NS-Copilot: An LLM-Driven Agent System for Autonomous Neuroscience Analysis

AI is rapidly advancing neuroscience, yet many laboratories fail to fully unleash its potential due to significant interdisciplinary barriers. While pre-trained neural models for physiological data are progressing quickly, their heterogeneous architectures and modality-specific constraints hinder systematic integration, selection, and evaluation. Despite recent advances in large language model (LLM)-based agent systems for intelligent scientific applications, existing approaches often still lack the domain expertise required to effectively select and coordinate diverse neuroscience pre-trained models and handle unique data types in this domain. We present NS-Copilot, an LLM-driven multi-agent system for neuroscience analysis that autonomously supports end-to-end workflows for diverse professional tasks. It unifies domain-specific pre-trained models and supports key neuroscience modalities, including EEG and extracellular spike data, through a natural-language interface. Given raw data and a task description, NS-Copilot orchestrates agents with specialized roles for planning, adaptive control, code generation, and result synthesis, enabling analysis without dataset-specific heuristics. We evaluate NS-Copilot on neuroscience benchmarks spanning Alzheimer's disease, Parkinson's disease, and working memory spike decoding. Across 8 trials per task, the system consistently outperforms strong baselines on the primary metric, demonstrating the ability of NS-Copilot for effective and scalable neuroscience analysis.

IRIS: A Visual Cortex-Inspired Framework for Analyzing Orientation Selectivity in Vision Transformers

Vision transformers (ViTs) have become the de facto standard for image encoding across many perception tasks. Despite their empirical success, it remains mechanistically unclear how they encode low-level features, given their lack of inductive biases: ViTs process information globally rather than relying on local structure. Biological visual systems, in contrast, build low-level features, such as orientation selectivity in the primary visual cortex, by combining information from small, localized regions of the visual field. These features are general-purpose representations, shared and required across multiple specialized neural pathways, unlike higher-level, task-specific semantic features. This raises the question if such biologically-grounded features arise in ViTs. In this work, we systematically study how orientation selectivity emerges in ViTs by introducing a suite of neuroscience-inspired metrics: representational similarity score (RSS), orientation recruitment score (ORS), and orientation tuning bandwidth to quantify how orientation is encoded in representational geometry and as a function of model depth. Through extensive analysis, we find that: (1) the training paradigm is the strongest determinant of orientation selectivity, with models sharing an objective, peaking at comparable relative depths regardless of scale (2) many units are orientation-selective early in training, with early-to-middle layers recruiting more such units over time, while deeper layers lose selectivity and broaden their tuning toward semantic encoding and (3) our metrics offer a mechanistic heuristic for how many layers to unfreeze for best downstream generalization. Our framework presents a way to track biologically-grounded features during ViT training, probes how desired properties are encoded in transformer representations, and builds a systematic understanding of how ViTs generalize across tasks.

Recursive Gaussian Processes and the Bayesian Brain

Predictive coding offers a powerful framework for cortical computation, yet scalable implementations that respect both Bayesian exactness and neurobiological constraints remain scarce. We bridge this gap by formally connecting predictive coding to Recursive Gaussian Processes (RGPs). RGPs employ a single Gaussian process \( g(t, \cdot) \) indexed by layer index and input value, preventing the representational collapse of standard deep Gaussian processes while allowing learnable cross-layer dependence via \( r_{1g} \). We demonstrate that RGPs intrinsically implement hierarchical Bayesian inference, uncertainty propagation, and precision-weighted prediction error. Critically, we map RGP components---the shared GP, spike-and-slab variable selection, and MCMC dynamics---onto the canonical cortical microcircuit, providing a neurobiological substrate for these computations. Drawing on the free energy principle, we show that RGP inference minimizes variational free energy, formally linking Bayesian mechanics to neuronal dynamics. Our synthesis positions RGPs as both a principled computational tool and a candidate model for the brain's predictive machinery, generating testable predictions for laminar-specific dynamics and spectral asymmetries between feedforward and feedback processing.

SeekBrain: An Autonomous Multi-Agent System for Accelerating Neuroscience Discovery

Modern neuroscience relies on integrating multi-scale, multimodal datasets to uncover the neural principles underlying intelligence. However, analytical challenges posed by highly heterogeneous data and fragmented workflows increasingly constrain discoveries. Here we introduce SeekBrain, an autonomous multi-agent framework designed to accelerate neuroscience discovery through domain-grounded hierarchical planning and cross-modal data analysis. SeekBrain dynamically constructs a repertoire of analysis recipes extracted from code-paper pairs. By coupling this codified expertise with agentic planning and execution engines, the framework scalably generates hypotheses and analytical pipelines on demand. Systematic evaluation on the expert-annotated BrainArena benchmark demonstrates that SeekBrain substantially outperforms state-of-the-art agent baselines across various analysis tasks. Crucially, when deployed in real-world research, SeekBrain integrated behavioral, neural, and anatomical data to reveal structured, distributed neural representations of larval zebrafish behavior and a shared axis of regional decoding strength across the brain in a mouse decision-making task. These results establish SeekBrain as a scalable and practical tool for accelerating data-driven discoveries in neuroscience.

