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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A Hippocampal-Entorhinal Cortex Neuronal Network for Dynamical Mechanisms of Epileptic Seizure

IEEE Transactions on Neural Systems and Rehabilitation Engineering, Journal Year: 2023, Volume and Issue: 31, P. 1986 - 1996

Published: Jan. 1, 2023

Temporal lobe epilepsy (TLE) is thought to be associated with neuronal hyperexcitability in the hippocampal-entorhinal cortical (EC) circuit. Due complexity of hippocampal-EC network connections, biophysical mechanisms different circuits generation and propagation are still not fully established. In this work, we propose a model explore mechanism epileptic generation. We demonstrate that enhanced excitability pyramidal neurons cornu ammonis 3 (CA3) can drive produce transition from background seizure state cause exaggerated phase-amplitude coupling (PAC) phenomenon theta modulated high-frequency oscillations (HFO) CA3, 1 (CA1), dentate gyrus, EC. Interestingly, PAC strength indirectly responds degree CA3 (PY) neuron hyperexcitability, suggesting used as potential marker seizures. Furthermore, find synaptic connectivity mossy cells granule PY drives system discharges. These two channels may play key role fiber sprouting. particular, delta-modulated HFO theta-modulated generated according degrees moss Finally, results suggest stellate EC lead seizures, which supports argument act an independent source Overall, these highlight providing theoretical basis new insights into TLE.

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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HCN channels promote Na/K‐ATPase activity during slow afterhyperpolarization after seizure‐like events in vitro

The Journal of Physiology, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 7, 2025

Hyperpolarization-activated cyclic nucleotide-gated (HCN) channels are strongly involved in the regulation of neuronal excitability, with their precise role being determined by subcellular localization and interaction other ion transporters. Their causing epileptic seizures is not fully understood. Using whole-cell patch-clamp recordings rat brain slices, we show that HCN constitute a substantial fraction membrane conductance deep entorhinal principal neurons. 4-aminopyridine model vitro, channel blockade ZD-7288 increases frequency seizure-like events (SLEs) alters time course afterhyperpolarization after SLEs (post-SLE AHP), promoting its faster onset making it more transient. Simultaneous K+ ion-selective electrode revealed changes potential extracellular concentration presence differed from control, which can be explained altered Na/K-ATPase [sodium-potassium adenosine triphosphatase (sodium-potassium pump)] activity SLEs. To confirm this hypothesis, demonstrated ouabain sensitivity post-SLE AHP showed loading neurons high intracellular Na+ prevented effect on AHP. Taken together, results obtained suggest during AHP, influx through helps to maintain hyperactivity, resulting longer pauses between Mathematical modelling confirmed feasibility proposed mechanism. Such an interplay may crucial for seizure termination epilepsy. KEY POINTS: significant resting modulate cortex. The reduces duration follows them. affect sodium dynamics, prolonging (sodium-potassium) pump] SLEs, turn

Language: Английский

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Kir4.1 channel and voltage-gated calcium channel of astrocyte account for the transition dynamics of seizures

Journal of Theoretical Biology, Journal Year: 2025, Volume and Issue: 604, P. 112082 - 112082

Published: Feb. 28, 2025

Language: Английский

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Miniaturized Iontronic Micropipettes for Precise and Dynamic Ionic Modulation of Neuronal and Astrocytic Activity

Small, Journal Year: 2025, Volume and Issue: unknown

Published: March 10, 2025

Abstract The composition of the extracellular milieu can vary significantly under physiological and pathological conditions, thereby altering functional set point brain cells. While global changes in are known to affect network activity, a detailed understanding how specific ion species impact individual cells remains elusive. Current modulation methods involve use diluted salts, such as KCl, where lack precise control complicates data interpretation. This study achieves enhanced resolution by using miniaturized iontronic micropipette. micropipette, with tip filled polyelectrolyte an outlet size below 2 µm, allows for on‐demand ionic manipulation single cells, without simultaneous co‐delivery solvents or other solutes. Electrical, chemical, optical characterizations, supported computational modeling, confirm device's high spatial temporal precision. Validated hippocampal slices, device demonstrates release potassium ions (K⁺), low current (<200 nA), that effectively, rapidly, reversibly modulates individually targeted neurons astrocytes. These findings underscore potential micropipettes elucidate distinct responses neuronal glial local milieu, offering insights neuroscience research therapeutic innovation.

Language: Английский

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Bifurcations and bursting in the Epileptor

PLoS Computational Biology, Journal Year: 2024, Volume and Issue: 20(3), P. e1011903 - e1011903

Published: March 6, 2024

The Epileptor is a phenomenological model for seizure activity that used in personalized large-scale brain modeling framework, the Virtual Epileptic Patient, with aim of improving surgery outcomes drug-resistant epileptic patients. Transitions between interictal and ictal states are modeled as bifurcations, enabling definition classes terms onset/offset bifurcations. This establishes taxonomy seizures grounded their essential underlying dynamics replicates most common class, observed patients focal epilepsy, which characterized by square-wave bursting properties. also encodes an additional mechanism to account spikes spike wave discharges. Here we use insights from more generic bursting, based on Unfolding Theory approach, guide bifurcation analysis gain deeper understanding role its parameters. We show how Epileptor’s parameters can be modified produce activities other taxonomy, patients, so models could further personalized. Some these have already been described literature Epileptor, others, predicted model, new. Finally, unveil interaction discharges alters structure main burster.

Language: Английский

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A neural mass model with neuromodulation

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: June 28, 2024

Abstract The study of brain activity and its function requires the development computational models alongside experimental investigations to explore different effects multiple mechanisms at play in central nervous system. Chemical neuromodulators such as dopamine roles regulating dynamics neuronal populations. In this work, we propose a modular framework capture neural mass level. Using framework, formulate specific model for affecting D1-type receptors. We detail dynamical repertoire associated with concentration evolution. Finally, give one example use basal-ganglia network healthy pathological conditions.

Language: Английский

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Modeling impairment of ionic regulation with extended Adaptive Exponential integrate-and-fire models

Journal of Computational Neuroscience, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 23, 2025

Language: Английский

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Biophysically inspired mean-field model of neuronal populations driven by ion exchange mechanisms

Published: Feb. 3, 2025

Whole-brain simulations are a valuable tool for gaining insight into the multiscale processes that regulate brain activity. Due to complexity of brain, it is impractical include all microscopic details in simulation. Hence, researchers often simulate as network coupled neural masses, each described by mean-field model. These models capture essential features neuronal populations while approximating most biophysical details. However, may be important certain parameters significantly impact function. The concentration ions extracellular space one key factor consider, its fluctuations can associated with healthy and pathological states. In this paper, we develop new model population Hodgkin–Huxley-type neurons, retaining perspective on ion-exchange mechanisms driving This allows us maintain interpretability bridging gap between micro- macro-scale mechanisms. Our able reproduce wide range activity patterns, also observed large simulations. Specifically, slow-changing ion concentrations modulate fast neuroelectric activity, feature our validated through vitro experiments. By studying how changes ionic conditions affect whole-brain dynamics, serves foundation measure biomarkers provide potential therapeutic targets cases dysfunctions like epilepsy.

Language: Английский

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