Biology subjects

Jirsa, V.

Publications and source records attributed to Jirsa, V..

68 records · Page 4Linked to original sources

bioRxiv2020

Evidence for spreading seizure as a cause of theta-alpha activity electrographic pattern in stereo-EEG seizure recordings

Intracranial electroencephalography is a standard tool in clinical evaluation of patients with focal epilepsy. Various early electrographic seizure patterns differing in frequency, amplitude, and waveform of the oscillations are observed. The pattern most common in the areas of seizure propagation is the so-called theta-alpha activity (TAA), whose defining features are oscillations in the{theta} - range and gradually increasing amplitude. A deeper understanding of the mechanism underlying the generation of the TAA pattern is however lacking. In this work we evaluate the hypothesis that the TAA patterns are caused by seizures spreading across the cortex. To do so, we perform simulations of seizure dynamics on detailed patient-derived cortical surfaces using the spreading seizure model as well as reference models with one or two homogeneous sources. We then detect the occurrences of the TAA patterns both in the simulated stereo-electroencephalographic signals and in the signals of recorded epileptic seizures from a cohort of fifty patients, and we compare the features of the groups of detected TAA patterns to assess the plausibility of the different models. Our results show that spreading seizure hypothesis is qualitatively consistent with the evidence available in the seizure recordings, and it can explain the features of the detected TAA groups best among the examined models.

neuroscience↗

bioRxiv2020

Orientation of Temporal Interference for Non-Invasive Deep Brain Stimulation in Epilepsy

In patients with focal drug-resistant epilepsy, electrical stimulation from intracranial electrodes is frequently used for the localization of seizure onset zones and related pathological networks. The ability of electrically stimulated tissue to generate beta and gamma range oscillations, called rapid-discharges, is a frequent indication of an epileptogenic zone. However, a limit of intracranial stimulation is the fixed physical location and number of implanted electrodes, leaving numerous clinically and functionally relevant brain regions unexplored. Here, we demonstrate an alternative technique relying exclusively on nonpenetrating surface electrodes, namely an orientation-tunable form of temporally-interfering (TI) electric fields to target the CA3 of the mouse hippocampus which focally evokes seizure-like events (SLEs) having the characteristic frequencies of rapid-discharges, but without the necessity of the implanted electrodes. The orientation of the topical electrodes with respect to the orientation of the hippocampus is demonstrated to strongly control the threshold for evoking SLEs. Additionally, we demonstrate the use of square waves as an alternative to sine waves for TI stimulation. An orientation-dependent analysis of classic implanted electrodes to evoke SLEs in the hippocampus is subsequently utilized to support the results of the minimally-invasive temporally-interfering fields. The principles of orientation-tunable TI stimulation seen here can be generally applicable in a wide range of other excitable tissues and brain regions, overcoming several limitations of fixed electrodes which penetrate tissue.

neuroscience↗

bioRxiv2020

Experimental and computational study on motor control and recovery after stroke: towards a constructive loop betweenexperimental and virtual embodiedneuroscience

Being able to replicate real experiments with computational simulations is a unique opportunity to refine and validate models with experimental data and redesign the experiments based on simulations. However, since it is technically demanding to model all components of an experiment, traditional approaches to modeling reduce the experimental setups as much as possible. In this study, our goal is to replicate all the relevant features of an experiment on motor control and motor rehabilitation after stroke. To this aim, we propose an approach that allows continuous integration of new experimental data into a computational modeling framework. First, results show that we could reproduce experimental object displacement with high accuracy via the simulated embodiment in the virtual world by feeding a spinal cord model with experimental registration of the cortical activity. Second, by using computational models of multiple granularities, our preliminary results show the possibility of simulating several features of the brain after stroke, from the local alteration in neuronal activity to long-range connectivity remodeling. Finally, strategies are proposed to merge the two pipelines. We further suggest that additional models could be integrated into the framework thanks to the versatility of the proposed approach, thus allowing many researchers to achieve continuously improved experimental design.

