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Uncertainpy: A Python toolbox for uncertainty quantification and sensitivity analysis in computational neuroscience.

Computational models in neuroscience typically contain many parameters that are poorly constrained by experimental data. Uncertainty quantification and sensitivity analysis provide rigorous procedures to quantify how the model output depends on this parameter uncertainty. Unfortunately, the application of such methods is not yet standard within the field of neuroscience.\n\nHere we present Uncertainpy, an open-source Python toolbox, tailored to perform uncertainty quantification and sensitivity analysis of neuroscience models. Uncertainpy aims to make it easy and quick to get started with uncertainty analysis, without any need for detailed prior knowledge. The toolbox allows uncertainty quantification and sensitivity analysis to be performed on already existing models without needing to modify the model equations or model implementation. Uncertainpy bases its analysis on polynomial chaos expansions, which are more efficient than the more standard Monte-Carlo based approaches.\n\nUncertainpy is tailored for neuroscience applications by its built-in capability for calculating characteristic features in the model output. The toolbox does not merely perform a point-to- point comparison of the \"raw\" model output (e.g. membrane voltage traces), but can also calculate the uncertainty and sensitivity of salient model response features such as spike timing, action potential width, mean interspike interval, and other features relevant for various neural and neural network models. Uncertainpy comes with several common models and features built in, and including custom models and new features is easy.\n\nThe aim of the current paper is to present Uncertainpy for the neuroscience community in a user- oriented manner. To demonstrate its broad applicability, we perform an uncertainty quantification and sensitivity analysis on three case studies relevant for neuroscience: the original Hodgkin-Huxley point-neuron model for action potential generation, a multi-compartmental model of a thalamic interneuron implemented in the NEURON simulator, and a sparsely connected recurrent network model implemented in the NEST simulator.\n\nSIGNIFICANCE STATEMENTA major challenge in computational neuroscience is to specify the often large number of parameters that define the neuron and neural network models. Many of these parameters have an inherent variability, and some may even be actively regulated and change with time. It is important to know how the uncertainty in model parameters affects the model predictions. To address this need we here present Uncertainpy, an open-source Python toolbox tailored to perform uncertainty quantification and sensitivity analysis of neuroscience models.

neuroscience

Is there a problem with methods skills in cognitive neuroscience? Evidence from an online survey.

Cognitive neuroscience increasingly relies on complex data analysis methods. Researchers in this field come from highly diverse scientific backgrounds, such as psychology, engineering and medicine. This poses challenges with respect to acquisition of appropriate scientific computing and data analysis skills, as well as communication among researchers with different knowledge and skills sets. Are researchers in cognitive neuroscience adequately equipped to address these challenges? Here, we present evidence from an online survey of methods skills. Respondents (n=305) mainly comprised students and post-doctoral researchers working in the cognitive neurosciences. Multiple choice questions addressed a variety of basic and fundamental aspects of neuroimaging data analysis, such as signal analysis, linear algebra, and statistics. We analysed performance with respect to the following factors: undergraduate degree (grouped into Psychology, Methods, Biology), current researcher status (undergraduate student, PhD student, post-doctoral researcher), gender, and self-rated expertise levels. Overall accuracy was 72%. Not surprisingly, the Methods group performed best (87%), followed by Biology (73%) and Psychology (66%). Accuracy increased from undergraduate (59%) to PhD (74%) level, but not from PhD to post-doctoral (74%) level. The difference in performance for the Methods versus non-methods (Psychology/Biology) groups was particularly striking for questions related to signal analysis and linear algebra, two areas especially relevant to neuroimaging research. Self-rated methods expertise was not strongly predictive of performance. The majority of respondents (93%) indicated they would like to receive at least some additional training on the topics covered in this survey. In conclusion, methods skills among junior researchers in cognitive neuroscience can be improved, researchers are aware of this, and there is strong demand for more skills-oriented training opportunities. We hope that this survey will provide an empirical basis for the development of bespoke skills-oriented training programmes in cognitive neuroscience institutions.

