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An editorial is presented which discusses the collaborative writing with multiple authors which has additional challenges including varied levels of engagement of coauthors, provision of fair credit through authorship or acknowledgements and acceptance of diversity of work styles. Also discussed are the 10 simple rules for collaboratively writing a multi-authored paper which include to build a writing team wisely; to create a data management plan and to jointly decide on authorship guidelines.

The Free Energy Principle (FEP) and Integrated Information Theory (IIT) are two ambitious theoretical approaches. The first aims to make a formal framework for describing self-organizing and life-like systems in general, and the second attempts a mathematical theory of conscious experience based on the intrinsic properties of a system. They are each concerned with complementary aspects of the properties of systems, one with life and behavior, the other with meaning and experience, so combining them has potential for scientific value. In this paper, we take a first step towards such a synthesis by expanding on the results of an earlier published evolutionary simulation study, which show a relationship between IIT-measures and fitness in differing complexities of tasks. We relate a basic information theoretic measure from the FEP, surprisal, to this result, finding that the surprisal of simulated agents' observations is inversely related to the general increase in fitness and integration over evolutionary time. Moreover, surprisal fluctuates together with IIT-based consciousness measures in within-trial time. This suggests that the consciousness measures used in IIT indirectly depend on the relation between the agent and the external world, and that it should therefore be possible to relate them to the theoretical concepts used in the FEP. Lastly, we suggest a future approach for investigating this relationship empirically. Author summary: Two influential theoretical frameworks in cognitive science, neuroscience and computational biology, are the Free Energy Principle and Integrated Information Theory. The first is a formal approach to self-organization and adaptive behavior ‐ in short, life ‐ based on first principles from statistical physics. The second is an attempt at formally describing the intrinsic experience of a given system, that is, how it feels to be that system. In this way, these two theories provide tools for understanding two complementary aspects of a given organism; namely, how it acts in a goal-directed manner based on statistical beliefs about the world, and how it feels to be that system in that process. In this paper, we provide an initial numerical investigation of the potential relation of these theoretical frameworks. We simulate agents that undergo evolution, and show that as their level of integration (Φ, a measure from Integrated Information Theory) increases, information theoretic surprisal (a quantity used in the Free Energy Principle) decreases. We also see that Φ and surprisal fluctuate together, and that these fluctuations depend on sensory input. Finally we provide considerations for future simulation work, and how to bring these two theoretical frameworks closer together. [ABSTRACT FROM AUTHOR]

We propose the "runtime learning" hypothesis which states that people quickly learn to perform unfamiliar tasks as the tasks arise by using task-relevant instances of concepts stored in memory during mental training. To make learning rapid, the hypothesis claims that only a few class instances are used, but these instances are especially valuable for training. The paper motivates the hypothesis by describing related ideas from the cognitive science and machine learning literatures. Using computer simulation, we show that deep neural networks (DNNs) can learn effectively from small, curated training sets, and that valuable training items tend to lie toward the centers of data item clusters in an abstract feature space. In a series of three behavioral experiments, we show that people can also learn effectively from small, curated training sets. Critically, we find that participant reaction times and fitted drift rates are best accounted for by the confidences of DNNs trained on small datasets of highly valuable items. We conclude that the runtime learning hypothesis is a novel conjecture about the relationship between learning and memory with the potential for explaining a wide variety of cognitive phenomena. Author summary: Human cognition is remarkably flexible, with the ability to reliably perform a wide variety of tasks, including idiosyncratic and unfamiliar ones, in a wide variety of contexts. However, despite impressive advances in machine learning, leading to artificial intelligences capable of outperforming humans on select individual tasks, this flexibility has yet to be replicated by computational models. Doing so is essential to both creating general artificial intelligence and to achieving a deeper understanding of the human brain and mind. To account for this vital property of human cognition, we introduce the "runtime learning hypothesis", in which the brain rapidly constructs task-specific models in response to the needs of the moment using an internal training process based on valuable exemplars of the relevant concepts. We examine the plausibility of this hypothesis using human behavioral experiments and machine-learning-based computational modeling. The results are consistent with the human brain using runtime learning to flexibly perform tasks. [ABSTRACT FROM AUTHOR]

