The maturation of quantitative tools for studying the high-level structure of animal behavior, and especially tools which represent spontaneous behavior as a sequence of stereotyped and neurally well-defined 'syllables', demands that the field revisit a fundamental theoretical question: if the coarse structure of behavior can be accurately described by Markov models, what do these models really tell us about behavior? In this work, we explore the theoretical implications of these models and discuss how they allow us to quantitatively formulate questions about the sequence-like nature and effective dimensionality of behavior. One important insight is that the eigenvalues and eigenvectors of various model-associated matrices furnish interpretable time scales and modifications of behavior that occur on those time scales. We illustrate our points using both toy examples and Markov models fit to real data. By analyzing the consequences of Markov representations, we clarify the theoretical meaning of progress in quantifying behavior.

Continuous Attractor Neural Networks (CANNs) traditionally rely on pre-wired recurrent connectivity to model spatial representations, path integration, and anticipatory dynamics. However, the biological mechanisms through which this structured connectivity emerges via learning remain relatively unexplored. This work presents a theoretical framework revealing how continuous attractor connectivity and its computational properties self-organize through Hebbian plasticity, firing-rate adaptation, and global inhibition. We show that translationally invariant inputs naturally drive the emergence of stable, Gaussian-profiled feedforward weights. Crucially, anticipatory dynamics arise spontaneously within these feedforward architectures, shifting the activity bump forward without requiring recurrent excitatory collaterals. This predictive shift can be linearly amplified across multilayer networks, consistent with anticipatory activity observed in the superficial layers of the entorhinal cortex. Furthermore, introducing recurrent interactions allows the network to learn connections capable of self-sustaining a moving bump of activity. Finally, by modulating the network with an external, time-varying baseline current that encodes speed, the system adjusts its intrinsic velocity to function as a precise unidirectional path integrator. Ultimately, this study suggests that prospective coding and path integration are not manually engineered features, but rather naturally co-emergent properties of a single self-organizing competitive network.

Picture naming requires the transformation of visual object information into a spoken lexical response through perceptual, semantic, lexical, and articulatory processes. This study asked whether semantic-category information is recoverable from high-density EEG during overt picture naming. Sixteen native French-speaking participants performed a picture-naming task using line drawings. Picture labels were embedded with a multilingual text-embedding model and organized into nine interpretable semantic categories, providing a data-driven semantic target space for neural decoding. EEG activity was represented channel-wise using a pre-trained single-channel EEG encoder over an early post-stimulus window, a later naming-related window, and their combination. Nine-class decoding showed above-chance semantic-category discrimination in all temporal representations. Balanced accuracy increased from 0.562 in the early window to 0.610 in the naming-related window, and reached 0.781 when both windows were combined, with a maximum Macro-F1 of 0.784. Class-level F1 scores showed consistent gains across semantic categories, and sensor-level decoding maps indicated spatially distributed category information. These findings suggest that semantic-category structure is reflected in EEG activity during overt picture naming and that early and naming-related temporal windows provide complementary information. The results support the use of modern neural decoding methods as tools for investigating lexical-semantic processing in spoken language production.

Agent-based modelling is gaining recognition as a powerful approach for simulating complex cellular pathways, owing to its ability to reproduce emergent biological behaviours without requiring extensive kinetic parameterisation. In this article, we present a GPU-accelerated agent-based simulator specifically designed to model and analyse signalling pathways involved in cancer progression, and to evaluate therapeutic interventions. Our approach leverages the computing capabilities of FLAME GPU 2, a GPU-accelerated agent-based modelling framework, to efficiently manage simulations involving millions of molecules interacting within a three-dimensional environment. Each molecule is represented as an autonomous agent with defined physical properties, capable of binding, releasing reaction products, migrating between compartments, and interacting based on spatial proximity. An intuitive graphical interface supports model construction, parameter setup, and real-time modification of treatment strategies. As the primary focus of this paper, we validate the simulator on the MAPK/ERK cascade affected by the BRAFV600E mutation, demonstrating that it accurately reproduces dose-response trends observed in clinical data and outperforms both deterministic models and our prior agent-based implementations. A second case study extends the approach to nuclear signalling by reproducing the dynamics of cFos expression and phosphorylation. This demonstrates the simulator's ability to capture compartmentalised regulation, reproducing transient mRNA responses and protein accumulation, including the effect of an unresolved negative transcriptional regulator. Together, these results show that GPU-accelerated ABM can faithfully replicate both drug response and emergent gene expression dynamics, providing a scalable and biologically grounded computational tool for supporting precision oncology.

