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Hazi, V.

Publications and source records attributed to Hazi, V..

3 recordsLinked to original sources

State-Dependent Stimulation for Seizure Termination in a Morris-Lecar Network: A Reinforcement Learning Approach

The efficacy of neurostimulation for seizure termination depends not only on the stimulus itself but also on the dynamical state of the epileptic network. Here, we develop a dynamical-systems-informed reinforcement-learning framework that learns when to deliver a predefined pulse to terminate seizure-like activity. We simulate a sparsely connected network of 100 extended three-dimensional Morris-Lecar neurons. Bifurcation analysis of the single-neuron model identifies bistable regimes and provides a mechanistic basis for considering transitions between resting and oscillatory activity. The learning agent uses semi-gradient Q-learning with tile coding and receives a two-dimensional time-delay embedding of either the population-averaged membrane potential or a derivative-based proxy for extracellular potential. It learns a state-dependent policy that selects between stimulation and no stimulation, without modifying the pulse waveform. Across 30 independently generated test networks, both learned policies markedly reduced median seizure duration compared with trigger-only and state-independent stimulation controls. The two learned policies performed comparably, indicating that the estimated extracellular potential proxy retained sufficient dynamical information for control in this model. These results provide a proof of concept that combining dynamical-systems-based state reconstruction with online reinforcement learning can identify effective stimulation timing for terminating seizure-like activity.

neuroscience↗

Low-intensity ultrasound drives offline neuromodulation through passive membrane mechanisms in synaptically isolated hippocampal neurons

Low-intensity ultrasound alters neuronal excitability long after exposure ends, but the basis of this offline effect is unclear and most proposed mechanisms require synaptic receptors. We recorded from cultured mouse hippocampal neurons in whole-cell current clamp, before and 20 min after 1 min of 850 kHz continuous-wave ultrasound at 0.5 W/cm2 or sham, with synaptic transmission blocked throughout, each neuron re-patched. Sonicated neurons remained intact and firing, yet depolarized, with smaller action potentials and more noise. A passive-membrane fit showed reduced capacitance and a depolarized leak reversal potential in every sonicated cell, with a shortened time constant and no detectable change in input conductance, while sham cells showed no significant change. Changes in the time constant and reversal potential, both independent of membrane area, indicate a modification of the membrane itself rather than a loss of area. Brief ultrasound therefore leaves a lasting, receptor-independent imprint on passive membrane properties.

neuroscience↗

Phase-dependent closed-loop intersectional short-pulse stimulation reduces seizure duration: From computational modeling to clinical application

Drug-resistant epilepsy affects one-third of patients with persistent seizures despite optimal therapy. Intersectional short-pulse (ISP) stimulation is a novel transcranial electrical stimulation technique designed to deliver temporally precise, spatially targeted modulation of pathological brain activity. Here, we combined computational modeling with measurements in a rat epilepsy model and in patients with epilepsy to map the relationship between stimulation phase and seizure attenuation. In silico simulations of epileptiform networks showed that ISP stimulation significantly shortened seizure duration, with efficacy strongly depending on the phase of delivery. Phase-targeted stimulation during the rising phase and around the peaks (~45-90{degrees}) of the seizure oscillations led to the greatest reduction in seizure length. In rodents, ISP decreased seizure duration by 42.4% and shortened generalized seizure segments by 58.3%. In humans, stimulation reduced seizure length by 60.9% compared to control seizures. Phase dependence was evident across models and species, with a prominent efficacy window in the rising-to-peak portion of the ictal oscillation and model-specific secondary windows. These findings show that phase-targeted ISP can substantially shorten seizures and support phase-resolved stimulation as a precision-neuromodulation approach for epilepsy.

neuroscience↗