Inferring the natural history of HPV from global cancer registries: insights from a multi-country calibration.

Human papillomavirus (HPV) is the cause of almost all cases of cervical cancer, a disease that kills some 340,000 women per year. The timeline from initial infection with HPV to the onset of invasive cervical cancer spans decades, and observational studies of this process are limited to settings in which treatment of precancerous lesions was withheld or inadequate. Such studies have been critical for understanding the natural history of HPV. Modeling can shed additional insight on the natural history of HPV, especially across geographical settings with varying prevalence of factors known to affect the host-side immune response to HPV, such as HIV and tobacco use. In this study, we create models for the 30 most populous countries in Sub-Saharan Africa, each with country-specific demographic, and behavioral inputs. We found that it was not possible to fit the data if we assumed that the natural history parameters were exactly identical for all countries, even after accounting for demographic and behavioral differences, but that we could achieve a good fit with the addition of a single immunocompetence parameter for each country. Our results indicate that variation in host immune responses may play a role in explaining the differences in the burden of cervical cancer between countries, which in turn implies a greater need for more geographically diverse data collection to understand the natural history of HPV.

El nuevo código de deontología (2022) y sus principios generales / The new code of medical ethics (2022) and its general principles pilar

El artículo describe y analiza los Principios Generales del Código de Deontología Médica de 2022 que están recogidos en los artículos 4 a 6 del capítulo segundo. Los Principios Generales permiten comprender e interpretar el conjunto de preceptos y recomendaciones del Código, por lo que el estu dio de estos artículos tiene especial relevancia. Además, se contextualizan relacionándolos con otros documentos internacionales ético-deontológicos actuales. También revisaremos cómo se prolongan en el amplio articulado del nuevo Código. Observaremos que hay una clara relación entre los Principios Generales del nuevo Código respecto a Códigos de Deontología de la Organización Médica Colegial anteriores, lo cual es lógico puesto que reúnen valores permanentes de la ética médica. Se propone que el médico está al servicio del ser humano y de la sociedad y tiene como deberes primordiales, el respeto a la vida humana, a la dignidad de la persona, así como el cuidado de la salud del individuo y de la comunidad (Artículo 4.1) (AU)

The article describes and analyses the General Principles of the 2022 Code of Medical Ethics that are included in the articles 4 to 6 of the second chapter. The General Principles make it possible to understand and interpret the set of precepts and recommendations of the code, for which reason the study of this second chapter is of special relevance. In addition, I contextualize General Principles by relating them to other current international ethical-deontological documents. We will also review how they are extended in the broad articles of the new code. We will observe that there is a clear relationship between the General Principles of the new code with respect to previous Spanish Medical Codes, which is logical since they gather permanent values of Medical Ethics. In the General Principles is proposed that each doctor is at the service of the human being and of society and has as primary duties, respect for human life, dignity of each person, as well as the health care of the individual and the society (Article 4.1) (AU)

Mechanisms of imbalanced frontostriatal functional connectivity in obsessive-compulsive disorder.

The diagnosis of obsessive-compulsive disorder (OCD) has been linked with changes in frontostriatal resting-state connectivity. However, replication of prior findings is lacking, and the mechanistic understanding of these effects is incomplete. To confirm and advance knowledge on changes in frontostriatal functional connectivity in OCD, participants with OCD and matched healthy controls underwent resting-state functional, structural and diffusion neuroimaging. Functional connectivity changes in frontostriatal systems were here replicated in individuals with OCD (n = 52) compared with controls (n = 45). OCD participants showed greater functional connectivity (t = 4.3, PFWE = 0.01) between the nucleus accumbens (NAcc) and the orbitofrontal cortex (OFC) but lower functional connectivity between the dorsal putamen and lateral prefrontal cortex (t = 3.8, PFWE = 0.04) relative to controls. Computational modelling suggests that NAcc-OFC connectivity changes reflect an increased influence of NAcc over OFC activity and reduced OFC influence over NAcc activity (posterior probability, Pp > 0.66). Conversely, dorsal putamen showed reduced modulation over lateral prefrontal cortex activity (Pp > 0.90). These functional deregulations emerged on top of a generally intact anatomical substrate. We provide out-of-sample replication of opposite changes in ventro-anterior and dorso-posterior frontostriatal connectivity in OCD and advance the understanding of the neural underpinnings of these functional perturbations. These findings inform the development of targeted therapies normalizing frontostriatal dynamics in OCD.

