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arXiv2026

What Does a System Modify When It Modifies Itself?

When a cognitive system modifies its own functioning, what exactly does it modify: a low-level rule, a control rule, or the criterion that evaluates its revisions? Cognitive science describes executive control, metacognition, and hierarchical learning, while artificial intelligence modifies policies, parameters, and learning mechanisms, but the two fields lack common criteria for comparing these transformations. We propose a minimal analytical model distinguishing functional rules Phi_t = {R0, ..., Rk}, modification mechanisms Mt, and evaluation criteria Nt. It separates two independent dimensions: the depth of the modified target and whether the modification is blind or reflexive. Internal representational access AtR and endogenous causal control AtC are further distinguished from external inspectability and modifiability by a designer. Four regimes are defined by the target of modification: action without organizational modification, modification of low-level rules, modification of control rules or mechanisms, and revision of the evaluation criterion. Each is related to cognitive phenomena and artificial systems while making explicit the system boundary on which attribution of endogenous self-modification depends. The comparison yields a conditional crossed-opacities hypothesis: humans often have richer endogenous self-description at abstract and strategic levels than at implementation levels, whereas current artificial systems may be externally inspectable and modifiable at operational levels without corresponding self-representation or endogenous control. The framework also identifies three difficulties - viability, evaluation of revisions to evaluation criteria, and continuity of identity - and proposes two empirical discriminants for identifying the target of a modification and the causal role of self-representation.

cs.AI↗
arXiv2026

Backspace as a Natural Experiment: An Accelerated Failure Time Model of Selective Post-Error Motor Impairment in Parkinsons Disease

Parkinson's disease (PD) selectively impairs distinct stages of motor control. Using backspace events as natural error-correction episodes in the public neuroQWERTY MIT-CSXPD dataset (n=57 subjects, 27 PD with UPDRS-III scores), we test whether passively-collected keystroke timing dissociates a variability-based pre-error monitoring signal from a speed-based post-error recovery signal. Pre-error typing instability does not track PD severity (r=-0.072, p=0.721), while post-error pause duration does (r=+0.656, p=0.0002; subject-level OLS p=1.2x10^-4, n=27, primary analysis given within-subject event clustering). A mixed-effects log-normal model with a random subject intercept confirms this while retaining full event-level power (coef=0.0250, p=1.2x10^-4, n=1,563 events), closely matching the subject-level OLS despite an unrelated estimation strategy. Error-detection latency also correlates with UPDRS-III (r=+0.660), confirming the dissociation is between variability and speed, not detection and correction per se. A log-normal accelerated failure time model yields a coefficient of 0.0255 (bootstrap 95% CI [0.0146, 0.0357]), a 2.6% increase per UPDRS-III point. After controlling the immediately thecoefficient attenuates to 0.0133 (p=3.1x10^-21),consistent w timingincrement above general bradykinesia. Results reacross both S2:r=+0.645), survive jackknife exclusion of every subject, andnatingfinger-tapping and mPower smartphone tapping (group AUC=0.836). cellent(ICC(2,1)=0.945, n=20).

q-bio.NC↗
arXiv2026

Prospective Coding Improves Learning in Deep Continuous-Time Recurrent Networks

Temporal integration gives continuous-time recurrent networks memory, but in deep stacks it also delays bottom-up signals and attenuates top-down errors. We develop Recursive Quadrature Filters (RQFs), biologically motivated complex-valued temporal filters that are a special case of diagonal state-space models (SSMs), and ask whether this failure mode can be addressed by making each layer's bottom-up input prospective. Starting from an energy model, we derive the RQF dynamics and show that each RQF is a band-pass filter whose learnable parameters control its tuning frequency and bandwidth. We then make each layer's bottom-up input prospective using a parameter-free two-tap update that leaves the recurrent transition and parallel scan unchanged. We extend this correction to general diagonal SSMs and show that it mitigates depth-dependent gradient attenuation when temporal gradients are truncated, i.e., spatial-only backpropagation. We evaluate the intervention in RQFs, S5, and ORGaNICs (a nonlinear gated RNN) trained using full backpropagation through time (BPTT) and spatial-only backpropagation. Under full BPTT, prospective variants match or outperform their non-prospective controls in every model and configuration. A non-residual width-32 six-layer RQF reaches 96.09% accuracy on raw-audio Speech Commands with 31.9k parameters; a width-64 six-layer RQF reaches 83.56% on the 16,384-step Path-X task. These results identify RQFs as a parameter-efficient recurrent substrate and prospective-input coding as an input-side correction for deep continuous-time recurrent networks.

