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REVIEW 3 major objections 6 minor

Model Discovery Agent: LLM-assisted Bayesian experiment design for data-efficient discovery of mechanistic world models

T0 review · 3 major / 6 minor · reviewed 2026-08-11 · deepseek-v4-flash

Pith's one-line read A Bayesian evidence layer turns an LLM proposer into a data-efficient discoverer of mechanistic laws, beating pure LLM agents even when the true mechanism is absent from the initial pool.

desk verdict Serious, unusually honest integration of LLM proposers with SMC/VoI, but the FORCEBENCH SOTA claim is confounded by prompt and design-menu pre-specification; still deserves refereeing. read the letter →

arxiv 2608.09696 v2 pith:2S3DN5VR submitted 2026-08-10 cs.AI

classification cs.AI
keywords mechanisticmodeldiscoveryBayesianexperimentdesignvalueofinformationsequentialMonteCarlolargelanguagemodelsM-openselectionsimulation-basedinferenceinterventionalprediction
verification ladder T0 review T1 audit T2 compute T3 formal

The pith

A machine-rendered reading of the paper's core claim, the machinery that carries it, and where it could break.

The reading

Predicting the outcome of an intervention never performed requires a mechanistic causal model, and passive data cannot identify which mechanism generated what you saw — experiments are needed, and experiments are expensive. This paper claims that an LLM used only as a proposer of candidate mechanisms, paired with sequential Monte Carlo for posteriors and evidence, simulation-based inference for intractable likelihoods, and value-of-information maximization to choose the next intervention, identifies the true mechanism from only a handful of experiments, even in the M-open regime where the truth is not in the initial hypothesis pool. A residual-based predictive check detects when the current pool is inadequate and prompts the LLM to expand it, so discovery and experiment design reinforce each other. On physics, chemistry, and neuron-electrophysiology benchmarks, the resulting Model Discovery Agent beats pure LLM agents by a wide margin at matched budgets and matches the previous best agent's final accuracy with roughly a fifth of the experiments. If the claim holds, the bottleneck of automated scientific discovery shifts from proposing candidate forms to designing discriminative experiments and scoring evidence honestly.

What carries the argument

The load-bearing identity is the value-of-information reduction of Eq. (5): with Gaussian observation noise, the mutual information between the mechanism $M$ and the outcome of experiment $\xi$ is $\frac{1}{2}\ln(1 + \mathrm{Var}_{p(M|D)}[\mu(\xi)]/\sigma^2)$, a monotone function of the between-class variance of the posterior predictive mean, so optimal design reduces to choosing the intervention on which the candidate mechanisms disagree most. The paper makes this concrete with the Yukawa world, where only a probe launched past the screening length $\lambda$ splits the Bessel kernel from its power-law near-misses, and the Coulomb world, where only a charge intervention — a mechanism-level $do(a)$ — separates the true law from a curve fit that agrees with it on all unit-charge data. Around this identity sits the inference stack that feeds it: nested adaptive-tempered SMC computes each candidate's marginal likelihood (evidence) $Z_m = \int p(D|m,\theta)p(\theta|m)\,d\theta$, whose automatic Occam factor trades complexity against fit; a model-level SMC maintains the posterior over structures, with LLM proposals conditioned on the whole pool's residuals; a residual-based predictive check triggers the M-open expansion of the hypothesis space; and an ESS-adaptive rule prunes near-duplicate pools. For the stochastic neuron benchmark the likelihood is intractable, so a bootstrap particle filter inside the tempered SMC estimates it, with a learned 1-D CNN summary statistic and synthetic Gaussian likelihood as a roughly $10^4\times$ cheaper surrogate, guarded by a particle-filter spot-check that falls back to the exact filter when the cheap summary disagrees.

What would settle it

Run the Yukawa world with the design menu's longest launch kept inside the screening length ($r_0 \le \lambda$) and a proposer prompt that never mentions screened, Helmholtz, or Bessel kernels. The paper's own account predicts the true $K_1(r/\lambda)/\lambda$ law is never recovered — short-range probes leave the candidates indistinguishable and the residual check has no family to propose — so recovering the correct form under these restrictions would falsify the claimed necessity of discriminative design and supplied vocabulary.

