Biology subjects

Laszlovszky, T.

Publications and source records attributed to Laszlovszky, T..

5 recordsLinked to original sources

bioRxiv2026

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↗

bioRxiv2026

From Scalp to Source: Precise Phase Retrieval of Intracerebral Epileptic Sources Based on Surface EEG

Accurate phase tracking of deep-brain activity is critical for effective closed-loop and phase-locked neuromodulation therapies. However, direct access to deep neural phase through intracranial recordings remains clinically restrictive due to the invasiveness. Here we validate and clinically benchmark the Gabor-Nelson (GN) dipole estimation method for reconstructing deep-brain oscillatory phase from non-invasive scalp EEG. GN is a geometry-based, imaging-independent approach that offers computationally efficient dipole reconstruction and has rarely been applied to source-level phase estimation in human neuroscience. We compared GN with an established MRI-informed Inverse Solution (IS) method using a three-stage reconstruction pipeline consisting of dipole modeling, dimensionality reduction, and frequency-dependent phase-delay correction. Validation is performed using (i) cadaveric recordings, where known ground-truth seizure waveforms were replayed through implanted deep electrodes, and (ii) simultaneous scalp EEG and SEEG recordings in human patients, where pseudo-ground truth was approximated via the intracranial contacts. GN achieved phase accuracy and signal fidelity comparable to IS across both datasets despite requiring no anatomical imaging. In cadaver recordings, phase-corrected reconstruction correlations exceeded r > 0.91 and {Delta}{Phi} < 9{degrees} in mean phase error. In patient SEEG data, GN reached up to r {approx} 0.80 with phase offsets suitable for neuromodulatory timing. GN offers a viable, low-barrier, imaging-independent alternative to traditional inverse modeling for non-invasive seizure phase tracking. This framework opens pathways for scalable, phase-locked and closed-loop stimulation therapies in epilepsy and potentially other network-based brain disorders.

neuroscience↗

bioRxiv2025

Non-vectorial Integration of Intersectional Short-Pulse Stimulation Enables Enhanced Deep Brain Modulation and Effective Seizure Control

Transcranial electrical stimulation (TES) holds promise to treat neurological disorders, but its efficacy is limited by poor spatial focality and depth of penetration. Here, we examined the potential utility of Intersectional Short-Pulse (ISP) stimulation of deeper brain penetration. Using computational modeling and in vivo patch-clamp recordings in rats, we demonstrate that neurons integrate ISP-induced electric fields in a non-vectorial manner. This mechanism allows ISP to overcome some limits of conventional TES, achieving spatially limited stimulation across cortical and subcortical structures. In a rat model of temporal lobe epilepsy, closed-loop ISP stimulation significantly outperformed conventional TES in reducing seizure duration and severity. ISP reduced hippocampal seizure duration by 49% and 41% compared to sham stimulation and conventional TES and significantly reduced motor seizure severity. Our findings demonstrate that ISP stimulation can rapidly terminate hippocampal seizures, offering a potential new approach for non-invasive neuromodulation with applications across diverse neurologic and psychiatric disorders.

neuroscience↗

bioRxiv2019

Distinct synchronization, cortical coupling and behavioural function of basal forebrain cholinergic neuron types

Basal forebrain cholinergic neurons (BFCN) densely innervate the forebrain and modulate synaptic plasticity, cortical processing, brain states and oscillations. However, little is known about the functional diversity of cholinergic neurons and whether distinct types support different functions. To examine this question we recorded BFCN in vivo, to examine their behavioral functions, and in vitro, to study their intrinsic properties. We identified two distinct types of BFCN that markedly differ in their firing modes, synchronization properties and behavioral correlates. Bursting cholinergic neurons (BFCNBURST) fired in zero-lag synchrony with each other, phase-locked to cortical theta activity and fired precisely timed bursts of action potentials after reward and punishment. Regular firing cholinergic neurons (BFCNREG) were found predominantly in the posterior basal forebrain, displayed strong theta rhythmicity (5-10 Hz), fired asynchronously with each other and responded with precise single spikes after behavioral outcomes. In an auditory detection task, synchronization of BFCNBURST neurons to auditory cortex predicted the timing of mouse responses, whereas tone-evoked cortical coupling of BFCNREG predicted correct detections. We propose that cortical activation relevant for behavior is controlled by the balance of two cholinergic cell types, where the precise proportion of the strongly activating BFCNBURST follows an anatomical gradient along the antero-posterior axis of the basal forebrain.

neuroscience↗

bioRxiv2018

Open source toolkit for temporally controlled rodent behavior suitable for electrophysiology and optogenetic manipulations

Understanding how the brain controls behavior requires observing and manipulating neural activity in awake behaving animals. Neuronal firing is timed at millisecond precision. Therefore, to decipher temporal coding, it is necessary to monitor and control animal behavior at the same level of temporal accuracy. However, it is technically challenging to deliver sensory stimuli and reinforcers as well as to read the behavioral responses they elicit with millisecond precision. Presently available commercial systems often excel in specific aspects of behavior control, but they do not provide a customizable environment allowing flexible experimental design while maintaining high standards for temporal control necessary for interpreting neuronal activity. Moreover, delay measurements of stimulus and reinforcement delivery are largely unavailable. We combined microcontroller-based behavior control with a sound delivery system for playing complex acoustic stimuli, fast solenoid valves for precisely timed reinforcement delivery and a custom-built sound attenuated chamber using high-end industrial insulation materials. Together this setup provides a physical environment to train head-fixed animals, enables calibrated sound stimuli and precisely timed fluid and air puff presentation as reinforcers. We provide latency measurements for stimulus and reinforcement delivery and an algorithm to perform such measurements on other behavior control systems. Combined with electrophysiology and optogenetic manipulations, the millisecond timing accuracy will help interpret temporally precise neural signals and behavioral changes. Additionally, since software and hardware provided here can be readily customized to achieve a large variety of paradigms, these solutions enable an unusually flexible design of rodent behavioral experiments.

neuroscience↗