Biology subjects

Yochum, M.

Publications and source records attributed to Yochum, M..

8 recordsLinked to original sources

bioRxiv2026

Computational Insights into the tACS Modulation in Healthy and Epileptic Brain Networks

Transcranial Electric stimulation (tES) is a safe and noninvasive technique increasingly used in treating brain disorders. Despite many studies on tES, there is still a lack of understanding of its mechanisms at the microscale network level. This is crucial for optimized parameter selection in therapy approaches such as the treatment of pharmacoresistant epilepsy. In this study, we made use of a recently published neuroinspired microscale model of the neocortex, known as NeoCoMM, and integrated a "Lambda E"-based model of tES. This updated version was used to investigate the acute effects of tES (tDCS and tACS), on the neural activity of various neuron types in both healthy and epileptic brain states. Results showed that in the case of healthy alpha and gamma rhythms, tACS induced electric field entrainment at the peak power frequency of the network oscillations as measured by the Local field Potentials (LFPs). This resonance-like entrainment was independent from the individual firing rate of cell types. For epileptic activity, tACS did not provide consistent results. Cathodal tDCS resulted in a promising decrease in hyperexcitable activity throughout simulations. These results advance our understanding of the impact of tES on network dynamics at both the extracellular and intracellular activity levels. Author summary

neuroscience↗

bioRxiv2025

Fully Automated EEG Source Imaging Using Structured Sparsity for Single and Multiple Synchronous Epileptic Activities

Accurate localization of epileptic zones from High-Resolution ElectroEncephaloGraphy (HR-EEG) data can be challenging, especially when multiple synchronous zones are involved, and is highly dependent on the chosen EEG Source Imaging (ESI) method. Since a given scalp-level electrical pattern can result from multiple source configurations, ESI methods address this ill-posed inverse problem by imposing constraints on the structure of underlying sources. Here, we present an efficient approach that imposes sparsity on both the source-level activity and its spatial gradient. Unlike other methods that generally require a heuristic choice of a regularization parameter that balances between data fidelity and constraints, our method iteratively adjusts the parameter value based on the noise level in a fully automated way. The performance of the new method is evaluated across different scenarios of realistic synthetic HR-EEG data, including unifocal and synchronous multifocal cortical epileptic activity. Based on multiple performance indices, we demonstrate that the proposed approach outperforms traditional methods in accurately reconstructing epileptic sources. We also show that the method reduces polarity artifacts responsible for ghost sources and spatial discontinuities. Its ability to recover homogeneous, well-delineated regions of activity is further confirmed using real EEG data capturing a typical absence seizure.

neuroscience↗

bioRxiv2024

NeoCoMM: Neocortical Computational Microscale Model

The Neocortical Computational Microscale model (NeoCoMM) is a unique neurophysiologically-inspired software. It offers a friendly graphical user interface that allows for the simulation of the intracellular and extracellular neural activity of a neocortical column. This software provides a realistic framework that can portray the neural activity and underlying cellular mechanisms related to different brain pathologies such as epilepsy. NeoCoMM is capable of (1) simulating the cortical tissue of three different species, (2) visualizing individual cell responses to external stimulation, (3) visualizing the corresponding local field potential, (4) studying the impact of the recording electrode features on simulated signals, and (5) testing various physiological and pathological hypotheses. While NeoCoMM was primarily developed for simulating epileptiform activity, it can also generate healthy brain rhythms or be adapted to other brain disorders.

bioengineering↗

bioRxiv2024

NeoCOMM: A Neocortical Neuroinspired Computational Model for the Reconstruction and Simulation of Epileptiform Events

