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Epileptic high-frequency network activity in a model of non-lesional temporal lobe epilepsy.

ABSTRACT: High-frequency cortical activity, particularly in the 250-600 Hz (fast ripple) band, has been implicated in playing a crucial role in epileptogenesis and seizure generation. Fast ripples are highly specific for the seizure initiation zone. However, evidence for the association of fast ripples with epileptic foci depends on animal models and human cases with substantial lesions in the form of hippocampal sclerosis, which suggests that neuronal loss may be required for fast ripples. In the present work, we tested whether cell loss is a necessary prerequisite for the generation of fast ripples, using a non-lesional model of temporal lobe epilepsy that lacks hippocampal sclerosis. The model is induced by unilateral intrahippocampal injection of tetanus toxin. Recordings from the hippocampi of freely-moving epileptic rats revealed high-frequency activity (>100 Hz), including fast ripples. High-frequency activity was present both during interictal discharges and seizure onset. Interictal fast ripples proved a significantly more reliable marker of the primary epileptogenic zone than the presence of either interictal discharges or ripples (100-250 Hz). These results suggest that fast ripple activity should be considered for its potential value in the pre-surgical workup of non-lesional temporal lobe epilepsy.

SUBMITTER: Jiruska P

PROVIDER: S-EPMC2859153 | biostudies-literature | 2010 May

REPOSITORIES: biostudies-literature

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Epileptic high-frequency network activity in a model of non-lesional temporal lobe epilepsy.

Jiruska Premysl P Finnerty Gerald T GT Powell Andrew D AD Lofti Noosheen N Cmejla Roman R Jefferys John G R JG

Brain : a journal of neurology 20100416 Pt 5

High-frequency cortical activity, particularly in the 250-600 Hz (fast ripple) band, has been implicated in playing a crucial role in epileptogenesis and seizure generation. Fast ripples are highly specific for the seizure initiation zone. However, evidence for the association of fast ripples with epileptic foci depends on animal models and human cases with substantial lesions in the form of hippocampal sclerosis, which suggests that neuronal loss may be required for fast ripples. In the present ...[more]

PMID: 20400525

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Project description:Together with hippocampus, the amygdala is important in the epileptogenic network of patients with temporal lobe epilepsy. Recently, an increase in amygdala volumes (i.e. amygdala enlargement) has been proposed as morphological biomarker of a subtype of temporal lobe epilepsy patients without MRI abnormalities, although other data suggest that this finding might be unspecific and not exclusive to temporal lobe epilepsy. In these studies, the amygdala is treated as a single entity, while instead it is composed of different nuclei, each with peculiar function and connection. By adopting a recently developed methodology of amygdala's subnuclei parcellation based of high-resolution T1-weighted image, this study aims to map specific amygdalar subnuclei participation in temporal lobe epilepsy due to hippocampal sclerosis (n = 24) and non-lesional temporal lobe epilepsy (n = 24) with respect to patients with focal extratemporal lobe epilepsies (n = 20) and healthy controls (n = 30). The volumes of amygdala subnuclei were compared between groups adopting multivariate analyses of covariance and correlated with clinical variables. Additionally, a logistic regression analysis on the nuclei resulting statistically different across groups was performed. Compared with other populations, temporal lobe epilepsy with hippocampal sclerosis showed a significant atrophy of the whole amygdala (p Bonferroni = 0.040), particularly the basolateral complex (p Bonferroni = 0.033), while the non-lesional temporal lobe epilepsy group demonstrated an isolated hypertrophy of the medial nucleus (p Bonferroni = 0.012). In both scenarios, the involved amygdala was ipsilateral to the epileptic focus. The medial nucleus demonstrated a volume increase even in extratemporal lobe epilepsies although contralateral to the seizure onset hemisphere (p Bonferroni = 0.037). Non-lesional patients with psychiatric comorbidities showed a larger ipsilateral lateral nucleus compared with those without psychiatric disorders. This exploratory study corroborates the involvement of the amygdala in temporal lobe epilepsy, particularly in mesial temporal lobe epilepsy and suggests a different amygdala subnuclei engagement depending on the aetiology and lateralization of epilepsy. Furthermore, the logistic regression analysis indicated that the basolateral complex and the medial nucleus of amygdala can be helpful to differentiate temporal lobe epilepsy with hippocampal sclerosis and with MRI negative, respectively, versus controls with a consequent potential clinical yield. Finally, the present results contribute to the literature about the amygdala enlargement in temporal lobe epilepsy, suggesting that the increased volume of amygdala can be regarded as epilepsy-related structural changes common across different syndromes whose meaning should be clarified.

