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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.

There has been considerable debate and concern as to whether there is a replication crisis in the scientific literature. A likely cause of poor replication is the multiple comparisons problem. An important way in which this problem can manifest in the M/EEG context is through post hoc tailoring of analysis windows (a.k.a. regions-of-interest, ROIs) to landmarks in the collected data. Post hoc tailoring of ROIs is used because it allows researchers to adapt to inter-experiment variability and discover novel differences that fall outside of windows defined by prior precedent, thereby reducing Type II errors. However, this approach can dramatically inflate Type I error rates. One way to avoid this problem is to tailor windows according to a contrast that is orthogonal (strictly parametrically orthogonal) to the contrast being tested. A key approach of this kind is to identify windows on a fully flattened average. On the basis of simulations, this approach has been argued to be safe for post hoc tailoring of analysis windows under many conditions. Here, we present further simulations and mathematical proofs to show exactly why the Fully Flattened Average approach is unbiased, providing a formal grounding to the approach, clarifying the limits of its applicability and resolving published misconceptions about the method. We also provide a statistical power analysis, which shows that, in specific contexts, the fully flattened average approach provides higher statistical power than Fieldtrip cluster inference. This suggests that the Fully Flattened Average approach will enable researchers to identify more effects from their data without incurring an inflation of the false positive rate. Author summary: It is clear from recent replicability studies that the replication rate in psychology and cognitive neuroscience is not high. One reason for this is that the noise in high dimensional neuroimaging data sets can "look-like" signal. A classic manifestation would be selecting a region in the data volume where an effect is biggest and then specifically reporting results on that region. There is a key trade-off in the selection of such regions of interest: liberal selection will inflate false positive rates, but conservative selection (e.g. strictly on the basis of prior precedent in the literature) can reduce statistical power, causing real effects to be missed. We propose a means to reconcile these two possibilities, by which regions of interest can be tailored to the pattern in the collected data, while not inflating false-positive rates. This is based upon generating what we call the Flattened Average. Critically, we validate the correctness of this method both in (ground-truth) simulations and with formal mathematical proofs. Given the replication "crisis", there may be no more important issue in psychology and cognitive neuroscience than improving the application of methods. This paper makes a valuable contribution to this improvement. [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.

In cognitive neuroscience and psychology, reaction times are an important behavioral measure. However, in instrumental learning and goal-directed decision making experiments, findings often rely only on choice probabilities from a value-based model, instead of reaction times. Recent advancements have shown that it is possible to connect value-based decision models with reaction time models. However, typically these models do not provide an integrated account of both value-based choices and reaction times, but simply link two types of models. Here, we propose a novel integrative joint model of both choices and reaction times by combining a computational account of Bayesian sequential decision making with a sampling procedure. This allows us to describe how internal uncertainty in the planning process shapes reaction time distributions. Specifically, we use a recent context-specific Bayesian forward planning model which we extend by a Markov chain Monte Carlo (MCMC) sampler to obtain both choices and reaction times. As we will show this makes the sampler an integral part of the decision making process and enables us to reproduce, using simulations, well-known experimental findings in value based-decision making as well as classical inhibition and switching tasks. Specifically, we use the proposed model to explain both choice behavior and reaction times in instrumental learning and automatized behavior, in the Eriksen flanker task and in task switching. These findings show that the proposed joint behavioral model may describe common underlying processes in these different decision making paradigms. Author summary: Many influential results in psychology and cognitive neuroscience rest on reaction time effects in behavioral experiments, for example in studies about human decision making. For the particular case of decisions based on the value of options, however, findings often rely on analyses of choices using specific computational models. Until recently, these models did not allow for analysis of reaction times. In this article we introduce a new model of how to explain both choices and reaction times in decision making experiments that involve evaluating expected outcomes over multiple steps. Importantly, the model explains how the brain can make good decisions quickly, even in the face of many potential choices and in complex environments. [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]

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]

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).