scientific communication and education

BRAINformat: A Data Standardization Framework for Neuroscience Data

Neuroscience is entering the era of extreme data with little experience and few plans for the associated volume, velocity, variety, and veracity challenges. This is a serious impediment for both the sharing of data across labs, as well as the utilization of modern and high-performance computing capabilities to enable data driven discovery. Here, we introduce BRAINformat, a novel file format and model for management and storage of neuroscience data. The BRAINformat library defines application-independent design concepts and modules that together create a general framework for standardization of scientific data.\n\nWe describe the formal specification of scientific data standards, which facilitates sharing and verification of data and formats. We introduce the concept of Managed Objects, enabling semantic components of data formats to be specified as self-contained units, supporting modular and reusable design of data format components and file storage. The BRAINformat is built off of HDF5, enabling portable, scalable, and self-describing data storage. We introduce the novel concept of Relationship Attributes for modeling and use of semantic relationships between data objects, and discuss the annotation of data using dedicated data annotation modules provided by the BRAINformat library. Based on these concepts we implement dedicated, application-oriented modules and design a data standard for neuroscience data. The BRAINformat software library is open source, easy-to-use, and provides detailed user and developer documentation and is freely available at: https://bitbucket.org/oruebel/brainformat.

Neuroscience

Empirical assessment of published effect sizes and power in the recent cognitive neuroscience and psychology literature

We have empirically assessed the distribution of published effect sizes and estimated power by extracting more than 100,000 statistical records from about 10,000 cognitive neuroscience and psychology papers published during the past 5 years. The reported median effect size was d=0.93 (inter-quartile range: 0.64-1.46) for nominally statistically significant results and d=0.24 (0.11-0.42) for non-significant results. Median power to detect small, medium and large effects was 0.12, 0.44 and 0.73, reflecting no improvement through the past half-century. Power was lowest for cognitive neuroscience journals. 14% of papers reported some statistically significant results, although the respective F statistic and degrees of freedom proved that these were non-significant; p value errors positively correlated with journal impact factors. False report probability is likely to exceed 50% for the whole literature. In light of our findings the recently reported low replication success in psychology is realistic and worse performance may be expected for cognitive neuroscience.

Neuroscience

The Role Of Diffusion MRI In Neuroscience

Diffusion weighted imaging has further pushed the boundaries of neuroscience by allowing us to peer farther into the white matter microstructure of the living human brain. By doing so, it has provided answers to fundamental neuroscientific questions, launching a new field of research that had been largely inaccessible. We will briefly summarise key questions, that have historically been raised in neuroscience, concerning the brains white matter. We will then expand on the benefits of diffusion weighted imaging and its contribution to the fields of brain anatomy, functional models and plasticity. In doing so, this review will highlight the invaluable contribution of diffusion weighted imaging in neuroscience, present its limitations and put forth new challenges for the future generations who may wish to exploit this powerful technology to gain novel insights.

neuroscience

Neural data science: accelerating the experiment-analysis-theory cycle in large-scale neuroscience

Modern large - scale multineuronal recording methodologies, including multielectrode arrays, calcium imaging, and optogenetic techniques, produce single - neuron resolution data of a magnitude and precision that were the realm of science fiction twenty years ago. The major bottlenecks in systems and circuit neuroscience no longer lie in simply collecting data from large neural populations, but also in understanding this data: developing novel scientific questions, with corresponding analysis techniques and experimental designs to fully harness these new capabilities and meaningfully interrogate these questions. Advances in methods for signal processing, network analysis, dimensionality reduction, and optimal control - developed in lockstep with advances in experimental neurotechnology - - promise major breakthroughs in multiple fundamental neuroscience problems. These trends are clear in a broad array of subfields of modern neuroscience; this review focuses on recent advances in methods for analyzing neural time - series data with single - neuronal precision.\n\nO_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=46 SRC=\"FIGDIR/small/196949_fig1.gif\" ALT=\"Figure 1\">\nView larger version (13K):\norg.highwire.dtl.DTLVardef@16fff01org.highwire.dtl.DTLVardef@1ceacd4org.highwire.dtl.DTLVardef@1b49960org.highwire.dtl.DTLVardef@1c1ad13_HPS_FORMAT_FIGEXP M_FIG O_FLOATNOFigure 1.C_FLOATNO The central role of data science in modern large - scale neuroscience.Topics reviewed herein are indicated in black.\n\nC_FIG

