Computational Neuroscience Models Research Articles

Using automated controlled rearing to explore the origins of object permanence.

What are the origins of object permanence? Despite widespread interest in this question, methodological barriers have prevented detailed analysis of how experience shapes the development of object permanence in newborn organisms. Here, we introduce an automated controlled-rearing method for studying the emergence of object permanence in strictly controlled virtual environments. We used newborn chicks as an animal model and recorded their behavior continuously (24/7) from the onset of vision. Across four experiments, we found that object permanence can develop rapidly, within the first few days of life. This ability developed even when chicks were reared in impoverished visual environments containing no object occlusion events. Object permanence failed to develop, however, when chicks were reared in environments containing temporally non-smooth objects (objects moving on discontinuous spatiotemporal paths). These results suggest that experience with temporally smooth objects facilitates the development of object permanence, confirming a key prediction of temporal learning models in computational neuroscience.

Code Generation in Computational Neuroscience: A Review of Tools and Techniques.

Advances in experimental techniques and computational power allowing researchers to gather anatomical and electrophysiological data at unprecedented levels of detail have fostered the development of increasingly complex models in computational neuroscience. Large-scale, biophysically detailed cell models pose a particular set of computational challenges, and this has led to the development of a number of domain-specific simulators. At the other level of detail, the ever growing variety of point neuron models increases the implementation barrier even for those based on the relatively simple integrate-and-fire neuron model. Independently of the model complexity, all modeling methods crucially depend on an efficient and accurate transformation of mathematical model descriptions into efficiently executable code. Neuroscientists usually publish model descriptions in terms of the mathematical equations underlying them. However, actually simulating them requires they be translated into code. This can cause problems because errors may be introduced if this process is carried out by hand, and code written by neuroscientists may not be very computationally efficient. Furthermore, the translated code might be generated for different hardware platforms, operating system variants or even written in different languages and thus cannot easily be combined or even compared. Two main approaches to addressing this issues have been followed. The first is to limit users to a fixed set of optimized models, which limits flexibility. The second is to allow model definitions in a high level interpreted language, although this may limit performance. Recently, a third approach has become increasingly popular: using code generation to automatically translate high level descriptions into efficient low level code to combine the best of previous approaches. This approach also greatly enriches efforts to standardize simulator-independent model description languages. In the past few years, a number of code generation pipelines have been developed in the computational neuroscience community, which differ considerably in aim, scope and functionality. This article provides an overview of existing pipelines currently used within the community and contrasts their capabilities and the technologies and concepts behind them.

Automated Metadata Suggestion During Repository Submission

Knowledge discovery via an informatics resource is constrained by the completeness of the resource, both in terms of the amount of data it contains and in terms of the metadata that exists to describe the data. Increasing completeness in one of these categories risks reducing completeness in the other because manually curating metadata is time consuming and is restricted by familiarity with both the data and the metadata annotation scheme. The diverse interests of a research community may drive a resource to have hundreds of metadata tags with few examples for each making it challenging for humans or machine learning algorithms to learn how to assign metadata tags properly. We demonstrate with ModelDB, a computational neuroscience model discovery resource, that using manually-curated regular-expression based rules can overcome this challenge by parsing existing texts from data providers during user data entry to suggest metadata annotations and prompt them to suggest other related metadata annotations rather than leaving the task to a curator. In the ModelDB implementation, analyzing the abstract identified 6.4 metadata tags per abstract at 79% precision. Using the full-text produced higher recall with low precision (41%), and the title alone produced few (1.3) metadata annotations per entry; we thus recommend data providers use their abstract during upload. Grouping the possible metadata annotations into categories (e.g. cell type, biological topic) revealed that precision and recall for the different text sources varies by category. Given this proof-of-concept, other bioinformatics resources can likewise improve the quality of their metadata by adopting our approach of prompting data uploaders with relevant metadata at the minimal cost of formalizing rules for each potential metadata annotation.

Geppetto: a reusable modular open platform for exploring neuroscience data and models.

Geppetto is an open-source platform that provides generic middleware infrastructure for building both online and desktop tools for visualizing neuroscience models and data and managing simulations. Geppetto underpins a number of neuroscience applications, including Open Source Brain (OSB), Virtual Fly Brain (VFB), NEURON-UI and NetPyNE-UI. OSB is used by researchers to create and visualize computational neuroscience models described in NeuroML and simulate them through the browser. VFB is the reference hub for Drosophila melanogaster neural anatomy and imaging data including neuropil, segmented neurons, microscopy stacks and gene expression pattern data. Geppetto is also being used to build a new user interface for NEURON, a widely used neuronal simulation environment, and for NetPyNE, a Python package for network modelling using NEURON. Geppetto defines domain agnostic abstractions used by all these applications to represent their models and data and offers a set of modules and components to integrate, visualize and control simulations in a highly accessible way. The platform comprises a backend which can connect to external data sources, model repositories and simulators together with a highly customizable frontend.This article is part of a discussion meeting issue ‘Connectome to behaviour: modelling C. elegans at cellular resolution’.