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]

In operant learning, behaviors are reinforced or inhibited in response to the consequences of similar actions taken in the past. However, because in natural environments the “same” situation never recurs, it is essential for the learner to decide what “similar” is so that he can generalize from experience in one state of the world to future actions in different states of the world. The computational principles underlying this generalization are poorly understood, in particular because natural environments are typically too complex to study quantitatively. In this paper we study the principles underlying generalization in operant learning of professional basketball players. In particular, we utilize detailed information about the spatial organization of shot locations to study how players adapt their attacking strategy in real time according to recent events in the game. To quantify this learning, we study how a make \ miss from one location in the court affects the probabilities of shooting from different locations. We show that generalization is not a spatially-local process, nor is governed by the difficulty of the shot. Rather, to a first approximation, players use a simplified binary representation of the court into 2 pt and 3 pt zones. This result indicates that rather than using low-level features, generalization is determined by high-level cognitive processes that incorporate the abstract rules of the game. [ABSTRACT FROM AUTHOR]

The free-energy principle has recently been proposed as a unified Bayesian account of perception, learning and action. Despite the inextricable link between emotion and cognition, emotion has not yet been formulated under this framework. A core concept that permeates many perspectives on emotion is valence, which broadly refers to the positive and negative character of emotion or some of its aspects. In the present paper, we propose a definition of emotional valence in terms of the negative rate of change of free-energy over time. If the second time-derivative of free-energy is taken into account, the dynamics of basic forms of emotion such as happiness, unhappiness, hope, fear, disappointment and relief can be explained. In this formulation, an important function of emotional valence turns out to regulate the learning rate of the causes of sensory inputs. When sensations increasingly violate the agent's expectations, valence is negative and increases the learning rate. Conversely, when sensations increasingly fulfil the agent's expectations, valence is positive and decreases the learning rate. This dynamic interaction between emotional valence and learning rate highlights the crucial role played by emotions in biological agents' adaptation to unexpected changes in their world. [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.

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]

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]

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]

Humans and other animals are able to discover underlying statistical structure in their environments and exploit it to achieve efficient and effective performance. However, such structure is often difficult to learn and use because it is obscure, involving long-range temporal dependencies. Here, we analysed behavioural data from an extended experiment with rats, showing that the subjects learned the underlying statistical structure, albeit suffering at times from immediate inferential imperfections as to their current state within it. We accounted for their behaviour using a Hidden Markov Model, in which recent observations are integrated with evidence from the past. We found that over the course of training, subjects came to track their progress through the task more accurately, a change that our model largely attributed to improved integration of past evidence. This learning reflected the structure of the task, decreasing reliance on recent observations, which were potentially misleading. [ABSTRACT FROM AUTHOR]

Computational modeling plays an important role in modern neuroscience research. Much previous research has relied on statistical methods, separately, to address two problems that are actually interdependent. First, given a particular computational model, Bayesian hierarchical techniques have been used to estimate individual variation in parameters over a population of subjects, leveraging their population-level distributions. Second, candidate models are themselves compared, and individual variation in the expressed model estimated, according to the fits of the models to each subject. The interdependence between these two problems arises because the relevant population for estimating parameters of a model depends on which other subjects express the model. Here, we propose a hierarchical Bayesian inference (HBI) framework for concurrent model comparison, parameter estimation and inference at the population level, combining previous approaches. We show that this framework has important advantages for both parameter estimation and model comparison theoretically and experimentally. The parameters estimated by the HBI show smaller errors compared to other methods. Model comparison by HBI is robust against outliers and is not biased towards overly simplistic models. Furthermore, the fully Bayesian approach of our theory enables researchers to make inference on group-level parameters by performing HBI t-test. [ABSTRACT FROM AUTHOR]

The Iowa Gambling Task (IGT) is one of the most common paradigms used to assess decision-making and executive functioning in neurological and psychiatric disorders. Several reinforcement-learning (RL) models were recently proposed to refine the qualitative and quantitative inferences that can be made about these processes based on IGT data. Yet, these models do not account for the complex exploratory patterns which characterize participants’ behavior in the task. Using a dataset of more than 500 subjects, we demonstrate the existence of sequential exploration in the IGT and we describe a new computational architecture disentangling exploitation, random exploration and sequential exploration in this large population of participants. The new Value plus Sequential Exploration (VSE) architecture provided a better fit than previous models. Parameter recovery, model recovery and simulation analyses confirmed the superiority of the VSE scheme. Furthermore, using the VSE model, we confirmed the existence of a significant reduction in directed exploration across lifespan in the IGT, as previously reported with other paradigms. Finally, we provide a user-friendly toolbox enabling researchers to easily and flexibly fit computational models on the IGT data, hence promoting reanalysis of the numerous datasets acquired in various populations of patients and contributing to the development of computational psychiatry. [ABSTRACT FROM AUTHOR]

