It is generally believed that patients with primary generalized epilepsy have normal cognition and neuroimaging studies. We have previously shown that patients with juvenile myoclonic epilepsy (JME) have impaired visual working memory. In this study we examined relative regional changes in 18FDG uptake during a visual working memory paradigm in patients with JME. At rest, there were regional decreases in relative glucose uptake compared to controls. Unlike control subjects, increased activity in the dorsolateral prefrontal cortex was not found during the working memory task. Other regions with increased uptake in controls, such as premotor cortex and basal frontal cortex, also showed no increases, whereas medical temporal structures appeared to play a role in JME but not in control subjects' task performance. The data suggest that JME, a type of primary generalized epilepsy, may suffer from cortical disorganization that affects both the epileptogenic potential and frontal lobe cognitive functioning.