In this note, we show that, for all $n\ge 2$, the number of distinct rooted binary phylogenetic $X$-trees displayed by a binary tree-child network $\mathcal{N}$ on $X$ with $n$ leaves is at most $2^{n-1}-1$ and that this upper bound is sharp. Furthermore, if $\mathcal{N}$ displays exactly $2^{n-1}-1$ such trees, then exactly one rooted binary phylogenetic $X$-tree is displayed twice, and this tree can be canonically found by iteratively replacing a reticulated cherry with a cherry.

Cryogenic electron microscopy images sample individual biomolecules from their conformational landscapes, offering a route to infer the distributions underlying molecular mechanisms. However, because images are indirect measurements, they limit which features of an underlying landscape are statistically identifiable. In ensemble reweighting, this problem appears as a choice of resolution: conformational space is discretized into representative structures whose population weights are inferred from images. Adding structures increases nominal resolution, but nearby conformations may generate overlapping image distributions and indistinguishable weights. Here, we develop an information-theoretic framework that selects representative conformations by maximizing mutual information between ensemble weights and images under a probabilistic forward model. Analytically, we show in a one-dimensional Gaussian model that measurement noise sets the optimal spacing. Applied to molecular conformations sampled from simulation, the framework constructs near-optimal ensembles that span heterogeneity while avoiding redundancy. Thus, the measurement process induces a maximally learnable coarse graining of conformation space.

Accurate prediction of protein-ligand binding affinity is essential for structure-based drug discovery. Recent geometric deep learning methods have achieved promising performance by representing protein-ligand complexes as three-dimensional graphs. However, most existing approaches mainly rely on static interaction geometry from a single bound conformation, while neglecting molecular flexibility and binding-induced conformational changes. To address this limitation, we propose a curvature-informed potential energy surface (CPES) graph neural network for protein-ligand binding affinity prediction, which incorporates physics-informed curvature representations to model conformational flexibility. CPES first derives curvature spectral descriptors from the Hessian of the potential energy surface evaluated at equilibrium configurations, whose eigenvalues define the local principal curvatures of the potential energy surface. It then uses spectral cross-attention to compare the unbound ligand and protein with the bound complex, thereby capturing binding-induced changes in conformational dynamics. In parallel, hierarchical protein-ligand interaction representations are learned from static structural features through geometry-aware message passing, soft clustering, and bidirectional cross-attention. Finally, CPES fuses the curvature-informed dynamic representations with static interaction representations for affinity regression. Extensive evaluations on multiple benchmark datasets demonstrate that CPES achieves improved predictive performance and offers physical interpretability.

Protein-ligand binding affinity (PLA) prediction is critical in drug discovery. Despite the notable advancements in machine learning-based approaches, existing methods struggle to jointly characterize local geometric organization and globally coordinated cross-molecular interactions, limiting their ability to model complex binding mechanisms. Here, we propose RicciBind, a geometric representation framework that integrates curvature-guided hierarchical structure learning with optimal transport (OT)-based cross-domain alignment to model molecular interactions. Specifically, RicciBind leverages Ricci curvature to capture local interaction tightness within molecular structures, enhancing structural awareness and organizing atomic interactions into curvature-aware hierarchical representations. An OT-based cluster matching mechanism then aligns protein and ligand clusters across heterogeneous domains under geometric constraints, enabling globally consistent correspondences and revealing higher-order interaction patterns beyond local neighborhoods. By coupling curvature-guided structure encoding with OT-driven cross-domain alignment, RicciBind effectively models complex interaction semantics and substantially improves both the accuracy and interpretability of binding affinity prediction. Extensive experiments demonstrate that RicciBind achieved superior predictive performance and generalization across PLA benchmarks and virtual screening tasks. Ablation studies further confirmed the essential role of Ricci curvature in enhancing molecular interaction representations.

