Effects of age and cortical infarction on EEG dynamic changes associated with spike wave discharges in F344 rats.

Rodent models of absence seizures are used to investigate the network properties and regulatory mechanisms of the seizure's generalized spike and wave discharge (SWD). As rats age, SWDs occur more frequently, suggesting aging-related changes in the regulation of the corticothalamic mechanisms generating the SWD. We hypothesized that brain resetting mechanisms - how the brain "resets" itself to a more normal functional state following a transient period of abnormal function, e.g., a SWD - are impaired in aged animals and that brain infarction would further affect these resetting mechanisms. The main objective of this study was to determine the effects of aging, infarction, and their potential interaction on the resetting of EEG dynamics assessed by quantitative EEG (qEEG) measures of linear (signal energy measured by amplitude variation; signal frequency measured by mean zero-crossings) and nonlinear (signal complexity measured by the pattern match regularity statistic and the short-term maximum Lyapunov exponent) brain EEG dynamics in 4- and 20-month-old F344 rats with and without brain infarction. The main findings of the study were: 1) dynamic resetting of both linear and nonlinear EEG characteristics occurred following SWDs; 2) animal age significantly affected the degree of dynamic resetting in all four qEEG measures: SWDs in older rats exhibited a lower degree of dynamic resetting; 3) infarction significantly affected the degree of dynamic resetting only in terms of EEG signal complexity: SWDs in infarcted rats exhibited a lower degree of dynamic resetting; and 4) in all four qEEG measures, there was no significant interaction effect between age and infarction on dynamic resetting. We conclude that recovery of the brain to its interictal state following SWDs was better in young adult animals compared with aged animals, and to a lesser degree, in age-matched controls compared with infarction-injured animal groups, suggesting possible effects of brain resetting mechanisms and/or the disruption of the epileptogenic network that triggers SWDs.

An investigation of EEG dynamics in an animal model of temporal lobe epilepsy using the maximum Lyapunov exponent.

Analysis of intracranial electroencephalographic (iEEG) recordings in patients with temporal lobe epilepsy (TLE) has revealed characteristic dynamical features that distinguish the interictal, ictal, and postictal states and inter-state transitions. Experimental investigations into the mechanisms underlying these observations require the use of an animal model. A rat TLE model was used to test for differences in iEEG dynamics between well-defined states and to test specific hypotheses: 1) the short-term maximum Lyapunov exponent (STL(max)), a measure of signal order, is lowest and closest in value among cortical sites during the ictal state, and highest and most divergent during the postictal state; 2) STL(max) values estimated from the stimulated hippocampus are the lowest among all cortical sites; and 3) the transition from the interictal to ictal state is associated with a convergence in STL(max) values among cortical sites. iEEGs were recorded from bilateral frontal cortices and hippocampi. STL(max) and T-index (a measure of convergence/divergence of STL(max) between recorded brain areas) were compared among the four different periods. Statistical tests (ANOVA and multiple comparisons) revealed that ictal STL(max) was lower (p<0.05) than other periods, STL(max) values corresponding to the stimulated hippocampus were lower than those estimated from other cortical regions, and T-index values were highest during the postictal period and lowest during the ictal period. Also, the T-index values corresponding to the preictal period were lower than those during the interictal period (p<0.05). These results indicate that a rat TLE model demonstrates several important dynamical signal characteristics similar to those found in human TLE and support future use of the model to study epileptic state transitions.

Effects of acute hippocampal stimulation on EEG dynamics.

Progressive preictal dynamical convergence and postictal divergence of dynamical EEG descriptors among brain regions has been reported in human temporal lobe epilepsy (TLE) and in a rodent model of TLE. There are also reports of anticonvulsant effects of high frequency stimulation of the hippocampus in humans. We postulate that this anticonvulsant effect is due to dynamical resetting by the electrical stimulation. The following study investigated the effects of acute hippocampal electrical stimulation on dynamical transitions in the brain of a spontaneously seizing animal model of TLE to test the hypothesis of divergence in dynamical values by electrical stimulation of the hippocampus.