis techniques, including representational similarity metrics, dynamical systems analysis, and the linear decodability of task-relevant variables. Moreover, these alternative solutions can sometimes achieve superior performance in difficult or out-of-distribution task regimes. Our findings underscore the importance of moving beyond the simplicity bias to uncover richer and more varied models of neural computation.

The hippocampus contains neurons whose firing correlates with an animal's location and orientation in space. Collectively, these neurons are held to support a cognitive map of the environment, enabling the recall of and navigation to specific locations. Although recent studies have characterised the timelines of spatial neuron development, no unifying mechanistic model has yet been proposed. Moreover, the processes driving the emergence of spatial representations in the hippocampus remain unclear (Tan et al., 2017). Here, we combine computational analysis of postnatal locomotor development with a recurrent neural network (RNN) model of hippocampal function to demonstrate how changes in movement statistics -- and the resulting sensory experiences -- shape the formation of spatial tuning. First, we identify distinct developmental stages in rat locomotion during open-field exploration using published experimental data. Then, we train shallow RNNs to predict upcoming visual stimuli from concurrent visual and vestibular inputs, exposing them to trajectories that reflect progressively maturing locomotor patterns. Our findings reveal that these changing movement statistics drive the sequential emergence of spatially tuned units, mirroring the developmental timeline observed in rats. The models generate testable predictions about how spatial tuning properties mature -- predictions we confirm through analysis of hippocampal recordings. Critically, we demonstrate that replicating the specific statistics of developmental locomotion -- rather than merely accelerating sensory change -- is essential for the emergence of an allocentric spatial representation. These results establish a mechanistic link between embodied sensorimotor experience and the ontogeny of hippocampal spatial neurons, with significant implications for neurodevelopmental research and predictive models of navigational brain circuits.

Enabling natural communication through brain–computer interfaces (BCIs) remains one of the most profound challenges in neuroscience and neurotechnology. While existing frameworks offer partial solutions, they are constrained by oversimplified semantic representations and a lack of interpretability. To overcome these limitations, we introduce **Semantic Intent Decoding(SID)**, a novel framework that translates neural activity into natural language by modeling meaning as a flexible set of compositional semantic units. SID is built on three core principles: semantic compositionality, continuity and expandability of semantic space, and fidelity in reconstruction. We present **BrainMosaic**, a deep learning architecture implementing SID. BrainMosaic decodes multiple semantic units from EEG/SEEG signals using set matching and then reconstructs coherent sentences through semantic-guided reconstruction. This approach moves beyond traditional pipelines that rely on fixed-class classification or unconstrained generation, enabling a more interpretable and expressive communication paradigm. Extensive experiments on multilingual EEG and clinical SEEG datasets demonstrate that SID and BrainMosaic offer substantial advantages over existing frameworks, paving the way for natural and effective BCI-mediated communication.

Understanding how the brain encodes visual information is a central challenge in neuroscience and machine learning. A promising approach is to reconstruct visual stimuli—essentially images—from functional Magnetic Resonance Imaging (fMRI) signals. This involves two stages: transforming fMRI signals into a latent space and then using a pre-trained generative model to reconstruct images. The reconstruction quality depends on how similar the latent space is to the structure of neural activity and how well the generative model produces images from that space. Yet, it remains unclear which type of latent space best supports this transformation and how it should be organized to represent visual stimuli effectively. We present two key findings. First, fMRI signals are more similar to the text space of a language model than to either a vision-based space or a joint text–image space. Second, text representations and the generative model should be adapted to capture the compositional nature of visual stimuli, including objects, their detailed attributes, and relationships. Building on these insights, we propose PRISM, a model that Projects fMRI sIgnals into a Structured text space as an interMediate representation for visual stimuli reconstruction. It includes an object-centric diffusion module that generates images by composing individual objects to reduce object detection errors, and an attribute–relationship search module that automatically identifies key attributes and relationships that best align with the neural activity. Extensive experiments on real-world datasets demonstrate that our framework outperforms existing methods, achieving up to an 8% reduction in perceptual loss. These results highlight the importance of using structured text as the intermediate space to bridge fMRI signals and image reconstruction.