Modelling herd immunity requirements in Queensland: impact of vaccination effectiveness, hesitancy and variants of SARS-CoV-2.

Long-term control of SARS-CoV-2 outbreaks depends on the widespread coverage of effective vaccines. In Australia, two-dose vaccination coverage of above 90% of the adult population was achieved. However, between August 2020 and August 2021, hesitancy fluctuated dramatically. This raised the question of whether settings with low naturally derived immunity, such as Queensland where less than [Formula: see text] of the population is known to have been infected in 2020, could have achieved herd immunity against 2021's variants of concern. To address this question, we used the agent-based model Covasim. We simulated outbreak scenarios (with the Alpha, Delta and Omicron variants) and assumed ongoing interventions (testing, tracing, isolation and quarantine). We modelled vaccination using two approaches with different levels of realism. Hesitancy was modelled using Australian survey data. We found that with a vaccine effectiveness against infection of 80%, it was possible to control outbreaks of Alpha, but not Delta or Omicron. With 90% effectiveness, Delta outbreaks may have been preventable, but not Omicron outbreaks. We also estimated that a decrease in hesitancy from 20% to 14% reduced the number of infections, hospitalizations and deaths by over 30%. Overall, we demonstrate that while herd immunity may not be attainable, modest reductions in hesitancy and increases in vaccine uptake may greatly improve health outcomes. This article is part of the theme issue 'Technical challenges of modelling real-life epidemics and examples of overcoming these'.

Risk of sustained SARS-CoV-2 transmission in Queensland, Australia.

We used an agent-based model Covasim to assess the risk of sustained community transmission of SARSCoV-2/COVID-19 in Queensland (Australia) in the presence of high-transmission variants of the virus. The model was calibrated using the demographics, policies, and interventions implemented in the state. Then, using the calibrated model, we simulated possible epidemic trajectories that could eventuate due to leakage of infected cases with high-transmission variants, during a period without recorded cases of locally acquired infections, known in Australian settings as "zero community transmission". We also examined how the threat of new variants reduces given a range of vaccination levels. Specifically, the model calibration covered the first-wave period from early March 2020 to May 2020. Predicted epidemic trajectories were simulated from early February 2021 to late March 2021. Our simulations showed that one infected agent with the ancestral (A.2.2) variant has a 14% chance of crossing a threshold of sustained community transmission (SCT) (i.e., > 5 infections per day, more than 3 days in a row), assuming no change in the prevailing preventative and counteracting policies. However, one agent carrying the alpha (B.1.1.7) variant has a 43% chance of crossing the same threshold; a threefold increase with respect to the ancestral strain; while, one agent carrying the delta (B.1.617.2) variant has a 60% chance of the same threshold, a fourfold increase with respect to the ancestral strain. The delta variant is 50% more likely to trigger SCT than the alpha variant. Doubling the average number of daily tests from ∼ 6,000 to 12,000 results in a decrease of this SCT probability from 43 to 33% for the alpha variant. However, if the delta variant is circulating we would need an average of 100,000 daily tests to achieve a similar decrease in SCT risk. Further, achieving a full-vaccination coverage of 70% of the adult population, with a vaccine with 70% effectiveness against infection, would decrease the probability of SCT from a single seed of alpha from 43 to 20%, on par with the ancestral strain in a naive population. In contrast, for the same vaccine coverage and same effectiveness, the probability of SCT from a single seed of delta would decrease from 62 to 48%, a risk slightly above the alpha variant in a naive population. Our results demonstrate that the introduction of even a small number of people infected with high-transmission variants dramatically increases the probability of sustained community transmission in Queensland. Until very high vaccine coverage is achieved, a swift implementation of policies and interventions, together with high quarantine adherence rates, will be required to minimise the probability of sustained community transmission.

