Abstracts

Rationale: There is a growing interest in deep brain stimulation (DBS) as an alternative therapy for drug-resistant non-surgical epilepsies. Many uncertainties still persist, and several targets and stimulation methods and paradigms are evaluated.Methods: We report the first direct observation of the suppression of focal interictal paroxysmal activity by centromedian thalamic nucleus (CM) stimulation in humans using depth recordings. The stimulation of the CM was performed during presurgical depth recordings in a patient with drug-resistant partial epilepsy related to a premotor focal cortical dysplasia (FCD). The same stimulations were subsequently simulated in a ex sillico thalamocortical network model.Results: We show that DBS influenced interictal FCD activity to the extent of abolishing its characteristic continuous spiking and fast rhythms pattern at low-frequency stimulation (LFS) and high-frequency stimulation (HFS) while the intermediate-frequency stimulation (IFS) had no effect. Moreover evoked potentials (EPs) during FCD stimulation were observed at the all the thalamic recording sites, but were highest in the CM. EPs during CM stimulation were observed throughout the dysplasia. Whether the subcortical network of the FCD is physiological, or FCD-specific is not clear. We developed a neural mass model of the thalamocortical network which comprises three main compartments: cortical, thalamic and reticular, each one with specific cell populations. According to this model, the key elements, which explain the suppression of the epileptic activity in the FCD, include the feed-forward inhibition and synaptic short-term depression of the thalamocortical connections at LFS; and the inhibition of the thalamic output at HFS. Conversely, modeling results indicate that IFS favors thalamic oscillations and raises epileptic dynamics.Conclusions: The DBS of the CM or many other targets in drug-resistant epilepsies is still experimental. We report a unique case, these results need further confirmation but they suggest that the CM is a worthwhile stimulation target for DBS in selected cases of drug-resistant non-surgical epilepsy. They also suggest that the DBS in epileptic patients could be tailored like cortectomies are. Other analysis and models may be useful for a better understanding of these results and of the epilepsy use of DBS.