About 20% of epileptic patients do not respond to pharmacological and surgical treatment. Another therapeutic option is the neurostimulation of neural circuits involved in the control or in the initiation of paroxysmal activity. Deep brain stimulation constitutes the main therapeutic alternative approach in some forms of pharmaco-resistant epilepsy which cannot benefit from resective surgery. The aim of this work was to develop a new system of adaptative deep brain stimulation which is effective for the long term suppression of seizures in a genetic rat model of absence epilepsy. Three main points were approached: (i) the characterisation of basal ganglia (BG) activities during seizures; (ii) the development of a new system based on deep brain stimulation combined to seizure-detection; (iii) the validation of long term closed loop deep brain stimulation. These data confirm the existence of a rapid propagation of spike-and-wave discharges (SWDs) from the cortex towards the thalamus and the BG, and an endogenous control of seizures by the substantia nigra pars reticulata (SNr) target used for seizures modulation. Despite a refractory period of 40 seconds during which the deep brain stimulation is ineffective, we show an antiepileptic effects of closed loop deep brain stimulation by the SNr. During long term closed loop SNr stimulation up to 97% of SWDs were interrupted accompanied by a decrease of SWDs with time. These results constitute a proof of concept for the use of closed loop device for the control of some forms of epileptic seizures.
