Makhalova, J. | Search bioRxiv

bioRxiv2022

Multi-scale structural alterations of basal ganglia in focal epilepsy as demonstrated by 7T MRI

Focal epilepsy is characterized by repeated spontaneous seizures that originate from cortical epileptogenic zone networks (EZN). More recently, analysis of intracerebral recordings showed that subcortical structures, and in particular the thalamus, play an important role in facilitating and/or propagating epileptic activity. This supports previously reported structural alterations of these structures. Nonetheless, between-patient differences in EZN (e.g., temporal vs. non-temporal lobe epilepsy) as well as other clinical features (e.g., number of epileptogenic regions) might impact the magnitude as well as spatial distribution of subcortical structural changes. Here we used 7 Tesla MRI T1 data to provide a comprehensive description of subcortical morphological (volume, tissue deformation, and shape) and longitudinal relaxation (T1) changes in focal epilepsy patients to evaluate the impact of the EZN and patient-specific clinical features. Our results showed widespread morphometric and T1 changes. Focusing on the thalamus, atrophy varied across nuclei but appeared most prominent for the TLE group and the ipsilateral side, while shortening of T1 was observed for the lateral thalamus, in particular. Multivariate analyses across thalamic nuclei and basal ganglia showed that volume acted as the dominant discriminator between patients and controls, while (posterolateral) thalamic T1 measures looked promising to further differentiate patients based on EZN. In particular, the observed differences in T1 changes between thalamic nuclei indicated differential involvement of thalamic nuclei based on EZN. Finally, the number of epileptogenic regions was found to best explain the observed variability between patients. To conclude, this work revealed multi-scale subcortical alterations in focal epilepsy as well as their dependence on several clinical characteristics. Our results provide a basis for further, in-depth investigations using (quantitative) MRI and SEEG data and warrant further personalization of intervention strategies, such as deep brain stimulation, for treating focal epilepsy patients.

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↗