Epilepsy; DBS; spike; Microelectrode; ripple; deep brain stimulation; temporal lobe
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BackgroundThis research project is the continuation of the ongoing project entitled "Optimization of Deep Brain Stimulation in Epilepsy”. It has been shown that the success of deep brain stimulation (DBS) is dependant not only of the stimulation parameters that have to be studied, but it is dependent of the precise localization of the irritative zone to where the stimulation electrodes must be placed.GoalsThis project will develop measurements of advanced biomarkers of epilepsy devoted to optimize DBS. These biomarkers will be exploited to distinguish the irritative zone from the epileptogenic zone in order to optimize the localization of the stimulation electrodes. These biomarkers will be used to evaluate the effects of the stimulation of the irritative zone, not only for the standard parameters, but also for completely innovative parameters in the field of DBS, i.e. very high frequency and stochastic frequency of stimulation. At the same time, they will be evaluated and possibly exploited to tailor resection surgeries in epilepsy.Working hypothesesWe make the hypothesis that similarly to interictal epileptic discharge rates (IEDRs), fast ripples and multi-unit activity (MUA) can be used as biomarkers of epileptogenesis. Similarly to IED rates, fast ripples can be detected from intracranial EEG recorded with particular technical precautions and from microelectrodes. MUA are studied from micro-electrode recordings. We make the hypothesis that fast ripples and MUA can be used to identify the neuronal substrates at the source of epileptic discharges and to evaluate their changes when DBS is applied.MethodsThese measurements will be conducted at the time of invasive presurgical evaluation, during implantation of chronic DBS electrodes, and also intra-operatively during resection surgeries. Scalp EEG, intracranial EEG, and microelectrode recordings will be conducted. They will be analyzed with advanced methods of digital signal processing. They will be compared between each others, correlated with interictal events, seizures and DBS parameters.Expected outcomeBeyond the optimization of DBS, this research project will provide biomarkers that could be used to trigger electric stimulation, in the perspective to develop closed-loop systems (which stimulate only at the time a seizure might occur). This research will contribute, to understand the fundamental mechanisms of action of DBS. These developments will be exploited to monitor intraoperavitely resection surgeries in order to correlate the surgical process to the epileptogenicity, and to develop super selective resection surgery. This project will provide the scientific community a wealth of data from the human brain during several states, i.e. wakefulness and sleep, cognitively active or resting. The results are of potential relevance of a number of brain diseases, i.e. beyond epilepsy, and possibly also for rehabilitation.