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The role of cortical inhibitory cells in human epilepsy

Principal Investigator:
  • Adrien Peyrache, McGill University
  • Azrieli Foundation

Project Overview

Epilepsy is a debilitating neurological disorder that affects up to one percent of the world’s population. A third of epileptic patients suffer from drug-resistant form of the disease for which brain surgical intervention is often necessary. The current scientific challenge is twofold: first to advance our understanding of the biological underpinnings of epilepsy and second to improve diagnostic methods, especially a better localization of the affected brain regions to minimize the side effects of surgery. While epilepsy has many underlying causes, it is eventually characterized in all cases by abnormal electrical brain activity. Decades of animal research have provided key insights in the underlying genetic and physiological basis of epilepsy. However, animal research cannot reproduce all aspects of human epilepsy. It has thus become crucial to improve our understanding of how neurons – the electrically charged cells of the nervous system – participate in human epilepsy. Prior to the surgery that aims to resect the affected brain area, some patients are implanted with intra-cerebral electrodes that record brain electrical waves generated by ensembles of millions of neurons. Examination of these recordings during epileptic seizures allows the neurologists to localize the epileptic focus. Recently developed micro-electrodes now enable recording from individual neurons in the human brain. This technology opens avenues for the investigation of the neuronal mechanisms of epilepsy. Neurons are highly diverse in the brain but can be broadly divided into excitatory and inhibitory neurons, which activate or bring to silence, respectively, the neurons they make contact with. A large body of literature in animal research suggests that inhibitory neurons may play a key role in the onset of seizures. We will test the hypothesis that similar mechanisms are at play in human epilepsy. This research program will provide foundation for the development of future treatment and diagnostic methods.