13C metabolic flux analysis (13C-MFA) has been widely used to measure in vivo enzyme reaction rates (i.e., metabolic flux) in microorganisms. Mining the relationship between environmental and genetic factors and metabolic fluxes hidden in existing fluxomic data will lead to predictive models that can significantly accelerate flux quantification. In this paper, we present a web-based platform MFlux () that predicts the bacterial central metabolism via machine learning, leveraging data from approximately 100 13C-MFA papers on heterotrophic bacterial metabolisms. Three machine learning methods, namely Support Vector Machine (SVM), k-Nearest Neighbors (k-NN), and Decision Tree, were employed to study the sophisticated relationship between influential factors and metabolic fluxes. We performed a grid search of the best parameter set for each algorithm and verified their performance through 10-fold cross validations. SVM yields the highest accuracy among all three algorithms. Further, we employed quadratic programming to adjust flux profiles to satisfy stoichiometric constraints. Multiple case studies have shown that MFlux can reasonably predict fluxomes as a function of bacterial species, substrate types, growth rate, oxygen conditions, and cultivation methods. Due to the interest of studying model organism under particular carbon sources, bias of fluxome in the dataset may limit the applicability of machine learning models. This problem can be resolved after more papers on 13C-MFA are published for non-model species. [ABSTRACT FROM AUTHOR]

The article outlines the rules for a bioinformatics journal club which, according to the authors, is a great way to take in the scientific literature, keep up with developments in their field, and hone their communication and analytical skills. The rules include holding a journal club at eight in the morning, finding good articles for discussion, and expanding the roster of leaders as people join the journal club.

A major tenet in theoretical neuroscience is that cognitive and behavioral processes are ultimately implemented in terms of the neural system dynamics. Accordingly, a major aim for the analysis of neurophysiological measurements should lie in the identification of the computational dynamics underlying task processing. Here we advance a state space model (SSM) based on generative piecewise-linear recurrent neural networks (PLRNN) to assess dynamics from neuroimaging data. In contrast to many other nonlinear time series models which have been proposed for reconstructing latent dynamics, our model is easily interpretable in neural terms, amenable to systematic dynamical systems analysis of the resulting set of equations, and can straightforwardly be transformed into an equivalent continuous-time dynamical system. The major contributions of this paper are the introduction of a new observation model suitable for functional magnetic resonance imaging (fMRI) coupled to the latent PLRNN, an efficient stepwise training procedure that forces the latent model to capture the ‘true’ underlying dynamics rather than just fitting (or predicting) the observations, and of an empirical measure based on the Kullback-Leibler divergence to evaluate from empirical time series how well this goal of approximating the underlying dynamics has been achieved. We validate and illustrate the power of our approach on simulated ‘ground-truth’ dynamical systems as well as on experimental fMRI time series, and demonstrate that the learnt dynamics harbors task-related nonlinear structure that a linear dynamical model fails to capture. Given that fMRI is one of the most common techniques for measuring brain activity non-invasively in human subjects, this approach may provide a novel step toward analyzing aberrant (nonlinear) dynamics for clinical assessment or neuroscientific research. [ABSTRACT FROM AUTHOR]

When listening to music, humans can easily identify and move to the beat. Numerous experimental studies have identified brain regions that may be involved with beat perception and representation. Several theoretical and algorithmic approaches have been proposed to account for this ability. Related to, but different from the issue of how we perceive a beat, is the question of how we learn to generate and hold a beat. In this paper, we introduce a neuronal framework for a beat generator that is capable of learning isochronous rhythms over a range of frequencies that are relevant to music and speech. Our approach combines ideas from error-correction and entrainment models to investigate the dynamics of how a biophysically-based neuronal network model synchronizes its period and phase to match that of an external stimulus. The model makes novel use of on-going faster gamma rhythms to form a set of discrete clocks that provide estimates, but not exact information, of how well the beat generator spike times match those of a stimulus sequence. The beat generator is endowed with plasticity allowing it to quickly learn and thereby adjust its spike times to achieve synchronization. Our model makes generalizable predictions about the existence of asymmetries in the synchronization process, as well as specific predictions about resynchronization times after changes in stimulus tempo or phase. Analysis of the model demonstrates that accurate rhythmic time keeping can be achieved over a range of frequencies relevant to music, in a manner that is robust to changes in parameters and to the presence of noise. [ABSTRACT FROM AUTHOR]

Human populations show rich cultural diversity. Underpinning this diversity of tools, rituals, and cultural norms are complex interactions between cultural evolutionary and demographic processes. Most models of cultural change assume that individuals use the same learning modes and methods throughout their lives. However, empirical data on ‘learning life histories’—the balance of dominant modes of learning (for example, learning from parents, peers, or unrelated elders) throughout an individual’s lifetime—suggest that age structure may play a crucial role in determining learning modes and cultural evolutionary trajectories. Thus, studied in isolation, demographic and cultural evolutionary models show only part of the picture. This paper describes a mathematical and computational framework that combines demographic and cultural evolutionary methods. Using this general framework, we examine interactions between the ways in which culture is spread throughout an individual’s lifetime and cultural change across generations. We show that including demographic structure alongside cultural dynamics can help to explain domain-specific patterns of cultural evolution that are a persistent feature of cultural data, and can shed new light on rare but significant demographic events. [ABSTRACT FROM AUTHOR]

