Organizations: Institute of Medical Technology, Peking University Health Science Center, Beijing, China · Beijing Key Laboratory of Intelligent Neuromodulation and Brain Disorder Treatment, Beijing, China · Department of Radiology, Peking University Third Hospital, Beijing, China · National Biomedical Imaging Center, College of Future Technology, Peking University, Beijing, China
Mechanistic discovery in neuronal microenvironments requires interventions and measurements that separate competing explanations of solute transport and neuronal response. Predictive accuracy cannot settle the question: a real mechanistic change and an error in the computational twin leave the same signature in sparse observations. We formalize this twin confounding and reason over a joint mechanism--discrepancy belief, designing experiments that separate the two. NeuronDiscover is an Agent-in-Twin framework whose shared, mechanism-grounded World Action Model (WAM) couples prediction, intervention proposals, and observation design; independently adjudicated outcomes revise a scoped Mechanism--Intervention--Observation--Outcome (MIOY) graph, whose supported relations compile into executable programs carrying discrepancy-adjusted acceptance bounds. We evaluate on simulated brain-fluid tracer-transport worlds adjudicated by an independently frozen finer-mesh reference solver, and on donor-disjoint public current-clamp recordings of cortical neurons. Counting only relations that reach a certified terminal status, and scoring abstentions as unresolved for every method, at a matched budget of 16 experiments over 32 source units NeuronDiscover resolves 4.0 relations per assigned world against 3.4 for the strongest baseline and 3.2 without graph revision, at 5% false support and 82% scope accuracy. Joint mechanism--discrepancy acquisition resolves 3.8 relations versus 2.9 for plug-in expected information gain; discrepancy-adjusted verification lowers accepted-program failure from 15% to 9% at 60% acceptance coverage; and transfer to the recordings yields 1.94 versus 1.53 relations per assigned world. Correctness is adjudicated within declared model worlds and archival recordings.
Prioritizing central nervous system (CNS) interventions requires predicting how a dose, route, and schedule act on a partially observed microenvironment, then choosing the measurement that would change the decision. Action-conditioned predictors reduce a regimen to an identity token or a scalar exposure, discarding where and when the target is engaged; handing a point estimate to a separate planner then discards the joint uncertainty that makes a measurement worth running. We therefore treat decision quality as a property of the intervention interface, not of controller placement. NeuronSifter compiles regimens into state-conditional target-occupancy fields with support masks, propagates them through microenvironment dynamics with an occupancy-conditioned diffusion operator, and selects measurements by their expected reduction in intervention loss, assimilating typed outcomes into the same posterior. In a declared synthetic Alzheimer's disease (AD) evaluation over 64 paired scenario blocks, occupancy conditioning lowers trajectory continuous ranked probability score from 0.165 to 0.110 and raises intervention ordering accuracy from 0.760 to 0.880, and every paired benchmark contrast remains separated after Holm correction. Decision-directed acquisition attains terminal risk 0.160 against 0.166 for a matched numerical Bayesian experimental design planner, and reaches the target risk at 0.796 [0.732,0.873] of an earlier design control's cost, while the corresponding ratio against the matched planner, 0.963 [0.907,1.025], is not separated from equality; point-state and dependence-ablated interfaces instead raise risk to 0.220 and 0.199, and a full-posterior external controller ties exactly. Published AD trials supply a separate retrospective endpoint bridge.
Understanding the brain increasingly depends on integrating evidence across scales, modalities, and disciplines. Addressing a single research question therefore requires a coordinated sequence of operations, from surveying prior work to executing analyses and interpreting results in light of domain knowledge. AI agents promise to accelerate this process, but current agents lack domain expertise in brain science, may fabricate claims, drift during multi-step reasoning, and offer few defined points for expert intervention. These failures are especially costly in brain science, where conclusions feed into downstream scientific claims and depend on laboratory-specific expertise and careful human judgment. We present \textbf{BrainPilot} a \textbf{fully open-source} multi-agent system that accelerates brain science research with traceable logs and agent-verified results. A principal investigator (PI) agent coordinates specialist agents grounded in curated domain knowledge: a unified brain science knowledge base containing 7{,}233 indexed items and a skill library of 72 reusable methodology units across seven research domains. Every major step is recorded in the Graph of Trace, an auditable record that links subgoals, tool use, evidence, and claims and allows researchers to follow and inspect the workflow. An Auditor agent further integrates fabrication checking into the workflow. For evaluation, we run three brain science tasks from Agents' Last Exam, introduce our own benchmark, \textbf{BrainPilotBench-v0}, and present additional end-to-end case studies. Across these evaluations, BrainPilot with an open-source backbone model attains performance comparable to state-of-the-art agent framework with less costs.
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.