neuroscience↗

bioRxiv2020

Identifying optimal working points of individual Virtual Brains: A large-scale brain network modelling study

Brain network modeling studies are often limited with respect to the number of data features fitted, although capturing multiple empirical features is important to validate the models overall biological plausibility. Here we construct personalized models from multimodal data of 50 healthy individuals (18-80 years) with The Virtual Brain and demonstrate that an individuals brain has its own converging optimal working point in the parameter space that predicts multiple empirical features in functional magnetic resonance imaging (fMRI) and electroencephalography (EEG). We further show that bimodality in the alpha band power - as an explored novel feature - arises as a function of global coupling and exhibits inter-regional differences depending on the degree. Reliable inter-individual differences with respect to these optimal working points were found that seem to be driven by the individual structural rather than by the functional connectivity. Our results provide the groundwork for future multimodal brain modeling studies.

neuroscience↗

bioRxiv2020

Epidynamics characterize and navigate the map of seizure dynamics

Seizures are a disruption of normal brain activity present across a vast range of species, diseases, and conditions. Here we introduce an organizing principle that leads to the first objective Taxonomy of Seizure Dynamics (TSD) based on bifurcation theory, and applied it to the analysis of EEG data. The "dynamotype" of a seizure is the part of its dynamic composition that defines its observable characteristics, including how it starts, evolves and terminates. Analyzing over 2000 focal-onset seizures recorded from 7 epilepsy centers on five continents, we find evidence of all 16 dynamotypes predicted in TSD. We demonstrate that patients dynamotypes evolve during their lifetime and display complex but systematic variations including hierarchy (certain dynamotypes are more common), non-bijectivity (a patient may display multiple dynamotypes) and pairing preference (multiple dynamotypes may occur during one seizure). TSD not only provides a way to stratify patients in complement to present practical classifications but also guides biophysically based mechanistic approaches and provides a language to describe the most critical features of seizure dynamics. Impact statementTaxonomy of Seizure Dynamics (TSD) provides a rigorous method for classifying and quantifying seizures and a principled framework for understanding seizure initiation and propagation.

bioinformatics↗

bioRxiv2020

Modular slowing of resting-state dynamic Functional Connectivity as a marker of cognitive dysfunction induced by sleep deprivation

Dynamic Functional Connectivity (dFC) in the resting state (rs) is considered as a correlate of cognitive processing. Describing dFC as a flow across morphing connectivity configurations, our notion of dFC speed quantifies the rate at which FC networks evolve in time. Here we probe the hypothesis that variations of rs dFC speed and cognitive performance are selectively interrelated within specific functional subnetworks. In particular, we focus on Sleep Deprivation (SD) as a reversible model of cognitive dysfunction. We found that whole-brain level (global) dFC speed significantly slows down after 24h of SD. However, the reduction in global dFC speed does not correlate with variations of cognitive performance in individual tasks, which are subtle and highly heterogeneous. On the contrary, we found strong correlations between performance variations in individual tasks -including Rapid Visual Processing (RVP, assessing sustained visual attention)- and dFC speed quantified at the level of functional subnetworks of interest. Providing a compromise between classic static FC (no time) and global dFC (no space), modular dFC speed analyses allow quantifying a different speed of dFC reconfiguration independently for sub-networks overseeing different tasks. Importantly, we found that RVP performance robustly correlates with the modular dFC speed of a characteristic frontoparietal module. HighlightsO_LISleep Deprivation (SD) slows down the random walk in FC space implemented by Dynamic Functional Connectivity (dFC) at rest. C_LIO_LIWhole-brain level slowing of dFC speed does not selectively correlate with fine and taskspecific changes in performance C_LIO_LIWe quantify dFC speed separately for different link-based modules coordinated by distinct regional "meta-hubs" C_LIO_LIModular dFC speed variations capture subtle and task-specific variations of cognitive performance induced by SD. C_LI Author summaryWe interpreted dynamic Functional Connectivity (dFC) as a random walk in the space of possible FC networks performed with a quantifiable "speed". Here, we analyze a fMRI dataset in which subjects are scanned and cognitively tested both before and after Sleep Deprivation (SD), used as a reversible model of cognitive dysfunction. While global dFC speed slows down after a sleepless night, it is not a sufficiently sensitive metric to correlate with fine and specific cognitive performance changes. To boost the capacity of dFC speed analyses to account for fine and specific cognitive decline, we introduce the notion of modular dFC speed. Capitalizing on an edge-centric measure of functional connectivity, which we call Meta-Connectivity, we isolate subgraphs of FC describing relatively independent random walks (dFC modules) and controlled by distinct "puppet masters" (meta-hubs). We then find that variations of the random walk speed of distinct dFC modules now selectively correlate with SD-induced variations of performance in the different tasks. This is in agreement with the fact that different subsystems - distributed but functionally distinct- oversee different tasks. The high sensitivity of modular dFC analyses bear promise of future applications to the early detection and longitudinal characterization of pathologies such as Alzheimers disease.