Current video avatar models can generate fluid animations but struggle to capture a character's authentic essence, primarily synchronizing motion with low-level audio cues instead of understanding higher-level semantics like emotion or intent. To bridge this gap, we propose a novel framework for generating character animations that are not only physically plausible but also semantically rich and expressive. Our model is built on two technical innovations. First, we employ Multimodal Large Language Models to generate a structured textual representation from input conditions, providing high-level semantic guidance for creating contextually and emotionally resonant actions. Second, to ensure robust fusion of multimodal signals, we introduce a specialized Multimodal Diffusion Transformer architecture featuring a novel Pseudo Last Frame design. This allows our model to accurately interpret the joint semantics of audio, images and text, generating motions that are deeply coherent with the overall context. Comprehensive experiments validate the superiority of our method, which achieves compelling results in lip-sync accuracy, video quality, motion naturalness, and semantic consistency. The approach also shows strong generalization to challenging scenarios, including multi-person and non-human subjects. Our video results are linked in https://omnihuman-lab.github.io/v1_5/ .

Whereas most brain–computer interface research has focused on decoding neural signals into behavior or intent, the reverse challenge—using controlled stimuli to steer brain activity—remains far less understood, particularly in the visual domain. However, designing images that consistently elicit desired neural responses is difficult: subjective states lack clear quantitative measures, and EEG feedback is both noisy and non-differentiable. We introduce MindPilot, the first closed-loop framework that uses EEG signals as optimization feedback to guide naturalistic image generation. Unlike prior work limited to invasive settings or low-level flicker stimuli, MindPilot leverages non-invasive EEG with natural images, treating the brain as a black-box function and employing a pseudo-model guidance mechanism to iteratively refine images without requiring explicit rewards or gradients. We validate MindPilot in both simulation and human experiments, demonstrating (i) efficient retrieval of semantic targets, (ii) closed-loop optimization of EEG features, and (iii) human-subject validations in mental matching and emotion regulation tasks. Our results establish the feasibility of EEG-guided image synthesis and open new avenues for non-invasive closed-loop brain modulation, bidirectional brain–computer interfaces, and neural signal–guided generative modeling.

Normative and task-driven theories offer powerful top-down explanations for biological systems, yet the goals of quantitatively arbitrating between competing theories, and utilizing them as inductive biases to improve data-driven fits of real biological datasets are prohibitively laborious, and often impossible. To this end, we introduce a Bayesian meta-learning framework designed to automatically convert raw functional predictions from normative theories into tractable probabilistic models. We employ adaptive deep kernel Gaussian processes, meta-learning a kernel on synthetic data generated from a normative theory. This Theory-Informed Kernel specifies a probabilistic model representing the predictions of a given theoretical model: usable for both fitting data and rigorously validating the theory. As a demonstration, we apply our framework to the early visual system, using efficient coding as our normative theory. We show improved response prediction accuracy in ex vivo recordings of mouse retinal ganglion cells stimulated by natural scenes compared to conventional data-driven baselines, while providing accurate uncertainty estimates and interpretable representations. Using exact Bayesian model selection, we also show that our informed kernel can accurately infer the degree of theory-match from data, confirming faithful encapsulation of theory structure. This work provides a more general, scalable, and automated approach for integrating theoretical knowledge into data-driven scientific inquiry in neuroscience and beyond.

Many real-world data science tasks involve complex web-based interactions: finding appropriate data available on the internet, synthesizing multimodal data from different locations, and producing summarized analyses. Existing web benchmarks often focus on simplistic interactions and often do not require diverse tool-using capabilities. Conversely, traditional data science benchmarks typically concentrate on static, highly structured datasets and do not assess end-to-end workflows that encompass data acquisition, cleaning, analysis, and insight generation. In response, we introduce WebDS, the first end-to-end web-based data science benchmark. It comprises 870 web-based data science tasks across 29 diverse websites from structured government data portals to unstructured news media, challenging agents to perform complex, multi-step, tool-based operations, across heterogeneous data formats, to better reflect the realities of modern data analytics. Evaluations of current SOTA LLM agents indicate significant performance gaps in accomplishing these tasks. For instance, Browser Use, which accomplishes 80% of tasks on Web Voyager, completes only 15% of tasks in WebDS, which our analysis suggests is due to new failure modes like poor information grounding, repetitive behavior and shortcut-taking that agents performing WebDS' tasks display. By contrast, humans achieve around 90% accuracy, highlighting a substantial gap between current agents and human performance. By providing a more robust and realistic testing ground, WebDS sets the stage for significant advances in the development of practically useful LLM-based data science.

