A Model for the Propagation of Seizure Activity in Normal Brain Tissue

eNeuro, Journal Year: 2022, Volume and Issue: 9(6), P. ENEURO.0234 - 21.2022

Published: Nov. 1, 2022

Epilepsies are characterized by paroxysmal electrophysiological events and seizures, which can propagate across the brain. One of main unsolved questions in epilepsy is how epileptic activity invade normal tissue thus To investigate this question, we consider three computational models at neural network scale to study underlying dynamics seizure propagation, understand specific features play a role, relate them clinical or experimental observations. We both internal connectivity structure between neurons input properties our characterization. show that sometimes controlled while other instances, it lead itself produce activity, will further efferent networks. details architecture essential determine switch seizure-like regime. investigated nature instability involved particular found central role for inhibitory connectivity. propose probabilistic approach propagative/non-propagative scenarios, may serve as guide control using appropriate stimuli.

Language: Английский

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Can transsynaptic viral strategies be used to reveal functional aspects of neural circuitry?

Journal of Neuroscience Methods, Journal Year: 2020, Volume and Issue: 348, P. 109005 - 109005

Published: Nov. 20, 2020

Language: Английский

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On the influence of prior information evaluated by fully Bayesian criteria in a personalized whole-brain model of epilepsy spread

PLoS Computational Biology, Journal Year: 2021, Volume and Issue: 17(7), P. e1009129 - e1009129

Published: July 14, 2021

Individualized anatomical information has been used as prior knowledge in Bayesian inference paradigms of whole-brain network models. However, the actual sensitivity to such personalized priors is still unknown. In this study, we introduce use fully criteria and leave-one-out cross-validation technique on subject-specific assess different epileptogenicity hypotheses regarding location pathological brain areas based a priori from dynamical system properties. The Virtual Epileptic Patient (BVEP) model, which relies fusion structural data individuals, generative model epileptiform discharges, self-tuning Monte Carlo sampling algorithm, infer spatial map across areas. Our results indicate that measuring out-of-sample prediction accuracy BVEP with informative enables reliable efficient evaluation potential degree regions. contrast, while using uninformative priors, are unable provide strong evidence about We also show correctly both functional components models differ individuals. information-theory approach study suggests patient-specific strategy for hypothesis testing epilepsy improve surgical outcomes.

Language: Английский

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Aspartate Metabolism Facilitates IL-1β Production in Inflammatory Macrophages

Frontiers in Immunology, Journal Year: 2021, Volume and Issue: 12

Published: Oct. 21, 2021

Increasing evidence support that cellular amino acid metabolism shapes the fate of immune cells; however, whether aspartate dictates macrophage function is still enigmatic. Here, we found metabolites in are depleted lipopolysaccharide (LPS) plus interferon gamma (IFN-γ)-stimulated macrophages. Aspartate promotes interleukin-1β (IL-1β) secretion M1 Mechanistically, boosts activation hypoxia-inducible factor-1α (HIF-1α) and inflammasome increases levels metabolism, such as asparagine. Interestingly, asparagine also accelerates signaling pathways production inflammatory cytokines from Moreover, supplementation augments macrophage-mediated responses mice piglets. These results uncover a previously uncharacterized role for directing polarization.

Language: Английский

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Neural Field Models: A mathematical overview and unifying framework

Mathematical Neuroscience and Applications, Journal Year: 2022, Volume and Issue: Volume 2

Published: March 19, 2022

Mathematical modelling of the macroscopic electrical activity brain is highly non-trivial and requires a detailed understanding not only associated mathematical techniques, but also underlying physiology anatomy. Neural field theory population-level approach to non-linear dynamics large populations neurons, while maintaining degree tractability. This class models provides solid theoretical perspective on fundamental processes neural tissue such as state transitions between different activities observed during epilepsy or sleep. Various anatomical, physiological, assumptions are essential for deriving minimal set equations that strike balance biophysical realism However, these always made explicit throughout literature. Even though (NFMs) first appeared in literature early 1970's, relationships them have been systematically addressed. may partially be explained by fact inter-dependencies often implicit non-trivial. Herein we provide review key stages history development contemporary uses this branch neuroscience. First, principles summarised discussion pioneering Wilson Cowan, Amari Nunez. Upon thorough models, then present unified framework which all can derived applying assumptions. We use i) derive Robinson, Jansen Rit, Wendling, Liley, Steyn-Ross, ii) make many significant inherited exist current

Language: Английский

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Focal seizures are organized by feedback between neural activity and ion concentration changes

eLife, Journal Year: 2022, Volume and Issue: 11

Published: Aug. 2, 2022

Human and animal EEG data demonstrate that focal seizures start with low-voltage fast activity, evolve into rhythmic burst discharges are followed by a period of suppressed background activity. This suggests processes dynamics in the range tens seconds govern seizure evolution. We investigate associated complementing Hodgkin-Huxley mathematical model physical laws dictate ion movement maintain ionic gradients. Our biophysically realistic computational closely replicates electrographic pattern typical human characterized low voltage activity onset, tonic phase, clonic phase postictal suppression. study demonstrates, for first time silico, potential mechanism initiation inhibitory interneurons via initial build-up extracellular K + due to intense interneuronal spiking. The also identifies mechanisms may underlie key feature dynamics, is, progressive slowing down ictal towards end seizure. prediction specific scaling inter-burst intervals is confirmed recorded whole guinea pig brain vitro humans, suggesting observed termination hold across different species. results emphasize as elementary behind generation indicate targets new therapeutic strategies.