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Extended reading notes

Core claim

Stated in the paper's own terms: discovery and experiment design reinforce each other. The value-of-information objective selects the intervention on which the candidate mechanisms' predictions disagree most; the outcome identifies the mechanism the LLM proposer introduced; and the identified mechanism improves interventional forecasts, shrinking residuals and exposing subtler predictive errors that trigger the next round of hypothesis expansion. The paper demonstrates this reinforcement on FORCEBENCH (force laws: MDA passes numerically in ~93% of 8-experiment runs versus ~31% for a budget-matched pure LLM agent, and reaches the previously reported state-of-the-art accuracy with ~5x fewer experiments), on CHEMBENCH (enzyme rate laws: ~56% symbolic accuracy within ~8 experiments versus ~42% for the previous state of the art at a budget of 60), and on NEURONBENCH (a new single-neuron electrophysiology benchmark with partial observability and, in its stochastic form, an intractable likelihood, where the model-based Bayes forecaster beats in-context LLM forecasting on every world). The recovered models are mechanistic — the screened Yukawa kernel $K_1(r/\lambda)/\lambda$, the enzyme-kinetic inhibition structure, the Hodgkin–Huxley channel composition — rather than numerically accurate but mechanistically meaningless expressions, and in the M-open miss cases (e.g., a neuron world whose novel current the LLM never proposed) the residual-triggered expansion still recovers the mechanism.

Load-bearing premise

MDA's gains rest on the pre-specified experiment menu and the proposer prompt containing, at least implicitly, the one intervention and the one mechanism family that can separate the true law from its near-misses — if no probe reaches past the screening length, or the prompt never names the screened-Bessel family, the value-of-information maximizer has no discriminating experiment to choose and the residual check has no vocabulary to invoke.

Editorial extensions

If this is right

  • On FORCEBENCH, MDA's ~93% numeric pass rate with 8 one-per-round experiments versus ~31% for a budget-matched LLM agent implies that the bottleneck for pure LLM discovery is inference and experiment design, not capability.
  • In the M-open setting (e.g., a neuron world whose true current the LLM never proposed), residual-triggered expansion lets the agent recover mechanisms absent from the initial pool — a route to genuinely new knowledge rather than recall.
  • For interventional forecasting, a model-based Bayes forecaster built on the SMC posterior dominates in-context LLM forecasting by roughly two orders of magnitude on the noisy stochastic neuron benchmark.
  • Intractable-likelihood discovery is workable when the likelihood is replaced by a learned summary statistic plus synthetic likelihood, with cost-aware auto-selection of the observation model and a particle-filter spot-check as the safety anchor.
  • The benchmark's LLM-judged explanation metric is unreliable — flat and non-monotonic in the number of experiments — so held-out interventional forecast error, justified by the theorem that robust interventional prediction requires a causally correct model, is the more trustworthy evaluation.

Reading between the lines

Editorial extensions of the paper, not claims the author makes directly.

  • Editorial inference: the same VoI-as-disagreement identity should transfer to any domain where an LLM can propose mechanistic simulators rather than symbolic laws — dose-response models, policy simulators, engineering control laws — because the identity only requires simulating each candidate's predicted outcome, not closed-form expressions.
  • Editorial inference: the paper's base-model sweep, in which a much stronger LLM closes most of the gap and even leads on exact-form naming while scoring only ~11% numeric on Coulomb, suggests MDA's durable value is honest model selection — evidence over naming — and that 'can name the law' versus 'can compute with the law' will become the defining benchmark distinction as proposers improve.
  • Editorial inference: the paper's observation that random design matches VoI on the noisy stochastic benchmark hints that the marginal value of optimal design shrinks as observation noise dominates; repeat-aware VoI — spending budget re-running the discriminating experiment — is demonstrated on neurons and should generalize to any noisy experimental domain.
  • Editorial inference: the least automatic input left in the loop is the human-written prompt vocabulary (screened/Helmholtz kernels, enzyme-kinetics grammar, channel archetypes); a testable next step is to have the residual check propose that vocabulary itself, removing the last hand-engineered element from the discovery pipeline.
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Editorial analysis

A structured set of objections, weighed in public.

Desk editor's note, referee report, and a circularity audit.