An important goal in researching the biology of olfaction is to link the perception of smells to the chemistry of odorants. In other words, why do some odorants smell like fruits and others like flowers? While the so-called stimulus-percept issue was resolved in the field of color vision some time ago, the relationship between the chemistry and psycho-biology of odors remains unclear up to the present day. Although a series of investigations have demonstrated that this relationship exists, the descriptive and explicative aspects of the proposed models that are currently in use require greater sophistication. One reason for this is that the algorithms of current models do not consistently consider the possibility that multiple chemical rules can describe a single quality despite the fact that this is the case in reality, whereby two very different molecules can evoke a similar odor. Moreover, the available datasets are often large and heterogeneous, thus rendering the generation of multiple rules without any use of a computational approach overly complex. We considered these two issues in the present paper. First, we built a new database containing 1689 odorants characterized by physicochemical properties and olfactory qualities. Second, we developed a computational method based on a subgroup discovery algorithm that discriminated perceptual qualities of smells on the basis of physicochemical properties. Third, we ran a series of experiments on 74 distinct olfactory qualities and showed that the generation and validation of rules linking chemistry to odor perception was possible. Taken together, our findings provide significant new insights into the relationship between stimulus and percept in olfaction. In addition, by automatically extracting new knowledge linking chemistry of odorants and psychology of smells, our results provide a new computational framework of analysis enabling scientists in the field to test original hypotheses using descriptive or predictive modeling. [ABSTRACT FROM AUTHOR]

In this paper, we present a novel Bayesian adaptive dual controller (ADC) for autonomously programming deep brain stimulation devices. We evaluated the Bayesian ADC’s performance in the context of reducing beta power in a computational model of Parkinson’s disease, in which it was tasked with finding the set of stimulation parameters which optimally reduced beta power as fast as possible. Here, the Bayesian ADC has dual goals: (a) to minimize beta power by exploiting the best parameters found so far, and (b) to explore the space to find better parameters, thus allowing for better control in the future. The Bayesian ADC is composed of two parts: an inner parameterized feedback stimulator and an outer parameter adjustment loop. The inner loop operates on a short time scale, delivering stimulus based upon the phase and power of the beta oscillation. The outer loop operates on a long time scale, observing the effects of the stimulation parameters and using Bayesian optimization to intelligently select new parameters to minimize the beta power. We show that the Bayesian ADC can efficiently optimize stimulation parameters, and is superior to other optimization algorithms. The Bayesian ADC provides a robust and general framework for tuning stimulation parameters, can be adapted to use any feedback signal, and is applicable across diseases and stimulator designs. [ABSTRACT FROM AUTHOR]

Integrated Information Theory (IIT) has become nowadays the most sensible general theory of consciousness. In addition to very important statements, it opens the door for an abstract (mathematical) formulation of the theory. Given a mechanism in a particular state, IIT identifies a conscious experience with a conceptual structure, an informational object which exists, is composed of identified parts, is informative, integrated and maximally irreducible. This paper introduces a space-time continuous version of the concept of integrated information. To this aim, a graph and a dynamical systems treatment is used to define, for a given mechanism in a state for which a dynamics is settled, an Informational Structure, which is associated to the global attractor at each time of the system. By definition, the informational structure determines all the past and future behavior of the system, possesses an informational nature and, moreover, enriches all the points of the phase space with cause-effect power by means of its associated Informational Field. A detailed description of its inner structure by invariants and connections between them allows to associate a transition probability matrix to each informational structure and to develop a measure for the level of integrated information of the system. [ABSTRACT FROM AUTHOR]

Workshops are used to explore a specific topic, to transfer knowledge, to solve identified problems, or to create something new. In funded research projects and other research endeavours, workshops are the mechanism used to gather the wider project, community, or interested people together around a particular topic. However, natural questions arise: how do we measure the impact of these workshops? Do we know whether they are meeting the goals and objectives we set for them? What indicators should we use? In response to these questions, this paper will outline rules that will improve the measurement of the impact of workshops. [ABSTRACT FROM AUTHOR]

The mammalian hippocampus plays a crucial role in producing a cognitive map of space—an internalized representation of the animal’s environment. We have previously shown that it is possible to model this map formation using a topological framework, in which information about the environment is transmitted through the temporal organization of neuronal spiking activity, particularly those occasions in which the firing of different place cells overlaps. In this paper, we discuss how gamma rhythm, one of the main components of the extracellular electrical field potential affects the efficiency of place cell map formation. Using methods of algebraic topology and the maximal entropy principle, we demonstrate that gamma modulation synchronizes the spiking of dynamical cell assemblies, which enables learning a spatial map at faster timescales. [ABSTRACT FROM AUTHOR]

