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Creators/Authors contains: "Josić, Krešimir"

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  1. NA (Ed.)
    Foraging strategies are shaped by interactions with the environment, and evolve under metabolic constraints. Optimal strategies for isolated and competing organisms have been studied extensively in the absence of evolution. Much less is understood about how metabolic constraints shape the evolution of an organism’s ability to detect and reach food. To address this question, we introduce a minimal agent-based model of the coevolution of two phenotypic attributes critical for successful foraging in crowded environments: movement speed and perceptual acuity. Under competition higher speed and acuity lead to better foraging success, but at higher metabolic cost. We derive the optimal foraging strategy for a single agent, and show that this strategy is no longer optimal for foragers in a group. We show that mutation and selection can lead to the coexistence of two strategies: A metabolically costly strategy with high acuity and velocity, and a metabolically cheap strategy. Generally, in evolving populations speed and acuity co-vary. Therefore, even under metabolic constraints, trade-offs between metabolically expensive traits are not guaranteed. 
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    Free, publicly-accessible full text available February 1, 2026
  2. Two facts about cortex are widely accepted: neuronal responses show large spiking variability with near Poisson statistics and cortical circuits feature abundant recurrent connections between neurons. How these spiking and circuit properties combine to support sensory representation and information processing is not well understood. We build a theoretical framework showing that these two ubiquitous features of cortex combine to produce optimal sampling-based Bayesian inference. Recurrent connections store an internal model of the external world, and Poissonian variability of spike responses drives flexible sampling from the posterior stimulus distributions obtained by combining feedforward and recurrent neuronal inputs. We illustrate how this framework for sampling-based inference can be used by cortex to represent latent multivariate stimuli organized either hierarchically or in parallel. A neural signature of such network sampling are internally generated differential correlations whose amplitude is determined by the prior stored in the circuit, which provides an experimentally testable prediction for our framework. 
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  3. The structure of neural circuitry plays a crucial role in brain function. Previous studies of brain organization generally had to trade off between coarse descriptions at a large scale and fine descriptions on a small scale. Researchers have now reconstructed tens to hundreds of thousands of neurons at synaptic resolution, enabling investigations into the interplay between global, modular organization, and cell type-specific wiring. Analyzing data of this scale, however, presents unique challenges. To address this problem, we applied novel community detection methods to analyze the synapse-level reconstruction of an adult femaleDrosophila melanogasterbrain containing >20,000 neurons and 10 million synapses. Using a machine-learning algorithm, we find the most densely connected communities of neurons by maximizing a generalized modularity density measure. We resolve the community structure at a range of scales, from large (on the order of thousands of neurons) to small (on the order of tens of neurons). We find that the network is organized hierarchically, and larger-scale communities are composed of smaller-scale structures. Our methods identify well-known features of the fly brain, including its sensory pathways. Moreover, focusing on specific brain regions, we are able to identify subnetworks with distinct connectivity types. For example, manual efforts have identified layered structures in the fan-shaped body. Our methods not only automatically recover this layered structure, but also resolve finer connectivity patterns to downstream and upstream areas. We also find a novel modular organization of the superior neuropil, with distinct clusters of upstream and downstream brain regions dividing the neuropil into several pathways. These methods show that the fine-scale, local network reconstruction made possible by modern experimental methods are sufficiently detailed to identify the organization of the brain across scales, and enable novel predictions about the structure and function of its parts. Significance StatementThe Hemibrain is a partial connectome of an adult femaleDrosophila melanogasterbrain containing >20,000 neurons and 10 million synapses. Analyzing the structure of a network of this size requires novel and efficient computational tools. We applied a new community detection method to automatically uncover the modular structure in the Hemibrain dataset by maximizing a generalized modularity measure. This allowed us to resolve the community structure of the fly hemibrain at a range of spatial scales revealing a hierarchical organization of the network, where larger-scale modules are composed of smaller-scale structures. The method also allowed us to identify subnetworks with distinct cell and connectivity structures, such as the layered structures in the fan-shaped body, and the modular organization of the superior neuropil. Thus, network analysis methods can be adopted to the connectomes being reconstructed using modern experimental methods to reveal the organization of the brain across scales. This supports the view that such connectomes will allow us to uncover the organizational structure of the brain, which can ultimately lead to a better understanding of its function. 