Referee Report

3 major / 6 minor

Summary. The paper introduces the Model Discovery Agent (MDA), which couples an LLM-based proposer of mechanistic structures with sequential Monte Carlo (SMC) for parameter and structure posteriors, simulation-based likelihoods for intractable cases, and value-of-information (VoI) experiment design. MDA is designed to operate in the M-open regime: when the current hypothesis pool fits poorly, a predictive-check residual triggers the LLM to propose new mechanisms. The authors evaluate MDA on three benchmarks (FORCEBENCH physics, CHEMBENCH chemistry, and a new NEURONBENCH electrophysiology benchmark plus a stochastic extension), reporting substantially improved data efficiency over LLM-only baselines. The central claim is that MDAs coupling of Bayesian inference with LLM proposal yields faster held-out interventional prediction and more reliable mechanistic recovery than pure LLM agents, including in the M-open setting.

Significance. If the results hold, MDA is a valuable architecture for interactive scientific discovery, and NEURONBENCH and NEURONBENCHSTOCH are useful new benchmarks that add partial observability and stochastic dynamics to the existing evaluation landscape. The paper has several notable strengths: the VoI derivation in Eq. (5) is a standard, clearly stated Bayesian objective; the algorithms are given in sufficient pseudocode to be reproduced; the ablation study in Section D.3 and the base-model robustness study in Section C.8 are honest and informative; and the authors ship interactive apps and code for their new benchmark. However, the strongest empirical claims are currently supported by comparisons that do not fully isolate the contribution of the Bayesian machinery from prompt pre-specification, and the biology benchmark does not compare against a full LLM agent. The core idea is credible and the weaknesses are addressable, but the paper as written overstates the breadth of its M-open and SOTA claims.

major comments (3)
  1. [Section G.1.1, Table 5, Section C.10] The FORCEBENCH demonstration does not support the M-open discovery claim as cleanly as stated. The proposer prompt in Section G.1.1 explicitly names the screened-Poisson/Helmholtz family, including `K1(r/lam)/lam`, which is exactly the true Yukawa form, and Table 5 includes the long-range launches (r0=5,6) that Section C.10 identifies as decisive for Yukawa. Thus the correct mechanism is inside the initial hypothesis class and the decisive probe is inside the fixed design menu. The control in Section C.5 gives the LLM baseline the same menu but not the same physical vocabulary, so it does not isolate whether the data-efficiency gain comes from SMC/VoI or from prompt content. A no-hint control, in which the proposer prompt omits the true family and the menu omits the decisive probes, is needed before the paper can claim open-ended M-open discovery on FORCEBENCH.
  2. [Section 4.3, Fig. 4, Section G.3.2] The NEURONBENCH evaluation does not compare MDA against a full LLM agent. Figure 4 compares the Bayes-forecaster with the in-context (ICL) forecaster; the LLM baselines in Section G.3.2 are acquisition and ICL-forecasting prompts, not an agent that proposes candidate mechanisms, simulates them, and forecasts from a fitted model. The paper's general claim that MDA is more data-efficient than pure LLM agents is therefore not established for the biology benchmark. In addition, Fig. 4 shows that within the Bayes-forecaster family, VoI and LLM acquisition perform similarly, and random acquisition is sometimes close; Section F.4 states that random designs are similar to, and arguably slightly better than, VoI designs in the stochastic setting. These results should be reported as a more nuanced boundary on the VoI contribution, and a full LLM-agent baseline should be added for NEURONBENCH.
  3. [Section D.2, Table 9, Table 2] The CHEMBENCH SOTA claim rests on thin evidence. The main comparison uses a 36-task subset with two seeds, and the 'reported' baseline row in Table 9 is based on a different, unreleased 36-task subset using gpt-4o-mini rather than the matched proposer model, so the headline comparison against the published number is not apples-to-apples. The head-to-head 'LLM-AUTOSCILAB(us)' row is fairer, but it is still only two seeds. Furthermore, key M-open and pool-size thresholds (tau_r=0.05, tau_p=0.9 in Table 2, and the Occam penalty lambda=2.5 in Section C.4) are set per benchmark with no sensitivity analysis, so it is unclear how robust the method is to these choices. Per-seed results, confidence intervals, and a sensitivity sweep over these thresholds are needed to support the data-efficiency and M-open claims.
minor comments (6)
  1. [Section 4] There is a typo in 'we summarize some our our experimental results' which should read 'some of our experimental results'.
  2. [Section E.4] The text contains a typo: 'The summary statsitic we use' should be 'The summary statistic we use'.
  3. [Section E.3] The phrase 'candidate mechansims' should be 'candidate mechanisms'.
  4. [Section G.3.2] The caption and text refer to the 'LLM baseline' in NEURONBENCH, but the implemented baseline is an in-context forecaster; please use consistent terminology to avoid overstating the comparison.
  5. [Section C.8] The base model 'Fable 5' is used without a version or citation; please provide a reference or model card so that the robustness sweep can be reproduced.
  6. [Section F.4] The sentence 'Note only do we see that MDA is more sample efficient' has inverted word order; consider rewriting as 'Note that not only is MDA more sample efficient...'.