It has recently been suggested that movement variability directly increases the speed of motor learning. Here we use computational modeling of motor adaptation to show that variability can have a broad range of effects on learning, both negative and positive. Experimentally, we also find contributing and decelerating effects. Lastly, through a meta-analysis of published papers, we verify that across a wide range of experiments, movement variability has no statistical relation with learning rate. While motor learning is a complex process that can be modeled, further research is needed to understand the relative importance of the involved factors. [ABSTRACT FROM AUTHOR]

Learning the reliability of different sources of rewards is critical for making optimal choices. However, despite the existence of detailed theory describing how the expected reward is learned in the basal ganglia, it is not known how reward uncertainty is estimated in these circuits. This paper presents a class of models that encode both the mean reward and the spread of the rewards, the former in the difference between the synaptic weights of D1 and D2 neurons, and the latter in their sum. In the models, the tendency to seek (or avoid) options with variable reward can be controlled by increasing (or decreasing) the tonic level of dopamine. The models are consistent with the physiology of and synaptic plasticity in the basal ganglia, they explain the effects of dopaminergic manipulations on choices involving risks, and they make multiple experimental predictions. [ABSTRACT FROM AUTHOR]

Shotgun metagenomic analysis of the human associated microbiome provides a rich set of microbial features for prediction and biomarker discovery in the context of human diseases and health conditions. However, the use of such high-resolution microbial features presents new challenges, and validated computational tools for learning tasks are lacking. Moreover, classification rules have scarcely been validated in independent studies, posing questions about the generality and generalization of disease-predictive models across cohorts. In this paper, we comprehensively assess approaches to metagenomics-based prediction tasks and for quantitative assessment of the strength of potential microbiome-phenotype associations. We develop a computational framework for prediction tasks using quantitative microbiome profiles, including species-level relative abundances and presence of strain-specific markers. A comprehensive meta-analysis, with particular emphasis on generalization across cohorts, was performed in a collection of 2424 publicly available metagenomic samples from eight large-scale studies. Cross-validation revealed good disease-prediction capabilities, which were in general improved by feature selection and use of strain-specific markers instead of species-level taxonomic abundance. In cross-study analysis, models transferred between studies were in some cases less accurate than models tested by within-study cross-validation. Interestingly, the addition of healthy (control) samples from other studies to training sets improved disease prediction capabilities. Some microbial species (most notably Streptococcus anginosus) seem to characterize general dysbiotic states of the microbiome rather than connections with a specific disease. Our results in modelling features of the “healthy” microbiome can be considered a first step toward defining general microbial dysbiosis. The software framework, microbiome profiles, and metadata for thousands of samples are publicly available at . [ABSTRACT FROM AUTHOR]

Pitch perception is important for understanding speech prosody, music perception, recognizing tones in tonal languages, and perceiving speech in noisy environments. The two principal pitch perception theories consider the place of maximum neural excitation along the auditory nerve and the temporal pattern of the auditory neurons’ action potentials (spikes) as pitch cues. This paper describes a biophysical mechanism by which fine-structure temporal information can be extracted from the spikes generated at the auditory periphery. Deriving meaningful pitch-related information from spike times requires neural structures specialized in capturing synchronous or correlated activity from amongst neural events. The emergence of such pitch-processing neural mechanisms is described through a computational model of auditory processing. Simulation results show that a correlation-based, unsupervised, spike-based form of Hebbian learning can explain the development of neural structures required for recognizing the pitch of simple and complex tones, with or without the fundamental frequency. The temporal code is robust to variations in the spectral shape of the signal and thus can explain the phenomenon of pitch constancy. [ABSTRACT FROM AUTHOR]

The author discusses aspects of her career and system approaches to stress response in eukaryotes. Topics include protein expression associated to environmental stress, project management, and motivation for laboratory members. In addition, she also presents advice to beginning researchers and principal investigators (PIs).

