Journal of Theoretical Biology最新文献

{"title":"Modeling the Action-Perception loop and its role in phantom limb pain using active inference.","authors":"Malin Ramne, Torbjörn Lundh, Jon Sensinger","doi":"10.1016/j.jtbi.2026.112634","DOIUrl":"https://doi.org/10.1016/j.jtbi.2026.112634","url":null,"abstract":"<p><p>Mathematical models grounded in the Bayesian inference framework have been used to describe various aspects of pain perception. However, pain is not only passively inferred but actively shaped through interactions with the environment - a dimension that classical Bayesian approaches typically do not capture. Here, we investigate the role of the action-perception loop in phantom limb pain using a model within the active inference framework, which extends Bayesian inference to include action selection. Despite being one of the most prevalent and distressing consequences of limb amputation, theories regarding the underlying mechanisms of phantom limb pain remain disputed. Because amputation disrupts both sensory input related to the limb and the ability to perform actions, a model incorporating both sensory and active components of pain may provide new mechanistic insight into this condition. The presented model provides a conceptual account of how loss of limb control, ambiguity in sensory input pertaining to limb position, residual noxious input, and pre-amputation pain may contribute to the emergence and persistence of phantom limb pain. Furthermore, the model offers insight into the possible mechanisms underlying common interventions and may help account for their variable efficacy across individuals.</p>","PeriodicalId":54763,"journal":{"name":"Journal of Theoretical Biology","volume":" ","pages":"112634"},"PeriodicalIF":1.9,"publicationDate":"2026-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149327566","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"数学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Unbeatable imitation of a friend.","authors":"Masahiko Ueda","doi":"10.1016/j.jtbi.2026.112635","DOIUrl":"https://doi.org/10.1016/j.jtbi.2026.112635","url":null,"abstract":"<p><p>Imitation sometimes achieves success in multi-agent situations even though it is very simple. In repeated games, success of imitation has been characterized by unbeatability against other agents. Previous studies specified conditions under which imitation is unbeatable against co-players in repeated symmetric games, and clarified that the existence of unbeatable imitation is strongly related to the existence of payoff-controlling strategies, called zero-determinant strategies. However, these results were on the situations in which one repeated game is played by one group of players. It was pointed out that imitation of other players in the same group and imitation of other players in the same role in other groups generally result in different outcomes. Here, we investigate the existence condition of unbeatable imitation in the latter situations, described by two concurrent repeated games played by two different groups of players. We find that the existence condition of unbeatable imitation is stronger than the existence condition of unbeatable zero-determinant strategies, whereas both are very limited. Furthermore, we find that adding exploration can make an imitation strategy unbeatable even in games where imitation without exploration can be beaten. Our findings suggest a strong relation between unbeatable imitation and payoff control even in the two concurrent repeated game situations.</p>","PeriodicalId":54763,"journal":{"name":"Journal of Theoretical Biology","volume":"637 ","pages":"112635"},"PeriodicalIF":1.9,"publicationDate":"2026-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149327567","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"数学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A neutral epidemic model of tick-borne pathogen transmission with co-infection and co-transmission.","authors":"Giulia Belluccini, Qianying Lin, Bevelynn Williams, Yijun Lou, Zati Vatansever, Martín López-García, Grant Lythe, Thomas Leitner, Ethan Romero-Severson, Carmen Molina-París","doi":"10.1016/j.jtbi.2026.112629","DOIUrl":"https://doi.org/10.1016/j.jtbi.2026.112629","url":null,"abstract":"<p><p>With a single circulating tick-borne pathogen in a population of ticks and vertebrate hosts, the basic reproduction number incorporates contributions from tick-to-tick, tick-to-vertebrate host, and vertebrate host-to-tick transmission routes. With two co-circulating tick-borne pathogens, resident and invasive, and under the assumption that tick-to-tick is the only transmission route in a tick population feeding on vertebrate hosts, the invasion reproduction number is a measure of the ability of the invasive strain to take over the population at the resident-strain equilibrium. Predicting whether an invasive strain, that is identical to the resident one, will dominate depends on whether the mathematical model characterising the system possesses the neutrality property. However, even if a model is neutral and the strains not identical, its associated invasion reproduction number depends on model structure. We propose a two-slot model for tick-borne pathogen transmission in the presence of tick co-feeding, co-infection, and co-transmission, which is an extension of a previous co-infection and co-transmission model proposed by Alizon in 2013. Our two-slot model, with one population of susceptible (not infected) ticks, two populations of ticks infected with a single strain (resident or invasive), one population of co-infected (infected with both strains) ticks, and two populations doubly-infected with the same strain (resident or invasive), satisfies the neutrality property. We analyse the invasion reproduction number with the next-generation method and numerical simulations. We apply the two-slot model to compute the fraction of co-infected questing adult ticks at the end of a season as a function of the co-transmission probability, and discuss the potential risk posed to humans by such co-infected ticks.