Understanding the pathophysiological dynamics which underline interictal epileptiform events (IEEs) such as epileptic spikes, spike-and-waves or High-frequency oscillations (HFOs) is of major importance in the context of neocortical refractory epilepsy, as it paves the way for the development of novel therapies. Typically, these events are detected in local field potential (LFP) recordings obtained through depth electrodes during pre-surgical investigations. Although essential, the underlying pathophysiological mechanisms for the generation of these epileptic neuromarkers remain unclear. The aim of this paper is to propose a novel neurophysiologically relevant reconstruction of the neocortical microcircuitry in the context of epilepsy. This reconstruction intends to facilitate the analysis of a comprehensive set of parameters encompassing physiological, morphological, and biophysical aspects that directly impact the generation and recording of different IEEs. Accordingly, a novel microscale computational model of an epileptic neocortical column was introduced. This model incorporates the intricate multilayered structure of the cortex and allows for the simulation of realistic interictal epileptic signals. The proposed model was validated through comparisons with real IEEs recorded using intracranial stereo-electroencephalography (SEEG) signals from both humans and animals. Using the model, the user can recreate epileptiform patterns observed in different species (human, rodent, and mouse) and study the intracellular activity associated with these patterns. Our model allowed us to unravel the relationship between glutamatergic and GABAergic synaptic transmission of the epileptic neural network and the type of generated IEE. Moreover, sensitivity analyses allowed for the exploration of the pathophysiological parameters responsible for the transitions between these events. Finally, the presented modeling framework also provides an Electrode Tissue Model (ETI) that adds realism to the simulated signals and offers the possibility of studying their sensitivity to the electrode characteristics. The model (NeoCoMM) presented in this work can be of great use in different applications since it offers an in silico framework for sensitivity analysis and hypothesis testing. It can also be used as a starting point for more complex studies.

bioengineering↗

bioRxiv2023

Frequency-dependent phase entrainment of cortical cell types during tACS: Converging modeling evidence

BackgroundTranscranial alternating current stimulation (tACS) enables non-invasive modulation of brain activity, holding promise for clinical and research applications. Yet, it remains unclear how the stimulation frequency affects various neuron types. ObjectiveTo quantify the frequency-dependent behavior of key neocortical cell types. MethodsWe used both detailed (anatomical multicompartments) and simplified (three compartments) single-cell modeling approaches based on the Hodgkin-Huxley formalism to study neocortical excitatory and inhibitory cells under various-amplitude tACS frequencies within the 5-50 Hz range at rest and during basal 10 Hz activity. ResultsL5 pyramidal cells exhibited the highest polarizability at DC, ranging from 0.21 to 0.25mm and decaying exponentially with frequency. Inhibitory neurons displayed membrane resonance in the 5-15 Hz range with lower polarizability, although bipolar cells had higher polarizability. Layer 5 PC demonstrated the highest entrainment close to 10 Hz, which decayed with frequency. In contrast, inhibitory neurons entrainment increased with frequency, reaching level akin to PC. Results from simplified models could replicate the phase preferences, while amplitudes tend to follow opposite trends in PC. ConclusiontACS-induced membrane polarization is frequency-dependent, revealing observable resonance behavior. This finding motivates further experimental studies of cell-specific frequency-dependent membrane responses to weak electric stimuli. Whilst optimal phase entrainment of sustained activity is achieved in PC when tACS frequency matches the activity, inhibitory neurons tend to be entrained at higher frequencies. Consequently, this presents the potential for precise, cell-specific targeting. O_LISingle-cell models of frequency response to tACS for a wide variety of neurons C_LIO_LISimplified and morphologically accurate models were compared C_LIO_LIPyramidal cells (PC) show resonant-like response close to intrinsic firing frequency C_LIO_LIEntrainement of GABAergic neurons increases with the frequency of tACS C_LIO_LIMembrane polarization resonance in GABAergic neurons within the 5-15 Hz range C_LI

neuroscience↗

bioRxiv2021

A personalizable autonomous neural mass model of epileptic seizures

Work in the last two decades has shown that neural mass models (NMM) can realistically reproduce and explain epileptic seizure transitions as recorded by electrophysiological methods (EEG, SEEG). In previous work, advances were achieved by increasing excitation and heuristically varying network inhibitory coupling parameters in the models. Based on these early studies, we provide a laminar NMM capable of realistically reproducing the electrical activity recorded by SEEG in the epileptogenic zone during interictal to ictal states. With the exception of the external noise input into the pyramidal cell population, the model dynamics are autonomous. By setting the system at a point close to bifurcation, seizure-like transitions are generated, including pre-ictal spikes, low voltage fast activity, and ictal rhythmic activity. A novel element in the model is a physiologically motivated algorithm for chloride dynamics: the gain of GABAergic post-synaptic potentials is modulated by the pathological accumulation of chloride in pyramidal cells due to high inhibitory input and/or dysfunctional chloride transport. In addition, in order to simulate SEEG signals for comparison with real seizure recordings, the NMM is embedded first in a layered model of the neocortex and then in a realistic physical model. We compare modeling results with data from four epilepsy patient cases. By including key pathophysiological mechanisms, the proposed framework captures succinctly the electrophysiological phenomenology observed in ictal states, paving the way for robust personalization methods based on NMMs.