Coarse-grained (CG) molecular simulations offer an efficient alternative to atomistic molecular dynamics to study large and complex biological systems. The accuracy of CG simulations has been increased dramatically by the introduction of machine-learned coarse-grained (MLCG) models. However, these models are typically designed to be used at a single thermodynamic point, lack temperature transferability, and can not be used to predict temperature dependent quantities like the heat capacity. Here we introduce a thermodynamically informed, temperature-transferable MLCG framework for proteins that explicitly decomposes the CG potential of mean force (PMF) into its energetic and entropic components. The model architecture enforces an exact thermodynamic relation between the energetic and entropic components of the PMF and guarantees physically consistent extrapolation and interpolation across temperature regimes. We validate this framework on an extensive dataset spanning a total of 250 $μ$s of molecular dynamics simulations across five temperatures between 300 K and 400 K for the Chignolin protein, and demonstrate that it reproduces the temperature dependency of the reference atomistic free energy surfaces, correcting the temperature-unaware baselines. Furthermore, we show that it is possible to apply an inexpensive, post-hoc temperature-dependent correction that does not require retraining the MLCG potential, accurately recovering the atomistic heat capacity at different temperatures. Overall, this work provides a physically grounded pathway toward thermodynamically transferable MLCG simulations of complex biomolecular systems.

The capacity of dynamical systems to resist and recover from perturbations, broadly referred to as resilience, is commonly expressed by two complementary quantities: ecological and engineering resilience. As many complex systems exhibit critical transitions, or tipping points, understanding how these resiliences jointly change nearby them is central to characterising and anticipating such shifts. Here, we develop a theoretical framework that clarifies this for bifurcation-induced tipping, i.e., critical transitions triggered by the crossing of a local bifurcation. Using normal form theory, we derive explicit scaling laws for commonly used resilience metrics as functions of the distance to the bifurcation point in parameter space, and show that these extend to general models up to a scaling factor. They are particularly relevant for detecting tipping, where the relative behaviour of metrics matters more than their absolute values. The rates at which metrics decrease as the bifurcation is approached depend on both the type of bifurcation and the metric considered. Furthermore, our results show that, sufficiently close to a local bifurcation, resiliences are intrinsically linked. Our predictions, which replace previously proposed scalings based on heuristic arguments, are validated for three representative models covering all commonly encountered local bifurcations in one-dimensional systems.

We study the mean first-passage time of a random walker to a small absorbing target at the center of a two-dimensional annulus with a specularly reflecting outer boundary. The problem is motivated by natural killer cell migration toward a target cancer cell, where the goal is to quantify how long it takes immune cells to reach the target and how search efficiency depends on directional persistence and chemotactic bias. Cell motion is modeled as a velocity-jump process. We first consider a correlated random walk with a von Mises turning kernel, with a concentration parameter controlling directional persistence. We then extend the model to a biased correlated random walk using a phase-shifted turning kernel that represents preferential motion, for example following a concentration gradient. Our analysis combines closed-form benchmarks for simple and biased random walks, Fourier-mode reductions of the transport equations for the correlated and biased correlated models, and a fast-turning perturbation expansion that gives an analytical correction to the diffusion-limit mean first-passage time for the random walker. Our analytical results are supported by numerical methods that include a semi-Lagrangian solver in radial and angular coordinates, a stationary discretisation designed to handle biased transport, and an event-driven Monte Carlo simulator for cross-validation. Together, our results provide a framework relating persistent and biased immune-cell motion to target-search times in confined two-dimensional domains.