Susceptibility of zero community transmission regimes to new variants of SARS-CoV-2: a modelling study of Queensland

We used an agent-based model Covasim to assess the risk of sustained community transmission of SARS-CoV-2/COVID-19 in Queensland (Australia) in the presence of high-transmission variants of the virus. The model was calibrated using the demographics, policies, and interventions implemented in the state. Then, using the calibrated model, we simulated possible epidemic trajectories that could eventuate due to leakage of infected cases with high-transmission variants, during a period without recorded cases of locally acquired infections, known in Australian settings as "zero community transmission". We also examined how the threat of new variants reduces given a range of vaccination levels. Specifically, the model calibration covered the first-wave period from early March 2020 to May 2020. Predicted epidemic trajectories were simulated from early February 2021 to late March 2021. Our simulations showed that one infected agent with the ancestral (A.2.2) variant has a 14% chance of crossing a threshold of sustained community transmission (SCT) (i.e., > 5 infections per day, more than 3 days in a row), assuming no change in the prevailing preventative and counteracting policies. However, one agent carrying the alpha (B.1.1.7) variant has a 43% chance of crossing the same threshold; a threefold increase with respect to the ancestral strain; while, one agent carrying the delta (B.1.617.2) variant has a 60% chance of the same threshold, a fourfold increase with respect to the ancestral strain. The delta variant is 50% more likely to trigger SCT than the alpha variant. Doubling the average number of daily tests from [~] 6,000 to 12,000 results in a decrease of this SCT probability from 43% to 33% for the alpha variant. However, if the delta variant is circulating we would need an average of 100,000 daily tests to achieve a similar decrease in SCT risk. Further, achieving a full-vaccination coverage of 70% of the adult population, with a vaccine with 70% effectiveness against infection, would decrease the probability of SCT from a single seed of alpha from 43% to 20%, on par with the ancestral strain in a naive population. In contrast, for the same vaccine coverage and same effectiveness, the probability of SCT from a single seed of delta would decrease from 62% to 48%, a risk slightly above the alpha variant in a naive population. Our results demonstrate that the introduction of even a small number of people infected with high-transmission variants dramatically increases the probability of sustained community transmission in Queensland. Until very high vaccine coverage is achieved, a swift implementation of policies and interventions, together with high quarantine adherence rates, will be required to minimise the probability of sustained community transmission.

ADHD symptoms map onto noise-driven structure-function decoupling between hub and peripheral brain regions.

Adults with childhood-onset attention-deficit hyperactivity disorder (ADHD) show altered whole-brain connectivity. However, the relationship between structural and functional brain abnormalities, the implications for the development of life-long debilitating symptoms, and the underlying mechanisms remain uncharted. We recruited a unique sample of 80 medication-naive adults with a clinical diagnosis of childhood-onset ADHD without psychiatric comorbidities, and 123 age-, sex-, and intelligence-matched healthy controls. Structural and functional connectivity matrices were derived from diffusion spectrum imaging and multi-echo resting-state functional MRI data. Hub, feeder, and local connections were defined using diffusion data. Individual-level measures of structural connectivity and structure-function coupling were used to contrast groups and link behavior to brain abnormalities. Computational modeling was used to test possible neural mechanisms underpinning observed group differences in the structure-function coupling. Structural connectivity did not significantly differ between groups but, relative to controls, ADHD showed a reduction in structure-function coupling in feeder connections linking hubs with peripheral regions. This abnormality involved connections linking fronto-parietal control systems with sensory networks. Crucially, lower structure-function coupling was associated with higher ADHD symptoms. Results from our computational model further suggest that the observed structure-function decoupling in ADHD is driven by heterogeneity in neural noise variability across brain regions. By highlighting a neural cause of a clinically meaningful breakdown in the structure-function relationship, our work provides novel information on the nature of chronic ADHD. The current results encourage future work assessing the genetic and neurobiological underpinnings of neural noise in ADHD, particularly in brain regions encompassed by fronto-parietal systems.

