NFTsim: Theory and Simulation of Multiscale Neural Field Dynamics.

A user ready, portable, documented software package, NFTsim, is presented to facilitate numerical simulations of a wide range of brain systems using continuum neural field modeling. NFTsim enables users to simulate key aspects of brain activity at multiple scales. At the microscopic scale, it incorporates characteristics of local interactions between cells, neurotransmitter effects, synaptodendritic delays and feedbacks. At the mesoscopic scale, it incorporates information about medium to large scale axonal ranges of fibers, which are essential to model dissipative wave transmission and to produce synchronous oscillations and associated cross-correlation patterns as observed in local field potential recordings of active tissue. At the scale of the whole brain, NFTsim allows for the inclusion of long range pathways, such as thalamocortical projections, when generating macroscopic activity fields. The multiscale nature of the neural activity produced by NFTsim has the potential to enable the modeling of resulting quantities measurable via various neuroimaging techniques. In this work, we give a comprehensive description of the design and implementation of the software. Due to its modularity and flexibility, NFTsim enables the systematic study of an unlimited number of neural systems with multiple neural populations under a unified framework and allows for direct comparison with analytic and experimental predictions. The code is written in C++ and bundled with Matlab routines for a rapid quantitative analysis and visualization of the outputs. The output of NFTsim is stored in plain text file enabling users to select from a broad range of tools for offline analysis. This software enables a wide and convenient use of powerful physiologically-based neural field approaches to brain modeling. NFTsim is distributed under the Apache 2.0 license.

Mathematical framework for large-scale brain network modeling in The Virtual Brain.

In this article, we describe the mathematical framework of the computational model at the core of the tool The Virtual Brain (TVB), designed to simulate collective whole brain dynamics by virtualizing brain structure and function, allowing simultaneous outputs of a number of experimental modalities such as electro- and magnetoencephalography (EEG, MEG) and functional Magnetic Resonance Imaging (fMRI). The implementation allows for a systematic exploration and manipulation of every underlying component of a large-scale brain network model (BNM), such as the neural mass model governing the local dynamics or the structural connectivity constraining the space time structure of the network couplings. Here, a consistent notation for the generalized BNM is given, so that in this form the equations represent a direct link between the mathematical description of BNMs and the components of the numerical implementation in TVB. Finally, we made a summary of the forward models implemented for mapping simulated neural activity (EEG, MEG, sterotactic electroencephalogram (sEEG), fMRI), identifying their advantages and limitations.

Prediction of shiftworker alertness, sleep, and circadian phase using a model of arousal dynamics constrained by shift schedules and light exposure.

STUDY OBJECTIVES: The study aimed to, for the first time, (1) compare sleep, circadian phase, and alertness of intensive care unit (ICU) nurses working rotating shifts with those predicted by a model of arousal dynamics; and (2) investigate how different environmental constraints affect predictions and agreement with data. METHODS: The model was used to simulate individual sleep-wake cycles, urinary 6-sulphatoxymelatonin (aMT6s) profiles, subjective sleepiness on the Karolinska Sleepiness Scale (KSS), and performance on a Psychomotor Vigilance Task (PVT) of 21 ICU nurses working day, evening, and night shifts. Combinations of individual shift schedules, forced wake time before/after work and lighting, were used as inputs to the model. Predictions were compared to empirical data. Simulations with self-reported sleep as an input were performed for comparison. RESULTS: All input constraints produced similar prediction for KSS, with 56%-60% of KSS scores predicted within ±1 on a day and 48%-52% on a night shift. Accurate prediction of an individual's circadian phase required individualized light input. Combinations including light information predicted aMT6s acrophase within ±1 h of the study data for 65% and 35%-47% of nurses on diurnal and nocturnal schedules. Minute-by-minute sleep-wake state overlap between the model and the data was between 81 ± 6% and 87 ± 5% depending on choice of input constraint. CONCLUSIONS: The use of individualized environmental constraints in the model of arousal dynamics allowed for accurate prediction of alertness, circadian phase, and sleep for more than half of the nurses. Individual differences in physiological parameters will need to be accounted for in the future to further improve predictions.