Language: Английский

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Intrinsic neural diversity quenches the dynamic volatility of neural networks

Proceedings of the National Academy of Sciences, Journal Year: 2023, Volume and Issue: 120(28)

Published: July 3, 2023

Heterogeneity is the norm in biology. The brain no different: Neuronal cell types are myriad, reflected through their cellular morphology, type, excitability, connectivity motifs, and ion channel distributions. While this biophysical diversity enriches neural systems' dynamical repertoire, it remains challenging to reconcile with robustness persistence of function over time (resilience). To better understand relationship between excitability heterogeneity (variability within a population neurons) resilience, we analyzed both analytically numerically nonlinear sparse network balanced excitatory inhibitory connections evolving long scales. Homogeneous networks demonstrated increases strong firing rate correlations-signs instability-in response slowly varying modulatory fluctuation. Excitability tuned stability context-dependent way by restraining responses challenges limiting correlations, while enriching dynamics during states low drive. was found implement homeostatic control mechanism enhancing resilience changes size, connection probability, strength variability synaptic weights, quenching volatility (i.e., its susceptibility critical transitions) dynamics. Together, these results highlight fundamental role played cell-to-cell face change.

Language: Английский

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From phenomenological to biophysical models of seizures

Neurobiology of Disease, Journal Year: 2023, Volume and Issue: 182, P. 106131 - 106131

Published: April 21, 2023

Epilepsy is a complex disease that requires various approaches for its study. This short review discusses the contribution of theoretical and computational models. The presents frameworks underlie understanding certain seizure properties their classification based on dynamical at onset offset seizures. Dynamical system tools are valuable resources in study These can provide insights into mechanisms offer framework classification, by analyzing complex, dynamic behavior Additionally, models have high potential clinical applications, as they be used to develop more accurate diagnostic personalized medicine tools. We discuss modeling span different scales levels, while also questioning neurocentric view, emphasizing importance considering glial cells. Finally, we explore epistemic value provided this type approach.

Language: Английский

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Stimulation to probe, excite, and inhibit the epileptic brain

Epilepsia, Journal Year: 2023, Volume and Issue: 64(S3)

Published: May 17, 2023

Direct cortical stimulation has been applied in epilepsy for nearly one century and experienced a renaissance given unprecedented opportunities to probe, excite inhibit the human brain. Evidence suggests can increase diagnostic therapeutic utility patients with drug-resistant epilepsies. However, choosing appropriate parameters is not trivial issue, which further complicated by fact that characterized complex brain state dynamics. In this article derived from discussions at ICTALS 2022 conference, we succinctly review literature on acutely chronically epileptic localization, monitoring, purposes. particular, discuss how used probe excitability, evidence usefulness of trigger stop seizures, applications stimulation, finally are impacted Although research advanced considerably over past decade, there still significant hurdles optimize use technique. For example, it remains unclear what extent short timescale biomarkers predict long-term outcomes these add information already existing passive EEG recordings. Further questions include closed loop offers advantages open optimal timescales may be, whether biomarker-informed lead seizure freedom. The ultimate goal bioelectronic medicine just seizures but rather cure its comorbidities.

Language: Английский

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Sleep, oscillations, and epilepsy

Epilepsia, Journal Year: 2023, Volume and Issue: 64(S3)

Published: May 25, 2023

Abstract Sleep and wake are defined through physiological behavioral criteria can be typically separated into non‐rapid eye movement (NREM) sleep stages N1, N2, N3, rapid (REM) sleep, wake. states not homogenous in time. Their properties vary during the night day cycle. Given that brain activity changes as a function of NREM, REM, cycle, seizures more likely to occur or at specific time? More generally, what is relationship between sleep–wake cycles epilepsy? We will review examples from clinical data results experimental models, focusing on diversity heterogeneity these relationships. use top‐down approach, starting with general architecture followed by oscillatory activities, ending ionic correlates selected for illustrative purposes, respect interictal spikes. The picture emerges complexity; disruption pathological epileptic activities emerge reorganized circuits. That different circuit alterations across patients models may explain why timing cycle patient‐specific.

Language: Английский

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