Protein representation learning has achieved major advances using large sequence and structure datasets, yet current models primarily operate at the level of individual residues or entire proteins. This overlooks a critical aspect of protein biology: proteins are composed of recurrent, evolutionarily conserved substructures that mediate core molecular functions. Despite decades of curated biological knowledge, these substructures remain largely unexploited in modern protein models. We introduce Magneton, an integrated environment for developing substructure-aware protein models. Magneton provides (1) a large-scale dataset of 530,601 proteins annotated with over 1.7 million substructures spanning 13,075 types, (2) a training framework for incorporating substructures into existing models, and (3) a benchmark suite of 13 tasks probing residue-, substructure-, and protein-level representations. Using Magneton, we develop substructure-tuning, a supervised fine-tuning method that distills substructural knowledge into pretrained protein models. Across state-of-the-art sequence- and structure-based models, substructure-tuning improves function-related tasks while revealing that substructural signals are complementary to global structural information. The Magneton environment, datasets, and substructure-tuned models are all openly available.

Accurate registration of brain MRI scans is fundamental for cross-subject analysis in neuroscientific studies. This involves aligning both the cortical surface of the brain and the interior volume. Traditional methods treat volumetric and surface-based registration separately, which often leads to inconsistencies that limit downstream analyses. We propose a deep learning framework, UCS, that registers 3D brain MRI images by jointly aligning both cortical and subcortical regions, through a unified volume-and-surface-based representation. Our approach leverages an intermediate spherical coordinate space to bridge anatomical surface topology with volumetric anatomy, enabling consistent and anatomically accurate alignment. By integrating spherical registration into the learning, our method ensures geometric coherence between volume and surface domains. In a series of experiments on both in-domain and out-of-domain datasets, our method consistently outperforms both classical and machine learning-based registration methods--improving the Dice score by up to 7 points while maintaining regular deformation fields. Additionally, it is orders of magnitude faster than the standard method for this task, and is simpler to use because it requires no additional inputs beyond an MRI scan. Its superior accuracy, fast inference, and ease of use sets a new standard for joint cortical and subcortical registration.

Spiking Transformer has sparked growing interest, with the Spiking Self-Attention merging spikes with self-attention to deliver both energy efficiency and competitive performance. However, existing work primarily focuses on 2D visual tasks, and in the domain of 3D point clouds, the disorder and complexity of spatial information, along with the scale of the point clouds, present significant challenges. For point clouds, we introduce spiking discrepancy, measuring differences in spike features to highlight key information, and then construct the Spiking Discrepancy Attention Mechanism (SDAM). SDAM contains two variants: the Spiking Element Discrepancy Attention captures local geometric correlations between central points and neighboring points, while the Spiking Intensity Discrepancy Attention characterizes structural patterns of point clouds based on macroscopic spike statistics. Moreover, we propose a Spatially-Aware Spiking Neuron. Based on these, we construct a hierarchical Spiking Discrepancy Transformer. Experimental results demonstrate that our method achieves state-of-the-art performance within the Spiking Neural Networks and exhibits impressive performance compared to Artificial Neural Networks along with a few parameters and significantly lower theoretical energy consumption.

Spiking Neural Networks (SNNs) offer a promising, energy-efficient paradigm for computation, but their practical application is hindered by challenges in architecture design and training costs. For example, Spiking ResNet exhibits relatively low performance, whereas high-performance Spiking Transformers are not truly event driven and cannot be implemented on asynchronous chips. Moreover, the intrinsic time steps and neuron state dynamics result in a substantial computational overhead for training SNNs on GPUs. In response to these problems, we discuss rational architectural design for SNNs and argue that such designs should exhibit three key characteristics: operations fully supported by asynchronous scenarios, low training overhead and competitive performance. In light of this, we adopt the event-driven friendly Spiking Mixer (SMixer) as the foundational architecture and develop a spike feature Spatial-Temporal Pruning (STP) framework with a high pruning ratio and no trainable parameters to reduce the training overhead. Based on a statistical analysis of sparse spike features, STP eliminates redundant spike features across both spatial and temporal dimensions, thereby reducing the input features and computational load during training. It adaptively selects the most salient spike tokens spatially and dynamically constrains neuron firing rates temporally. By leveraging STP and architectural adaptation, SMixer accelerates training while ensuring a fully event-driven characteristics and maintaining competitive performance, offering valuable insights for the design of efficient, event-driven SNNs.