In pharmaceutical sciences, a crucial step of the drug discovery process is the identification of drug-target interactions. However, only a small portion of the drug-target interactions have been experimentally validated, as the experimental validation is laborious and costly. To improve the drug discovery efficiency, there is a great need for the development of accurate computational approaches that can predict potential drug-target interactions to direct the experimental verification. In this paper, we propose a novel drug-target interaction prediction algorithm, namely neighborhood regularized logistic matrix factorization (NRLMF). Specifically, the proposed NRLMF method focuses on modeling the probability that a drug would interact with a target by logistic matrix factorization, where the properties of drugs and targets are represented by drug-specific and target-specific latent vectors, respectively. Moreover, NRLMF assigns higher importance levels to positive observations (i.e., the observed interacting drug-target pairs) than negative observations (i.e., the unknown pairs). Because the positive observations are already experimentally verified, they are usually more trustworthy. Furthermore, the local structure of the drug-target interaction data has also been exploited via neighborhood regularization to achieve better prediction accuracy. We conducted extensive experiments over four benchmark datasets, and NRLMF demonstrated its effectiveness compared with five state-of-the-art approaches. [ABSTRACT FROM AUTHOR]

Most models of learning and memory assume that memories are maintained in neuronal circuits by persistent synaptic modifications induced by specific patterns of pre- and postsynaptic activity. For this scenario to be viable, synaptic modifications must survive the ubiquitous ongoing activity present in neural circuits in vivo. In this paper, we investigate the time scales of memory maintenance in a calcium-based synaptic plasticity model that has been shown recently to be able to fit different experimental data-sets from hippocampal and neocortical preparations. We find that in the presence of background activity on the order of 1 Hz parameters that fit pyramidal layer 5 neocortical data lead to a very fast decay of synaptic efficacy, with time scales of minutes. We then identify two ways in which this memory time scale can be extended: (i) the extracellular calcium concentration in the experiments used to fit the model are larger than estimated concentrations in vivo. Lowering extracellular calcium concentration to in vivo levels leads to an increase in memory time scales of several orders of magnitude; (ii) adding a bistability mechanism so that each synapse has two stable states at sufficiently low background activity leads to a further boost in memory time scale, since memory decay is no longer described by an exponential decay from an initial state, but by an escape from a potential well. We argue that both features are expected to be present in synapses in vivo. These results are obtained first in a single synapse connecting two independent Poisson neurons, and then in simulations of a large network of excitatory and inhibitory integrate-and-fire neurons. Our results emphasise the need for studying plasticity at physiological extracellular calcium concentration, and highlight the role of synaptic bi- or multistability in the stability of learned synaptic structures. [ABSTRACT FROM AUTHOR]

Statistical books can provide deep insights into statistics and software. There are, however, many resources available to the practitioner. Book reviews have the capacity to function as a critical mechanism for the learner to assess the merits of engaging in part, in full, or at all with a book. The “ten simple rules” format, pioneered in computational biology, was applied here to writing effective book reviews for statistics because of the wide breadth of offerings in this domain, including topical introductions, computational solutions, and theory. Learning by doing is a popular paradigm in statistics and computation, but there is still a niche for books in the pedagogy of self-taught and instruction-based learning. Primarily, these rules ensure that book reviews function as a form of short syntheses to inform and guide readers in deciding to use a specific book relative to other options for resolving statistical challenges. [ABSTRACT FROM AUTHOR]

The article presents author's comments on the rules that should be considered during retirement. It focuses on the retirement in computational biology. It offers information on autobiographical perspective on biomedical data. It focuses on the need for expertise in science, technology, engineering, and medicine (STEM).

The article focuses on main points to be considered by a budding author while writing a book. It is advised to write a complete draft, put it in a drawer, then forget about it while writing a good novel. It is recommended to find the right topic for the book and it is better if the topic is timely and new.

The article presents guidelines for drawing scientific comics for efficient communication of difficult ideas. Suggestions mentioned include finding the right shapes for use in conveying the appropriate message one is trying to make, making one's comics simple to convey a complicated idea easier to understand, and taking time to ensure that the details in one's comics are right.

This article offers tips for students to complete a graduate degree in biological sciences in Latin America. Topics discussed include the features that underlie the performance of graduate programs around the world, the importance of investigating the graduate program and the adviser, scholarship programs for graduate students, and the need to follow administrative procedures from admission to graduation.

The author offers rules for getting the most out of a summer laboratory internship. The rules discussed include summer internships afford no such luxury which is important to optimize learning by working diligently and efficiently, productive stream of communication with mentor and internship has a programming course which can start learning computational skills. It mentions satisfying project, a supportive group, and unique social interactions.

