Abstract

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.

Highlights

  • Computational modeling has become a useful tool for examining various phenomena in biology in general (Brodland, 2015) and neuroscience in particular (Koch and Segev, 1998; Dayan and Abbott, 2001; Sterratt et al, 2011)

  • We demonstrate how to use Uncertainpy by applying it to four different case studies: (i) a simple model for the temperature of a cooling coffee cup implemented in Python, (ii) the original Hodgkin-Huxley model implemented in Python, (iii) a multi-compartmental model of a thalamic interneuron implemented in NEURON, and (iv) a sparsely connected recurrent network model implemented in NEST

  • A major challenge with models in neuroscience is that they tend to contain several uncertain parameters whose values are critical for the model behavior

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Summary

SIGNIFICANCE STATEMENT

A major challenge in computational neuroscience is to specify the often large number of parameters that define neuron and neural network models. Many of these parameters have an inherent variability, and some are even actively regulated and change with time. It is important to know how the uncertainty in the 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

INTRODUCTION
THEORY ON UNCERTAINTY
Problem Definition
Uncertainty Quantification
Sensitivity Analysis
Polynomial Chaos Expansions
Dependency Between Uncertain
Feature-Based Analysis
USER GUIDE FOR UNCERTAINPY
The Uncertainty Quantification Class
Models
NEURON Model Class
Parameters of the Model
Features
Uncertainty Calculations in Uncertainpy
Data Format
Visualization
Technical Aspects
EXAMPLE APPLICATIONS
Cooling Coffee Cup
Cooling Coffee Cup With Statistically
Hodgkin-Huxley Model
Multi-Compartmental Model of a Thalamic Interneuron
Recurrent Network of Integrate-and-Fire Neurons
Comparing the Quasi-Monte Carlo Method to Polynomial Chaos Expansions
Additional Examples
DISCUSSION
Application of Uncertainpy
Further Development of Uncertainpy
Findings
Outlook
Full Text
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