cs.LG↗
arXiv2026

Persistent Memory Through Triple-Loop Consolidation Under Stochastic Unit Turnover

Dissipative cognitive architectures maintain computation through continuous energy expenditure, where units that exhaust their energy are stochastically replaced with fresh random state. This creates a fundamental challenge: how can persistent, context-specific memory survive when all learnable state is periodically destroyed? Existing memory mechanisms -- including elastic weight consolidation, synaptic intelligence, and surprise-driven gating -- rely on gradient computation and are inapplicable to systems that do not perform it. We introduce Deep Memory (DM), a backpropagation-free persistent memory mechanism operating through a triple-loop consolidation cycle: (1) recording of expert-specific content centroids, (2) seeding of replaced units with stored representations, and (3) stabilization through continuous re-entry. Discrete expert routing via Mixture-of-Experts (MoE) gating is required, in the regimes tested, to prevent the centroid convergence that would render stored memories identical. We derive a Foster-Lyapunov drift bound for the full triple loop, showing that seeding rescales the turnover noise floor. Across $1{,}007$ simulation runs over thirteen blocks: (i) removing stable context-expert binding removes specialization ($\mathrm{MI}=1.10$ vs. $0.001$; $n=91$); (ii) DM achieves $R=0.984$ vs. $0.385$ without memory ($n=16$); (iii) continuous seeding reconstructs representations after interference ($R_\mathrm{recon}=0.978$; one-shot fails; $n=30$); (iv) the mechanism operates within a characterized $(K,p)$ envelope ($n=350$); (v) recording $\times$ seeding is the minimal critical dyad ($n=40$); (vi) associative and reservoir baselines (Hopfield, ESN) are compared under matched turnover ($n=370$). DM is thus a falsifiable, bounded mechanism for persistent memory in backpropagation-free cognitive systems, with functional parallels to hippocampal consolidation.

cs.NE↗
arXiv2026

Higher-order rich clubs and configuration models on general directed hypergraphs

Detecting structure in complex networks, especially those arising from physical systems, is a central problem across the sciences. One approach is via rich club analysis, which identifies important vertices using a centrality metric and measures whether those vertices are more tightly interconnected than expected by chance. While informative, this approach captures only pairwise interactions, missing out on higher-order ones known to shape the structure and function of many complex systems. We propose a hyper-rich club pipeline that asks whether central vertices are more tightly interconnected than expected by chance through hyperedges encoding higher-order interactions, which also enables the inclusion of important, often omitted, directional information. We work in a broad class of hypergraphs, which we call general directed hypergraphs, that includes as special cases undirected hypergraphs, head-and-tail directed hypergraphs, and totally ordered hypergraphs (a hypergraph related to directed simplicial complexes from topological data analysis). This unifies several non-equivalent notions of directed hypergraph under one definition. On these hypergraphs we define a hyper-rich club framework whose concrete construction depends on explicit choices the domain scientist fixes according to their research goals. Particular choices recover the existing rich club notions for graphs and undirected hypergraphs, and yield the first such notion for each version of directed hypergraphs. We demonstrate that the pipeline recovers meaningful structure in data by studying networks of very different origins: connectomes, temporal networks of infectious spread, networks of poems, and the XGI hypergraph database, in each case detecting structure the standard graph rich club misses.