A growing body of evidence highlights the intricate linkage of exteroceptive perception to the rhythmic activity of the visceral body. In parallel, interoceptive inference theories of affective perception and self-consciousness are on the rise in cognitive science. However, thus far no formal theory has emerged to integrate these twin domains; instead, most extant work is conceptual in nature. Here, we introduce a formal model of cardiac active inference, which explains how ascending cardiac signals entrain exteroceptive sensory perception and uncertainty. Through simulated psychophysics, we reproduce the defensive startle reflex and commonly reported effects linking the cardiac cycle to affective behaviour. We further show that simulated 'interoceptive lesions' blunt affective expectations, induce psychosomatic hallucinations, and exacerbate biases in perceptual uncertainty. Through synthetic heart-rate variability analyses, we illustrate how the balance of arousal-priors and visceral prediction errors produces idiosyncratic patterns of physiological reactivity. Our model thus offers a roadmap for computationally phenotyping disordered brain-body interaction. Author summary: Understanding interactions between the brain and the body has become a topic of increased interest in computational neuroscience and psychiatry. A particular question here concerns how visceral, homeostatic rhythms such as the heart beat influence sensory, affective, and cognitive processing. To better understand these and other oscillatory brain-body interactions, we here introduce a novel computational model of interoceptive inference in which a synthetic agent's perceptual beliefs are coupled to the rhythm of the heart. Our model both helps to explain emerging empirical data indicating that perceptual inference depends upon beat-to-beat heart rhythms, and can be used to better quantify intra- and inter-individual differences in heart-brain coupling. Using proof-of-principle simulations, we demonstrate how future empirical works could utilize our model to better understand and stratify disorders of interoception and brain-body interaction. [ABSTRACT FROM AUTHOR]

You can help your principal investigator on the oversight of grant rules and procedures, keeping protocols up to date, writing reports, and fulfilling requests from the Institutional Review Board (IRB). Regardless, what is important is for the administrator to be curious about science and make the effort to get a basic familiarity with the scientific discipline and academic working environment they are supporting. Although human resources, principal investigators, and lab managers are a large part of the onboarding process for a new employee, administrative staff are typically involved in the process as well. [Extracted from the article]

Many models of classical conditioning fail to describe important phenomena, notably the rapid return of fear after extinction. To address this shortfall, evidence converged on the idea that learning agents rely on latent-state inferences, i.e. an ability to index disparate associations from cues to rewards (or penalties) and infer which index (i.e. latent state) is presently active. Our goal was to develop a model of latent-state inferences that uses latent states to predict rewards from cues efficiently and that can describe behavior in a diverse set of experiments. The resulting model combines a Rescorla-Wagner rule, for which updates to associations are proportional to prediction error, with an approximate Bayesian rule, for which beliefs in latent states are proportional to prior beliefs and an approximate likelihood based on current associations. In simulation, we demonstrate the model’s ability to reproduce learning effects both famously explained and not explained by the Rescorla-Wagner model, including rapid return of fear after extinction, the Hall-Pearce effect, partial reinforcement extinction effect, backwards blocking, and memory modification. Lastly, we derive our model as an online algorithm to maximum likelihood estimation, demonstrating it is an efficient approach to outcome prediction. Establishing such a framework is a key step towards quantifying normative and pathological ranges of latent-state inferences in various contexts. [ABSTRACT FROM AUTHOR]

The scientific method has been guiding biological research for a long time. It not only prescribes the order and types of activities that give a scientific study validity and a stamp of approval but also has substantially shaped how we collectively think about the endeavor of investigating nature. The advent of high-throughput data generation, data mining, and advanced computational modeling has thrown the formerly undisputed, monolithic status of the scientific method into turmoil. On the one hand, the new approaches are clearly successful and expect the same acceptance as the traditional methods, but on the other hand, they replace much of the hypothesis-driven reasoning with inductive argumentation, which philosophers of science consider problematic. Intrigued by the enormous wealth of data and the power of machine learning, some scientists have even argued that significant correlations within datasets could make the entire quest for causation obsolete. Many of these issues have been passionately debated during the past two decades, often with scant agreement. It is proffered here that hypothesis-driven, data-mining–inspired, and “allochthonous” knowledge acquisition, based on mathematical and computational models, are vectors spanning a 3D space of an expanded scientific method. The combination of methods within this space will most certainly shape our thinking about nature, with implications for experimental design, peer review and funding, sharing of result, education, medical diagnostics, and even questions of litigation. [ABSTRACT FROM AUTHOR]