Neural responses in cortex exhibit substantial trial-to-trial variability in response to repeated stimuli, while peripheral sensory neurons respond far more consistently, leading many to wonder whether stochasticity may carry meaning. Existing work has argued that noise and signal correlations may be optimized for discrimination in animals, whereas artificial neural network (ANN) studies have shown similar benefits of noise in machine learning tasks, although most ANN work has neglected the effects of correlations. Here we investigate whether correlated noise improves the robustness of artificial neural networks to adversarial attacks and naturalistic image modifications. Using the covariance of activations under modified versus clean inputs, we find that structured noise may significantly improve network robustness. Robustness to naturalistic image modifications benefits most from structure, but this structure transfers poorly across modification types. In contrast, noise structure from adversarial attacks can generalize to other kinds of attacks. These results suggest that structured noise in ANN activations generally improves robustness, establishing a biologically plausible strategy for creating robust artificial neural networks that only relies on local information.

The emergence of biological complexity can be viewed as a transition from fragmented local interactions to extensive integrated organization, raising the question of how large-scale connectivity emerges from simple interacting elements. We investigated whether this transition can be understood as a consequence of hypergraph percolation driven by higher-order interactions. We performed computational simulations where elementary units constituted nodes and collective interactions formed hyperedges of variable size. Increasing hyperedge density enabled the characterization of connected-component growth, fragmentation, interaction overlap, participation and structural redundancy. Critical transition regions were identified as sparse local assemblies rapidly reorganized into extensive connected structures. These transitions were characterized by abrupt expansion of the largest connected component, progressive consolidation of previously disconnected clusters and increasing overlap among higher-order interactions. Connectivity growth was accompanied by the accumulation of alternative pathways and nested interaction patterns, pointing towards large-scale reorganization over a narrow range of interaction densities. Our findings suggest that, alongside the progressive evolution of molecular complexity, the origin of life and the emergence of biological organization may have involved rapid organizational transitions driven by higher-order connectivity and interaction architecture.

Predicting cellular transcriptional responses to genetic perturbations is a central problem in single-cell biology, especially in the zero-shot setting where the perturbed gene or gene combination is unseen during training. A major difficulty is that perturbation effects are not determined by expression state alone: they depend on how the perturbed gene product influences other genes and proteins, how those downstream factors act on cis-regulatory elements, and which regulatory programs are active in the current cell state. To better capture this biological complexity, we propose CisTransCell, a cell-conditioned multi-modal framework for single-cell perturbation prediction that augments each gene with two complementary priors: a regulatory-sequence prior that captures how the gene is controlled, and a coding-sequence prior that captures what the gene product does. By integrating these priors with cellular expression state, CisTransCell models perturbation response as a cascade from gene function to regulatory control to downstream transcriptional change. Experiments on benchmark single-cell perturbation datasets show that CisTransCell achieves strong performance in zero-shot perturbation prediction.

Personalized health AI systems face a fundamental cold-start problem: machine learning models for physiological interpretation require weeks of individual behavioral data before they can distinguish constitutional variation from environmentally driven deviation. We propose a solution grounded in causal inference and Bayesian prior design. An individual's genomic profile serves as an exogenous genetic anchor -- a domain-informed, personalized prior that is fixed at conception, immune to reverse causation, and available before a single behavioral observation is collected. The anchor initializes a Bayesian belief state over an individual's physiological set point G-hat = mu + sum(beta_i * g_i), where beta_i are GWAS-derived effect sizes and g_i are risk-allele counts. Each incoming physiological measurement P produces a non-constitutional deviation delta = P - G-hat that separates the signal attributable to environment and state from the constitutionally fixed baseline. As behavioral data accrue, the prior decays according to G-hat_t = w(t)*G-hat_genomic + [1-w(t)]*P-bar_t, transitioning from genome-dominated to empirical-baseline-dominated inference. The same observed HRV of 55 ms generates a suppression hypothesis for a person whose prior predicts 80 ms, and an enhancement hypothesis for a person whose prior predicts 30 ms -- a reversal impossible without a personalized anchor. We develop this architecture across six physiological domains, grading genomic priors by evidence strength, distinguishing robustly replicated anchors (FTO, FADS1/2, FKBP5) from contested candidate genes (SLC6A4, MAOA, DRD2). We address the inference boundary between association, Mendelian randomization, and individual token causation, and define four constraints for deployment: evidence-graded priors, dynamic decay, ancestry-matched effect sizes, and attribution rather than deterministic output.