cs.SI↗
arXiv2026

Relational Knowledge Distillation Brings DNN Representations Close Enough to Humans to Be Aligned Without Supervision

Linking the internal representations of deep neural networks (DNNs) to human mental representations is important for using DNNs as computational models of human vision. Existing DNN representations remain insufficiently similar to human mental representations, which are not directly observable and are therefore commonly measured through large-scale similarity judgments of object images. A natural approach to narrowing this gap is to directly transfer the relational structure of human representations into DNNs, and previous studies have reported improved human-DNN representational similarity. However, whether this improvement holds under stricter evaluation remains untested in two respects: fine-grained alignment at the individual-object level, and generalization to a human embedding derived from a dataset independent of the training data. Here, we employ an unsupervised comparison method, Gromov-Wasserstein optimal transport (GWOT), which estimates human-DNN correspondences from the internal distance structure alone and thereby tests fine-grained alignment. We further assess generalization on a curated test set of concepts non-overlapping with the training data. We show that fine-tuning pre-trained DNNs with Relational Knowledge Distillation (RKD), an established relational transfer method, brings DNNs close enough to humans to be aligned at the individual-object level on this test set. We also show that this improvement is driven by a more human-like global structure, as reflected in the ordering of distances among coarse categories, while the local human-DNN nearest-neighbor overlap rate remains largely unchanged. These findings indicate that relational transfer from humans brings the global structure of pre-trained DNNs close enough to the human structure to enable fine-grained human-DNN alignment without supervision.

cs.CV↗
arXiv2026

A Common Measure of Communication for Speech Brain-Computer Interfaces

Speech brain-computer interfaces (speech BCIs) translate neural activity into language, offering a path towards restoring speech for people with paralysis and, more broadly, enabling new forms of natural human-computer interaction. Despite this promise, the field lacks a common measure of progress because systems use different datasets, recording methods, types of speech, and vocabularies, so their reported scores are rarely comparable. Underlying this measurement problem are two unresolved questions: (i) what distribution of words should a speech BCI enable a user to communicate, and (ii) how much information from this distribution can a system convey. We address both by deriving open-vocabulary mutual information (OVMI), an information-theoretic quantity that measures the information conveyed by a decoder relative to a reference distribution over the words a user may wish to communicate. This allows capabilities measured under different conditions, such as distinct vocabularies, to be evaluated on a common communication scale. We show that ordinarily reported accuracy, word error rate (WER), and other metrics computed only over the words a system supports can overstate how much of a user's intended speech the system can communicate. We then use OVMI to compare existing systems, expose trade-offs between how much of the user's language a system supports and how accurately it decodes those words, show that these comparisons depend on what the user is expected to communicate, and demonstrate that selecting a vocabulary to maximise OVMI yields up to 16.3% relative improvement in accuracy across three speech domains. OVMI therefore provides the speech BCI community with a principled way to compare heterogeneous systems, improve vocabulary design, and measure progress in the field.

cs.LG↗
arXiv2026

Attention as Conditioning: What Classical Learning Theory Predicts About Linear Transformers

Attention is widely understood as an associative memory, but that description alone does not predict how the memory will behave. Predictive theories do exist, but in the literature on animal learning. We show that the state updates of the major linear-attention families are term-for-term identical with named models from a century of animal learning theory: linear attention implements Hebbian contiguity, DeltaNet implements Rescorla--Wagner error correction, and decay variants such as RetNet implement contiguity with a stimulus trace. This dictionary turns conditioning phenomena into testable statements about the in-context behavior of linear transformers, while distinguishing algebraic consequences from empirical measurements. Algebraically, it yields an exact closed form for Kamin blocking, verified in simulation to $<10^{-7}$ across five learning rates. Empirically, it predicts a dissociation that survives training on generic in-context association: error-correcting attention exhibits cue competition, whereas contiguity-based attention does not. A single state also has two capacity regimes, with measured scaling exponents of 1.22 for faithful retrieval and 1.89 for identification, consistent with linear and near-quadratic predictions. Across the full head grid, retrieval error is governed primarily by total state size rather than its partition across heads, indicating that heads provide capacity rather than redundant copies. We also prove no spontaneous recovery for the analyzed single-state recurrences under cue-orthogonal retention trials; with a never-presented-cue control and probes within the trained positional range, we likewise find no recovery in trained models. Finally, we introduce PH-attention, a Pearce--Hall-inspired rule with an explicit feature-indexed associability state that yields cue-dependent learning rates and is absent from the token-computed gates we compare.