In many brain areas, sensory responses are heavily modulated by factors including attentional state, context, reward history, motor preparation, learned associations, and other cognitive variables. Modelling the effect of these modulatory factors on sensory responses has proven challenging, mostly due to the time-varying and nonlinear nature of the underlying computations. Here we present a computational model capable of capturing and dissociating multiple time-varying modulatory effects on neuronal responses on the order of milliseconds. The model’s performance is tested on extrastriate perisaccadic visual responses in nonhuman primates. Visual neurons respond to stimuli presented around the time of saccades differently than during fixation. These perisaccadic changes include sensitivity to the stimuli presented at locations outside the neuron’s receptive field, which suggests a contribution of multiple sources to perisaccadic response generation. Current computational approaches cannot quantitatively characterize the contribution of each modulatory source in response generation, mainly due to the very short timescale on which the saccade takes place. In this study, we use a high spatiotemporal resolution experimental paradigm along with a novel extension of the generalized linear model framework (GLM), termed the sparse-variable GLM, to allow for time-varying model parameters representing the temporal evolution of the system with a resolution on the order of milliseconds. We used this model framework to precisely map the temporal evolution of the spatiotemporal receptive field of visual neurons in the middle temporal area during the execution of a saccade. Moreover, an extended model based on a factorization of the sparse-variable GLM allowed us to disassociate and quantify the contribution of individual sources to the perisaccadic response. Our results show that our novel framework can precisely capture the changes in sensitivity of neurons around the time of saccades, and provide a general framework to quantitatively track the role of multiple modulatory sources over time. [ABSTRACT FROM AUTHOR]

Open-source software projects are also communities of effort. "...developers who join an organization through these programs are half as likely to transition into long-term community members than developers who do not use these programs... although developers who do succeed through these programs find them valuable". 47 Fagerholm F, Guinea AS, Münch J, Borenstein J. The role of mentoring and project characteristics for onboarding in open source software projects. [Extracted from the article]

State-space and action representations form the building blocks of decision-making processes in the brain; states map external cues to the current situation of the agent whereas actions provide the set of motor commands from which the agent can choose to achieve specific goals. Although these factors differ across environments, it is currently unknown whether or how accurately state and action representations are acquired by the agent because previous experiments have typically provided this information a priori through instruction or pre-training. Here we studied how state and action representations adapt to reflect the structure of the world when such a priori knowledge is not available. We used a sequential decision-making task in rats in which they were required to pass through multiple states before reaching the goal, and for which the number of states and how they map onto external cues were unknown a priori. We found that, early in training, animals selected actions as if the task was not sequential and outcomes were the immediate consequence of the most proximal action. During the course of training, however, rats recovered the true structure of the environment and made decisions based on the expanded state-space, reflecting the multiple stages of the task. Similarly, we found that the set of actions expanded with training, although the emergence of new action sequences was sensitive to the experimental parameters and specifics of the training procedure. We conclude that the profile of choices shows a gradual shift from simple representations to more complex structures compatible with the structure of the world. [ABSTRACT FROM AUTHOR]

The popularity of CRISPR-based gene editing has resulted in an abundance of tools to design CRISPR-Cas9 guides. This is also driven by the fact that designing highly specific and efficient guides is a crucial, but not trivial, task in using CRISPR for gene editing. Here, we thoroughly analyse the performance of 18 design tools. They are evaluated based on runtime performance, compute requirements, and guides generated. To achieve this, we implemented a method for auditing system resources while a given tool executes, and tested each tool on datasets of increasing size, derived from the mouse genome. We found that only five tools had a computational performance that would allow them to analyse an entire genome in a reasonable time, and without exhausting computing resources. There was wide variation in the guides identified, with some tools reporting every possible guide while others filtered for predicted efficiency. Some tools also failed to exclude guides that would target multiple positions in the genome. We also considered two collections with over a thousand guides each, for which experimental data is available. There is a lot of variation in performance between the datasets, but the relative order of the tools is partially conserved. Importantly, the most striking result is a lack of consensus between the tools. Our results show that CRISPR-Cas9 guide design tools need further work in order to achieve rapid whole-genome analysis and that improvements in guide design will likely require combining multiple approaches. [ABSTRACT FROM AUTHOR]

We provide a novel computational framework on how biological and artificial agents can learn to flexibly couple and decouple neural task modules for cognitive processing. In this way, they can address the stability-plasticity dilemma. For this purpose, we combine two prominent computational neuroscience principles, namely Binding by Synchrony and Reinforcement Learning. The model learns to synchronize task-relevant modules, while also learning to desynchronize currently task-irrelevant modules. As a result, old (but currently task-irrelevant) information is protected from overwriting (stability) while new information can be learned quickly in currently task-relevant modules (plasticity). We combine learning to synchronize with task modules that learn via one of several classical learning algorithms (Rescorla-Wagner, backpropagation, Boltzmann machines). The resulting combined model is tested on a reversal learning paradigm where it must learn to switch between three different task rules. We demonstrate that our combined model has significant computational advantages over the original network without synchrony, in terms of both stability and plasticity. Importantly, the resulting models’ processing dynamics are also consistent with empirical data and provide empirically testable hypotheses for future MEG/EEG studies. [ABSTRACT FROM AUTHOR]