</p>","PeriodicalId":54763,"journal":{"name":"Journal of Theoretical Biology","volume":" ","pages":"112629"},"PeriodicalIF":1.9,"publicationDate":"2026-10-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149290012","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"数学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Leveling biological Systems: Material organization and scaffolding scientific Advance.","authors":"Daniel Stephen Brooks, María Alejandra Petino Zappala, Susanne Ressl","doi":"10.1016/j.jtbi.2026.112632","DOIUrl":"https://doi.org/10.1016/j.jtbi.2026.112632","url":null,"abstract":"<p><p>While general calls for more theory in biology are on the rise, less attention has been paid to the practical usefulness of theorizing about biological phenomena. Furthermore, the increased interdisciplinarity needed to address complex biological problems introduces challenges into how we think about knowledge advancement. All too often, consensus for how to bring the resources of different disciplines together into ordered and coherent frameworks can remain elusive. Here, we address these issues as it especially concerns how we should think about the future of the life sciences. We turn to biological neuroscience as a case study, where recent and profound technological changes in this field bring these questions acutely into relief. We argue that conceptual reasoning, the scrutiny of concepts and their roles in structuring scientific endeavors, can enrich biological practice and help understand how new, locally stable knowledge is generated. The centerpiece of this discussion features a renewed look at the concept of levels of organization, a familiar concept in biology that is often assumed, but rarely developed in detail. We describe the roles of this concept in structuring practical scientific reasoning and as a source of 'stable variation' in characterizing and manipulating biological phenomena. Second, we propose supplementing our understanding of knowledge advancement by considering how we scaffold new achievements and insight from the present into the future. We suggest that the features of the levels concept allow accommodating variability and continuity across experimental reasoning in biology, serving as a scaffolding device for fields such as biological neuroscience.</p>","PeriodicalId":54763,"journal":{"name":"Journal of Theoretical Biology","volume":" ","pages":"112632"},"PeriodicalIF":1.9,"publicationDate":"2026-10-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149277223","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"数学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Model topology determines parameter accessibility in Markov models of voltage-gated ion channels.","authors":"Alon Korngreen","doi":"10.1016/j.jtbi.2026.112633","DOIUrl":"10.1016/j.jtbi.2026.112633","url":null,"abstract":"<p><p>Markov models are widely used to describe the gating kinetics of voltage-gated ion channels, but increasing model complexity can introduce parameters that are difficult to constrain from macroscopic measurements. In this study, global variance-based Sobol sensitivity analysis was used to examine how model topology, stimulation protocol, and parameter uncertainty shape the accessibility of kinetic parameters in voltage-gated ion channel models. Progressively more complex Markov schemes were analyzed, beginning with a two-state closed-open model, extending to a three-state linear closed-closed-open model, a cyclic three-state model with a direct closed-open transition, and a four-state closed-closed-open-inactivated model. Sensitivity was quantified for the open probability (P_o) under voltage-step and sinusoidal protocols. In linear models, parameter influence was concentrated in transitions directly connected to the open state, whereas distal closed-closed transitions contributed little to output variance. This weak influence was not rescued by higher-order interaction effects. Multi-frequency sinusoidal stimulation (20-200 Hz) preserved the transition-level sensitivity hierarchy observed under step protocols, indicating that dynamic stimulation does not overcome the structural limitations of serial topologies. In contrast, introducing a cyclic pathway fundamentally redistributed sensitivity, showing that distal-parameter weakness is a consequence of serial arrangement rather than a universal property of Markov gating. Adding inactivation shifted dominant variance control to the open-inactivated transition during sustained depolarization, yet distal closed-closed transitions remained weak. Finally, constraining variability at the dominant activation edge shifted variance upstream, demonstrating that low Sobol indices reflect the relative flexibility of competing bottlenecks within a given ensemble rather than the intrinsic irrelevance of a transition. Together, these results define topology-dependent limits on parameter accessibility in Markov models of voltage-gated ion channels and provide practical guidance for selecting model complexity, designing informative protocols, and favoring cyclic over extended linear topologies when constructing robust channel models.