Females with fragile X syndrome, the most common form of inherited developmental and learning problems, are known to be impaired in executive function. The current study is the first to investigate the performance of females with fragile X on a cognitive interference task utilizing functional magnetic resonance imaging (fMRI). Fourteen females with fragile X and 14 age-matched healthy controls were imaged while they performed a counting Stroop interference task. Compared to controls, females with fragile X appeared to have longer reaction times during the interference condition of the task, and adopted a strategy trading speed for accuracy. Females with fragile X also had a significantly different pattern of activation than controls. Whereas controls showed significant activation in the inferior/ middle frontal gyrus and inferior/superior parietal lobe, females with fragile X showed more extensive activation in the anterior region of the prefrontal cortex, and failed to show expected activation in the inferior/superior parietal lobe. Further, between-group analyses revealed that females with fragile X had reduced activation in the left orbitofrontal gyrus, thought to be involved in modulating goal-directed behavior. Females with fragile X also demonstrated a markedly different pattern of deactivation from controls. These findings suggest that deficits in cognitive interference processing during the counting Stroop task observed in females with fragile X may arise from inability to appropriately recruit and modulate lateral prefrontal and parietal resources.

Williams syndrome (WMS), a genetic condition resulting from a contiguous deletion on the long arm of chromosome 7, is associated with a relatively consistent profile of neurocognitive and neurobehavioral features. The distinctiveness and regularity of the profile of learning and behavioral characteristics in this genetic condition suggests that underlying neurobiological correlates may be identifiable. In this initial study, we report findings derived from a high-resolution neuroimaging study of 14 young adult subjects with WMS and an individually matched normal control group. Compared to controls, subjects with WMS were noted to have decreased overall brain and cerebral volumes, relative preservation of cerebellar and superior temporal gyrus (STG) volumes, and disproportionate volume reduction of the brainstem. Analyses also suggested that the pattern of cerebral lobe proportions in WMS may be altered compared to normal controls with a greater ratio of frontal to posterior (parietal+occipital) tissue. Assessment of tissue composition indicated that, relative to controls, individuals with WMS have relative preservation of cerebral gray matter volume and disproportionate reduction in cerebral white matter volume. However, within the cerebral gray matter tissue compartment, the right occipital lobe was noted to have excess volume loss. Combined with our growing knowledge of the function of genes in the commonly deleted region for WMS, more detailed information regarding the structure and function of the WMS brain will provide a unique opportunity for elucidating meaningful correlations amongst genetic, neurobiological, and neurobehavioral factors in humans.