Mathematical methods of information theory appear to provide a useful language to describe how stimuli are encoded in activities of signaling effectors. Exploring the information-theoretic perspective, however, remains conceptually, experimentally and computationally challenging. Specifically, existing computational tools enable efficient analysis of relatively simple systems, usually with one input and output only. Moreover, their robust and readily applicable implementations are missing. Here, we propose a novel algorithm, SLEMI—statistical learning based estimation of mutual information, to analyze signaling systems with high-dimensional outputs and a large number of input values. Our approach is efficient in terms of computational time as well as sample size needed for accurate estimation. Analysis of the NF-κB single—cell signaling responses to TNF-α reveals that NF-κB signaling dynamics improves discrimination of high concentrations of TNF-α with a relatively modest impact on discrimination of low concentrations. Provided R-package allows the approach to be used by computational biologists with only elementary knowledge of information theory. [ABSTRACT FROM AUTHOR]

The article offers information on the challenging scientific problems faced by humanity. Topics discussed include information on the efforts to empower Africans to join the global neuroscience community; discussions on the BRAIN initiative in the U.S. and the Human Brain Project in Europe; and the information on the limiting factor for computational neuroscience development in Africa.

We have now reached the genomics era within medicine; genomics is being used to personalise treatment, make diagnoses, prognoses, and predict adverse outcomes resulting from treatment with certain drugs. Genomic data is now abundant in healthcare, and the newly created profession of clinical bioinformaticians are responsible for its analysis. In the United Kingdom, clinical bioinformaticians are trained within a 3-year programme, integrating a work-based placement with a part-time Master’s degree. As this profession is still developing, trainees can feel isolated from their peers whom are located in other hospitals and can find it difficult to gain the mentorship that they require to complete their training. Building strong networks or communities of practice (CoPs) and allowing sharing of knowledge and experiences is one solution to addressing this isolation. Within the Master’s delivered at the University of Manchester, we have integrated group-centred problem-based learning (PBL) using real clinical case studies worked on during each course unit. This approach is combined with a flipped style of teaching providing access to online content in our Virtual Learning Environment before the course. The face-to-face teaching is used to focus on the application of the students’ knowledge to clinical case studies. In this study, we conducted semistructured interviews with 8 students, spanning 3 cohorts of students. We evaluated the effectiveness of this style of teaching and whether it had contributed to the formation of CoPs between our students. Our findings demonstrated that this style of teaching was preferred by our students to a more traditional lecture-based format and that the problem-based learning approach enabled the formation of CoPs within these cohorts. These CoPs are valuable in the development of this new profession and assist with the production of new guidelines and policies that are helping to professionalise this new group of healthcare scientists. [ABSTRACT FROM AUTHOR]

Supported by recent computational studies, there is increasing evidence that a wide range of neuronal responses can be understood as an emergent property of nonnegative sparse coding (NSC), an efficient population coding scheme based on dimensionality reduction and sparsity constraints. We review evidence that NSC might be employed by sensory areas to efficiently encode external stimulus spaces, by some associative areas to conjunctively represent multiple behaviorally relevant variables, and possibly by the basal ganglia to coordinate movement. In addition, NSC might provide a useful theoretical framework under which to understand the often complex and nonintuitive response properties of neurons in other brain areas. Although NSC might not apply to all brain areas (for example, motor or executive function areas) the success of NSC-based models, especially in sensory areas, warrants further investigation for neural correlates in other regions. [ABSTRACT FROM AUTHOR]

Studies to improve the efficacy of epilepsy surgery have focused on better refining the localization of the epileptogenic zone (EZ) with the aim of effectively resecting it. However, in a considerable number of patients, EZs are distributed across multiple brain regions and may involve eloquent areas that cannot be removed due to the risk of neurological complications. There is a clear need for developing alternative approaches to induce seizure relief, but minimal impact on normal brain functions. Here, we develop a personalized in-silico network approach, that suggests effective and safe surgical interventions for each patient. Based on the clinically identified EZ, we employ modularity analysis to identify target brain regions and fiber tracts involved in seizure propagation. We then construct and simulate a patient-specific brain network model comprising phenomenological neural mass models at the nodes, and patient-specific structural brain connectivity using the neuroinformatics platform The Virtual Brain (TVB), in order to evaluate effectiveness and safety of the target zones (TZs). In particular, we assess safety via electrical stimulation for pre- and post-surgical condition to quantify the impact on the signal transmission properties of the network. We demonstrate the existence of a large repertoire of efficient surgical interventions resulting in reduction of degree of seizure spread, but only a small subset of them proves safe. The identification of novel surgical interventions through modularity analysis and brain network simulations may provide exciting solutions to the treatment of inoperable epilepsies. [ABSTRACT FROM AUTHOR]