C3: Towards controlling pathological network dynamics - Terminating ictal epileptic activity by electrical stimulation of the epileptic focus
Andreas Schulze-BonhageI, Karl-Heinz BovenE and Ad AertsenA
I = Epilepsy Centre, University Medical Center
E = Multi Channel Systems GmbH
A = Neurobiology and Biophysics
Scientific background
Treatment of epilepsy has so far been confined to chronic medication (seizure prevention by affecting cortical excitation/inhibition balance) and surgical excision of the epileptogenic zone. By these means, 2/3 of epilepsy patients achieve complete seizure control. For the others, alternative treatment strategies remain to be established. In the transition from interictal state to ictal discharges, synchronization and recruitment in cortical networks play a key role. Since external input can modify these dynamics, approaches involving electrical stimulation have been applied during the last 30 years. Complete seizure control, however, is rarely achieved, possibly since stimuli were not specifically targeted or not temporally applied at the onset of ictal discharges. Little is known which stimulation parameters are suited to interfere with abnormal synchronization, or whether the ictal discharge pattern affects the efficacy of stimulation parameters. This project aims at danymical interference with epileptic activity by a combination of physiological and computational approaches based on studies on the initiation and propagation of epileptic waves, seizure detection and prediction in EEG data, and stability of propagating synchronous spiking in cortical networks.
Objectives
The project develops and applies means to control the dynamics of pathophysiological activity in biological neural network are used to establish crucial epochs in the abnormal synchronization of neuronal activity during which appropriately designed electrical stimuli can lead to effective suppression of ictal discharges, and to optimize stimulation parameters to intervene with the abnormal synchronization. Presently, two animal models of focal epilepsy are being established using intrahippocampal kainate injections and kindling. In parallel, modeling is used to put forward hypotheses on effective stimulus parameters which are to be tested in the animal models of epilepsy; results will be fed back to the model. In a later stage, effective stimulus paradigms will be applied to human epilepsy in patients with temporarily implanted intracranial electrodes.