Small-world properties of nonlinear brain activity in schizophrenia.

A disturbance in the interactions between distributed cortical regions may underlie the cognitive and perceptual dysfunction associated with schizophrenia. In this article, nonlinear measures of cortical interactions and graph-theoretical metrics of network topography are combined to investigate this schizophrenia "disconnection hypothesis." This is achieved by analyzing the spatiotemporal structure of resting state scalp EEG data previously acquired from 40 young subjects with a recent first episode of schizophrenia and 40 healthy matched controls. In each subject, a method of mapping the topography of nonlinear interactions between cortical regions was applied to a widely distributed array of these data. The resulting nonlinear correlation matrices were converted to weighted graphs. The path length (a measure of large-scale network integration), clustering coefficient (a measure of "cliquishness"), and hub structure of these graphs were used as metrics of the underlying brain network activity. The graphs of both groups exhibited high levels of local clustering combined with comparatively short path lengths--features consistent with a "small-world" topology--as well as the presence of strong, central hubs. The graphs in the schizophrenia group displayed lower clustering and shorter path lengths in comparison to the healthy group. Whilst still "small-world," these effects are consistent with a subtle randomization in the underlying network architecture--likely associated with a greater number of links connecting disparate clusters. This randomization may underlie the cognitive disturbances characteristic of schizophrenia.

Integrating neuroinformatics tools in TheVirtualBrain.

TheVirtualBrain (TVB) is a neuroinformatics Python package representing the convergence of clinical, systems, and theoretical neuroscience in the analysis, visualization and modeling of neural and neuroimaging dynamics. TVB is composed of a flexible simulator for neural dynamics measured across scales from local populations to large-scale dynamics measured by electroencephalography (EEG), magnetoencephalography (MEG) and functional magnetic resonance imaging (fMRI), and core analytic and visualization functions, all accessible through a web browser user interface. A datatype system modeling neuroscientific data ties together these pieces with persistent data storage, based on a combination of SQL and HDF5. These datatypes combine with adapters allowing TVB to integrate other algorithms or computational systems. TVB provides infrastructure for multiple projects and multiple users, possibly participating under multiple roles. For example, a clinician might import patient data to identify several potential lesion points in the patient's connectome. A modeler, working on the same project, tests these points for viability through whole brain simulation, based on the patient's connectome, and subsequent analysis of dynamical features. TVB also drives research forward: the simulator itself represents the culmination of several simulation frameworks in the modeling literature. The availability of the numerical methods, set of neural mass models and forward solutions allows for the construction of a wide range of brain-scale simulation scenarios. This paper briefly outlines the history and motivation for TVB, describing the framework and simulator, giving usage examples in the web UI and Python scripting.

The Virtual Brain: a simulator of primate brain network dynamics.

We present The Virtual Brain (TVB), a neuroinformatics platform for full brain network simulations using biologically realistic connectivity. This simulation environment enables the model-based inference of neurophysiological mechanisms across different brain scales that underlie the generation of macroscopic neuroimaging signals including functional MRI (fMRI), EEG and MEG. Researchers from different backgrounds can benefit from an integrative software platform including a supporting framework for data management (generation, organization, storage, integration and sharing) and a simulation core written in Python. TVB allows the reproduction and evaluation of personalized configurations of the brain by using individual subject data. This personalization facilitates an exploration of the consequences of pathological changes in the system, permitting to investigate potential ways to counteract such unfavorable processes. The architecture of TVB supports interaction with MATLAB packages, for example, the well known Brain Connectivity Toolbox. TVB can be used in a client-server configuration, such that it can be remotely accessed through the Internet thanks to its web-based HTML5, JS, and WebGL graphical user interface. TVB is also accessible as a standalone cross-platform Python library and application, and users can interact with the scientific core through the scripting interface IDLE, enabling easy modeling, development and debugging of the scientific kernel. This second interface makes TVB extensible by combining it with other libraries and modules developed by the Python scientific community. In this article, we describe the theoretical background and foundations that led to the development of TVB, the architecture and features of its major software components as well as potential neuroscience applications.