neuroscience

Building a Web of Linked Data Resources to Advance Neuroscience Research

The fundamental goal of neuroscience is to understand the nervous system at all levels of description, from molecular components to behavior. The complexity of achieving this goal in neuroscience, and biomedicine in general, poses many technical and sociological challenges. Among these are the need to organize neuroscientific data, information, and knowledge to facilitate new scientific endeavors, provide credibility and visibility of research findings, and increase the efficiency of data reuse. Linked Data is a set of principles based on Web technology that can aid this process as it organizes data as an interconnected network of information. This review examines the history, practical impact, potential, and challenges of applying Linked Data principles to neuroscience.

Scientific Communication and Education

A systematic review of sample size and power in leading neuroscience journals

Adequate sample size is key to reproducible research findings: low statistical power can increase the probability that a statistically significant result is a false positive. Journals are increasingly adopting methods to tackle issues of reproducibility, such as by introducing reporting checklists. We conducted a systematic review comparing articles submitted to Nature Neuroscience in the 3 months prior to checklists (n=36) that were subsequently published with articles submitted to Nature Neuroscience in the 3 months immediately after checklists (n=45), along with a comparison journal Neuroscience in this same 3-month period (n=123). We found that although the proportion of studies commenting on sample sizes increased after checklists (22% vs 53%), the proportion reporting formal power calculations decreased (14% vs 9%). Using sample size calculations for 80% power and a significance level of 5%, we found little evidence that sample sizes were adequate to achieve this level of statistical power, even for large effect sizes. Our analysis suggests that reporting checklists may not improve the use and reporting of formal power calculations.

scientific communication and education

Towards an integration of deep learning and neuroscience

Neuroscience has focused on the detailed implementation of computation, studying neural codes, dynamics and circuits. In machine learning, however, artificial neural networks tend to eschew precisely designed codes, dynamics or circuits in favor of brute force optimization of a cost function, often using simple and relatively uniform initial architectures. Two recent developments have emerged within machine learning that create an opportunity to connect these seemingly divergent perspectives. First, structured architectures are used, including dedicated systems for attention, recursion and various forms of short- and long-term memory storage. Second, cost functions and training procedures have become more complex and are varied across layers and over time. Here we think about the brain in terms of these ideas. We hypothesize that (1) the brain optimizes cost functions, (2) the cost functions are diverse and differ across brain locations and over development, and (3) optimization operates within a pre-structured architecture matched to the computational problems posed by behavior. In support of these hypotheses, we argue that a range of implementations of credit assignment through multiple layers of neurons are compatible with our current knowledge of neural circuitry, and that the brains specialized systems can be interpreted as enabling efficient optimization for specific problem classes. Such a heterogeneously optimized system, enabled by a series of interacting cost functions, serves to make learning data-efficient and precisely targeted to the needs of the organism. We suggest directions by which neuroscience could seek to refine and test these hypotheses.

Neuroscience

Deep Neural Networks In Computational Neuroscience

The goal of computational neuroscience is to find mechanistic explanations of how the nervous system processes information to give rise to cognitive function and behaviour. At the heart of the field are its models, i.e. mathematical and computational descriptions of the system being studied, which map sensory stimuli to neural responses and/or neural to behavioural responses. These models range from simple to complex. Recently, deep neural networks (DNNs) have come to dominate several domains of artificial intelligence (AI). As the term \"neural network\" suggests, these models are inspired by biological brains. However, current DNNs neglect many details of biological neural networks. These simplifications contribute to their computational efficiency, enabling them to perform complex feats of intelligence, ranging from perceptual (e.g. visual object and auditory speech recognition) to cognitive tasks (e.g. machine translation), and on to motor control (e.g. playing computer games or controlling a robot arm). In addition to their ability to model complex intelligent behaviours, DNNs excel at predicting neural responses to novel sensory stimuli with accuracies well beyond any other currently available model type. DNNs can have millions of parameters, which are required to capture the domain knowledge needed for successful task performance. Contrary to the intuition that this renders them into impenetrable black boxes, the computational properties of the network units are the result of four directly manipulable elements: input statistics, network structure, functional objective, and learning algorithm. With full access to the activity and connectivity of all units, advanced visualization techniques, and analytic tools to map network representations to neural data, DNNs represent a powerful framework for building task-performing models and will drive substantial insights in computational neuroscience.