Across biological and social systems, cooperation often depends on phenotypic cues rather than random encounters. To account for real-world interactions unfolding across multiple, simultaneous dimensions, here we develop a general framework for the evolution of cooperation in multiplex networks governed by multi-phenotype homophily. We derive analytical conditions for natural selection to favor cooperation across phenotypic traits that are independent or exhibit epistasis and under different modes of mutation coupling. Despite the integration of fitness across layers, the conditions for cooperation resolve into layer-specific $σ$-rules, depending only on the local payoff structure, the effective number of phenotypes, and the mutation rates. We show that phenotypic diversity fosters cooperation by partitioning populations into assortative niches. Furthermore, in finite populations, intensifying the prisoner's dilemma shifts the dependence of cooperation on strategy mutation from monotonically decreasing, through U-shaped, to monotonically increasing. Our work provides a unified account of how multi-phenotype homophily underpins the evolutionary dynamics of cooperation in heterogeneous populations.

Protein structure classification (PSC) uses supervised learning to predict a protein's CATH/SCOP(e) class from the protein's sequence or 3D structural feature(s). We already modeled 3D structures as (static) protein structure networks (PSNs), demonstrating the competitiveness of PSN-based features to sequence or direct (i.e. non-network) 3D structural features in the PSC task. More recently, we demonstrated the power of features extracted from dynamic PSNs over features extracted from static PSNs (and thus by transitivity over sequence and direct 3D structural features) in the same task. That dynamic PSN approach used traditional machine learning (ML), combining manual (pre-engineered) features with an off-the-shelf classifier. Here, we evaluate whether automatic deep learning (DL) from the dynamic PSNs yields improvements. Our evaluation on 72 datasets spanning ~44,000 CATH- or SCOPe-labeled dynamic PSNs reveals that in terms of PSC accuracy, traditional ML and DL are (close to) tied for a large majority of the datasets, while DL is on average 10+ times slower. We are the first to evaluate traditional ML vs. DL in the dynamic PSN-based PSC task.

Decoding visual experience from brain activity has advanced substantially, but current brain-to-text systems largely recover semantic content while discarding affect. Additionally, language models can generate emotional text when prompted with categorical labels, but such labels collapse rich inter-subject variability into coarse discrete bins. We present EmoMind, the first end-to-end pipeline for decoding affective captions directly from fMRI signals. EmoMind first retrieves a semantically grounded neutral scene description from brain-decoded visual features, then rewrites it using a continuous 34-dimensional emotion vector decoded from the same fMRI recording. To control the balance between content preservation and affective expression, we train the rewriter with classifier-free guidance against an identity-preserving null branch, enabling smooth interpolation between semantic fidelity and affective expressivity. We evaluate affective caption generation with a three-axis validation framework spanning subject-specificity, structural geometry, and causal control. We further augment this framework with a synthetic-brain substitution test that probes robustness to the measurement apparatus, and we benchmark each axis against GPT-4 prompted with brain-decoded top-5 emotion labels as a strong discrete baseline. Across two independent emotion fMRI datasets, EmoMind significantly outperforms label-prompted GPT-4 on all three axes, with the largest gains on metrics that require person-specific affective structure rather than population-level emotion aggregation. These results establish continuous brain-decoded affect as a viable control signal for individualized affective caption generation and open new directions for studying individual affective brain organisation.