From Observation to Intervention: Memory in Brains and Large Language Models

Brains and large language models (LLMs) are fundamentally different memory systems, but they can be compared through shared functional questions: where memory-related information is represented, how partial cues recover broader associations, how new information is written or updated, and how memory-related states can be perturbed. In biological systems, these questions span synapses, neuronal ensembles, hippocampal-cortical interactions, and plasticity; in LLMs, they span weights, activations, context windows, retrieval systems, and external stores. The comparison is therefore functional and experimental rather than anatomical. Human studies reveal sparse concept responses, temporal binding, rapid association formation, episode-specific coding, and recall-related reactivation, but selective intervention remains limited. Rodent studies provide more selective causal access to learning-related ensembles, whereas human and macaque interventions usually affect broader circuits. LLMs lack lived episodic memory, yet they permit unusually direct and repeatable manipulation of internal states and stored information. We argue that this asymmetry creates a new opportunity. LLMs are not ahead in memory itself, but in experimental access. Their tools may help turn broad questions about retrieval, updating, persistence, reversibility, and unintended effects into sharper biological hypotheses. The productive bridge is to transfer experimental logic, not anatomical parts.

Toward a mechanistic understanding of inference in visual cortex and diffusion models

We describe a model of perceptual inference in primary visual cortex (V1) equivalent to a minimal diffusion model whose function can be readily understood from its parameters. The model is based on sparse coding with a non-factorial prior over latent variables in the form of an unconstrained, pairwise interaction matrix, extending standard sparse coding inference to a general recurrent dynamical system. We efficiently train these recurrent dynamics using a denoising score-matching objective and implicit differentiation. After training on natural images, the learned interaction matrix mirrors the structure of horizontal connections in superficial layers of V1 that link neurons of similar orientation tuning. This model exhibits exceptionally good denoising performance, restoring image features such as extended contours amid extreme visual ambiguity, nearly matching the behavior of standard, black-box diffusion architectures in generalization regime. Owing to the model's simplicity, the network's Jacobian can be decomposed directly in terms of the interaction matrix between latent variables, revealing mechanistically how the recurrent dynamics assign high probability over a continuous family of natural structural deformations. Intriguingly, within this circuit, a large fraction of latent variables learn to disconnect from visual input altogether, essentially forming a hierarchical representation that appears to enforce global consistency among image features. Together, the model and results bridge two distinct domains: for neuroscience, it generates concrete, testable hypotheses regarding functional connectivity in recurrent neural circuits during perceptual inference tasks; for machine learning, it elucidates the internal mechanisms learned by diffusion models that allow them to generate infinitely many novel images from a finite training set.

STSBench: A Large-Scale Dataset for Modeling Neuronal Activity in the Dorsal Stream of Primate Visual Cortex

The primate visual system is typically divided into two streams - the ventral stream, responsible for object recognition, and the dorsal stream, responsible for encoding spatial relations and motion. Recent studies have shown that convolutional neural networks (CNNs) pretrained on object recognition tasks are remarkably effective at predicting neuronal responses in the ventral stream, shedding light on the neural mechanisms underlying object recognition. However, similar models of the dorsal stream remain underdeveloped due to the lack of large scale datasets encompassing dorsal stream areas. To address this gap, we present STSBench, a dataset of large-scale, single neuron recordings from over 2,000 neurons in the superior temporal sulcus (STS), a nearly 50-fold increase over existing dorsal stream datasets, collected while Rhesus macaques viewed thousands of unique, natural videos. We show that our dataset can be used for benchmarking encoding models of dorsal stream neuronal responses and reconstructing visual input from neural activity.

Grounded world models in biological organisms and future embodied AI

Recent advances in generative and embodied AI have been driven by large-scale predictive learning over multimodal data. However, the resulting systems remain largely based on passive training regimes where linguistic regularities create the scaffold onto which information from other modalities is attached. Conversely, neuroscience and cognitive science suggest that biological intelligence is organized in the opposite way, where grounded world models acquired through interaction with the environment provide the semantic scaffold to which language is attached. Here, we illustrate five examples of neural circuits supporting grounded world modelling, which underlie navigation in physical and conceptual spaces, affordance-based perception and interaction with objects, active perception and exploratory learning, allostatic control and emotion, and the distinction between self- and world-generated outcomes. These examples highlight several features largely missing from current embodied AI, including the role of intrinsic dynamics as a foundation for learning, the centrality of action in aligning these dynamics with the external world, the prominence of autonomous experience and open-ended learning over passive assimilation of externally provided data, and the fact that early predictive and control mechanisms scaffold higher cognitive abilities such as reasoning, conceptual navigation, planning, imagination, understanding others' minds, and communication. Finally, we discuss whether and how principles derived from biological systems may inform future embodied AI, including training regimes based on social interaction to construct world models that are not only grounded but also socially shared and aligned with human norms and values.