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. Here we present Uncertainpy, an open-source Python toolbox, tailored to perform uncertainty quantification and sensitivity analysis of neuroscience models. Uncertainpy aims to make it quick and easy 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. Uncertainpy 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, average 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. The aim of the current paper is to present Uncertainpy to the neuroscience community in a user-oriented manner. To demonstrate its broad applicability, we perform an uncertainty quantification and sensitivity analysis of 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.

Parameter Optimization Using Covariance Matrix Adaptation-Evolutionary Strategy (CMA-ES), an Approach to Investigate Differences in Channel Properties Between Neuron Subtypes.

Computational models in neuroscience can be used to predict causal relationships between biological mechanisms in neurons and networks, such as the effect of blocking an ion channel or synaptic connection on neuron activity. Since developing a biophysically realistic, single neuron model is exceedingly difficult, software has been developed for automatically adjusting parameters of computational neuronal models. The ideal optimization software should work with commonly used neural simulation software; thus, we present software which works with models specified in declarative format for the MOOSE simulator. Experimental data can be specified using one of two different file formats. The fitness function is customizable as a weighted combination of feature differences. The optimization itself uses the covariance matrix adaptation-evolutionary strategy, because it is robust in the face of local fluctuations of the fitness function, and deals well with a high-dimensional and discontinuous fitness landscape. We demonstrate the versatility of the software by creating several model examples of each of four types of neurons (two subtypes of spiny projection neurons and two subtypes of globus pallidus neurons) by tuning to current clamp data. Optimizations reached convergence within 1,600–4,000 model evaluations (200–500 generations × population size of 8). Analysis of the parameters of the best fitting models revealed differences between neuron subtypes, which are consistent with prior experimental results. Overall our results suggest that this easy-to-use, automatic approach for finding neuron channel parameters may be applied to current clamp recordings from neurons exhibiting different biochemical markers to help characterize ionic differences between other neuron subtypes.

The Brain Dynamics Toolbox for Matlab

Abstract Nonlinear dynamical systems are increasingly informing both theoretical and empirical branches of neuroscience. The Brain Dynamics Toolbox provides an interactive simulation platform for exploring such systems in Matlab . It supports the major classes of differential equations that arise in computational neuroscience: Ordinary Differential Equations, Delay Differential Equations and Stochastic Differential Equations. The design of the graphical interface fosters intuitive exploration of the dynamics while still supporting scripted parameter explorations and large-scale simulations. Although the toolbox is intended for dynamical models in computational neuroscience, it can be applied to dynamical systems from any domain.

An efficient coding approach to the debate on grounded cognition

The debate between the amodal and the grounded views of cognition seems to be stuck. Their only substantial disagreement is about the vehicle or format of concepts. Amodal theorists reject the grounded claim that concepts are couched in the same modality-specific format as representations in sensory systems. The problem is that there is no clear characterization of (modal or amodal) format or its neural correlate. In order to make the disagreement empirically meaningful and move forward in the discussion we need a neurocognitive criterion for representational format. I argue that efficient coding models in computational neuroscience can be used to characterize modal codes: These are codes which satisfy special informational demands imposed by sensory tasks. Additionally, I examine recent studies on neural coding and argue that although they do not provide conclusive evidence for either the grounded or the amodal views, they can be used to determine what predictions these approaches can make and what experimental and theoretical developments would be required to settle the debate.

Credibility, Replicability, and Reproducibility in Simulation for Biomedicine and Clinical Applications in Neuroscience.

Modeling and simulation in computational neuroscience is currently a research enterprise to better understand neural systems. It is not yet directly applicable to the problems of patients with brain disease. To be used for clinical applications, there must not only be considerable progress in the field but also a concerted effort to use best practices in order to demonstrate model credibility to regulatory bodies, to clinics and hospitals, to doctors, and to patients. In doing this for neuroscience, we can learn lessons from long-standing practices in other areas of simulation (aircraft, computer chips), from software engineering, and from other biomedical disciplines. In this manuscript, we introduce some basic concepts that will be important in the development of credible clinical neuroscience models: reproducibility and replicability; verification and validation; model configuration; and procedures and processes for credible mechanistic multiscale modeling. We also discuss how garnering strong community involvement can promote model credibility. Finally, in addition to direct usage with patients, we note the potential for simulation usage in the area of Simulation-Based Medical Education, an area which to date has been primarily reliant on physical models (mannequins) and scenario-based simulations rather than on numerical simulations.

The Development of Invariant Object Recognition Requires Visual Experience With Temporally Smooth Objects.