From subcellular structures to entire organisms, many natural systems generate complex organisation through self-organisation: local interactions that collectively give rise to global structure without any blueprint of the outcome. Yet a significant portion of the information driving such processes is not produced by self-organisation itself, instead, it is often offloaded to initial conditions of the system. Biological development is a prime example, where maternal pre-patterns encode positional and symmetry-breaking information that scaffolds the self-organising process. From maternal morphogen gradients in early embryogenesis to tissue-level morphogenetic pre-patterns guiding organ formation, this transfer of information to initial conditions, analogous to a memory-compute trade-off in computational systems, is a fundamental part of developmental processes. In this work, we study this offloading phenomenon by introducing a model that jointly learns both the self-organisation rules and the pre-patterns, allowing their interplay to be varied and measured under controlled conditions: a Neural Cellular Automaton (NCA) paired with a learned coordinate-based pattern generator (SIREN), both trained simultaneously to generate a set of patterns. We provide information-theoretic analyses of how information is distributed between pre-patterns and the self-organising process, and show that jointly learning both components yields improvements in robustness, encoding capacity, and symmetry breaking over purely self-organising alternatives. Our analysis further suggests that effective pre-patterns do not simply approximate their targets; rather, they bias the developmental dynamics in ways that facilitate convergence, pointing to a non-trivial relationship between the structure of initial conditions and the dynamics of self-organisation.

Encoding models provide a powerful framework for linking continuous stimulus features to neural activity; however, traditional voxelwise approaches are limited by measurement noise, inter-subject variability, and redundancy arising from spatially correlated voxels encoding overlapping neural signals. Here, we propose an independent component (IC)-based encoding framework that dissociates stimulus-driven and noise-driven signals in fMRI data. We decompose continuous fMRI data from naturalistic story listening into ICs using one subset of the data, and train encoding models on independent data to predict IC time series from large language model representations of linguistic input. Across subjects, a subset of ICs exhibited consistently high predictivity. These ICs were spatially and temporally consistent across subjects and included cognitive networks known to respond during story listening (auditory and language). Auditory component time series were strongly correlated with acoustic stimulus features, highlighting the interpretability of identified component time series. Components identified as noise or motion-related artifacts by ICA-AROMA showed uniformly poor predictive performance, confirming that highly predicted components reflect genuine stimulus-related neural signals rather than confounds. Overall, IC-based encoding models enable analyses at the level of functional networks, accommodating the variability in network locations across individuals and providing interpretable results that are easy to compare across subjects. Code provided at: https://github.com/kamyahari/IC-Encoding-Models.git

Human 3D vision involves two distinct stages: an Experience Module, where stereo depth is extracted relative to fixation, and an Inference Module, where this experience is interpreted to estimate 3D scene properties. Paradoxically, although stereo vision does not provide us with absolute distance information, it nonetheless affects our inferences about distance. We propose the Inference Module exploits a natural scene statistic: near scenes produce vivid disparity gradients, while far scenes appear comparatively flat. QualiaNet implements this two-stage architecture computationally: disparity maps simulating human stereo experience are passed to a CNN trained to estimate distance. The network can recover distance from disparity gradients alone, validating this approach.

Understanding the growth and form of complex morphological structures is one of the most fundamental problems in biology. While many prior works have analyzed the beak morphology of Darwin's finches, other cranial features are relatively less explored. In this work, we develop geometric and statistical methods for analyzing the skull morphology of Darwin's finches and their relatives, focusing on the relationship between their skull dimensions, orbit curvature, and neurocranial geometries. Unlike traditional landmark-based approaches that scale linearly with human labor, our framework is fully unsupervised. Specifically, by utilizing tools in computational geometry, differential geometry, and numerical optimization, we develop efficient algorithms for quantifying various key geometric features of the skull. We then perform a statistical analysis and discover a strong correlation between skull size and orbit curvature. Based on our findings, we further establish a predictive model that can estimate the orbit curvature using easily obtainable linear skull measurements. Our results show that the predictive model is highly effective and capable of explaining 85.48\% of the variance in curvature with an average prediction error of only 6.35\%. Altogether, our work establishes a rigorous foundation for the digital estimation and high-throughput phenotyping of large-scale museum collections, overcoming the scalability bottlenecks of manual methods.