Gamma-band correlations in the primary visual cortex.

This paper generalizes and extends previous work on using neural field theory to quantitatively analyze the two-dimensional (2D) spatiotemporal correlation properties of gamma-band (30-70 Hz) oscillations evoked by stimuli arriving at the primary visual cortex, and modulated by patchy connectivities that depend on orientation preference (OP). Correlation functions are derived analytically for general stimulus and measurement conditions. The theoretical results reproduce a range of published experimental results. These include (i) the existence of two-point oscillatory temporal cross correlations with zero time lag between neurons with similar OP; (ii) the influence of spatial separation of neurons on the strength of the correlations; and (iii) the effects of differing stimulus orientations. They go beyond prior work by incorporating experimentally observed patchy projection patterns to predict the 2D correlation structure including both OP and ocular dominance effects, thereby relaxing assumptions of translational invariance implicit in prior one-dimensional analysis.

Effects of physiological parameter evolution on the dynamics of tonic-clonic seizures.

The temporal and spectral characteristics of tonic-clonic seizures are investigated using a neural field model of the corticothalamic system in the presence of a temporally varying connection strength between the cerebral cortex and thalamus. Increasing connection strength drives the system into ∼ 10 Hz seizure oscillations once a threshold is passed and a subcritical Hopf bifurcation occurs. In this study, the spectral and temporal characteristics of tonic-clonic seizures are explored as functions of the relevant properties of physiological connection strengths, such as maximum strength, time above threshold, and the ramp rate at which the strength increases or decreases. Analysis shows that the seizure onset time decreases with the maximum connection strength and time above threshold, but increases with the ramp rate. Seizure duration and offset time increase with maximum connection strength, time above threshold, and rate of change. Spectral analysis reveals that the power of nonlinear harmonics and the duration of the oscillations increase as the maximum connection strength and the time above threshold increase. A secondary limit cycle at ∼ 18 Hz, termed a saddle-cycle, is also seen during seizure onset and becomes more prominent and robust with increasing ramp rate. If the time above the threshold is too small, the system does not reach the 10 Hz limit cycle, and only exhibits 18 Hz saddle-cycle oscillations. It is also seen that the time to reach the saturated large amplitude limit-cycle seizure oscillation from both the instability threshold and from the end of the saddle-cycle oscillations is inversely proportional to the square root of the ramp rate.

Unified dynamics of interictal events and absence seizures.

The dynamics of interictal events between absence seizures and their relationship to seizures themselves are investigated by employing a neural field model of the corticothalamic system. Interictal events are modeled as being due to transient parameter excursions beyond the seizure threshold, in the present case by sufficiently temporally varying the connection strength between the cerebral cortex and the thalamus. Increasing connection strength drives the system into ∼3-Hz seizure oscillations via a supercritical Hopf bifurcation once the linear instability threshold is passed. Depending on the time course of the excursion above threshold, different interictal activity event dynamics are seen in the time series of corticothalamic fields. These resemble experimental interictal time series observed via electroencephalography. It is found that the morphology of these events depends on the magnitude and duration of the excursion above threshold. For a large-amplitude excursion of short duration, events resemble interictal spikes, where one large spike is seen, followed by small damped oscillations. For a short excursion with long duration, events like observed interictal periodic sharp waves are seen. When both amplitude and duration above threshold are large, seizure oscillations are seen. Using these outcomes, proximity to seizure can be estimated and tracked.

Emergent dynamics of neuromorphic nanowire networks.

