Fragile X syndrome (FXS) is a neurodevelopmental disorder that represents the most common known cause of developmental delay. Recent neuropsychological findings indicate that females with FXS present with a specific pattern of cognitive deficits and that these difficulties primarily involve skills requiring executive control. The present study is the first to examine the extent to which neural activity of females with FXS can be observed on a task that specifically taps two core deficits, namely switching and response inhibition. Brain activity was measured using both event-related electrical potentials (ERPs) and event-related functional MRI (fMRI) neuroimaging in separate studies using the same cognitive paradigm. Compared to controls, females with FXS were significantly slower and made more errors on trials that required an immediate response (Go) to stimulus onset but were comparable on trials that required a delayed response (Wait) to stimulus onset. At the brain level, several areas showed significantly greater activation for females with FXS compared with controls, including the cingulate cortex and left and right ventral prefrontal areas. In contrast. no areas were found to show significantly greater activation for controls compared with females with FXS. (C) 2004 Elsevier Inc. All rights reserved.