How do newborns learn to recognize objects? According to temporal learning models in computational neuroscience, the brain constructs object representations by extracting smoothly changing features from the environment. To date, however, it is unknown whether newborns depend on smoothly changing features to build invariant object representations. Here, we used an automated controlled-rearing method to examine whether visual experience with smoothly changing features facilitates the development of view-invariant object recognition in a newborn animal model-the domestic chick (Gallus gallus). When newborn chicks were reared with a virtual object that moved smoothly over time, the chicks created view-invariant representations that were selective for object identity and tolerant to viewpoint changes. Conversely, when newborn chicks were reared with a temporally non-smooth object, the chicks developed less selectivity for identity features and less tolerance to viewpoint changes. These results provide evidence for a "smoothness constraint" on the development of invariant object recognition and indicate that newborns leverage the temporal smoothness of natural visual environments to build abstract mental models of objects.

Arkheia: Data Management and Communication for Open Computational Neuroscience.

Two trends have been unfolding in computational neuroscience during the last decade. First, a shift of focus to increasingly complex and heterogeneous neural network models, with a concomitant increase in the level of collaboration within the field (whether direct or in the form of building on top of existing tools and results). Second, a general trend in science toward more open communication, both internally, with other potential scientific collaborators, and externally, with the wider public. This multi-faceted development toward more integrative approaches and more intense communication within and outside of the field poses major new challenges for modelers, as currently there is a severe lack of tools to help with automatic communication and sharing of all aspects of a simulation workflow to the rest of the community. To address this important gap in the current computational modeling software infrastructure, here we introduce Arkheia. Arkheia is a web-based open science platform for computational models in systems neuroscience. It provides an automatic, interactive, graphical presentation of simulation results, experimental protocols, and interactive exploration of parameter searches, in a web browser-based application. Arkheia is focused on automatic presentation of these resources with minimal manual input from users. Arkheia is written in a modular fashion with a focus on future development of the platform. The platform is designed in an open manner, with a clearly defined and separated API for database access, so that any project can write its own backend translating its data into the Arkheia database format. Arkheia is not a centralized platform, but allows any user (or group of users) to set up their own repository, either for public access by the general population, or locally for internal use. Overall, Arkheia provides users with an automatic means to communicate information about not only their models but also individual simulation results and the entire experimental context in an approachable graphical manner, thus facilitating the user's ability to collaborate in the field and outreach to a wider audience.

A mechanistic perspective on canonical neural computation

Although it has been argued that mechanistic explanation is compatible with abstraction (i.e., that there are abstract mechanistic models), there are still doubts about whether mechanism can account for the explanatory power of significant abstract models in computational neuroscience. Chirimuuta has recently claimed that models describing canonical neural computations (CNCs) must be evaluated using a non-mechanistic framework. I defend two claims regarding these models. First, I argue that their prevailing neurocognitive interpretation is mechanistic. Additionally, a criterion recently proposed by Levy and Bechtel to legitimize mechanistic abstract models, and also a criterion proposed by Chirimuuta herself aimed to distinguish between causal and non-causal explanation, can be employed to show why these models are explanatory only under this interpretation (as opposed to a purely mathematical or non-causal interpretation). Second, I argue that mechanism is able to account for the special epistemic achievement implied by CNC models. Canonical neural components contribute to an integrated understanding of different cognitive functions. They make it possible for us to explain these functions by describing different mechanisms constituted by common basic components arranged in different ways.

Top-down models in biology: explanation and control of complex living systems above the molecular level.

It is widely assumed in developmental biology and bioengineering that optimal understanding and control of complex living systems follows from models of molecular events. The success of reductionism has overshadowed attempts at top-down models and control policies in biological systems. However, other fields, including physics, engineering and neuroscience, have successfully used the explanations and models at higher levels of organization, including least-action principles in physics and control-theoretic models in computational neuroscience. Exploiting the dynamic regulation of pattern formation in embryogenesis and regeneration requires new approaches to understand how cells cooperate towards large-scale anatomical goal states. Here, we argue that top-down models of pattern homeostasis serve as proof of principle for extending the current paradigm beyond emergence and molecule-level rules. We define top-down control in a biological context, discuss the examples of how cognitive neuroscience and physics exploit these strategies, and illustrate areas in which they may offer significant advantages as complements to the mainstream paradigm. By targeting system controls at multiple levels of organization and demystifying goal-directed (cybernetic) processes, top-down strategies represent a roadmap for using the deep insights of other fields for transformative advances in regenerative medicine and systems bioengineering.

Hierarchical winner-take-all particle swarm optimization social network for neural model fitting.