neuroscience

RTHybrid: a standardized and open-source real-time software model library for experimental neuroscience

Closed-loop technologies provide novel ways of online observation, control and bidirectional interaction with the nervous system, which help to study complex non-linear and partially observable neural dynamics. These protocols are often difficult to implement due to the temporal precision required when interacting with biological components, which in many cases can only be achieved using real-time technology. In this paper we introduce RTHybrid (www.github.com/GNB-UAM/RTHybrid), a free and open-source software that includes a neuron and synapse model library to build hybrid circuits with living neurons in a wide variety of experimental contexts. In an effort to encourage the standardization of real-time software technology in neuroscience research, we compared different open-source real-time operating system patches, RTAI, Xenomai 3 and Preempt-RT, according to their performance and usability. RTHybrid has been developed to run over Linux operating systems supporting both Xenomai 3 and Preempt-RT real-time patches, and thus allowing an easy implementation in any laboratory. We report a set of validation tests and latency benchmarks for the construction of hybrid circuits using this library. With this work we want to promote the dissemination of standardized, user-friendly and open-source software tools developed for open- and closed-loop experimental neuroscience.

neuroscience

De Novo PacBio long-read and phased avian genome assemblies correct and add to genes important in neuroscience research

Reference quality genomes are expected to provide a resource for studying gene structure and function. However, often genes of interest are not completely or accurately assembled, leading to unknown errors in analyses or additional cloning efforts for the correct sequences. A promising solution to this problem is long-read sequencing. Here we tested PacBio-based long-read sequencing and diploid assembly for potential improvements to the Sanger-based intermediate-read zebra finch reference and Illumina-based short-read Annas hummingbird reference, two vocal learning avian species widely studied in neuroscience and genomics. With DNA of the same individuals used to generate the reference genomes, we generated diploid assemblies with the FALCON-Unzip assembler, resulting in contigs with no gaps in the megabase range (N50s of 5.4 and 7.7 Mb, respectively), and representing 150-fold and 200-fold improvements over the current zebra finch and hummingbird references, respectively. These long-read assemblies corrected and resolved what we discovered to be misassemblies, including due to erroneous sequences flanking gaps, complex repeat structure errors in the references, base call errors in difficult to sequence regions, and inaccurate resolution of allelic differences between the two haplotypes. We analyzed protein-coding genes widely studied in neuroscience and specialized in vocal learning species, and found numerous assembly and sequence errors in the reference genes that the PacBio-based assemblies resolved completely, validated by single long genomic reads and transcriptome reads. These findings demonstrate, for the first time in non-human vocal learning species, the impact of higher quality, phased and gap-less assemblies for understanding gene structure and function.

genomics

Spikeling: a low-cost hardware implementation of a spiking neuron for neuroscience teaching and outreach.

Understanding of how neurons encode and compute information is fundamental to our study of the brain, but opportunities for hands-on experience with neurophysiological techniques on live neurons are scarce in science education. Here, we present Spikeling, an open source {pound}25 in silico implementation of a spiking neuron that mimics a wide range of neuronal behaviours for classroom education and public neuroscience outreach. Spikeling is based on an Arduino microcontroller running the computationally efficient Izhikevich model of a spiking neuron. The microcontroller is connected to input ports that simulate synaptic excitation or inhibition, dials controlling current injection and noise levels, a photodiode that makes Spikeling light-sensitive and an LED and speaker that allows spikes to be seen and heard. Output ports provide access to variables such as membrane potential for recording in experiments or digital signals that can be used to excite other connected Spikelings. These features allow for the intuitive exploration of the function of neurons and networks. We also report our experience of using Spikeling as a teaching tool for undergraduate and graduate neuroscience education in Nigeria and the UK.

scientific communication and education

Towards standard practices for sharing computer code and programs in neuroscience

Background Background References Many areas of neuroscience are now critically dependent on computational tools to help understand the large volumes of data being created. Furthermore, computer models are increasingly being used to help predict and understand the function of the nervous system. Many of these computations are complex and usually cannot be concisely reported in the methods section of a scientific article. In a few areas there are widely used software packages for analysis (e.g., SPM, FSL, AFNI, FreeSurfer, Civet in neuroimaging) or simulation (e.g. NEURON, NEST, Brian). However, we often write new computer programs to solve specific problems in the course of our research. Some of these programs may be relatively small scripts that help analyze all of our data, and these rarely get described in papers. As authors, how best can we maximize the chances that other scientists can reprod ...

