Dynamics underlying epileptic seizures span multiple scales in space and time, therefore, understanding seizure mechanisms requires identifying the relations between seizure components within and across these scales, together with the analysis of their dynamical repertoire. In this view, mathematical models have been developed, ranging from single neuron to neural population. In this study, we consider a neural mass model able to exactly reproduce the dynamics of heterogeneous spiking neural networks. We combine mathematical modeling with structural information from non invasive brain imaging, thus building large-scale brain network models to explore emergent dynamics and test the clinical hypothesis. We provide a comprehensive study on the effect of external drives on neuronal networks exhibiting multistability, in order to investigate the role played by the neuroanatomical connectivity matrices in shaping the emergent dynamics. In particular, we systematically investigate the conditions under which the network displays a transition from a low activity regime to a high activity state, which we identify with a seizure-like event. This approach allows us to study the biophysical parameters and variables leading to multiple recruitment events at the network level. We further exploit topological network measures in order to explain the differences and the analogies among the subjects and their brain regions, in showing recruitment events at different parameter values. We demonstrate, along with the example of diffusion-weighted magnetic resonance imaging (dMRI) connectomes of 20 healthy subjects and 15 epileptic patients, that individual variations in structural connectivity, when linked with mathematical dynamic models, have the capacity to explain changes in spatiotemporal organization of brain dynamics, as observed in network-based brain disorders. In particular, for epileptic patients, by means of the integration of the clinical hypotheses on the epileptogenic zone (EZ), i.e., the local network where highly synchronous seizures originate, we have identified the sequence of recruitment events and discussed their links with the topological properties of the specific connectomes. The predictions made on the basis of the implemented set of exact mean-field equations turn out to be in line with the clinical pre-surgical evaluation on recruited secondary networks.

• Klíčová slova
• epileptic seizure-like event, neural mass model, patient-specific brain network model, quadratic integrate-and-fire neuron, topological network measure,
• Publikační typ
• časopisecké články MeSH

Background: Chronic vagal nerve stimulation (VNS) is a well-established non-pharmacological treatment option for drug-resistant epilepsy. This study sought to develop a statistical model for prediction of VNS efficacy. We hypothesized that reactivity of the electroencephalogram (EEG) to external stimuli measured during routine preoperative evaluation differs between VNS responders and non-responders. Materials and Methods: Power spectral analyses were computed retrospectively on pre-operative EEG recordings from 60 epileptic patients with VNS. Thirty five responders and 25 non-responders were compared on the relative power values in four standard frequency bands and eight conditions of clinical assessment-eyes opening/closing, photic stimulation, and hyperventilation. Using logistic regression, groups of electrodes within anatomical areas identified as maximally discriminative by n leave-one-out iterations were used to classify patients. The reliability of the predictive model was verified with an independent data-set from 22 additional patients. Results: Power spectral analyses revealed significant differences in EEG reactivity between responders and non-responders; specifically, the dynamics of alpha and gamma activity strongly reflected VNS efficacy. Using individual EEG reactivity to develop and validate a predictive model, we discriminated between responders and non-responders with 86% accuracy, 83% sensitivity, and 90% specificity. Conclusion: We present a new statistical model with which EEG reactivity to external stimuli during routine presurgical evaluation can be seen as a promising avenue for the identification of patients with favorable VNS outcome. This novel method for the prediction of VNS efficacy might represent a breakthrough in the management of drug-resistant epilepsy, with wide-reaching medical and economic implications.

• Klíčová slova
• EEG reactivity, efficacy prediction, epilepsy, epilepsy treatment, neurostimulation, vagal nerve stimulation,
• Publikační typ
• časopisecké články MeSH