Circularity Check

1 steps flagged · score 2.0 of 10

No circular derivation: SMC evidence and VoI design are standard and evaluated on held-out interventional targets, but the FORCEBENCH 'M-open' demonstration is partially pre-specified by the proposer prompt naming the true kernel family and by a design menu containing the decisive probes.

  1. self definitional [Section G.1.1 (MDA proposer prompt) vs. Section 4.1 'Example: Yukawa world' and Section C.2, Table 5]
    "Note that the language spec names screened/power-law/oscillatory families (including the K1 Yukawa form) as examples, so the proposer is given the physical vocabulary — MDA's contribution is the inference and V oI design that identify which form the data support (see App. C, Fig. 14), not blind form-discovery."

    The paper defines the M-open setting as 'when the truth lies outside the current hypothesis class' and presents the Yukawa world as a discovery example, but the proposer prompt explicitly includes the true Yukawa kernel K1(r/lam)/lam among the allowed physical vocabulary. Thus the truth is inside the initial hypothesis class by construction, and the 'discovered' law is a selection from the provided vocabulary, not an M-open expansion. The design menu in Table 5 likewise pre-contains the long-range probes (r0=5,6) that Section C.10 identifies as decisive for Yukawa, so the VoI choice is a choice among pre-supplied informative options.

full rationale

The core Bayesian machinery is not circular: the SMC evidence computation (Algorithm 3) and the VoI objective (Eq. 5) are derived from standard Bayesian principles, parameter priors are stated, and held-out interventional predictive error is scored against ground-truth simulations rather than fit targets. The identified circularity-adjacent issue is confined to benchmark pre-specification: for FORCEBENCH the proposer prompt names the true family (including K1(r/lam)/lam) and the fixed 13-launch menu contains the probes that split Yukawa from its near-misses, so the headline physics demonstration reduces partly to selection from supplied vocabulary. The paper candidly admits this in G.1.1, and its menu-control (C.5) only shows the menu alone is insufficient; it does not remove the prompt-vocabulary confound. The M-open claim is nevertheless genuinely instantiated elsewhere, e.g., CHEMBENCH compound recovery and the NEURONBENCH Z-REBOUND miss where the truth is not proposed. Since no derivation step is equivalent to its own inputs and the benchmark confound is acknowledged and partially controlled, the circularity score is low.

Assumptions & free parameters 5 free parameters · 5 assumptions · 1 invented entities

The central method rests on standard Bayesian machinery plus a few hand-set thresholds and benchmark-specific design menus. It does not introduce new physical entities, but it does introduce synthetic benchmark mechanisms whose discovery may be easier than in real laboratories.