Computation in biological systems is fundamentally energy-constrained, yet standard theories of computation treat energy as freely available. Here, we argue that variational free energy minimization under a Poisson assumption offers a principled path toward an energy-aware theory of computation. Our key observation is that the Kullback-Leibler (KL) divergence term in the Poisson free energy objective becomes proportional to the prior firing rates of model neurons, yielding an emergent metabolic cost term that penalizes high baseline activity. This structure couples an abstract information-theoretic quantity -- the *coding rate* -- to a concrete biophysical variable -- the *firing rate* -- which enables a trade-off between coding fidelity and energy expenditure. Such a coupling arises naturally in the Poisson variational autoencoder (P-VAE) -- a brain-inspired generative model that encodes inputs as discrete spike counts and recovers a spiking form of *sparse coding* as a special case -- but is absent from standard Gaussian VAEs. To demonstrate that this metabolic cost structure is unique to the Poisson formulation, we compare the P-VAE against Grelu-VAE, a Gaussian VAE with ReLU rectification applied to latent samples, which controls for the non-negativity constraint. Across a systematic sweep of the KL term weighting coefficient $β$ and latent dimensionality, we find that increasing $β$ monotonically increases sparsity and reduces average spiking activity in the P-VAE. In contrast, Grelu-VAE representations remain unchanged, confirming that the effect is specific to Poisson statistics rather than a byproduct of non-negative representations. These results establish Poisson variational inference as a promising foundation for a resource-constrained theory of computation.

Topologically Associating Chromatin Domains are spatially distinct chromatin regions that regulate transcription by segregating active and inactive genomic elements. Empirical studies show that their formation correlates with local patterns of epigenetic markers, yet the precise mechanisms linking 1D epigenetic landscapes to 3D chromatin folding remain unclear. Recent models represent chromatin as a spin system, where nucleosomes are treated as discrete-state variables coupled by interaction strengths derived from genomic and epigenetic data. Classical samplers struggle with these models due to high frustration and dense couplings. Here, we present a quantum annealing (QA) approach to efficiently sample chromatin states, embedding an epigenetic Ising model into the topology of D-Wave quantum processors. Rather than reconstructing exact TAD size distributions or insulation scores, our method reproduces statistical features, such as mean marker incidences and intra-/inter-nucleosome correlations, while generating configurations that exhibit TAD-like structural motifs. These results demonstrate QA as an alternative to explore the chromatin architecture and provide a foundation in epigenetic modeling.

A rapidly alternating red and black display known as Ganzflicker induces visual hallucinations that reflect the generative capacity of the visual system. Individuals vary in their degree of visual imagery, ranging from absent to vivid imagery. Recent proposals suggest that differences in the visual system along this imagery spectrum should also influence the complexity of other internally generated visual experiences. Here, we used tools from natural language processing to analyze free-text descriptions of hallucinations from over 4,000 participants, asking whether people with different imagery phenotypes see different things in their mind's eye during Ganzflicker-induced hallucinations. Topic modeling of descriptions revealed that strong imagers described complex, naturalistic content, while weak imagers reported simple geometric patterns. Using crowd-sourced sensorimotor norms, we also found that participants with stronger imagery used language with richer perceptual associations. These findings may reflect individual variation in coordination between early visual areas and higher-order regions relevant for the imagery spectrum.

In cognition, response times and choices in decision-making tasks are commonly modeled using Drift Diffusion Models (DDMs), which describe the accumulation of evidence for a decision as a stochastic process, specifically a Brownian motion, with the drift rate reflecting the strength of the evidence. In the same vein, the Poisson counter model describes the accumulation of evidence as discrete events whose counts over time are modeled as Poisson processes, and has a spiking neurons interpretation as these processes are used to model neuronal activities. However, these models lack a learning mechanism and are limited to tasks where participants have prior knowledge of the categories. To bridge the gap between cognitive and biological models, we propose a biologically plausible Spiking Neural Network (SNN) model for decision-making that incorporates a learning mechanism and whose neurons activities are modeled by a multivariate Hawkes process. First, we show a coupling result between the DDM and the Poisson counter model, establishing that these two models provide similar categorizations and reaction times and that the DDM can be approximated by spiking Poisson neurons. To go further, we show that a particular DDM with correlated noise can be derived from a Hawkes network of spiking neurons governed by a local learning rule. In addition, we designed an online categorization task to evaluate the model predictions. This work provides a significant step toward integrating biologically relevant neural mechanisms into cognitive models, fostering a deeper understanding of the relationship between neural activity and behavior.