cs.LG↗
arXiv2026

Axonal delay dispersion decides whether a neuron detects an event or a sequence, and predicts cortical column diameter

Cortical neurons fire sparsely -- often fewer than one spike per sensory window -- making rate coding insufficient and temporal coding a necessity. That conduction delays convert firing order into synchrony is long established. What governs which class of temporal feature a neuron detects -- one volley of coincident input, or two in a particular order -- has not been examined. We propose a delay-signature framework in which the axonal conduction delays converging on a dendritic branch constitute a physical key: only input sequences whose spike-time differences the delays compensate arrive synchronously, and coincidence detection, via calcium plateau thresholds, converts that synchrony into an all-or-none output. In simulations of an integrator-neuron model we report three results. First, a single physical scalar -- the dispersion of the delay set -- moves a population from event detection to order-selective sequence detection. The transition is emergent under random delays and connectivity: at narrow dispersion sequence detectors do not exist, and the dispersion at which they overtake event detectors tracks the inter-event interval with a slope statistically indistinguishable from one. This maps a computational distinction onto the anatomical one between myelinated and unmyelinated projections, making myelination a switch on what a neuron computes, not only a regulator of speed. Second, the same dispersion sets the code's limits: it bounds the longest codable interval and fixes an absolute timing tolerance of about a millisecond, with slowing better tolerated than speeding. Third, that millisecond window and horizontal conduction velocity together predict cortical column diameter, and the two areas with direct measurements fall where the relation puts them. One anatomically measurable parameter thus sets what a neuron detects and the limits of what it can represent.

q-bio.NC↗
arXiv2026

Large-scale spatial variable gene atlas for spatial transcriptomics

Spatial variable genes (SVGs) reveal critical information about tissue architecture, cellular interactions, and disease microenvironments. As spatial transcriptomics (ST) technologies proliferate, accurately identifying SVGs across diverse platforms, tissue types, and disease contexts has become both a major opportunity and a significant computational challenge. Here, we present a comprehensive benchmarking study of 20 state-of-the-art SVG detection methods using human slides from STimage-1K4M, a large-scale resource of ST data comprising 662 slides from more than 18 tissue types. We evaluate each method across a range of biologically and technically meaningful criteria, including recovery of pathologist-annotated domain-specific markers, cross-slide reproducibility, scalability to high-resolution data, and robustness to technical variation. Our results reveal marked differences in performance depending on tissue type, spatial resolution, and study design. Beyond benchmarking, we construct the first cross-tissue atlas of SVGs, enabling comparative analysis of spatial gene programs across cancer and normal tissues. We observe similarities between pairs of tissues that reflect developmental and functional relationships, such as high overlap between thymus and lymph node, and uncover spatial gene programs associated with metastasis, immune infiltration, and tissue-of-origin identity in cancer. Together, our work defines a framework for evaluating and interpreting spatial gene expression and establishes a reference resource for the ST community.