free parameters (5)
  • Occam penalty lambda = 2.5
    Structure prior p(m) proportional to exp(-lambda*C_m) in Eq. 17; chosen by hand to penalize model complexity.
  • Fixed observation noise sigma = 0.03
    Fixes the Gaussian likelihood in FORCEBENCH (Table 7); the paper discusses marginalizing sigma but uses this fixed value.
  • M-open residual threshold tau_r = 0.18 (NEURONBENCH), 0.05 (CHEMBENCH)
    Triggers LLM proposal of new structures when the MAP model's residual is too high (Table 2).
  • Concentration threshold tau_p = 0.9
    Controls shrinking the hypothesis pool when the posterior is concentrated and the fit is good (Table 2).
  • Feature-kernel tolerances sigma_j = 0.3, 1.2, 0.06
    Fixed observation-model tolerances for spike counts and input resistance in NEURONBENCH (Table 14).
assumptions (5)
  • domain assumption The true data-generating process is a state-space model; any non-Markovian model can be converted to Markov form by enlarging the latent state (Eq. 1, Section A.1).
    Underlies the likelihood and particle filter; if the latent state cannot be enlarged tractably, the inference breaks.
  • domain assumption LLM proposals are drawn from a family that contains mechanisms close enough to the truth, and the prompts enumerate the relevant mechanism families (e.g., Green's function kernels in FORCEBENCH).
    The method cannot discover mechanisms not representable in the proposer's vocabulary; the paper states the language spec names the families.
  • ad hoc to paper The fixed design menus contain an experiment capable of discriminating the true mechanism from near-misses (e.g., long-range probes for Yukawa, hyperpolarizing pre-pulse for NEURONBENCH).
    VoI is maximized over a pre-specified menu; if the discriminating probe is absent, discovery fails.
  • standard math Richens and Everitt theorem: robust interventional prediction implies causal model learning.
    Used to justify evaluating interventional forecast accuracy instead of model identity; cited in Section C.7 and Section 5.
  • standard math SMC marginal likelihood provides an automatic Occam penalty; the explicit exp(-lambda*C_m) prior is added because marginal likelihood alone overfits on near-deterministic data.
    The paper explains in Section C.4 that marginal likelihood alone rewards fitting observation noise, so a hand-set Occam prior is needed.
invented entities (1)
  • NEURONBENCH mystery mechanisms (Z-REBOUND, H-SAG, CA-REBOUND, D-TYPE, NA-FATIGUE, TEXTBOOK-M)
    purpose: Synthetic benchmark tasks to test MDA's ability to discover hidden ion-channel mechanisms.
    These are simulated constructs designed for the benchmark; the paper does not claim they exist in real neurons.

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Cite this review

Pith. "Pith review of Model Discovery Agent: LLM-assisted Bayesian experiment design for data-efficient discovery of mechanistic world models." pith.science (2026). https://pith.science/paper/2S3DN5VR

@misc{pith2026260809696,
  author       = {Pith},
  title        = {Pith review of: Model Discovery Agent: LLM-assisted Bayesian experiment design for data-efficient discovery of mechanistic world models},
  year         = {2026},
  howpublished = {\url{https://pith.science/paper/2S3DN5VR}},
  note         = {Machine review of arXiv:2608.09696}
}
read the original abstract

Predicting the answer to interventional ``what if'' questions --- the outcome of an action never taken --- requires a \emph{mechanistic}, causal model, not a curve fit; and learning such a model requires \emph{experiments}, because passive data leaves its mechanisms unidentified. Experiments are expensive, so the central problem is \emph{data efficiency}. We present the Model Discovery Agent (MDA), which couples a large language model (LLM), used as a \emph{proposer} of candidate structures, with standard Bayesian machinery --- sequential Monte Carlo (SMC) for parameter and structure posteriors, simulation-based inference (SBI) for intractable likelihoods, and value-of-information (VoI) for experiment design --- to discover latent mechanistic world models from few interventions. MDA operates in the M-open setting: when the truth lies outside the current hypothesis class, a predictive check flags the inadequacy and the proposer expands the hypothesis space with a new model whose parameters are then identified by designed experiments. We show that \emph{discovery and design reinforce}: the design step identifies the mechanism the discovery step proposes, and the identified mechanism improves predictions, enabling further discoveries from the remaining unexplained residuals. On three different benchmarks --- covering physics (\DPbench, \citep{wiemann2026discoverphysics}), chemistry (\CHEMbench, \citep{kabra2026autoscilab}) and biology (\HHbench, a new partially observed single-neuron electrophysiology benchmark we create) --- we show that MDA sets a new SOTA in terms of data-efficient model learning and reliable interventional prediction ability.

Figures

Figures reproduced from arXiv: 2608.09696 by the authors.