Neuromorphic networks are formed by random self-assembly of silver nanowires. Silver nanowires are coated with a polymer layer after synthesis in which junctions between two nanowires act as resistive switches, often compared with neurosynapses. We analyze the role of single junction switching in the dynamical properties of the neuromorphic network. Network transitions to a high-conductance state under the application of a voltage bias higher than a threshold value. The stability and permanence of this state is studied by shifting the voltage bias in order to activate or deactivate the network. A model of the electrical network with atomic switches reproduces the relation between individual nanowire junctions switching events with current pathway formation or destruction. This relation is further manifested in changes in 1/f power-law scaling of the spectral distribution of current. The current fluctuations involved in this scaling shift are considered to arise from an essential equilibrium between formation, stochastic-mediated breakdown of individual nanowire-nanowire junctions and the onset of different current pathways that optimize power dissipation. This emergent dynamics shown by polymer-coated Ag nanowire networks places this system in the class of optimal transport networks, from which new fundamental parallels with neural dynamics and natural computing problem-solving can be drawn.

Characterization of glutamatergic VTA neural population responses to aversive and rewarding conditioning in freely-moving mice.

The Ventral Tegmental Area (VTA) is a midbrain structure known to integrate aversive and rewarding stimuli, but little is known about the role of VTA glutamatergic (VGluT2) neurons in these functions. Direct activation of VGluT2 soma evokes rewarding behaviors, while activation of their downstream projections evokes aversive behaviors. To facilitate our understanding of these conflicting properties, we recorded calcium signals from VTAVGluT2+ neurons using fiber photometry in VGluT2-cre mice to investigate how this population was recruited by aversive and rewarding stimulation, both during unconditioned and conditioned protocols. Our results revealed that, as a population, VTAVGluT2+ neurons responded similarly to unconditioned-aversive and unconditioned-rewarding stimulation. During aversive and rewarding conditioning, the CS-evoked responses gradually increased across trials whilst the US-evoked response remained stable. Retrieval 24 h after conditioning, during which mice received only CS presentation, resulted in VTAVGluT2+ neurons strongly responding to CS presentation and to the expected-US but only for aversive conditioning. To help understand these differences based on VTAVGluT2+ neuronal networks, the inputs and outputs of VTAVGluT2+ neurons were investigated using Cholera Toxin B (CTB) and rabies virus. Based on our results, we propose that the divergent VTAVGluT2+ neuronal responses to aversion and reward conditioning may be partly due to the existence of VTAVGluT2+ subpopulations that are characterized by their connectivity.

Spiking patterns and synchronization of thalamic neurons along the sleep-wake cycle.

Spiking patterns and synchronization dynamics of thalamic neurons along the sleep-wake cycle are studied in a minimal model of four coupled conductance-based neurons. The model simulates two thalamic neurons coupled via a gap junction and driven by a synaptic input from a two-neuron model of sleep regulation by the hypothalamus. In accord with experimental data, the model shows that during sleep, when hypothalamic wake-active neurons are silent, the thalamic neurons discharge bursts of spikes. During wake, the excitatory synaptic input from the hypothalamus drives the coupled thalamic neurons to a state of tonic firing (single spikes). In the deterministic case, the thalamic neurons synchronize in-phase in the bursting regime but demonstrate multi-stability of out-of-phase, in-phase, and asynchronous states in the tonic firing. However, along the sleep-wake cycle, once the neurons synchronize in-phase during sleep (bursting), they stay synchronized in wake (tonic firing). It is thus found that noise is needed to reproduce the experimentally observed transitions between synchronized bursting during sleep and asynchronous tonic firing during wake. Overall, synchronization of bursting is found to be more robust to noise than synchronization of tonic firing, where a small disturbance is sufficient to desynchronize the thalamic neurons. The model predicts that the transitions between sleep and wake happen via chaos because a single thalamic neuron exhibits chaos between regular bursting and tonic activity. The results of this study suggest that the sleep- and wake-related dynamics in the thalamus may be generated at a level of gap junction-coupled clusters of thalamic neurons driven from the hypothalamus which would then propagate throughout the thalamus and cortex via axonal long-range connections.