</p>","PeriodicalId":54763,"journal":{"name":"Journal of Theoretical Biology","volume":" ","pages":"112633"},"PeriodicalIF":1.9,"publicationDate":"2026-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149247623","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"数学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"From individual-based models to macroscopic dynamics of antimicrobial resistance.","authors":"Marco Menale, Giuseppe Toscani, Mattia Zanella","doi":"10.1016/j.jtbi.2026.112631","DOIUrl":"10.1016/j.jtbi.2026.112631","url":null,"abstract":"<p><p>We introduce and discuss a kinetic framework describing the time evolution of the statistical distributions of a population divided into the compartments of susceptible, infectious, recovered, and resistant in the presence of a microbial infection driven by susceptible-infectious interactions. Our main objective is to quantify the impact of excessive and inappropriate antimicrobial use, which accelerates the spread of resistance by enabling a fraction of infectious individuals to transition into the resistant compartment. The model consists of a system of Boltzmann-type equations capturing binary interactions between susceptible and infectious individuals, complemented by linear redistribution operators that represent recovery, the development of resistance, and reinfection processes. In the grazing-collision limit, we show that this Boltzmann system is well approximated by a system of coupled Fokker-Planck equations. This limiting description allows for a more tractable analysis of the dynamics, including the characterization of the long-time behavior of the population densities. Our analysis highlights how interaction terms drive the system toward a stable equilibrium and quantifies the effects of inappropriate antimicrobial use on the distribution of resistant individuals. Overall, the results offer a multi-scale perspective that bridges kinetic theory with classical epidemic modeling.</p>","PeriodicalId":54763,"journal":{"name":"Journal of Theoretical Biology","volume":" ","pages":"112631"},"PeriodicalIF":1.9,"publicationDate":"2026-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149247570","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"数学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cognitive agent neuron: Learning and decision-making inspired by dopaminergic neurons.","authors":"Masoumeh Zareh, Mohammad Hossein Manshaei, Sayed Jalal Zahabi, Mohammad Saghali, Golnoush Nematbakhsh","doi":"10.1016/j.jtbi.2026.112628","DOIUrl":"10.1016/j.jtbi.2026.112628","url":null,"abstract":"<p><p>Decision-making is a critical function of the brain as an information-processing system that can be understood using mathematical models, computer simulations, and theoretical analysis. In this paper, we introduce a computational neuron model inspired by dopaminergic functionality, which we call Cognitive Agent Neurons (CANs). Dopaminergic neurons play an important role in transmitting global reward prediction errors (RPEs) across a wide array of brain regions. RPEs serve as a key signal in adaptive learning and behavior, directly impacting reinforcement learning mechanisms. We propose a rational neuron model as a neuronal agent that can communicate with its environment and improve its decision-making skills over time, inspired by dopaminergic neurons. The network of neuronal agents can cooperate to solve any task and improve their functionality with the reinforcement learning algorithm over time. So, the CAN model is an information processing system that is based on the premise that each neuron functions as an autonomous and rational agent. We examine the functionality of the CAN model based on the classification task. Due to the chemical synapse, we proposed two Dynamic (extensive-form) games with imperfect information to model the interaction of neurons in the CAN model. After training the model with approximate Q-learning, each neuron can choose the neuron that sends its signal. The results reveal that the CAN model's accuracy rate for dividing the banknote authentication dataset is 97%, its accuracy rate for dividing two classes of the notMNIST dataset is 92%, and its accuracy rate for dividing the non-linear dataset is 96%. After training the model with approximate Q-learning, the results show that the CAN model performs better in classification due to its extensive action space. It performs comparably to traditional machine learning methods.</p>","PeriodicalId":54763,"journal":{"name":"Journal of Theoretical Biology","volume":" ","pages":"112628"},"PeriodicalIF":1.9,"publicationDate":"2026-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149247562","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"数学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The role of the lymphatic micro-vasculature in malignant tissue fluid and drug transport.","authors":"Andrew Brown, Raimondo Penta","doi":"10.1016/j.jtbi.2026.112630","DOIUrl":"10.1016/j.jtbi.2026.112630","url":null,"abstract":"<p><p>The contribution of lymphatic capillaries in the fluid and drug transport throughout vascularised malignant tissue is qualitatively and quantitatively discussed. Our starting point is the derivation of differential equations for coupled fluid and drug transport across three physical domains present in vascularised tissue: the interstitium, capillary vessels and lymphatic vessels. We begin from mass and momentum balance equations in each physical domain, which are geometrically characterised by the inter-capillary distance (microscale). The Kedem-Katchalsky equations are used to account for blood and drug exchange across the vessel walls. Employing asymptotic homogenisation, we can formulate a multiscale model which allows for a complex microstructure, under the regular assumptions such as local periodicity, accounting for spatial heterogeneity of the angiogenic nature of the capillary and lymphatic networks. At the macroscale, the fluid dynamics are governed by a triple-compartmental porous medium problem characterised by Darcy's law; whereas drug dynamics are characterised by a triple-compartmental advection-diffusion-reaction model. The microscopic properties of the malignant tissue are effectively encoded into a series of macroscopic coefficients, which enable the analysis of geometric changes at the microscale from a macroscopic perspective. Analysis of the models' isotropic case reveals the existence of a favourable permeability for lymphatic vessels, allowing for optimised fluid and drug transport. The purpose of this work is to create a robust theoretical platform that can account for the role of the networks of vessels that are to be considered to improve anti-cancer strategies.