Figure 1
Figure 1. (a) The MDA discovery loop. See Algorithm [PITH_FULL_IMAGE:figures/full_fig_p003_1.png] view at source ↗
Figure 2
Figure 2. Data efficiency on FORCEBENCH, aggregated over all six two-particle worlds. Left: we plot nMSE (geometric mean over the 6 × 9 runs) vs number of experiments. Error bars are ±1 standard error. The red square is the result of the “unthrottled” baseline agent, and matches the paper. Right: we plot fraction of runs where nMSE drops below the 0.1 threshold. See text for details. runs where the prediction “passes”, follow… view at source ↗
Figure 3
Figure 3. Data efficiency curves for CHEMBENCH. We plot mean performance ±1 SE over the 36 tasks, two seeds. Left: symbolic accuracy. Right: numerical equivalence (EXACC, RMSLE < 0.01; the head-to-head [PITH_FULL_IMAGE:figures/full_fig_p007_3.png] view at source ↗
Figures from the paper (29 more)
Figure 4
Figure 4. Figure 4: Data efficiency on all six NEURONBENCH worlds (Opus 4.7). For each world the LLM proposes the candidate channels from the phenotype (2–5 hypotheses, shown in the panel title), and then MDA designs experiments to confirm or refute these hypotheses. After each experiment…
Figure 5
Figure 5. Figure 5: The world as a controlled, intervenable state-space model (Eq. (1)). A latent state zt (white) evolves under the mechanism θ (orange; it parameterizes every transition) and emits a lossy, noisy observation yt (grey) — in general only y1:T is seen. Optional exogenous in…
Figure 6
Figure 6. Figure 6: App for FORCEBENCH. The goal is to identify a hidden central-force law from a few probe orbits, then predict held-out launches — including one under a perturbed source. Training orbits (top left), held-out interventional test forecasts (top right), and the reader’s own…
Figure 7
Figure 7. Figure 7: Per-world data efficiency on TWOPARTICLEWORLDS (Opus 4.7; the compact aggregate is [PITH_FULL_IMAGE:figures/full_fig_p023_7.png]
Figure 8
Figure 8. Figure 8: Data efficiency on MULTIPARTICLEWORLDS using Opus 4.7. We plot held-out forecast MSE vs. experiments for MDA (solid, mean±SE over seeds) against the pure agent (dashed). MDA is orders of magnitude better at every budget. Several worlds clear the pass line (error of 0.0…
Figure 9
Figure 9. Figure 9: Numeric and symbolic data efficiency on FORCEBENCH (Opus 4.7; the numeric-only, multi-base￾model version is [PITH_FULL_IMAGE:figures/full_fig_p024_9.png]
Figure 10
Figure 10. Figure 10: The LLM explanation score vs. number of experiments (six worlds, Opus 4.7). Flat and un￾reliable: sometimes monotonically decreasing with more data (Coulomb 0.83→0.77→0.73), sometimes non￾monotonic (Yukawa 0.37→0.70→0.60) — either way more data can lower the score, a …
Figure 11
Figure 11. Figure 11: Effect of changing the proposer LLM on data efficiency: held-out test MSE vs. experiment budget B, per world, for three proposer LLMs (Opus 4.7, Fable 5, DeepSeek v4 Pro; colour). Solid: MDA (Bayes￾forecast + VoI acquisition), the best-so-far MSE(B) trajectory with a …
Figure 12
Figure 12. Figure 12: Data-efficiency curves with the strongest base model (Fable 5) on both arms, aggregated over all six FORCEBENCH worlds. (left) Exact-form accuracy vs. budget: the parsimony submission (green) lifts MDA (blue) toward the strong unaided agent (purple), which leads on pu…
Figure 13
Figure 13. Figure 13: Visualising COULOMB world and its design space. On the right, we plot the VoI over a 2d slice of the design space, namely the release radius r0 (an initial condition) × source charge p1 (an intervention knob). The red × are the seed drops: the unit￾charge probes the a…
Figure 14
Figure 14. Figure 14: Probe orbits under the candidate force laws for YUKAWA world: a short-range vs. a long￾range design. The screened Yukawa kernel K1(r/λ)/λ and the power laws fit to the short-range seed data nearly coincide for r ≤ λ and diverge only beyond it. (left) Launched within t…
Figure 15
Figure 15. Figure 15: The hidden-mass rung. Left: trans-dimensional model selection p(K | D) from the seed probes — the deflections demand a hidden mass (K=0 excluded), and Bayesian Occam rejects the surplus second mass (K=2). Middle: the scene. The visible source (star) sits at the origin…
Figure 16
Figure 16. Figure 16: Ablation of MDA’s extensions beyond ModelSMC: symbolic accuracy per tier and overall, added incrementally on the 36-task subset at B=60. Each extension helps a distinct tier. M-open exploration lifts the easy tier (42→75%, single-mechanism correction; also the only ro…
Figure 17