Neuroscience

Control without controllers: Towards a distributed neuroscience of executive control

Executive control refers to the regulation of cognition and behavior by mental processes and is a hallmark of higher cognition. Most approaches to understanding its mechanisms begin with the assumption that our brains have anatomically segregated and functionally specialized control modules. The modular approach is intuitive: control is conceptually distinct from basic mental processing, so an organization that reifies that distinction makes sense. An alternative approach sees executive control as self-organizing principles of a distributed organization. In distributed systems, control and controlled processes are co-localized within large numbers of dispersed computational agents. Control then is often an emergent consequence of simple rules governing the interaction between agents. Because these systems are unfamiliar and unintuitive, here we review several well-understood examples of distributed control systems, group living insects and social animals, and emphasize their parallels with neural systems. We then re-examine the cognitive neuroscience literature on executive control for evidence that its neural control systems may be distributed.

Neuroscience

Computational cognitive neuroscience: what is a good model of brain processes?

Cognitive neuroscience, especially in the fields of learning and decision-making, is witnessing the blossoming of computational model-based analyses. Several methodological and review papers have indicated how and why candidate models should be compared by trading off their ability to predict the data as a function of their complexity. However, the importance of simulating candidate models has been so far largely overlooked, which entails several drawbacks and leads to invalid conclusions. Here we argue that the analysis of model simulations is often necessary to support the specific claims about behavioral function that most of model-based studies make. We defend this argument both informally by providing a large-scale (N>300) review of recent studies, and formally by showing how model simulations are necessary to interpret model comparison results. Finally, we propose guidelines for future work, which combine model comparison and simulation.

Neuroscience

Developmental cognitive neuroscience using Latent Change Score models: A tutorial and applications

Assessing and analysing individual differences in change over time is of central scientific importance to developmental neuroscience. However, the literature is based largely on cross-sectional comparisons, which reflect a variety of influences and cannot directly represent change. We advocate using latent change score (LCS) models in longitudinal samples as a statistical framework to tease apart the complex processes underlying lifespan development in brain and behaviour using longitudinal data. LCS models provide a flexible framework that naturally accommodates key developmental questions as model parameters and can even be used, with some limitations, in cases with only two measurement occasions. We illustrate the use of LCS models with two empirical examples. In a lifespan cognitive training study (COGITO, N=204 (N=32 imaging) on two waves) we observe correlated change in brain and behaviour in the context of a high-intensity training intervention. In an adolescent development cohort (NSPN, N=176, two waves) we find greater variability in cortical thinning in males than in females. To facilitate the adoption of LCS by the developmental community, we provide analysis code that can be adapted by other researchers and basic primers in two freely available SEM software packages (lavaan and {Omega}nyx).\n\nHighlightsO_LIWe describe Latent change score modelling as a flexible statistical tool\nC_LIO_LIKey developmental questions can be readily formalized using LCS models\nC_LIO_LIWe provide accessible open source code and software examples to fit LCS models\nC_LIO_LIWhite matter structural change is negatively correlated with processing speed gains\nC_LIO_LIFrontal lobe thinning in adolescence is more variable in males than females\nC_LI

neuroscience

Beyond differences in means: robust graphical methods to compare two groups in neuroscience

If many changes are necessary to improve the quality of neuroscience research, one relatively simple step could have great pay-offs: to promote the adoption of detailed graphical methods, combined with robust inferential statistics. Here we illustrate how such methods can lead to a much more detailed understanding of group differences than bar graphs and t-tests on means. To complement the neuroscientists toolbox, we present two powerful tools that can help us understand how groups of observations differ: the shift function and the difference asymmetry function. These tools can be combined with detailed visualisations to provide complementary perspectives about the data. We provide implementations in R and Matlab of the graphical tools, and all the examples in the article can be reproduced using R scripts.

neuroscience