TY - JOUR
T1 - Homeostasis of brain dynamics in epilepsy
T2 - A feedback control systems perspective of Seizures
AU - Chakravarthy, Niranjan
AU - Tsakalis, Konstantinos
AU - Sabesan, Shivkumar
AU - Iasemidis, Leon
N1 - Funding Information:
This work was supported in part by the American Epilepsy Research Foundation and Ali Paris Fund for LKS Research and Education, and NSF Grant ECS-0601740. We would also like to acknowledge Prof. Piotr Suffczynski for providing the Simulink code for his thalamocortical model.
PY - 2009/3
Y1 - 2009/3
N2 - In an effort to understand basic functional mechanisms that can produce epileptic seizures, some key features are introduced in coupled lumped-parameter neural population models that produce "seizure"-like events and dynamics similar to the ones during the route of the epileptic brain towards seizures. In these models, modified from existing ones in the literature, internal feedback mechanisms are incorporated to maintain the normal low level of synchronous behavior in the presence of coupling variations. While the internal feedback is developed using basic feedback systems principles, it is also functionally equivalent to actual neurophysiological mechanisms such as homeostasis that act to maintain normal activity in neural systems that are subject to extrinsic and intrinsic perturbations. Here it is hypothesized that a plausible cause of seizures is a pathology in the internal feedback action; normal internal feedback quickly regulates an abnormally high coupling between the neural populations, whereas pathological internal feedback can lead to "seizure"-like high amplitude oscillations. Several external seizure-control paradigms, that act to achieve the operational objective of maintaining normal levels of synchronous behavior, are also developed and tested in this paper. In particular, closed-loop "modulating" control with predefined stimuli, and closed-loop feedback decoupling control are considered. Among these, feedback decoupling control is the consistently successful and robust seizure-control strategy. The proposed model and remedies are consistent with a variety of recent observations in the human and animal epileptic brain, and with theories from nonlinear systems, adaptive systems, optimization, and neurophysiology. The results from the analysis of these models have two key implications, namely, developing a basic theory for epilepsy and other brain disorders, and the development of a robust seizure-control device through electrical stimulation and/or drug intervention modalities.
AB - In an effort to understand basic functional mechanisms that can produce epileptic seizures, some key features are introduced in coupled lumped-parameter neural population models that produce "seizure"-like events and dynamics similar to the ones during the route of the epileptic brain towards seizures. In these models, modified from existing ones in the literature, internal feedback mechanisms are incorporated to maintain the normal low level of synchronous behavior in the presence of coupling variations. While the internal feedback is developed using basic feedback systems principles, it is also functionally equivalent to actual neurophysiological mechanisms such as homeostasis that act to maintain normal activity in neural systems that are subject to extrinsic and intrinsic perturbations. Here it is hypothesized that a plausible cause of seizures is a pathology in the internal feedback action; normal internal feedback quickly regulates an abnormally high coupling between the neural populations, whereas pathological internal feedback can lead to "seizure"-like high amplitude oscillations. Several external seizure-control paradigms, that act to achieve the operational objective of maintaining normal levels of synchronous behavior, are also developed and tested in this paper. In particular, closed-loop "modulating" control with predefined stimuli, and closed-loop feedback decoupling control are considered. Among these, feedback decoupling control is the consistently successful and robust seizure-control strategy. The proposed model and remedies are consistent with a variety of recent observations in the human and animal epileptic brain, and with theories from nonlinear systems, adaptive systems, optimization, and neurophysiology. The results from the analysis of these models have two key implications, namely, developing a basic theory for epilepsy and other brain disorders, and the development of a robust seizure-control device through electrical stimulation and/or drug intervention modalities.
KW - Coupled systems
KW - Epileptic seizures
KW - Feedback control
KW - Neural population models
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U2 - 10.1007/s10439-008-9625-6
DO - 10.1007/s10439-008-9625-6
M3 - Article
C2 - 19125333
AN - SCOPUS:59449105277
SN - 0090-6964
VL - 37
SP - 565
EP - 585
JO - Annals of Biomedical Engineering
JF - Annals of Biomedical Engineering
IS - 3
ER -