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  4. Abstract MotivationCell function is regulated by gene regulatory networks (GRNs) defined by protein-mediated interaction between constituent genes. Despite advances in experimental techniques, we can still measure only a fraction of the processes that govern GRN dynamics. To infer the properties of GRNs using partial observation, unobserved sequential processes can be replaced with distributed time delays, yielding non-Markovian models. Inference methods based on the resulting model suffer from the curse of dimensionality. ResultsWe develop a simulation-based Bayesian MCMC method employing an approximate likelihood for the efficient and accurate inference of GRN parameters when only some of their products are observed. We illustrate our approach using a two-step activation model: an activation signal leads to the accumulation of an unobserved regulatory protein, which triggers the expression of observed fluorescent proteins. With prior information about observed fluorescent protein synthesis, our method successfully infers the dynamics of the unobserved regulatory protein. We can estimate the delay and kinetic parameters characterizing target regulation including transcription, translation, and target searching of an unobserved protein from experimental measurements of the products of its target gene. Our method is scalable and can be used to analyze non-Markovian models with hidden components. Availability and implementationOur code is implemented in R and is freely available with a simple example data at https://github.com/Mathbiomed/SimMCMC. 
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  5. Beierholm, Ulrik R. (Ed.)
    Solutions to challenging inference problems are often subject to a fundamental trade-off between: 1) bias (being systematically wrong) that is minimized with complex inference strategies, and 2) variance (being oversensitive to uncertain observations) that is minimized with simple inference strategies. However, this trade-off is based on the assumption that the strategies being considered are optimal for their given complexity and thus has unclear relevance to forms of inference based on suboptimal strategies. We examined inference problems applied to rare, asymmetrically available evidence, which a large population of human subjects solved using a diverse set of strategies that varied in form and complexity. In general, subjects using more complex strategies tended to have lower bias and variance, but with a dependence on the form of strategy that reflected an inversion of the classic bias-variance trade-off: subjects who used more complex, but imperfect, Bayesian-like strategies tended to have lower variance but higher bias because of incorrect tuning to latent task features, whereas subjects who used simpler heuristic strategies tended to have higher variance because they operated more directly on the observed samples but lower, near-normative bias. Our results help define new principles that govern individual differences in behavior that depends on rare-event inference and, more generally, about the information-processing trade-offs that can be sensitive to not just the complexity, but also the optimality, of the inference process. 
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  6. Working memory, the brain’s ability to temporarily store and recall information, is a critical part of decision making – but it has its limits. The brain can only store so much information, for so long. Since decisions are not often acted on immediately, information held in working memory ‘degrades’ over time. However, it is unknown whether or not this degradation of information over time affects the accuracy of later decisions. The tactics that people use, knowingly or otherwise, to store information in working memory also remain unclear. Do people store pieces of information such as numbers, objects and particular details? Or do they tend to compute that information, make some preliminary judgement and recall their verdict later? Does the strategy chosen impact people’s decision-making? To investigate, Schapiro et al. devised a series of experiments to test whether the limitations of working memory, and how people store information, affect the accuracy of decisions they make. First, participants were shown an array of colored discs on a screen. Then, either immediately after seeing the disks or a few seconds later, the participants were asked to recall the position of one of the disks they had seen, or the average position of all the disks. This measured how much information degraded for a decision based on multiple items, and how much for a decision based on a single item. From this, the method of information storage used to make a decision could be inferred. Schapiro et al. found that the accuracy of people’s responses worsened over time, whether they remembered the position of each individual disk, or computed their average location before responding. The greater the delay between seeing the disks and reporting their location, the less accurate people’s responses tended to be. Similarly, the more disks a participant saw, the less accurate their response became. This suggests that however people store information, if working memory reaches capacity, decision-making suffers and that, over time, stored information decays. Schapiro et al. also noticed that participants remembered location information in different ways depending on the task and how many disks they were shown at once. This suggests people adopt different strategies to retain information momentarily. In summary, these findings help to explain how people process and store information to make decisions and how the limitations of working memory impact their decision-making ability. A better understanding of how people use working memory to make decisions may also shed light on situations or brain conditions where decision-making is impaired. 
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