stat.AP↗
arXiv2026

Propensity Straight-Through Gradients for Discrete Stochastic Systems

Continuous-time Markov chains (CTMCs) provide the backbone for modeling discrete stochastic dynamics across applied, physical, and biological sciences. Their integration with modern gradient-based machine learning, however, is limited by the hard categorical event selection intrinsic to Gillespie-type simulation algorithms. We exploit the affine state update to obtain the exact one-step conditional-mean sensitivity by differentiating normalized reaction propensities. We pair this backward rule with exact forward trajectories to define the propensity straight-through (PST) estimator. At the trajectory level, we show that one-step sensitivities composed across events can depart from the exact multistep sensitivity. We derive the resulting per-step discrepancy in closed form and prove that it vanishes identically for affine downstream dependence. PST matches the accuracy of Gumbel-Softmax straight-through across all benchmarks: reversible dimerization (0.06% error), a genetic oscillator (1.7% error), a 50-task repressilator suite (0.17% median error), and patch-clamp ion-channel recordings ($R^2$ = 0.988). Under matched settings, PST converges 3.0-fold faster on the oscillator and 2.1-fold faster on the ion channel. At deep-learning scale, PST trains a 203,796-parameter stochastic reaction network with hard sampling, reaching 98.22% MNIST digit classification accuracy. By differentiating an exact conditional mean rather than a relaxed sample, PST offers a temperature- and Gumbel-free path to scalable gradient-based learning through exact stochastic trajectories.

q-bio.QM↗
arXiv2026

Storage-Centric System Designs for Enabling Fast, Efficient, and Low-Cost Genomic and Metagenomic Analyses

Genomic and metagenomic analyses play critical roles in many fields, such as precision medicine, urgent clinical settings, discovering early warnings of communicable diseases, ensuring food safety through pathogen monitoring, agriculture, and scientific discovery. Due to the challenges of analyzing and storing massive volumes of genomic and metagenomic sequence data, significant efforts have been made to accelerate (meta)genomic analyses and store sequence data compressed. Despite the benefits of these techniques, we identify two major outstanding problems in accessing stored sequence data and supplying it to the analysis units: (i) the data movement bottleneck due to moving large amounts of low-reuse data from storage and the unnecessary burden on the rest of the system, and (ii) the data preparation bottleneck, where compressed sequence data needs to be first decompressed and formatted before analysis. In this dissertation, we present customized storage-centric systems, which efficiently (i) analyze (meta)genomic data inside the storage system, and (ii) enable highly-compressed storage and high-performance access of large-scale sequence data, thereby alleviating the overheads of data movement, computation, and data preparation. We demonstrate that the proposed systems significantly improve system performance, energy efficiency, and system cost-efficiency of (meta)genomic analysis. We hope that the storage-centric systems proposed in this dissertation facilitate the broader adoption of (meta)genomic analyses and inspire future research to fundamentally improve the performance, energy efficiency, and cost-effectiveness of other data-intensive application domains related to health and life sciences.

cs.AR↗
arXiv2025

Intelligent Software System for Low-Cost, Brightfield Segmentation: Algorithmic Implementation for Cytometric Auto-Analysis

Bright-field microscopy, a cost-effective solution for live-cell culture, is often the only resource available, along with standard CPUs, for many low-budget labs. The inherent challenges of bright-field images -- their noisiness, low contrast, and dynamic morphology -- coupled with a lack of GPU resources and complex software interfaces, hinder the desired research output. This article presents a novel microscopy image analysis framework designed for low-budget labs equipped with a standard CPU desktop. The Python-based program enables cytometric analysis of live, unstained cells in culture through an advanced computer vision and machine learning pipeline. Crucially, the framework operates on label-free data, requiring no manually annotated training data or training phase. It is accessible via a user-friendly, cross-platform GUI that requires no programming skills, while also providing a scripting interface for programmatic control and integration by developers. The end-to-end workflow performs semantic and instance segmentation, feature extraction, analysis, evaluation, and automated report generation. Its modular architecture supports easy maintenance and flexible integration while supporting both single-image and batch processing. Validated on several unstained cell types from the public dataset of livecells, the framework demonstrates superior accuracy and reproducibility compared to contemporary tools like Cellpose and StarDist. Its competitive segmentation speed on a CPU-based platform highlights its significant potential for basic research and clinical applications -- particularly in cell transplantation for personalised medicine and muscle regeneration therapies. The access to the application is available for reproducibility

q-bio.QM↗
arXiv2026

Importance and methods to control, vary, and characterize mud strength for studying locomotion