neuroscience↗

bioRxiv2021

Assessing HD-EEG functional connectivity states using ahuman brain computational model

ObjectiveElectro/Magnetoencephalography (EEG/MEG) source-space network analysis is increasingly recognized as a powerful tool for tracking fast electrophysiological brain dynamics. However, an objective and quantitative evaluation of pipeline steps is challenging due to the lack of realistic controlled data. Here, our aim is two-folded: 1) provide a quantitative assessment of the advantages and limitations of the analyzed techniques and 2) introduce (and share) a complete framework that can be used to optimize the entire pipeline of EEG/MEG source connectivity. ApproachWe used a human brain computational model containing both physiologically based cellular GABAergic and Glutamatergic circuits coupled through Diffusion Tensor Imaging, to generate high-density EEG recordings. We designed a scenario of successive gamma-band oscillations in distinct cortical areas to emulate a virtual picture-naming task. We identified fast time-varying network states and quantified the performance of the key steps involved in the pipeline: 1) inverse models to reconstruct cortical-level sources, 2) functional connectivity measures to compute statistical interdependency between regional signals, and 3) dimensionality reduction methods to derive dominant brain network states (BNS). Main ResultsUsing a systematic evaluation of the different decomposition techniques, results show significant variability among tested algorithms in terms of spatial and temporal accuracy. We outlined the spatial precision, the temporal sensitivity, and the global accuracy of the extracted BNS relative to each method. Our findings suggest a good performance of wMNE/PLV combination to elucidate the appropriate functional networks and ICA techniques to derive relevant dynamic brain network states. SignificanceWe suggest using such brain models to go further in the evaluation of the different steps and parameters involved in the EEG/MEG source-space network analysis. This can reduce the empirical selection of inverse model, connectivity measure, and dimensionality reduction method as some of the methods can have a considerable impact on the results and interpretation.

neuroscience↗

bioRxiv2020

Mean-field modeling of brain-scale dynamics for the evaluation of EEG source-space networks

Understanding the dynamics of brain-scale functional networks at rest and during cognitive tasks is the subject of intense research efforts to unveil fundamental principles of brain functions. To estimate these large-scale brain networks, the emergent method called "electroencephalography (EEG) source connectivity" has generated increasing interest in the network neuroscience community, due to its ability to identify cortical brain networks with satisfactory spatio-temporal resolution, while reducing mixing and volume conduction effects. However, no consensus has been reached yet regarding a unified EEG source connectivity pipeline, and several methodological issues have to be carefully accounted for to avoid pitfalls. Thus, a validation toolbox that provides flexible "ground truth" models is needed for an objective methods/parameters evaluation and, thereby an optimization of the EEG source connectivity pipeline. In this paper, we show how a recently developed large-scale model of brain-scale activity, named COALIA, can provide to some extent such ground truth by providing realistic simulations of source-level and scalp-level activity. Using a bottom-up approach, the model bridges cortical micro-circuitry and large-scale network dynamics. Here, we provide an example of the potential use of COALIA to analyze, in the context of epileptiform activity, the effect of three key factors involved in the "EEG source connectivity" pipeline: (i) EEG sensors density, (ii) algorithm used to solve the inverse problem, and (iii) functional connectivity measure. Results showed that a high electrode density (at least 64 channels) is required to accurately estimate cortical networks. Regarding the inverse solution/connectivity measure combination, the best performance at high electrode density was obtained using the weighted minimum norm estimate (wMNE) combined with the weighted phase lag index (wPLI). Although those results are specific to the considered aforementioned context (epileptiform activity), we believe that this model-based approach can be successfully applied to other experimental questions/contexts. We aim at presenting a proof-of-concept of the interest of COALIA in the network neuroscience field, and its potential use in optimizing the EEG source-space network estimation pipeline.

neuroscience↗