</p>","PeriodicalId":54763,"journal":{"name":"Journal of Theoretical Biology","volume":" ","pages":"112630"},"PeriodicalIF":1.9,"publicationDate":"2026-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149229455","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"数学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A dynamic mathematical model for sub-lethal damage recovery: integrating recovery processes into multi-target theory to visualize damage states.","authors":"Renta Shibata, Fuminobu Sato, Yoko Akiyama, Yuichiro Manabe","doi":"10.1016/j.jtbi.2026.112620","DOIUrl":"10.1016/j.jtbi.2026.112620","url":null,"abstract":"<p><p>Quantifying the biological effects of radiation is essential for radiotherapy and radiation protection. While research has centered on statistical analyses of experimental data, this approach often fails to elucidate underlying mechanisms, limiting the development of generalizable models. Describing time-dependent phenomena, such as sub-lethal damage (SLD) recovery during fractionated irradiation, presents a particularly significant challenge for existing static models. To address this, we developed a mechanistic mathematical model that extends the classical multi-target, single-hit model by introducing explicit recovery transitions among damage states, allowing the simultaneous description of radiation-induced damage accumulation and biological recovery. We applied this model to Elkind and Sutton's classical split-dose experimental data to determine its parameters. The model reproduced the major features of split-dose survival curves for treatments with 0-, 2.5-, and 23-hour recovery intervals. We visualized the temporal changes in damage state distributions within the cell populations. These simulations provided a process-level interpretation of the characteristic shoulder-like response appearing after an inter-fraction recovery interval. Furthermore, the estimated recovery half-life was ∼120 min, which is broadly consistent with reported timescales of DNA double-strand break repair in mammalian cells, supporting the biological interpretability of the model parameters. The proposed framework provides a simple, interpretable description of radiation-induced cell death dynamics, including SLD recovery, and may serve as a basis for the improved mechanistic modeling of radiobiological effects under different irradiation protocols.</p>","PeriodicalId":54763,"journal":{"name":"Journal of Theoretical Biology","volume":" ","pages":"112620"},"PeriodicalIF":1.9,"publicationDate":"2026-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149217138","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"数学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prolonged transient persistence of polygenic polymorphism under stabilizing selection alone.","authors":"Xiang Shi, Jiayi Kang, Xin Zhao, Nan Sun, Stephen S-T Yau, Qi Wu","doi":"10.1016/j.jtbi.2026.112619","DOIUrl":"10.1016/j.jtbi.2026.112619","url":null,"abstract":"<p><p>In evolutionary theories of quantitative traits, a mutation-selection balance is essential to preserve polymorphism, where stabilizing selection is widely considered to eliminate genetic variation at underlying loci. To isolate the role of selection, we re-examine the effect of stabilizing selection on genetic polymorphism in a mathematically rigorous manner. Following the classical stabilizing-selection model, we explicitly decompose the population mean μ across all n contributing loci, transforming the model within a n-dimensional dynamical system. The fully polymorphic stationarity equations have a unique algebraic candidate, which is a biologically feasible interior equilibrium if and only if all its components lie in (0,1). Linearization at the equilibrium point reveals a saddle-point structure: under equal allelic effects, exactly one eigenvalue is negative, and n-1 eigenvalues are positive. Under equal allelic effects, the linear stable and unstable eigenspaces are E^s=span{1} and E^u=ker(1^T), respectively; the corresponding local nonlinear invariant manifolds are tangent to these spaces at p*. The stable mode restores the population mean toward the equilibrium value μ*, which need not equal the optimum θ, whereas the unstable modes are mean-neutral to first order. The relative rate ratio |λ_s|/λ_u=2n-1 shows that collective relaxation is faster than locus differentiation, while the absolute local residence time is controlled by λ_u and the initial unstable displacement. A nonzero unstable component causes local departure from the fully polymorphic saddle, but the local analysis does not classify the global limiting state. In the full nonlinear system, the non-trivial equilibrium is not asymptotically stable. Simulations show that escape from the polymorphic neighborhood is substantially delayed, producing long finite-time persistence of polymorphism. Consequently, the saddle geometry can generate potentially long deterministic finite-time persistence of polygenic polymorphism, but it does not provide asymptotically stable or finite-population maintenance in the absence of mutation.</p>","PeriodicalId":54763,"journal":{"name":"Journal of Theoretical Biology","volume":" ","pages":"112619"},"PeriodicalIF":1.9,"publicationDate":"2026-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149197885","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"数学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}