Diffusion learning reveals viable parameter manifolds and compensation geometry in biological dynamical systems

Models of complex systems often have many parameters, yet are constrained by far fewer experimentally accessible observables: similar activity can emerge from coordinated parameter changes. We formalize these compatible parameter sets as \emph{viable parameter manifolds}: the inverse images of a system's target dynamical behaviors under a parameter-to-feature map. The relevant codimension is not the number of reported features, but the effective rank of that map at the target scale. Co-varying features lower the codimension, while poor conditioning, high curvature, or regime mixing degrade learnability. We train conditional score-based diffusion models on simulated parameter--feature pairs and use them as amortized samplers of prior-weighted viable sets. In the Lorenz system, scalar trajectory statistics generate thin viable sheets, and two-feature conditioning localizes a transition-adjacent corridor. In the Izhikevich neuron model, four firing descriptors lie close to a nearly two-dimensional family of features, and the learned inverse images reveal distinct regular and irregular compensation geometries. In a recent ODE reduction of finite spiking networks, the same framework reveals excitatory--inhibitory compensation, timescale--coupling tradeoffs, and input-dependent viable manifolds across 4--12 parameter dimensions. In this view, robustness, compensation, and hidden parameter dependencies are organized as inverse geometry, with diffusion models providing practical tools for sampling, visualizing, and interrogating that geometry.

Learning Hybrid Biophysical Neuron Models with Neural ODEs

Biophysical neuron models link measurements of neural activity to underlying cellular mechanisms. Yet, a central challenge is that the kinetics of many ion channels are poorly characterized, and practical simplifications -- omitting channels or reducing morphological detail -- introduce systematic gaps between model and biology. Bridging these gaps requires approaches that can flexibly discover unmodeled dynamics while preserving mechanistic interpretability. Here, we introduce a hybrid modeling framework that embeds neural ordinary differential equations into conductance-based biophysical models to capture unknown currents or mis-specified channel kinetics. By parameterizing the neural ODE in terms of voltage-dependent steady-state and time-constant functions, we recover interpretable gating dynamics directly from voltage recordings without assuming a functional form. We show that the hybrid model fits the gating kinetics of 2400 ion channel models and recovers unknown gating dynamics from single current-clamp recordings, generalizing to out-of-distribution stimulus regimes under realistic inputs and parameter misspecification. We also use our method to reduce a multicompartment model of a cortical neuron into a single-compartment hybrid model with a learned axial current, yielding up to an order of magnitude lower computational cost. Together, our results establish a plug-and-play framework for selectively replacing unknown components of conductance-based models with neural ODEs while preserving their mechanistic structure.

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.

FlexiBrain: Resolution-Agnostic Voxel-Level Encoding for Native fMRI

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

Position: Hippocampal Explicit Memory Is the Cornerstone for AGI

Large Language Models (LLMs) have demonstrated remarkable capabilities across various tasks, raising expectations for Artificial General Intelligence (AGI). This position paper argues that integrating explicit memory is the cornerstone for advancing LLMs toward AGI. The key reason is that the underlying learning mechanism of LLMs is highly analogous to human implicit memory. However, higher-order cognitive functions necessary for AGI, such as long-term strategic planning, metacognition, and symbolic reasoning, heavily rely on hippocampal explicit memory and cannot arise solely from implicit statistical learning. Drawing on findings from neuroscience, I advance this perspective and complement it with computational requirements for artificial explicit memory systems, hoping to foster further research and lay the groundwork for explicit memory integration.

Cross-Species RSA Reveals Conserved Early Visual Alignment but Divergent Higher-Area Rankings Across Human fMRI and Macaque Electrophysiology

Does the relationship between learning rules and brain alignment generalize across species? We extend our prior finding that untrained CNNs match backpropagation at human V1 by testing the same five learning rules against macaque electrophysiology. The rules are backpropagation (BP), feedback alignment (FA), predictive coding (PC), spike-timing-dependent plasticity (STDP), and an untrained random-weights baseline. The macaque data come from two datasets: MajajHong2015 (V4/IT, 3,200 stimulus presentations, 88/168 neurons) and FreemanZiemba2013 (V1/V2, 135 stimuli, 102/103 neurons). Using RSA with identical model weights from our human study, we find: (1) all models achieve higher alignment with macaque early visual cortex (rho = 0.15-0.30 at V1/V2) than with human fMRI (rho = 0.01-0.08), consistent with the higher signal-to-noise ratio of electrophysiology; (2) STDP and PC produce the highest macaque V1/V2 alignment (rho ~ 0.30 and 0.28), consistent with their leading position among trained rules in human V1; (3) at IT, learning rule rankings show no detectable correlation across species (Kendall's tau = 0.00, p = 1.00), though this null result is expected given that n = 5 provides power only at tau = +/-1.0, and is further confounded by stimulus set differences; (4) a pretrained ResNet-50 (ImageNet) achieves rho = 0.25 at macaque IT, substantially above all custom CNN conditions (rho = 0.07-0.14), suggesting IT alignment is limited by model capacity and training data rather than by the learning rule. Noise ceilings, multi-seed variability (5 seeds), and a stimulus-control analysis are reported. These results demonstrate that early visual alignment is robust across species, while higher-area alignment is modulated by model capacity and stimulus domain.