To begin to study the importance of dopamine for executive function abilities dependent on prefrontal cortex during early childhood, the present investigation studied children in whom we predicted reduced dopamine in prefrontal cortex but otherwise normal brains. These are children treated early and continuously for the metabolic disorder phenylketonuria (PKU). Untreated PKU is the most common biochemical cause of mental retardation. The root problem is an inability to convert one amino acid, phenylalanine (Phe), into another, tyrosine (Tyr), the precursor of dopamine. Phe levels in the bloodstream soar; Tyr levels fall. Treatment with a diet low in Phe reduces the Phe:Tyr imbalance but cannot eliminate it. We hypothesized that the resultant modest elevation in the ratio of Phe to Tyr in the blood, which results in slightly less Tyr reaching the brain, uniquely affects the cognitive functions dependent on prefrontal cortex because of the special sensitivity of prefrontally projecting dopamine neurons to small decreases in Tyr. In a 4-year longitudinal study, we found that PKU children whose plasma Phe levels were three to five times normal (6-10 mg/dl) performed worse than other PKU children with lower Phe levels, matched controls, their own siblings, and children from the general population on tasks that required the working memory and inhibitory control abilities dependent on dorsolateral prefrontal cortex. The impairment was as evident in our oldest age range (3 1/2-7 years) as it was in the youngest (6-12 months). The higher a child's Phe level, the worse that child's performance. Girls were more adversely affected than boys. The deficit appears to be selective, affecting principally one neural system, since even PKU children with Phe levels three to five times normal performed well on the 13 control tasks. Clinical implications for the treatment of PKU and other neurodevelopmental disorders are discussed.

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The Stroop color-word task cannot be administered to children who are unable to read. However, our color-object Stroop task can. One hundred and sixty-eight children of 3½-6½ years (50% female; 24 children at each 6-month interval) were shown line drawings of familiar objects in a color that was congruent (e.g., an orange carrot), incongruent (e.g., a green carrot), or neutral (for objects having no canonical color [e.g., a red book]), and abstract shapes, each drawn in one of six colors. Half the children were asked to name the color in which each object was drawn, and half were to name each object. Children's predominant tendency was to say what the object was; when instructed to do otherwise they were slower and less accurate. Children were faster and more accurate at naming the color of a stimulus when the form could not be named (abstract shape) than when it could, even if in its canonical color. The heightened interference to color-naming versus object-naming was not due to lack of familiarity with color names or group differences: Children in the color condition were as fast and accurate at naming the colors of abstract shapes as were children in the form condition at naming familiar objects.

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