Popular computational models of decision-making make specific assumptions about learning processes that may cause them to underfit observed behaviours. Here we suggest an alternative method using recurrent neural networks (RNNs) to generate a flexible family of models that have sufficient capacity to represent the complex learning and decision- making strategies used by humans. In this approach, an RNN is trained to predict the next action that a subject will take in a decision-making task and, in this way, learns to imitate the processes underlying subjects’ choices and their learning abilities. We demonstrate the benefits of this approach using a new dataset drawn from patients with either unipolar (n = 34) or bipolar (n = 33) depression and matched healthy controls (n = 34) making decisions on a two-armed bandit task. The results indicate that this new approach is better than baseline reinforcement-learning methods in terms of overall performance and its capacity to predict subjects’ choices. We show that the model can be interpreted using off-policy simulations and thereby provides a novel clustering of subjects’ learning processes—something that often eludes traditional approaches to modelling and behavioural analysis. [ABSTRACT FROM AUTHOR]

We address the question of color-space interactions in the brain, by proposing a neural field model of color perception with spatial context for the visual area V1 of the cortex. Our framework reconciles two opposing perceptual phenomena, known as simultaneous contrast and chromatic assimilation. They have been previously shown to act synergistically, so that at some point in an image, the color seems perceptually more similar to that of adjacent neighbors, while being more dissimilar from that of remote ones. Thus, their combined effects are enhanced in the presence of a spatial pattern, and can be measured as larger shifts in color matching experiments. Our model supposes a hypercolumnar structure coding for colors in V1, and relies on the notion of color opponency introduced by Hering. The connectivity kernel of the neural field exploits the balance between attraction and repulsion in color and physical spaces, so as to reproduce the sign reversal in the influence of neighboring points. The color sensation at a point, defined from a steady state of the neural activities, is then extracted as a nonlinear percept conveyed by an assembly of neurons. It connects the cortical and perceptual levels, because we describe the search for a color match in asymmetric matching experiments as a mathematical projection on color sensations. We validate our color neural field alongside this color matching framework, by performing a multi-parameter regression to data produced by psychophysicists and ourselves. All the results show that we are able to explain the nonlinear behavior of shifts observed along one or two dimensions in color space, which cannot be done using a simple linear model. [ABSTRACT FROM AUTHOR]

In a flipped classroom, students complete automated modules to replace a traditional lecture, allowing the time devoted for the lecture to be devoted to constructive tasks reinforcing student knowledge. Yet although the flipped classroom offers a compelling approach for fostering a constructivist, student-centric learning environment, research on the efficacy of flipped classes has been mixed. For that matter, is it possible to successfully flip a classroom in an advanced, heavily specialized course like a bioinformatics algorithms course? Over the past several years, the author has implemented a flipped version of such a course and will discuss some of the successes and pitfalls encountered. [ABSTRACT FROM AUTHOR]

The activity of neural populations in the brains of humans and animals can exhibit vastly different spatial patterns when faced with different tasks or environmental stimuli. The degrees of similarity between these neural activity patterns in response to different events are used to characterize the representational structure of cognitive states in a neural population. The dominant methods of investigating this similarity structure first estimate neural activity patterns from noisy neural imaging data using linear regression, and then examine the similarity between the estimated patterns. Here, we show that this approach introduces spurious bias structure in the resulting similarity matrix, in particular when applied to fMRI data. This problem is especially severe when the signal-to-noise ratio is low and in cases where experimental conditions cannot be fully randomized in a task. We propose Bayesian Representational Similarity Analysis (BRSA), an alternative method for computing representational similarity, in which we treat the covariance structure of neural activity patterns as a hyper-parameter in a generative model of the neural data. By marginalizing over the unknown activity patterns, we can directly estimate this covariance structure from imaging data. This method offers significant reductions in bias and allows estimation of neural representational similarity with previously unattained levels of precision at low signal-to-noise ratio, without losing the possibility of deriving an interpretable distance measure from the estimated similarity. The method is closely related to Pattern Component Model (PCM), but instead of modeling the estimated neural patterns as in PCM, BRSA models the imaging data directly and is suited for analyzing data in which the order of task conditions is not fully counterbalanced. The probabilistic framework allows for jointly analyzing data from a group of participants. The method can also simultaneously estimate a signal-to-noise ratio map that shows where the learned representational structure is supported more strongly. Both this map and the learned covariance matrix can be used as a structured prior for maximum a posteriori estimation of neural activity patterns, which can be further used for fMRI decoding. Our method therefore paves the way towards a more unified and principled analysis of neural representations underlying fMRI signals. We make our tool freely available in Brain Imaging Analysis Kit (BrainIAK). [ABSTRACT FROM AUTHOR]