neuroscience↗

bioRxiv2020

Completion and augmentation of connectomic datasets in dementia and Alzheimer's Disease using Virtual Patient Cohorts

Large neuroimaging datasets, including information about structural (SC) and functional connectivity (FC), play an increasingly important role in clinical research, where they guide the design of algorithms for automated stratification, diagnosis or prediction. A major obstacle is, however, the problem of missing features (e.g., lack of concurrent DTI SC and resting-state fMRI FC measurements for many of the subjects). We propose here to address the missing connectivity features problem by introducing strategies based on computational whole-brain network modeling. Using two datasets, the ADNI dataset and a healthy aging dataset, for proof-of-concept, we demonstrate the feasibility of virtual data completion (i.e., inferring "virtual FC" from empirical SC or "virtual SC" from empirical FC), by using self-consistent simulations of linear and nonlinear brain network models. Furthermore, by performing machine learning classification (to separate age classes or control from patient subjects) we show that algorithms trained on virtual connectomes achieve discrimination performance comparable to when trained on actual empirical data; similarly, algorithms trained on virtual connectomes can be used to successfully classify novel empirical connectomes. Completion algorithms can be combined and reiterated to generate realistic surrogate connectivity matrices in arbitrarily large number, opening the way to the generation of virtual connectomic datasets with network connectivity information comparable to the one of the original data. Significance statementPersonalized information on anatomical connectivity ("structural connectivity", SC) or coordinated resting state activation patterns ("functional connectivity, FC) is a source of powerful neuromarkers to detect and track the development of neurodegenerative diseases. However, there are often "gaps" in the available information, with only SC (or FC) being known but not FC (or SC). Exploiting whole-brain modelling, we show that gap in databases can be filled by inferring the other connectome through computational simulations. The generated virtual connectomic data carry information analogous to the one of empirical connectomes, so that machine learning algorithms can be trained on them. This opens the way to the release in the future of cohorts of "virtual patients", complementing traditional datasets in data-driven predictive medicine.

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bioRxiv2019

Individual structural features constrain the functional connectome

Whole brain dynamics intuitively depends upon the internal wiring of the brain; but to which extent the individual structural connectome constrains the corresponding functional connectome is unknown, even though its importance is uncontested. After acquiring structural data from individual mice, we virtualized their brain networks and simulated in silico functional MRI data. Theoretical results were validated against empirical awake functional MRI data obtained from the same mice. We demonstrate that individual structural connectomes predict the functional organization of individual brains. Using a virtual mouse brain derived from the Allen Mouse Brain Connectivity Atlas, we further show that the dominant predictors of individual structure-function relations are the asymmetry and the weights of the structural links. Model predictions were validated experimentally using tracer injections, identifying which missing connections (not measurable with diffusion MRI) are important for whole brain dynamics in the mouse. Individual variations thus define a specific structural fingerprint with direct impact upon the functional organization of individual brains, a key feature for personalized medicine.\n\nSIGNIFICANCE STATEMENTThe structural connectome is a key determinant of brain function and dysfunction. The connectome-based model approach aims to understand the functional organization of the brain by modeling the brain as a dynamical system and then studying how the functional architecture rises from the underlying structural skeleton. Here, taking advantage of mice studies, we systematically investigated the informative content of different structural features in explaining the emergence of the functional ones. We demonstrate that individual variations define a specific structural fingerprint with a direct impact upon the functional organization of individual brains stressing the importance of using individualized models to understand brain function. We show how limitations of connectome reconstruction with the diffusion-MRI method restrict our comprehension of the structural-functional relation.