Project description:Background and Purpose: Temporal lobe epilepsy (TLE) is a common chronic neurological disease that is often invulnerable to anti-epileptic drugs. Increasing data have demonstrated that acetylcholine (ACh) and cholinergic neurotransmission are involved in the pathophysiology of epilepsy. Cytisine, a full agonist of α7 nicotinic acetylcholine receptors (α7nAChRs) and a partial agonist of α4β2nAChRs, has been widely applied for smoking cessation and has shown neuroprotection in neurological diseases. However, whether cytisine plays a role in treating TLE has not yet been determined. Experimental Approach: In this study, cytisine was injected intraperitoneally into pilocarpine-induced epileptic rats for three weeks. Alpha-bungarotoxin (α-bgt), a specific α7nAChR antagonist, was used to evaluate the mechanism of action of cytisine. Rats were assayed for the occurrence of seizures and cognitive function by video surveillance and Morris water maze. Hippocampal injuries and synaptic structure were assessed by Nissl staining and Golgi staining. Furthermore, levels of glutamate, γ-aminobutyric acid (GABA), ACh, and α7nAChRs were measured. Results: Cytisine significantly reduced seizures and hippocampal damage while improving cognition and inhibiting synaptic remodeling in TLE rats. Additionally, cytisine decreased glutamate levels without altering GABA levels, and increased ACh levels and α7nAChR expression in the hippocampi of TLE rats. α-bgt antagonized the above-mentioned effects of cytisine treatment. Conclusion and Implications: Taken together, these findings indicate that cytisine exerted an anti-epileptic and neuroprotective effect in TLE rats via activation of α7nAChRs, which was associated with a decrease in glutamate levels, inhibition of synaptic remodeling, and improvement of cholinergic transmission in the hippocampus. Hence, our findings not only suggest that cytisine represents a promising anti-epileptic drug, but provides evidence of α7nAChRs as a novel therapeutic target for TLE.

Project description:OBJECTIVE:The current practice under which patients with refractory epilepsy are surgically treated is based mainly on the identification of specific cortical areas, mainly the epileptogenic zone, which is believed to be responsible for generation of seizures. A better understanding of the whole epileptic network and its components and properties is required before more effective and less invasive therapies can be developed. The aim of the present study was to partially characterize the evolution of the functional network during the preictal-ictal transition in partial seizures in patients with temporal lobe epilepsy (TLE). METHODS:Scalp and foramen ovale (FOE) recordings from twenty-two TLE patients were analyzed under the complex network perspective. The density of links, average path length, average clustering coefficient, and modularity were calculated during the preictal and the ictal stages. Both linear-Pearson correlation-and non-linear-phase synchronization-measures were used as proxies of functional connectivity between the electrode locations areas. The transition from one stage to the other was evaluated in the whole network and in the mesial sub-networks. The results were compared with a voltage-dependent measure, namely, the spectral entropy. RESULTS:Changes in the global functional network during the transition from the preictal to the ictal stage show, in the linear case, that in sixteen cases (72.7%) the density of the links increased during the seizure, with a decrease in the average path length in fifteen cases (68.1%). There was also a preictal and ictal imbalance in functional connectivity during both stages (77.2% to 86.3%). The SE dropped during the seizure in 95.4% of the cases, but did not show any tendency towards lateralization. When using the nonlinear measure of functional connectivity, the phase synchronization, similar results were obtained. CONCLUSIONS:In TLE patients, the transition to the ictal stage is accompanied by increasing global synchronization and a more ordered spectral content of the signals, indicated by lower spectral entropy. The interictal connectivity imbalance (lower ipsilateral connectivity) is sustained during the seizure, irrespective of any appreciable imbalance in the spectral entropy of the mesial recordings.

Dataset Information

Epileptic high-frequency network activity in a model of non-lesional temporal lobe epilepsy.

Publications

Epileptic high-frequency network activity in a model of non-lesional temporal lobe epilepsy.

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