Cortico-basal-ganglia-thalamic (CBGT) networks are critical for adaptive decision-making, yet how changes to circuit-level properties impact cognitive algorithms remains unclear. Here we explore how dopaminergic plasticity at corticostriatal synapses alters competition between striatal pathways, impacting the evidence accumulation process during decision-making. Spike-timing dependent plasticity simulations showed that dopaminergic feedback based on rewards modified the ratio of direct and indirect corticostriatal weights within opposing action channels. Using the learned weight ratios in a full spiking CBGT network model, we simulated neural dynamics and decision outcomes in a reward-driven decision task and fit them with a drift diffusion model. Fits revealed that the rate of evidence accumulation varied with inter-channel differences in direct pathway activity while boundary height varied with overall indirect pathway activity. This multi-level modeling approach demonstrates how complementary learning and decision computations can emerge from corticostriatal plasticity. [ABSTRACT FROM AUTHOR]

In order to record the stream of autobiographical information that defines our unique personal history, our brains must form durable memories from single brief exposures to the patterned stimuli that impinge on them continuously throughout life. However, little is known about the computational strategies or neural mechanisms that underlie the brain's ability to perform this type of "online" learning. Based on increasing evidence that dendrites act as both signaling and learning units in the brain, we developed an analytical model that relates online recognition memory capacity to roughly a dozen dendritic, network, pattern, and task-related parameters. We used the model to determine what dendrite size maximizes storage capacity under varying assumptions about pattern density and noise level. We show that over a several-fold range of both of these parameters, and over multiple orders-of-magnitude of memory size, capacity is maximized when dendrites contain a few hundred synapses—roughly the natural number found in memory-related areas of the brain. Thus, in comparison to entire neurons, dendrites increase storage capacity by providing a larger number of better-sized learning units. Our model provides the first normative theory that explains how dendrites increase the brain’s capacity for online learning; predicts which combinations of parameter settings we should expect to find in the brain under normal operating conditions; leads to novel interpretations of an array of existing experimental results; and provides a tool for understanding which changes associated with neurological disorders, aging, or stress are most likely to produce memory deficits—knowledge that could eventually help in the design of improved clinical treatments for memory loss. [ABSTRACT FROM AUTHOR]

An editorial is presented on rules for providing a meaningful research experience to high school students. Topics discussed include ten rules for becoming an effective research mentor for high school students and their training, research opportunities as undergraduates and career consideration in science, technology, engineering, and mathematics and bridging the gap between scientists and the general public on scientific research.

We present 10 tips for building effective lessons that are grounded in empirical research on pedagogy and cognitive psychology and that we have found to be practically useful in both classroom and free-range settings [ABSTRACT FROM AUTHOR]

The ability to correctly estimate the probability of one’s choices being correct is fundamental to optimally re-evaluate previous choices or to arbitrate between different decision strategies. Experimental evidence nonetheless suggests that this metacognitive process—confidence judgment- is susceptible to numerous biases. Here, we investigate the effect of outcome valence (gains or losses) on confidence while participants learned stimulus-outcome associations by trial-and-error. In two experiments, participants were more confident in their choices when learning to seek gains compared to avoiding losses, despite equal difficulty and performance between those two contexts. Computational modelling revealed that this bias is driven by the context-value, a dynamically updated estimate of the average expected-value of choice options, necessary to explain equal performance in the gain and loss domain. The biasing effect of context-value on confidence, revealed here for the first time in a reinforcement-learning context, is therefore domain-general, with likely important functional consequences. We show that one such consequence emerges in volatile environments, where the (in)flexibility of individuals’ learning strategies differs when outcomes are framed as gains or losses. Despite apparent similar behavior- profound asymmetries might therefore exist between learning to avoid losses and learning to seek gains. [ABSTRACT FROM AUTHOR]

Evaluating the future consequences of actions is achievable by simulating a mental search tree into the future. Expanding deep trees, however, is computationally taxing. Therefore, machines and humans use a plan-until-habit scheme that simulates the environment up to a limited depth and then exploits habitual values as proxies for consequences that may arise in the future. Two outstanding questions in this scheme are “in which directions the search tree should be expanded?”, and “when should the expansion stop?”. Here we propose a principled solution to these questions based on a speed/accuracy tradeoff: deeper expansion in the appropriate directions leads to more accurate planning, but at the cost of slower decision-making. Our simulation results show how this algorithm expands the search tree effectively and efficiently in a grid-world environment. We further show that our algorithm can explain several behavioral patterns in animals and humans, namely the effect of time-pressure on the depth of planning, the effect of reward magnitudes on the direction of planning, and the gradual shift from goal-directed to habitual behavior over the course of training. The algorithm also provides several predictions testable in animal/human experiments. [ABSTRACT FROM AUTHOR]

