Grant success for our Neuroscience group
Members of our Neuroscience group have been awarded funding from Epilepsy Research UK. Details can be found below
Title: How activation of sensory regions can promote propagation of adjacent focal neocortical seizures
Investigators: Jason Berwick (PI), Sam Harris, Paul Overton, Theodore Schwartz (Cornell Weil Medical College, New York, USA) Ying Zheng (University of Reading) and Aneurin Kennerley.
Duration: 24 months
Understanding how seizures propagate across the brain is important to informing ictal semiology and symptomatology and enhancing treatments in pharmacoresistant focal epilepsy. Recent evidence has indicated seizure propagation to be restrained by powerful feed-forward inhibition in the ictal penumbra, but the mechanisms and circumstances which cause failure of the inhibitory restraint remain poorly understood. In a recent pilot study, we have found evidence that vibrissal stimulation in the urethane-anaesthetised rat promotes propagation of focal acute 4-aminopyridine (4-AP) seizures in visual cortex into neighbouring sensory-activated vibrissal cortex. Based on our previous work, we hypothesise that a reduced efficacy of inhibition during repetitive sensory stimulation results in a local weakening of the inhibitory restraint allowing seizure propagation. Using our established multi-modal methodology, we now propose to characterise how stimulus-induced shifts in the balance between excitation and inhibition in sensory cortex can facilitate its recruitment into an epileptic network, and describe the laterolaminar properties of electrographic epileptiform activity, and associated hemodynamic correlates, during seizure propagation. Investigating how normal cortical function can promote seizure propagation and the neurophysiological basis of haemodynamic signals in epilepsy may have important implications for our understanding of epileptic network properties and the localisation of epileptic foci.
Epileptic seizures can start in a small part of the brain before quickly spreading to others, but very little is known about how or why. Finding where seizures begin in the brain is important so that patients that aren’t helped by medication can be treated. Studying the way seizures spread is also important for learning how a person can feel and act during seizures. We have found that stimulating the whiskers of a rat can make seizures that start in different parts of the brain spread more easily to those that receive information from the whiskers. We believe that stimulation of the senses ‘weakens’ certain parts of the brain so that they give in to incoming seizures and allow their spread. We want to learn how, and measure the changes in the way brain cells work and are fed by blood during the spread of seizures. Our work in animals will help us understand how and when seizures can spread across the brain. What we find can then be tested in people in the medium to long-term and could improve how we find where seizures begin. This could help to improve treatments that control and cure seizures.