The effects of genetic make-up on cognition in juvenile myoclonic epilepsy

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Juvenile myoclonic epilepsy (JME) is a common epilepsy syndrome. There is a high genetic predisposition associated with JME and an involvement of several genes has been discussed.Within the last years, several clinical studies elicited subtle cognitive deficits in JME-patients, mainly affecting frontal brain functions, such as visual working memory and executive functions, i.e. planning. Advanced imaging studies suggest subtle structural and functional abnormalities, mainly involving specific areas of the frontal brain, as well as deeper brain structures (thalami). Taking the genetic predisposition into account, this strongly supports the concept of an age-related and genetically determined brain-network-dysfunction presenting with both seizures and cognitive deficits. So far, some studies could identify subtle cognitive deficits in otherwise healthy JME siblings.In the forthcoming study, we plan to investigate the influence of genetic make-up on cognitive deficits in JME using functional MRI imaging (fMRI). FMRI will help us to identify the brain areas which are activated during specific memory tasks. We will investigate JME patients, their healthy siblings and healthy controls using fMRI and neuropsychological testing. We hypothesize that patients and siblings will show different cognitive activation patterns in comparison to healthy controls on fMRI. A previous fMRI study on working memory of the Institute of Neurology could show a significant abnormal coactivation of the movement area of the brain, the motor cortex, in JME patients. In patients treated with the antiepileptic agent valproate (VPA) this coactiviation correlated negatively with VPA dosage. Assuming that these findings are specific for JME and genetically determinate, we also hypothesize a similar coactivation of motor cortex in JME siblings.