neuroscience↗

bioRxiv2019

Linking molecular pathways and large-scale computational modeling to assess candidate disease mechanisms and pharmacodynamics in Alzheimer's disease

IntroductionWhile the prevalence of neurodegenerative diseases associated with dementia such as Alzheimers disease (AD) increases, our knowledge on the underlying mechanisms, outcome predictors, or therapeutic targets is limited. In this work, we demonstrate how computational multi-scale brain modelling links phenomena of different scales and therefore identifies potential disease mechanisms leading the way to improved diagnostics and treatment. MethodsThe Virtual Brain (TVB; thevirtualbrain.org) neuroinformatics platform allows standardized large-scale structural connectivity-based simulations of whole brain dynamics. We provide proof of concept for a novel approach that quantitatively links the effects of altered molecular pathways onto neuronal population dynamics. As a novelty, we connect chemical compounds measured with positron emission tomography (PET) with neural function in TVB addressing the phenomenon of hyperexcitability in AD related to the protein amyloid beta (Abeta). We construct personalized virtual brains based on individual PET derived distributions of Abeta in patients with mild cognitive impairment (MCI, N=8) and Alzheimers Disease (AD, N=10) and in age-matched healthy controls (HC, N=15) using data from ADNI-3 data base (http://adni.lni.usc.edu). In the personalized virtual brains, individual Abeta burden modulates regional inhibition, leading to disinhibition and hyperexcitation with high Abeta loads. We analyze simulated regional neural activity and electroencephalograms (EEG). ResultsKnown empirical alterations of EEG in patients with AD compared to HCs were reproduced by simulations. The virtual AD group showed slower frequencies in simulated local field potentials and EEG compared to MCI and HC groups. The heterogeneity of the Abeta load is crucial for the virtual EEG slowing which is absent for control models with homogeneous Abeta distributions. Slowing phenomena primarily affect the network hubs, independent of the spatial distribution of Abeta. Modeling the N-methyl-D-aspartate (NMDA) receptor antagonism of memantine in local population models, reveals potential functional reversibility of the observed large-scale alterations (reflected by EEG slowing) in virtual AD brains. DiscussionWe demonstrate how TVB enables the simulation of systems effects caused by pathogenetic molecular candidate mechanisms in human virtual brains.

neuroscience↗

bioRxiv2019

THE HIDDEN REPERTOIRE OF BRAIN DYNAMICS AND DYSFUNCTION

The purpose of this paper is to describe a framework for the understanding of rules that govern how neural system dynamics are coordinated to produce behavior. The framework, structured flows on manifolds (SFM), posits that neural processes are flows depicting system interactions that occur on relatively low-dimension manifolds, which constrain possible functional configurations. Although this is a general framework, we focus on the application to brain disorders. We first explain the Epileptor, a phenomenological computational model showing fast and slow dynamics, but also a hidden repertoire whose expression is similar to refractory status epilepticus. We suggest that epilepsy represents an innate brain state whose potential may be realized only under certain circumstances. Conversely, deficits from damage or disease processes, such as stroke or dementia, may reflect both the disease process per se and the adaptation of the brain. SFM uniquely captures both scenarios.\n\nThe Hidden Repertoire of Brain Dynamics and Dysfunction