Figure 17. Figure 17: The f–I curve, and why we count spikes. (a) A constant supra-threshold current makes the model fire a periodic spike train; the readout is simply the spike count (red markers) — or, per unit time, the firing rate 1/T. (b) Sweeping the injected current traces the f–I c…
Figure 18
Figure 18. Figure 18: Example spike traces from a single neuron under different conditions. Membrane voltage under current injection: a supra-threshold step (10 µA) elicits overshooting action potentials (blue); the sodium blocker TTX (gNa=0, a do on the mechanism) abolishes them (red); a …
Figure 19
Figure 19. Figure 19: The Hodgkin–Huxley equivalent circuit (Eq. (21)). The membrane is a capacitor C; each ion channel is a branch with a variable conductance gcϕc (opening/closing gates ϕc) in series with a battery Ec (the reversal potential). The injected current Iext charges the capaci…
Figure 20
Figure 20. Figure 20: NEURONBENCH. Screenshot of our app, which lets users interact with the same environment we give our agents (except the agents see numerical data, not images.) The top left is the training set, Dtr, the top right is the test set, Dte, and the bottom row is the interact…
Figure 21
Figure 21. Figure 21: From a raw voltage trace to the per-trace feature vector s(y) of Eq. (30), computed on real NEURONBENCH traces. (a) On a paired-pulse protocol the spike-count features are the test- and pre-pulse counts (ntest, npre; upward 0 mV crossings, triangles), their use-depend…
Figure 22
Figure 22. Figure 22: Visualizing the predictions of two different models on CA-REBOUND. We show the observed recording (left) and the spike response predicted by each candidate structure (plain Na+K neuron in middle, augmented model with novel channel on right) under the VoI-designed expe…
Figure 23
Figure 23. Figure 23: M-open structure discovery on NEURONBENCH (H-SAG world). The LLM is given only the phenotype and proposes the candidate channel mechanisms; they are mapped onto four dynamical hypotheses (the truth Ih is not revealed). (a) Under the VoI-designed experiment — a hyperpo…
Figure 24
Figure 24. Figure 24: Parameter refinement on NEURONBENCH (H-SAG world: a hidden hyperpolarisation-activated Ih current, the second half of the discover-then-refine loop begun in [PITH_FULL_IMAGE:figures/full_fig_p041_24.png]
Figure 25
Figure 25. Figure 25: Learning the NEURONBENCH synthetic-likelihood summary from raw traces (proof-of￾concept; runs on a laptop). A 1-D CNN encoder sϕ(V1:T ) is trained on simulated (m, g) → V traces to classify the channel structure and regress its conductance. (a) On held-out traces the …
Figure 26
Figure 26. Figure 26: Stochastic-latent NEURONBENCH: the raw data. Noisy voltage traces from the two competing hypotheses under a moderate hyperpolarising-step protocol, at N=100 channels (thin: independent draws; bold: the noise-free mean). (a) A plain Na/K cell. (b) The same cell plus a …
Figure 27
Figure 27. Figure 27: Stochastic-latent NEURONBENCH: estimating the intractable likelihood by simulation. Both panels score the Ih-vs-plain decision on the data of [PITH_FULL_IMAGE:figures/full_fig_p044_27.png]
Figure 28
Figure 28. Figure 28: Three observation models on the stochastic six-world battery (fixed hypothesis space) (N=100 channels; correct-selection rate ±1 SE over 24 seeds; a dot marks an exact zero). The voltage particle filter (blue) is the robust generalist — correct on five of six worlds a…
Figure 29
Figure 29. Figure 29: An auto-selected observation model (N=100, six worlds, fixed hypothesis space; final posterior of the true mechanism under repeat-aware VoI). The feature synthetic likelihood (green) and voltage particle filter (blue) are complementary — the PF rescues CA-REBOUND’s bu…
Figure 30
Figure 30. Figure 30: The particle-filter spot-check (D-TYPE, fixed archetype pool, N=100). The two cheap observation models disagree with each other and with the particle filter: the fixed-feature synthetic likelihood picks T-type Ca and the learned sϕ picks slow-Na+, while only the assum…
Figure 31
Figure 31. Figure 31: Stochastic-NEURONBENCH forecaster grid (N=100, six worlds, fixed hypothesis space, held-out interventional-forecast MSE vs. the experiment budget Na; log scale). The model-based Bayes-forecast (blue; VoI-repeat solid, random design dashed) built on the design-loop pos…
Figure 32
Figure 32. Figure 32: Full six-world × noise-ladder stochastic NEURONBENCH. Mean posterior probability of the true mechanism over the six worlds vs. the channel count N (log axis; near-deterministic at left, noisiest at right), for the three acquisition policies (budget 8, 12 seeds). All d…

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Reviewed August 11, 2026 · model on record in the stance chip above.