Animals and robots encounter mud at the water-land interface. Like sand, mud can stay solid or flow like a fluid. Unlike sand, the yield strength of mud at which solid-fluid transitions occur depends on not only the amount of solid relative to fluid (water in mud, air in dry sand), but also how much coarse grains and fine clay are within the solid. Despite understanding of locomotion on/within dry sand dominated by coarse grains with repulsive normal forces and friction, little is known for mud dominated by fine clay with strong cohesion. Here, we developed methods to prepare uniform mud of controlled, variable yield strength and characterize and track its drift from water evaporation. Compared to other flowable substrates, mud strength measured by upward force during penetration is weaker and can vary more, and mud sticks more during extraction to pull downward, making it more challenging for locomotion.

physics.bio-ph↗
arXiv2026

BIRDS: Characterizing and Understanding Biodiversity Impact of Large Language Model Serving

Large language model (LLM) serving creates environmental impacts beyond carbon and water, including ecosystem damage through biodiversity-related pathways. We present BIRDS, a framework for Biodiversity Impact of Request-Driven LLM Serving. BIRDS defines request-level functional units, quantifies operational and embodied biodiversity impact, and introduces Quality-Normalized Biodiversity Impact (QNBI) to jointly analyze ecological impact and response quality. Across diverse workloads, models, GPUs, and regions, BIRDS reveals that biodiversity impact accumulates at scale and exposes quality-aware serving tradeoffs. The code is available at https://github.com/TianyaoShi/BIRDS.

q-bio.OT↗
arXiv2026

VizIt: A multi-view framework for exploring single-cell, spatial, and genetic data online

Multi-omic studies increasingly require data to be examined from complementary biological perspectives, yet interactive exploration remains fragmented across modalities and tools. We present VizIt, an open-source framework for multi-view exploration of single-cell and spatial transcriptomic, epigenomic and genetic data. VizIt connects gene-, cell type-, condition-, spatial-, genomic region- and variant-centered views, enabling seamless navigation across biological perspectives. We demonstrate VizIt through the Parkinson's Cell Atlas, a customizable interactive multi-omic resource.

cs.IR↗
arXiv2026

Agentic BAIM-LLM Evaluation (ABLE): Benchmarking LLM Use of Protein Design Tools

We introduce ABLE, a benchmark for evaluating LLM agents' ability to use biological AI models (BAIMs), such as ProteinMPNN and AlphaFold3, in dual-use protein design workflows. ABLE assesses agent performance through a set of tasks spanning structure retrieval, sequence generation, and design validation. We evaluate 15 frontier models and find that seven refuse all tasks, while the remaining models exhibit substantial performance differences. Claude Sonnet 4 and Gemini 3 Pro achieve the highest scores across information retrieval, tool selection, and tool use. We further compare model performance on a subset of tasks against an expert human baseline. Our results suggest that current LLMs can substantially lower barriers to protein design, but remain inconsistent in planning, strategy generation, and integrating biological knowledge with tool use.

cs.AI↗
arXiv2026

OmniBioTwin: A System-of-Twinned-Systems Framework for Health Digital Twins

Health digital twins (HDTs) promise patient-specific modeling and decision support but current approaches remain structurally fragmented: monolithic models that address a single organ or task lack cross-scale fidelity, while system-level twins lack generalizable architectural frameworks. We propose OmniBioTwin, a System-of-Twinned-Systems (SoTS) framework that organizes HDTs as modular computational entities coupled through explicit interaction operators within a multi-layer network architecture. The framework comprises seven coordinated layers - spanning data integration, autonomous twin modeling, cross-scale coupling, temporal synchronization, and human-in-the-loop decision support. We demonstrate OmniBioTwin by instantiating a multiscale twin for glucagon-like peptide-1 (GLP-1) signaling pathways in Alzheimer's disease, illustrating how molecular, cellular, and organ-level twins can be composed and coupled within a unified system.

q-bio.QM↗