Manipulating the dynamics of neural systems through targeted stimulation is a frontier of research and clinical neuroscience; however, the control schemes considered for neural systems are mismatched for the unique needs of manipulating neural dynamics. An appropriate control method should respect the variability in neural systems, incorporating moment to moment “input” to the neural dynamics and behaving based on the current neural state, irrespective of the past trajectory. We propose such a controller under a nonlinear state-space feedback framework that steers one dynamical system to function as through it were another dynamical system entirely. This “myopic” controller is formulated through a novel variant of a model reference control cost that manipulates dynamics in a short-sighted manner that only sets a target trajectory of a single time step into the future (hence its myopic nature), which omits the need to pre-calculate a rigid and computationally costly neural feedback control solution. To demonstrate the breadth of this control’s utility, two examples with distinctly different applications in neuroscience are studied. First, we show the myopic control’s utility to probe the causal link between dynamics and behavior for cognitive processes by transforming a winner-take-all decision-making system to operate as a robust neural integrator of evidence. Second, an unhealthy motor-like system containing an unwanted beta-oscillation spiral attractor is controlled to function as a healthy motor system, a relevant clinical example for neurological disorders. [ABSTRACT FROM AUTHOR]

Consideration of previous successes and failures is essential to mastering a motor skill. Much of what we know about how humans and animals learn from such reinforcement feedback comes from experiments that involve sampling from a small number of discrete actions. Yet, it is less understood how we learn through reinforcement feedback when sampling from a continuous set of possible actions. Navigating a continuous set of possible actions likely requires using gradient information to maximize success. Here we addressed how humans adapt the aim of their hand when experiencing reinforcement feedback that was associated with a continuous set of possible actions. Specifically, we manipulated the change in the probability of reward given a change in motor action—the reinforcement gradient—to study its influence on learning. We found that participants learned faster when exposed to a steep gradient compared to a shallow gradient. Further, when initially positioned between a steep and a shallow gradient that rose in opposite directions, participants were more likely to ascend the steep gradient. We introduce a model that captures our results and several features of motor learning. Taken together, our work suggests that the sensorimotor system relies on temporally recent and spatially local gradient information to drive learning. [ABSTRACT FROM AUTHOR]

A set of sub-cortical nuclei called basal ganglia is critical for learning the values of actions. The basal ganglia include two pathways, which have been associated with approach and avoid behavior respectively and are differentially modulated by dopamine projections from the midbrain. Inspired by the influential opponent actor learning model, we demonstrate that, under certain circumstances, these pathways may represent learned estimates of the positive and negative consequences (payoffs and costs) of individual actions. In the model, the level of dopamine activity encodes the motivational state and controls to what extent payoffs and costs enter the overall evaluation of actions. We show that a set of previously proposed plasticity rules is suitable to extract payoffs and costs from a prediction error signal if they occur at different moments in time. For those plasticity rules, successful learning requires differential effects of positive and negative outcome prediction errors on the two pathways and a weak decay of synaptic weights over trials. We also confirm through simulations that the model reproduces drug-induced changes of willingness to work, as observed in classical experiments with the D2-antagonist haloperidol. [ABSTRACT FROM AUTHOR]

A well-established notion in cognitive neuroscience proposes that multiple brain systems contribute to choice behaviour. These include: (1) a model-free system that uses values cached from the outcome history of alternative actions, and (2) a model-based system that considers action outcomes and the transition structure of the environment. The widespread use of this distinction, across a range of applications, renders it important to index their distinct influences with high reliability. Here we consider the two-stage task, widely considered as a gold standard measure for the contribution of model-based and model-free systems to human choice. We tested the internal/temporal stability of measures from this task, including those estimated via an established computational model, as well as an extended model using drift-diffusion. Drift-diffusion modeling suggested that both choice in the first stage, and RTs in the second stage, are directly affected by a model-based/free trade-off parameter. Both parameter recovery and the stability of model-based estimates were poor but improved substantially when both choice and RT were used (compared to choice only), and when more trials (than conventionally used in research practice) were included in our analysis. The findings have implications for interpretation of past and future studies based on the use of the two-stage task, as well as for characterising the contribution of model-based processes to choice behaviour. [ABSTRACT FROM AUTHOR]