neuroscience↗

bioRxiv2017

Inferring multi-scale neural mechanisms with brain network modelling

The neurophysiological processes underlying non-invasive brain activity measurements are not well understood. Here, we developed a novel connectome-based brain network model that integrates individual structural and functional data with neural population dynamics to support multi-scale neurophysiological inference. Simulated populations were linked by structural connectivity and, as a novelty, driven by electroencephalography (EEG) source activity. Simulations not only predicted subjects individual resting-state functional magnetic resonance imaging (fMRI) time series and spatial network topologies over 20 minutes of activity, but more importantly, they also revealed precise neurophysiological mechanisms that underlie and link six empirical observations from different scales and modalities: (1) slow resting-state fMRI oscillations, (2) spatial topologies of functional connectivity networks, (3) excitation-inhibition balance, (4, 5) pulsed inhibition on short and long time scales, and (6) fMRI power-law scaling. These findings underscore the potential of this new modelling framework for general inference and integration of neurophysiological knowledge to complement empirical studies.

bioinformatics↗

bioRxiv2017

The Virtual Mouse Brain: A Computational Neuroinformatics Platform To Study Whole Mouse Brain Dynamics

Connectome-based modeling of large-scale brain network dynamics enables causal in silico interrogation of the brains structure-function relationship, necessitating the close integration of diverse neuroinformatics fields.\n\nHere we extend the open-source simulation software The Virtual Brain to whole mouse brain network modeling based on individual diffusion Magnetic Resonance Imaging (dMRI)-based or tracer-based detailed mouse connectomes. We provide practical examples on how to use The Virtual Mouse Brain to simulate brain activity, such as seizure propagation and the switching behavior of the resting state dynamics in health and disease.\n\nThe Virtual Mouse Brain enables theoretically driven experimental planning and ways to test predictions in the numerous strains of mice available to study brain function in normal and pathological conditions.

neuroscience↗

bioRxiv2017

Functional Connectivity Dynamics of the Resting State across the Human Adult Lifespan

Functional Connectivity (FC) during resting-state or task conditions is not fixed but inherently dynamic. Yet, there is no consensus on whether fluctuations in FC may resemble isolated transitions between discrete FC states rather than continuous changes. This quarrel hampers advancing the study of dynamic FC. This is unfortunate as the structure of fluctuations in FC can certainly provide more information about developmental changes, aging, and progression of pathologies. We merge the two perspectives and consider dynamic FC as an ongoing network reconfiguration, including a stochastic exploration of the space of possible steady FC states. The statistical properties of this random walk deviate both from a purely "order-driven" dynamics, in which the mean FC is preserved, and from a purely "randomness-driven" scenario, in which fluctuations of FC remain uncorrelated over time. Instead, dynamic FC has a complex structure endowed with long-range sequential correlations that give rise to transient slowing and acceleration epochs in the continuous flow of reconfiguration. Our analysis for fMRI data in healthy elderly revealed that dynamic FC tends to slow down and becomes less complex as well as more random with increasing age. These effects appear to be strongly associated with age-related changes in behavioural and cognitive performance. HighlightsO_LIDynamic Functional Connectivity (dFC) at rest and during cognitive task performs a "complex" (anomalous) random walk. C_LIO_LISpeed of dFC slows down with aging. C_LIO_LIResting dFC replaces complexity by randomness with aging. C_LIO_LITask performance correlates with the speed and complexity of dFC. C_LI

neuroscience↗

bioRxiv2016

Bridging multiple scales in the human brain using computational modelling

Brain dynamics span multiple spatial and temporal scales, from fast spiking neurons to slow fluctuations over distributed areas. No single experimental method links data across scales. Here, we bridge this gap using The Virtual Brain connectome-based modelling platform to integrate multimodal data with biophysical models and support neurophysiological inference. Simulated cell populations were linked with subject-specific white-matter connectivity estimates and driven by electroencephalography-derived electric source activity. The models were fit to subject-specific resting-state functional magnetic resonance imaging data, and overfitting was excluded using 5-fold cross-validation. Further evaluation of the models show how balancing excitation with feedback inhibition generates an inverse relationship between -rhythms and population firing on a faster time scale and resting-state network oscillations on a slower time scale. Lastly, large-scale interactions in the model lead to the emergence of scale-free power-law spectra. Our novel findings underscore the integrative role for computational modelling to complement empirical studies.

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