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

青少年肌阵挛癫痫(JME)是一种常见的癫痫综合征。JME患者具有较高的遗传易感性，且涉及多个基因。在过去的几年中，几项临床研究发现JME患者存在微妙的认知缺陷，主要影响额脑功能，如视觉工作记忆和执行功能，即计划。先进的成像研究提示存在细微的结构和功能异常，主要涉及额脑的特定区域，以及更深层次的大脑结构(丘脑)。考虑到遗传易感性，这有力地支持了年龄相关和遗传决定的脑网络功能障碍的概念，表现为癫痫和认知缺陷。到目前为止，一些研究可以在其他健康的JME兄弟姐妹中识别出细微的认知缺陷。在即将到来的研究中，我们计划使用功能磁共振成像(FMRI)来研究遗传构成对JME认知缺陷的影响。功能磁共振成像将帮助我们识别在特定记忆任务中激活的大脑区域。我们将使用功能磁共振成像和神经心理测试对JME患者、他们的健康同胞和健康对照进行调查。我们假设，与健康对照组相比，患者和兄弟姐妹在功能磁共振成像上将显示出不同的认知激活模式。神经学研究所之前的一项关于工作记忆的fMRI研究可能显示，JME患者大脑运动区--运动皮质--的显著异常共激活。在接受抗癫痫药物丙戊酸盐(VPA)治疗的患者中，这种协同作用与VPA剂量呈负相关。假设这些发现是JME特有的，并且是基因决定的，我们也假设JME兄弟姐妹的运动皮质也有类似的共同激活。

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.