Spectrum of connectivity fluctuations including the effect of activity-dependent feedback.

The spatiotemporal spectrum of feedback-driven fluctuations of brain connectivity is investigated using nonlinear neural field theory of the corticothalamic system. Weakly nonlinear dynamics of neural feedbacks are expanded in terms of first order perturbations of neural activity relative to a fixed point. Susceptibilities are used to quantify the change in connectivity per unit change in presynaptic or postsynaptic activity caused by nonlinear feedbacks such as facilitation, depression, sensitization, potentiation, and the effects of discrete eigenmode structure are included for a spherical brain geometry. Spectral signatures such as resonances are identified that allow the presence of particular presynaptic and postsynaptic feedback effects to be inferred. These include additional resonances at high frequencies and shifts of existing spectral peaks, mostly visible in the lowest spatial modes of the response.

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.

Dependence of absence seizure dynamics on physiological parameter evolution.

A neural field model of the corticothalamic system is applied to investigate the temporal and spectral characteristics of absence seizures in the presence of a temporally varying connection strength between the cerebral cortex and thalamus. Increasing connection strength drives the system into an absence seizure-like state once a threshold is passed and a supercritical Hopf bifurcation occurs. The dynamics and spectral characteristics of the resulting model seizures are explored as functions of maximum connection strength, time above threshold, and the rate at which the connection strength increases (ramp rate). Our results enable spectral and temporal characteristics of seizures to be related to changes in the underlying physiological evolution of connections via nonlinear dynamics and neural field theory. Spectral analysis reveals that the power of the harmonics and the duration of the oscillations increase as the maximum connection strength and the time above threshold increase. It is also found that the time to reach the stable limit-cycle seizure oscillation from the instability threshold decreases with the square root of the ramp rate.

Multistability in the corticothalamic system.

Neural field theory of the corticothalamic system is used to analyze the properties of its steady-state solutions, including their linear stability, in the parameter space of synaptic couplings for physiological parameter ranges representing normal arousal waking states in adult humans. The independent connections of the corticothalamic model define an eight-dimensional parameter space, while specific combinations of these connections parameterize intracortical, corticothalamic, and intrathalamic loops. Multistable regions are systematically identified and the existence of up to five steady-state solutions is confirmed, up to three of which are linearly stable. A key determinant for the existence of five steady states is found to be the number of nonzero connections. This finding had not been previously proposed as the determining factor of high multiplicities of multistability in mesoscopic models of the brain. In the corticothalamic model presented here, multistability occurs when the intrathalamic loop is present (i.e., the reticular nucleus inhibits the relay nuclei), and when the net synaptic effect of the intracortical loop is inhibitory. The signature of these additional waking states is an overall increased level of thalamic activity. It is argued that the additional steady states found may represent hyperarousal states which occur when the corticothalamic projections do not attenuate the activity of the cortex.

Spectral signatures of activity-dependent neural feedback in the corticothalamic system.

The modulation of neural quantities by presynaptic and postsynaptic activities via local feedback processes is investigated by incorporating nonlinear phenomena such as relative refractory period, synaptic enhancement, synaptic depression, and habituation. This is done by introducing susceptibilities, which quantify the response in either firing threshold or synaptic strength to unit change in either presynaptic or postsynaptic activity. Effects on the power spectra are then analyzed for a realistic corticothalamic model to determine the spectral signatures of various nonlinear processes and to what extent these are distinct. Depending on the feedback processes, there can be enhancements or reductions in low-frequency and/or alpha power, splitting of the alpha resonance, and/or appearance of new resonances at high frequencies. These features in the power spectra allow processes to be fully distinguished where they are unique, or partly distinguished if they are common to only a subset of feedbacks, and can potentially be used to constrain the types, strengths, and dynamics of feedbacks present.

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.

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.