Cortical electrical stimulation in epilepsy patients

Abstract

Patients with epilepsy arising from the primary sensorimotor cortex have disabling seizures that are hard to treat with the standard treatment options e.g. anti-seizure medication and epilepsy surgery. The region where these seizures are generated, can be well localized due to the semiology involved with seizure onset. However, epilepsy surgery rarely leads to seizure freedom, because resections are incomplete to avoid functional deficits post-surgery. The fact that the seizure onset zone (SOZ) can be well localized facilitates targeted electrical neurostimulation, but direct electrical stimulation in this area might also affect motor performance. The aim of this thesis was to lay a foundation for a new treatment option with cortical network closed-loop electrical stimulation for patients with epilepsy arising from the primary sensorimotor cortex. For epilepsy surgery evaluation, we often implant subdural electrode grids on the cortex to determine the SOZ, that needs to be removed to render a patient seizure free post-surgery. We also delineate eloquent cortex that cannot be removed without risking functional deficits by applying electrical stimulation to evoke symptoms. Single pulse electrical stimulation is a technique that is used to perturbate brain regions. Evoked responses in other brain regions suggest a connection between the stimulated brain region, and the brain region that shows evoked responses. In the first part of this thesis, we construct a network by detecting responses in other regions to electrical stimuli. We analyze several aspects of these responses to distinguish epileptogenic from normal brain tissue. We find that the velocity of these responses change when a person gets older. We also show that this network changes only marginally when the patient is under anesthesia. Moreover, this network can be used to determine an optimal stimulation site when we intend to treat epilepsy with chronic electrical stimulation. In the second part, we investigate how to apply cortical electrical stimulation to treat epilepsy in specific patients who have seizures that start with movements in one limb. We implanted a dedicated pacemaker in five persons with such epilepsy. This stimulator was programmed to apply electrical stimuli when a seizure occurs. After one year, the number of seizures decreased with on average 50% in these patients. In the third part, we emphasize the importance of sharing our data with other researchers, because they might find answers to other questions. In the last chapter, we demonstrate a pipeline to process raw brain signals towards a more structured format which is widely used among other neuroscience researchers.