RESUMO
Epilepsy is one of the most common brain disorders worldwide, affecting millions of people every year. Given the partially successful existing treatments for epileptiform activity suppression, dynamic mathematical models have been proposed with the purpose of better understanding the factors that might trigger an epileptic seizure and how to mitigate it, among which Epileptor stands out, due to its relative simplicity and consistency with experimental observations. Recent studies using this model have provided evidence that establishing a feedback-based control approach is possible. However, for this strategy to work properly, Epileptor's parameters, which describe the dynamic characteristics of a seizure, must be known beforehand. Therefore, this work proposes a methodology for estimating such parameters based on a successive optimization technique. The results show that it is feasible to approximate their values as they converge to reference values based on different initial conditions, which are modeled by an uncertainty factor or noise addition. Also, interictal (healthy) and ictal (ongoing seizure) conditions, as well as time resolution, must be taken into account for an appropriate estimation. At last, integrating such a parameter estimation approach with observers and controllers for purposes of seizure suppression is carried out, which might provide an interesting alternative for seizure suppression in practice in the future.
Assuntos
Eletroencefalografia , Epilepsia , Humanos , Convulsões , Epilepsia/diagnóstico por imagemRESUMO
Epilepsy affects about 70 million people in the world. Every year, approximately 2.4 million people are diagnosed with epilepsy, two-thirds of them will not know the etiology of their disease, and 1% of these individuals will decease as a consequence of it. Due to the inherent complexity of predicting and explaining it, the mathematical model Epileptor was recently developed to reproduce seizure-like events, also providing insights to improve the understanding of the neural dynamics in the interictal and ictal periods, although the physics behind each parameter and variable of the model is not fully established in the literature. This paper introduces an approach to design a feedback-based controller for suppressing epileptic seizures described by Epileptor. Our work establishes how the nonlinear dynamics of this disorder can be written in terms of a combination of linear sub-models employing an exact solution. Additionally, we show how a feedback control gain can be computed to suppress seizures, as well as how specific shapes applied as input stimuli for this purpose can be obtained. The practical application of the approach is discussed and the results show that the proposed technique is promising for developing controllers in this field.
Assuntos
Epilepsia , Convulsões , Retroalimentação , Humanos , Modelos Lineares , Dinâmica não LinearRESUMO
Many patients with epilepsy do not obtain proper control of their seizures through conventional treatment. We review aspects of the pathophysiology underlying epileptic phenomena, with a special interest in the role of the amygdala, stressing the importance of hypersynchronism in both ictogenesis and epileptogenesis. We then review experimental studies on electrical stimulation of mesiotemporal epileptogenic areas, the amygdala included, as a means to treat medically refractory epilepsy. Regular high-frequency stimulation (HFS) commonly has anticonvulsant effects and sparse antiepileptogenic properties. On the other hand, HFS is related to acute and long-term increases in excitability related to direct neuronal activation, long-term potentiation, and kindling, raising concerns regarding its safety and jeopardizing in-depth understanding of its mechanisms. In turn, the safer regular low-frequency stimulation (LFS) has a robust antiepileptogenic effect, but its pro- or anticonvulsant effect seems to vary at random among studies. As an alternative, studies by our group on the development and investigation of temporally unstructured electrical stimulation applied to the amygdala have shown that nonperiodic stimulation (NPS), which is a nonstandard form of LFS, is capable of suppressing both acute and chronic spontaneous seizures. We hypothesize two noncompetitive mechanisms for the therapeutic role of amygdala in NPS, 1) a direct desynchronization of epileptic circuitry in the forebrain and brainstem and 2) an indirect desynchronization/inhibition through nucleus accumbens activation. We conclude by reintroducing the idea that hypersynchronism, rather than hyperexcitability, may be the key for epileptic phenomena and epilepsy treatment.