Particle swarm optimization (PSO) has gained widespread use as a general mathematical programming paradigm and seen use in a wide variety of optimization and machine learning problems. In this work, we introduce a new variant on the PSO social network and apply this method to the inverse problem of input parameter selection from recorded auditory neuron tuning curves. The topology of a PSO social network is a major contributor to optimization success. Here we propose a new social network which draws influence from winner-take-all coding found in visual cortical neurons. We show that the winner-take-all network performs exceptionally well on optimization problems with greater than 5 dimensions and runs at a lower iteration count as compared to other PSO topologies. Finally we show that this variant of PSO is able to recreate auditory frequency tuning curves and modulation transfer functions, making it a potentially useful tool for computational neuroscience models.

Twenty years of ModelDB and beyond: building essential modeling tools for the future of neuroscience.

Neuron modeling may be said to have originated with the Hodgkin and Huxley action potential model in 1952 and Rall's models of integrative activity of dendrites in 1964. Over the ensuing decades, these approaches have led to a massive development of increasingly accurate and complex data-based models of neurons and neuronal circuits. ModelDB was founded in 1996 to support this new field and enhance the scientific credibility and utility of computational neuroscience models by providing a convenient venue for sharing them. It has grown to include over 1100 published models covering more than 130 research topics. It is actively curated and developed to help researchers discover and understand models of interest. ModelDB also provides mechanisms to assist running models both locally and remotely, and has a graphical tool that enables users to explore the anatomical and biophysical properties that are represented in a model. Each of its capabilities is undergoing continued refinement and improvement in response to user experience. Large research groups (Allen Brain Institute, EU Human Brain Project, etc.) are emerging that collect data across multiple scales and integrate that data into many complex models, presenting new challenges of scale. We end by predicting a future for neuroscience increasingly fueled by new technology and high performance computation, and increasingly in need of comprehensive user-friendly databases such as ModelDB to provide the means to integrate the data for deeper insights into brain function in health and disease.

The promises and pitfalls of applying computational models to neurological and psychiatric disorders.

Computational models have become an integral part of basic neuroscience and have facilitated some of the major advances in the field. More recently, such models have also been applied to the understanding of disruptions in brain function. In this review, using examples and a simple analogy, we discuss the potential for computational models to inform our understanding of brain function and dysfunction. We argue that they may provide, in unprecedented detail, an understanding of the neurobiological and mental basis of brain disorders and that such insights will be key to progress in diagnosis and treatment. However, there are also potential problems attending this approach. We highlight these and identify simple principles that should always govern the use of computational models in clinical neuroscience, noting especially the importance of a clear specification of a model's purpose and of the mapping between mathematical concepts and reality.

25th Annual Computational Neuroscience Meeting: CNS-2016.

25th Annual Computational Neuroscience Meeting: CNS-2016.

Connections between Retinex, neural models and variational methods

This paper explores the interrelations between Retinex, neural models and variational methods by making an overview of relevant related works in the past few years. Taking all the essential elements of the Retinex theory as postulated by Land and McCann (channel independence, the ratio reset mechanism, local averages, non-linear correction), it has been shown that we can obtain a Retinex algorithm implementation that is intrinsically 2D, whose results comply with all the expected properties of the original, one-dimensional path-based Retinex algorithm (such as approximating color constancy while being unable to deal with overexposed images) but don't suffer from common shortcomings such as sensitivity to noise, appearance of halos, etc. An iterative application of this 2D Retinex algorithm takes the form of a partial differential equation (PDE) that it's proven not to minimize any energy functional, and this fact is linked to its limitations regarding over-exposed pictures. It was proposed to modify in this regard the iterative method in a certain way so that it is able to handle both under and over-exposed images, the resulting PDE now has a number of very relevant properties which allow to connect Retinex with variational models, histogram equalization and efficient coding, perceptual color correction algorithms, and computational neuroscience models of cortical activity and retinal models.

Neuromorphic VLSI realization of the hippocampal formation

The medial entorhinal cortex grid cells, aided by the subicular head direction cells, are thought to provide a matrix which is utilized by the hippocampal place cells for calculation of position of an animal during spatial navigation. The place cells are thought to function as an internal GPS for the brain and provide a spatiotemporal stamp on episodic memories. Several computational neuroscience models have been proposed to explain the place specific firing patterns of the cells of the hippocampal formation — including the GRIDSmap model for grid cells and Bayesian integration for place cells. In this work, we present design and measurement results from a first ever system of silicon circuits which successfully realize the function of the hippocampal formation of brain based on these models.

Neural Information Processing in Cognition: We Start to Understand the Orchestra, but Where is the Conductor?

Research in neural information processing has been successful in the past, providing useful approaches both to practical problems in computer science and to computational models in neuroscience. Recent developments in the area of cognitive neuroscience present new challenges for a computational or theoretical understanding asking for neural information processing models that fulfill criteria or constraints from cognitive psychology, neuroscience and computational efficiency. The most important of these criteria for the evaluation of present and future contributions to this new emerging field are listed at the end of this article.